bluuebunny/crossref_metadata_2025_split huggingface dataset:
Haloalkylphosphorus Hydrolases Purified from Sphingomonas sp. Strain TDK1 and Sphingobium sp. Strain TCM1
Authors: Abe Katsumasa , Yoshida Satoshi , Suzuki Yuto , Mori Junichi , Doi Yuka , Takahashi Shouji , Kera Yoshio 
Published: July 2014

ABSTRACT

Phosphotriesterases catalyze the first step of organophosphorus triester degradation. The bacterial phosphotriesterases purified and characterized to date hydrolyze mainly aryl dialkyl phosphates, such as parathion, paraoxon, and chlorpyrifos. In this study, we purified and cloned two novel phosphotriesterases from
Sphingomonas
sp. strain TDK1 and
Sphingobium
sp. strain TCM1 that hydrolyze tri(haloalkyl)phosphates, and we named these enzymes haloalkylphosphorus hydrolases (TDK-HAD and TCM-HAD, respectively). Both HADs are monomeric proteins with molecular masses of 59.6 (TDK-HAD) and 58.4 kDa (TCM-HAD). The enzyme activities were affected by the addition of divalent cations, and inductively coupled plasma mass spectrometry analysis suggested that zinc is a native cofactor for HADs. These enzymes hydrolyzed not only chlorinated organophosphates but also a brominated organophosphate [tris(2,3-dibromopropyl) phosphate], as well as triaryl phosphates (tricresyl and triphenyl phosphates). Paraoxon-methyl and paraoxon were efficiently degraded by TCM-HAD, whereas TDK-HAD showed weak activity toward these substrates. Dichlorvos was degraded only by TCM-HAD. The enzymes displayed weak or no activity against trialkyl phosphates and organophosphorothioates. The TCM-HAD and TDK-HAD genes were cloned and found to encode proteins of 583 and 574 amino acid residues, respectively. The primary structures of TCM-HAD and TDK-HAD were very similar, and the enzymes also shared sequence similarity with fenitrothion hydrolase (FedA) of
Burkholderia
sp. strain NF100 and organophosphorus hydrolase (OphB) of
Burkholderia
sp. strain JBA3. However, the substrate specificities and quaternary structures of the HADs were largely different from those of FedA and OphB. These results show that HADs from sphingomonads are novel members of the bacterial phosphotriesterase family.
Regulation of Natural mRNAs by the Nonsense-Mediated mRNA Decay Pathway
Authors: Peccarelli Megan , Kebaara Bessie W. 
Published: July 2014

ABSTRACT

The nonsense-mediated mRNA decay (NMD) pathway is a specialized mRNA degradation pathway that degrades select mRNAs. This pathway is conserved in all eukaryotes examined so far, and it triggers the degradation of mRNAs that prematurely terminate translation. Originally identified as a pathway that degrades mRNAs with premature termination codons as a result of errors during transcription, splicing, or damage to the mRNA, NMD is now also recognized as a pathway that degrades some natural mRNAs. The degradation of natural mRNAs by NMD has been identified in multiple eukaryotes, including
Saccharomyces cerevisiae
,
Drosophila melanogaster
,
Arabidopsis thaliana
, and humans.
S. cerevisiae
is used extensively as a model to study natural mRNA regulation by NMD. Inactivation of the NMD pathway in
S. cerevisiae
affects approximately 10% of the transcriptome. Similar percentages of natural mRNAs in the
D. melanogaster
and human transcriptomes are also sensitive to the pathway, indicating that NMD is important for the regulation of gene expression in multiple organisms. NMD can either directly or indirectly regulate the decay rate of natural mRNAs. Direct NMD targets possess NMD-inducing features. This minireview focuses on the regulation of natural mRNAs by the NMD pathway, as well as the features demonstrated to target these mRNAs for decay by the pathway in
S. cerevisiae
. We also compare NMD-targeting features identified in
S. cerevisiae
with known NMD-targeting features in other eukaryotic organisms.
Cross Kingdom Functional Conservation of the Core Universally Conserved Threonylcarbamoyladenosine tRNA Synthesis Enzymes
Authors: Thiaville Patrick C. , El Yacoubi Basma , Perrochia Ludovic , Hecker Arnaud , Prigent Magali , Thiaville Jennifer J. , Forterre Patrick , Namy Olivier , Basta Tamara , de Crécy-Lagard Valérie 
Published: July 2014

ABSTRACT

Threonylcarbamoyladenosine (t
6
A) is a universal modification located in the anticodon stem-loop of tRNAs. In yeast, both cytoplasmic and mitochondrial tRNAs are modified. The cytoplasmic t
6
A synthesis pathway was elucidated and requires Sua5p, Kae1p, and four other KEOPS complex proteins. Recent
in vitro
work suggested that the mitochondrial t
6
A machinery of
Saccharomyces cerevisiae
is composed of only two proteins, Sua5p and Qri7p, a member of the Kae1p/TsaD family (L. C. K. Wan et al., Nucleic Acids Res. 41:6332–6346, 2013,
http://dx.doi.org/10.1093/nar/gkt322
). Sua5p catalyzes the first step leading to the threonyl-carbamoyl-AMP intermediate (TC-AMP), while Qri7 transfers the threonyl-carbamoyl moiety from TC-AMP to tRNA to form t
6
A. Qri7p localizes to the mitochondria, but Sua5p was reported to be cytoplasmic. We show that Sua5p is targeted to both the cytoplasm and the mitochondria through the use of alternative start sites. The import of Sua5p into the mitochondria is required for this organelle to be functional, since the TC-AMP intermediate produced by Sua5p in the cytoplasm is not transported into the mitochondria in sufficient amounts. This minimal t
6
A pathway was characterized
in vitro
and, for the first time,
in vivo
by heterologous complementation studies in
Escherichia coli
. The data revealed a potential for TC-AMP channeling in the t
6
A pathway, as the coexpression of Qri7p and Sua5p is required to complement the essentiality of the
E. coli
tsaD
mutant. Our results firmly established that Qri7p and Sua5p constitute the mitochondrial pathway for the biosynthesis of t
6
A and bring additional advancement in our understanding of the reaction mechanism.
Towards creating the perfect electronic prescription
Authors: Dhavle Ajit A , Rupp Michael T 
Published: July 2014

Abstract
Significant strides have been made in electronic (e)-prescribing standards and software applications that have further fueled the adoption and use of e-prescribing. However, for e-prescribing to realize its full potential for improving the safety, effectiveness, and efficiency of prescription drug delivery, important work remains to be carried out. This perspective describes the ultimate goal of all e-prescribing stakeholders including prescribers and dispensing pharmacists: a clear, complete, and unambiguous e-prescription order that can be seamlessly received, processed, and fulfilled at the dispensing pharmacy without the need for additional clarification from the prescriber. We discuss the challenges to creating the perfect e-prescription by focusing on selected data segments and data fields that are available in the new e-prescription transaction as defined in the NCPDP SCRIPT Standard and suggest steps that could be taken to move the industry closer to achieving this vision.
Clinical findings just after return to play predict hamstring re-injury, but baseline MRI findings do not
Authors: De Vos Robert-Jan , Reurink Gustaaf , Goudswaard Gert-Jan , Moen Maarten H , Weir Adam , Tol Johannes L 
Published: July 2014

BackgroundAcute hamstring re-injuries are common and hard to predict. The aim of this study was to investigate the association between clinical and imaging findings and the occurrence of hamstring re-injuries.MethodsWe obtained baseline data (clinical and MRI findings) of athletes who sustained an acute hamstring injury within 5 days of initial injury. We also collected data of standardised clinical tests within 7 days after return to play (RTP). The number of re-injuries was recorded within 12 months. We analysed the association between the possible predictive variables and re-injuries with a multivariate Cox proportional-hazards regression model.ResultsEighty patients were included at baseline and 64 patients could be included in the final analysis because data after RTP were not available in 16 cases. There were 17 re-injuries (27%). None of the baseline MRI findings were univariately associated with re-injury. A higher number of previous hamstring injuries (adjusted OR (AOR) 1.33; 95% CI 1.11 to 1.61), more degrees of active knee extension deficit after RTP (AOR 1.13; 95% CI 1.03 to 1.25), isometric knee flexion force deficit at 15° after RTP (AOR 1.04; 95% CI 1.01 to 1.07) and presence of localised discomfort on hamstring palpation after RTP (AOR 3.95; 95% CI 1.38 to 11.37) were significant independent predictors of re-injury. Athletes with localised discomfort on hamstring palpation just after RTP were consequently almost four times more likely to sustain a re-injury.ConclusionsThe number of previous hamstring injuries, active knee extension deficit, isometric knee flexion force deficit at 15° and presence of localised discomfort on palpation just after RTP are associated with a higher hamstring re-injury rate. None of the baseline MRI parameters was a predictor of hamstring re-injury.Trial registration numberClinicalTrial.gov numberNCT01812564.
Assessing the effect of an interactive decision-aid smartphone smoking cessation application (app) on quit rates: a double-blind automated randomised control trial protocol
Authors: BinDhim Nasser F , McGeechan Kevin , Trevena Lyndal 
Published: July 2014

IntroductionIn a previous study exploring the feasibility of a smoking cessation application (app), we found that about 77% of the respondents from three countries were ready to quit in the next 30 days without significant differences between countries in terms of age, operating system and number of quitting attempts. However, the efficacy of smartphone apps for smoking cessation has not yet been established. This study tests the efficacy of a smartphone smoking cessation decision-aid app compared with an app that contains only smoking cessation information.Methods and analysisThis is an automated double-blind, randomised controlled trial of a smoking cessation app that contains the eligibility requirements and baseline questionnaire and will randomise the participants into one of the two subapps (the intervention and the control). Participants will be recruited directly from the Apple app stores in Australia, Singapore, the UK and the USA. Daily smokers aged 18 and above will be randomised into one of the subapps after completing the baseline questionnaire. Abstinence rates will be measured at 10 days, 1 month, 3 months and 6 months, with the 1-month follow-up abstinence rate as the primary outcome. Logistic regression mixed models will be used to analyse the primary outcome.Ethics and disseminationThis study was approved by the University of Sydney's Human Ethics Committee. The results of the trial will be published in peer-reviewed journals according to the CONSORT statement.Trial registration numberAustralian New Zealand ClinicalTrial RegistryACTRN12613000833763.
Public acceptability of financial incentives for smoking cessation in pregnancy and breast feeding: a survey of the British public
Authors: Hoddinott Pat , Morgan Heather , MacLennan Graeme , Sewel Kate , Thomson Gill , Bauld Linda , Yi Deokhee , Ludbrook Anne , Campbell Marion K 
Published: July 2014

ObjectiveTo survey public attitudes about incentives for smoking cessation in pregnancy and for breast feeding to inform trial design.DesignCross-sectional survey.Setting and participantsBritish general public.MethodsSeven promising incentive strategies had been identified from evidence syntheses and qualitative interview data from service users and providers. These were shopping vouchers for: (1) validated smoking cessation in pregnancy and (2) after birth; (3) for a smoke-free home; (4) for proven breast feeding; (5) a free breast pump; (6) payments to health services for reaching smoking cessation in pregnancy targets and (7) breastfeeding targets. Ipsos MORI used area quota sampling and home-administered computer-assisted questionnaires, with randomised question order to assess agreement with different incentives (measured on a five-point scale). Demographic data and target behaviour experience were recorded. Analysis used multivariable ordered logit models.ResultsAgreement with incentives was mixed (ranging from 34% to 46%) among a representative sample of 1144 British adults. Mean agreement score was highest for a free breast pump, and lowest for incentives for smoking abstinence after birth. More women disagreed with shopping vouchers than men. Those with lower levels of education disagreed more with smoking cessation incentives and a breast pump. Those aged 44 or under agreed more with all incentive strategies compared with those aged 65 and over, particularly provider targets for smoking cessation. Non-white ethnic groups agreed particularly with breastfeeding incentives. Current smokers with previous stop attempts and respondents who had breast fed children agreed with providing vouchers for the respective behaviours. Up to £40/month vouchers for behaviour change were acceptable (>85%).ConclusionsWomen and the less educated were more likely to disagree, but men and women of childbearing age to agree, with incentives designed for their benefit. Trials evaluating reach, impact on health inequalities and ethnic groups are required prior to implementing incentive interventions.Trial registration numberCRD42012001980.
Natural Killer Cells Eradicate Galectin-1–Deficient Glioma in the Absence of Adaptive Immunity
Authors: Baker Gregory J. , Chockley Peter , Yadav Viveka Nand , Doherty Robert , Ritt Michael , Sivaramakrishnan Sivaraj , Castro Maria G. , Lowenstein Pedro R. 
Published: July 2014

Abstract
Natural killer (NK) cells safeguard against early tumor formation by destroying transformed target cells in a process referred to as NK immune surveillance. However, the immune escape mechanisms used by malignant brain tumors to subvert this innate type of immune surveillance remain unclear. Here we show that malignant glioma cells suppress NK immune surveillance by overexpressing the β-galactoside–binding lectin galectin-1. Conversely, galectin-1–deficient glioma cells could be eradicated by host NK cells before the initiation of an antitumor T-cell response. In vitro experiments demonstrated that galectin-1–deficient GL26-Cit glioma cells are ∼3-fold more sensitive to NK-mediated tumor lysis than galectin-1–expressing cells. Our findings suggest that galectin-1 suppression in human glioma could improve patient survival by restoring NK immune surveillance that can eradicate glioma cells. Cancer Res; 74(18); 5079–90. ©2014 AACR.
Is the “3+3” Dose-Escalation Phase I Clinical Trial Design Suitable for Therapeutic Cancer Vaccine Development? A Recommendation for Alternative Design
Authors: Rahma Osama E. , Gammoh Emily , Simon Richard M. , Khleif Samir N. 
Published: July 2014

Abstract
Purpose: Phase I clinical trials are generally conducted to identify the maximum tolerated dose (MTD) or the biologically active dose (BAD) using a traditional dose-escalation design. This design may not be applied to cancer vaccines, given their unique mechanism of action. The FDA recently published “Guidance for Industry: Clinical Considerations for Therapeutic Cancer Vaccines.” However, many questions about the design of cancer vaccine studies remain unanswered.
Experimental Design: We analyzed the toxicity profile in 239 phase I therapeutic cancer vaccine trials. We addressed the ability of dose escalation to determine the MTD or the BAD in trials that used a dose-escalation design.
Results: The rate of grade 3/4 vaccine-related systemic toxicities was 1.25 adverse events per 100 patients and 2 per 1,000 vaccines. Only two of the 127 dose-escalation trials reported vaccine-related dose limiting toxicities, both of which used bacterial vector vaccines. Out of the 116 trials analyzed for the dose–immune response relationship, we found a statistically significant dose–immune response correlation only when the immune response was measured by antibodies (P &lt; 0.001) or delayed type hypersensitivity (P &lt; 0.05). However, the increase in cellular immune response did not appear further sustainable with the continued increase in dose.
Conclusions: Our analysis suggests that the risks of serious toxicities with therapeutic cancer vaccines are extremely low and that toxicities do not correlate with dose levels. Accordingly, the conventional dose-escalation design is not suitable for cancer vaccines with few exceptions. Here, we propose an alternative design for therapeutic cancer vaccine development. Clin Cancer Res; 20(18); 4758–67. ©2014 AACR.
Adult Moyamoya Disease in an Urban Center in the United States Is Associated With a High Burden of Watershed Ischemia
Authors: Zafar Sahar F. , Bershad Eric M. , Gildersleeve Kasey L. , Newmark Michael E. , Calvillo Eusebia , Suarez Jose I. , Venkatasubba Rao Chethan P. 
Published: July 2014

Background
Adult moyamoya disease is rare in the United States, and patients mostly present with cerebral ischemia. However, clinical and neurodiagnostic correlates of ischemia are not well known in this population. We sought to characterize the clinical and radiographic features of moyamoya disease in a large urban center in the United States, with a focus on angiographic and neuroimaging patterns of ischemia.

Methods and Results
We retrospectively reviewed charts of consecutive adult moyamoya disease patients evaluated at 2 centers in Houston, Texas from January 2002 to December 2011. We reviewed all available cerebral angiograms and neuroimaging studies to evaluate the Suzuki grades, presence of intracranial hemorrhage or ischemia, infarct patterns, and vascular territory distribution. Our analysis was mainly descriptive. We identified 31 adults with moyamoya disease who met our inclusion criteria. The female‐to‐male ratio was 2.4:1. The majority of patients were white, followed by Hispanic, black, and Asian. Most presented with ischemia (61%), followed by headaches, and intracranial hemorrhage. Of the 22 patients with available neuroimaging, 72.7% had ischemic findings, with the vast majority having a watershed pattern (81.3%).

Conclusions
We observed a high burden of ischemia, mostly watershed pattern on neuroimaging in our adult moyamoya disease patients. Long‐term monitoring of adult moyamoya disease patients in the United States would be useful to better understand the natural history of this condition.
Consumption and prey size selection of the nematode Caenorhabditis elegans by different juvenile stages of freshwater fish
Authors: Weber Sebastian , Weber Sebastian , Traunspurger Walter 
Published: July 2014

Meiofauna, and nematodes in particular, play an essential role in the diet of certain juvenile freshwater fish. However, the specific consumption and prey size selection of fishes on nematodes is largely unrecognised. In this study, the effects of different juvenile stages of widely distributed common European freshwater fish, gudgeon (Gobio gobio), roach (Rutilus rutilus), ninespine stickleback (Pungitius pungitius), and two strains of common carp (Cyprinus carpio(scaled) andC. carpio(mirror)), on abundances of the nematodeCaenorhabditis eleganswere investigated in controlled laboratory experiments with a known number of prey. Gudgeon, carp (scaled), and carp (mirror) consumed significant amounts of nematodes, whereas the roach and ninespine stickleback did not. Both strains of common carp reduced nematode abundance dependent on the size of the fish, with smaller fish causing a greater reduction than medium-size or large fish, although fish of all sizes fed significantly on nematodes of all size classes (<0.5, 0.5-1.0 and >1.0 mm). While the gudgeon also reduced nematode abundance dependent on the size of the fish, with increasing body length there was a dietary shift towards larger nematode size classes (0.5-1.0 and >1.0 mm). Morphometric analysis of the branchial basket indicated that the mesh width of gudgeon and both strains of common carp, but not of roach and ninespine stickleback, is suitable for feeding on specific size classes of nematodes. Together, the results showed that nematodes are used as a food source for different juvenile stages of certain species of freshwater fish.
Meloidogyne lopezi n. sp. (Nematoda: Meloidogynidae), a new root-knot nematode associated with coffee (Coffea arabica L.) in Costa Rica, its diagnosis and phylogenetic relationship with other coffee-parasitising Meloidogyne species
Authors: Humphreys-Pereira Danny A. , Humphreys-Pereira Danny A. , Flores-Chaves Lorena , Humphreys-Pereira Danny A. , Flores-Chaves Lorena , Gómez Melissa , Humphreys-Pereira Danny A. , Flores-Chaves Lorena , Gómez Melissa , Salazar Luis , Humphreys-Pereira Danny A. , Flores-Chaves Lorena , Gómez Melissa , Salazar Luis , Gómez-Alpízar Luis , Humphreys-Pereira Danny A. , Flores-Chaves Lorena , Gómez Melissa , Salazar Luis , Gómez-Alpízar Luis , Elling Axel A. 
Published: July 2014

Coffee (Coffea arabica L. cv. Catuai) seedlings with abundant small root galls caused by an unknown root-knot nematode were found in southern Costa Rica. Morphology, esterase and malate dehydrogenase isozyme phenotypes and DNA markers differentiated this nematode from known Meloidogyne spp. A new species, M. lopezi n. sp., with common name Costa Rican root-knot nematode, is suggested. Meloidogyne lopezi n. sp. is distinguished from other coffee-associated Meloidogyne spp. by size of female lips and stylet, male body length and stylet and second-stage juvenile body and tail morphology. The region of the mitochondrial genome between COII and 16S rRNA showed a unique amplicon size of 1370 bp, and digestions with restriction enzymes HinfI, AluI, DraI and DraIII revealed characteristic PCR-RFLP patterns that differed from the tropical root-knot nematode species M. arabicida, M. incognita, M. izalcoensis, M. javanica and M. paranaensis. Characterisation of the protein-coding map-1 gene and phylogenetic analyses suggested that M. lopezi n. sp. might reproduce by mitotic parthenogenesis. Phylogenies estimated using Bayesian analyses based on the region between the COII and 16S rRNA mitochondrial genes, as well as the 18S and 28S ribosomal nuclear genes, indicated that M. lopezi n. sp. is closely related to other tropical Meloidogyne spp. that infect coffee, especially M. arabicida, M. izalcoensis and M. paranaensis from Central and South America. Isozyme analyses and PCR-RFLP of the COII-16S rRNA mitochondrial gene region enable a clear diagnostic differentiation between these species.
Improving suppression of Meloidogyne spp. by Purpureocillium lilacinum strain 251
Authors: Parajuli Gita , Parajuli Gita , Kemerait Robert , Parajuli Gita , Kemerait Robert , Timper Patricia 
Published: July 2014

The fungus Purpureocillium lilacinum (syn. Paecilomyces lilacinus) is marketed for control of plant-parasitic nematodes in several countries. Our objectives in this study were to determine whether suppression of Meloidogyne spp. by P. lilacinum strain 251 was affected by the crop plant and whether growing winter cover crops such as rye and crimson clover would improve suppression of M. incognita on cotton by the fungus. All experiments were conducted in a glasshouse using non-sterilised field soil. To determine the relative efficacy of P. lilacinum on cotton (Gossypium hirsutum), peanut (Arachis hypogaea) and maize (Zea mays), four concentrations of P. lilacinum (NemOut™) were applied in furrow: 336, 252, 168 and 0 g ha−1. Although the fungus reduced numbers of eggs of Meloidogyne spp. on all crops, percentage suppression was lower on maize than on cotton and peanut at all inoculum levels of P. lilacinum. When rye and crimson clover were grown in pots for 30 days and then killed with a herbicide prior to applying P. lilacinum and M. incognita and planting cotton, the fungus failed to suppress numbers of nematode eggs when the surface residues of the cover crops were removed. However, when the residues were left on the soil surface, percentage suppression (49% for clover and 63% for rye) was greater than when the soil was left fallow (36%). The residues could have created conditions that were more conducive than bare soil to the fungus, such as lower soil temperatures and increase moisture retention.