bluuebunny/crossref_metadata_2025_split huggingface dataset:
The cyclase‐associated protein FgCap1 has both protein kinase A‐dependent and ‐independent functions during deoxynivalenol production and plant infection in Fusarium graminearum
Authors: Yin Tao , Zhang Qiang , Wang Jianhua , Liu Huiquan , Wang Chenfang , Xu Jin‐Rong , Jiang Cong 
Published: January 2017

SummaryFusarium graminearum is a causal agent of wheat scab and a producer of the trichothecene mycotoxin deoxynivalenol (DON). The expression of trichothecene biosynthesis (TRI) genes and DON production are mainly regulated by the cyclic adenosine monophosphate‐protein kinase A (cAMP‐PKA) pathway and two pathway‐specific transcription factors (TRI6 and TRI10). Interestingly, deletion mutants of TRI6 show reduced expression of several components of cAMP signalling, including the FgCAP1 adenylate‐binding protein gene that has not been functionally characterized in F. graminearum. In this study, we show that FgCap1 interacts with Fac1 adenylate cyclase and that deletion of FgCAP1 reduces the intracellular cAMP level and PKA activity. The Fgcap1 deletion mutant is defective in vegetative growth, conidiogenesis and plant infection. It also shows significantly reduced DON production and TRI gene expression, which can be suppressed by exogenous cAMP, indicating a PKA‐dependent regulation of DON biosynthesis by FgCap1. The wild‐type, but not tri6 mutant, shows increased levels of intracellular cAMP and FgCAP1 expression under DON‐producing conditions. Furthermore, the promoter of FgCAP1 contains one putative Tri6‐binding site that is important for its function during DON biosynthesis, but is dispensable for hyphal growth, conidiogenesis and pathogenesis. In addition, FgCap1 shows an actin‐like localization to the cortical patches at the apical region of hyphal tips. Phosphorylation of FgCap1 at S353 was identified by phosphoproteomics analysis. The S353A mutation in FgCAP1 has no effect on its functions during vegetative growth, conidiation and DON production. However, expression of the FgCAP1S353A allele fails to complement the defects of the Fgcap1 mutant in plant infection, indicating the importance of the phosphorylation of FgCap1 at S353 during pathogenesis. Taken together, our results suggest that FgCAP1 is involved in the regulation of DON production via cAMP signalling and subjected to a feedback regulation by TRI6, but the phosphorylation of FgCap1 at S353 is probably unrelated to the cAMP‐PKA pathway because the S353A mutation only affects plant infection.
Mapping and validation of the quantitative trait loci for leaf stay‐green‐associated parameters in maize
Authors: Yang Zhen , Li Xin , Zhang Ning , Wang Xiaolei , Zhang Yuna , Ding Yulong , Kuai Benke , Huang Xueqing 
Published: January 2017

AbstractFunctional stay‐green is generally regarded as a desirable trait of varieties in major crops including maize. In this study, we used an F3:4recombinant inbred line population with 165 lines from a cross between a stay‐green inbred line (Zheng58) and a model inbred line (B73) using 211 polymorphic simple sequence repeat markers to map quantitative trait loci for three stay‐green‐associated parameters, chlorophyll content, photosystemIIphotochemical efficiency and stay‐green area, at maturity stage, detected a total of 23 quantitative trait loci (QTL) on nine chromosomes. SingleQTLexplained 3.7–13.5% of the phenotypic variance. Additionally, we validated some important stay‐greenQTLusing a heterogeneous inbred family approach and found that the stay‐green‐associated parameters were significantly correlated with the plant yield. This study may contribute to a better insight into the regulatory mechanism behind leaf stay‐green in maize and a novel development of elite maize varieties with delayed leaf senescence through molecular marker‐assisted selection.
Eosinophil transendothelial migration induced by the bronchoalveolar lavage fluid of acute eosinophilic pneumonia
Authors: Nakagome Kazuyuki , Shoda Hisakazu , Shirai Tetsu , Nishihara Fuyumi , Soma Tomoyuki , Uchida Yoshitaka , Sakamoto Yoshio , Nagata Makoto 
Published: January 2017

ABSTRACT
Background and objectiveAcute eosinophilic pneumonia (AEP) is characterized by a massive pulmonary infiltration of eosinophils. Mechanisms regulating the selective accumulation of eosinophils in AEP have not been fully established. The objective of this study was to evaluate the mechanisms of eosinophil accumulation in alveolar spaces through examination of bronchoalveolar lavage fluid (BALF) from AEP patients (AEP‐BALF).MethodsEosinophils were isolated from the blood of healthy subjects and were placed on a human pulmonary microvascular endothelial cell monolayer cultured on Transwell filters (Coster, Cambridge, MA, USA). A saline control solution or BALF from patients with AEP, sarcoidosis or hypersensitivity pneumonitis was applied to the lower compartment, and the transendothelial migration of the eosinophils was evaluated. The concentrations of cytokines and chemokines in BALF were also measured.ResultsTransmigration of eosinophils across endothelial cells was only induced by the AEP‐BALF. This transmigration was blocked by anti‐β2 integrin mAb. The concentrations of eotaxin‐2 and monocyte chemotactic protein (MCP)‐4, which are CC chemokine receptor (CCR) 3 ligands, were elevated in the AEP‐BALF, and anti‐CCR3 mAb or anti‐MCP‐4 mAb inhibited the AEP‐BALF‐induced transmigration of eosinophils. Furthermore, the concentration of leukotriene (LT) B4
was increased in the AEP‐BALF, and an LTB4
receptor antagonist partially suppressed the AEP‐BALF‐induced transmigration of eosinophils.ConclusionThese findings suggest that CCR3 ligands including eotaxin‐2 and MCP‐4, and LTB4
play a role in the accumulation of eosinophils in AEP.
Performance trends in age‐group runners from 100 m to marathon—The World Championships from 1975 to 2015
Authors: Nikolaidis P. T. , Zingg M. A. , Knechtle B. 
Published: January 2017

This study examined changes in performance in age‐group track runners across years from 1975 to 2015 for 100, 200, 400, 800, 1500, 5000, 10 000 m, and marathon and the corresponding sex differences. Athletes were ranked in 5‐year age‐group intervals from 35‐39 to 95‐99 years. For all races and all years, the eight female and male finalists for each age‐group were included. Men were faster than women and this observation was more pronounced in the shorter distances. The younger age‐groups were faster than the older age‐groups and age exerted the largest effect on speed in 800 m and the smallest in marathon. There was a small variation of speed by calendar years. The competition density varied by sex and race distance. Half of participants were from USA, Germany, Australia, and Great Britain, but the participants' nationality varied by sex and race distance. In summary, the variation of competitiveness by sex in short race distances might be important for athletes and coaches. Considering the event's competitiveness and that athletes are participating in both 100 and 200 m or in 200 and 400 m, master women should be oriented to 200 m and master men should be oriented to 100 and 400 m.
Stretch training induces unequal adaptation in muscle fascicles and thickness in medial and lateral gastrocnemii
Authors: Simpson C. L. , Kim B. D. H. , Bourcet M. R. , Jones G. R. , Jakobi J. M. 
Published: January 2017

This study compared adaptations in fascicle lengths, pennation angles, and muscle thickness of the lateral and medial gastrocnemii in response to 6 weeks of stretch training. The nondominant plantar flexors of 11 males were stretched five times per week for 6 weeks and compared with the contralateral leg and a nonstretched control group of 10 males. During stretch training, instantaneous electromyography was utilized to ensure passive muscle stretch. At baseline, week three, week six and 1 week after the conclusion of stretch training, ultrasound was used to measure fascicle lengths, pennation angles, muscle thickness of the lateral gastrocnemius and medial gastrocnemius, and Achilles tendon thickness and length. Plantar flexion torque was measured, and voluntary activation was assessed. Muscle thickness increased 5.6% after 6 weeks of stretch training (P=.009). The fascicles in the lateral gastrocnemius lengthened to a greater extent than the medial. Overall, fascicles lengthened 25% (P<.001) in the muscle tendon junction and 5.1% (P<.001) in the muscle belly. Pennation angles were unchanged in the medial gastrocnemius but decreased in the lateral gastrocnemius 7.1% (P=.02). There was no change in maximal voluntary contraction, voluntary activation, tendon length, or thickness. This study demonstrates that stretch training is a viable modality to alter muscle architecture of the human gastrocnemius through lengthening of muscle fascicles, decreasing pennation angles, and increasing muscle thickness, albeit adaptations are unequal between the lateral and medial heads.
Chlamydomonas carries out fatty acid β‐oxidation in ancestral peroxisomes using a bona fide acyl‐CoA oxidase
Authors: Kong Fantao , Liang Yuanxue , Légeret Bertrand , Beyly‐Adriano Audrey , Blangy Stéphanie , Haslam Richard P. , Napier Johnathan A. , Beisson Fred , Peltier Gilles , Li‐Beisson Yonghua 
Published: January 2017

SummaryPeroxisomes are thought to have played a key role in the evolution of metabolic networks of photosynthetic organisms by connecting oxidative and biosynthetic routes operating in different compartments. While the various oxidative pathways operating in the peroxisomes of higher plants are fairly well characterized, the reactions present in the primitive peroxisomes (microbodies) of algae are poorly understood. Screening of a Chlamydomonas insertional mutant library identified a strain strongly impaired in oil remobilization and defective in Cre05.g232002 (CrACX2), a gene encoding a member of the acyl‐CoA oxidase/dehydrogenase superfamily. The purified recombinant CrACX2 expressed in Escherichia coli catalyzed the oxidation of fatty acyl‐CoAs into trans‐2‐enoyl‐CoA and produced H2O2. This result demonstrated that CrACX2 is a genuine acyl‐CoA oxidase, which is responsible for the first step of the peroxisomal fatty acid (FA) β‐oxidation spiral. A fluorescent protein‐tagging study pointed to a peroxisomal location of CrACX2. The importance of peroxisomal FA β‐oxidation in algal physiology was shown by the impact of the mutation on FA turnover during day/night cycles. Moreover, under nitrogen depletion the mutant accumulated 20% more oil than the wild type, illustrating the potential of β‐oxidation mutants for algal biotechnology. This study provides experimental evidence that a plant‐type FA β‐oxidation involving H2O2‐producing acyl‐CoA oxidation activity has already evolved in the microbodies of the unicellular green alga Chlamydomonas reinhardtii.
Importance of the Exopolysaccharide Matrix in Antimicrobial Tolerance of Pseudomonas aeruginosa Aggregates
Authors: Goltermann Lise , Tolker-Nielsen Tim 
Published: January 2017

ABSTRACT

Pseudomonas aeruginosa
is an opportunistic pathogen that can infect the lungs of cystic fibrosis (CF) patients and persist in the form of antibiotic-tolerant aggregates in the mucus. It has recently been suggested that such aggregates are formed due to restricted bacterial motility independent of the production of extracellular matrix components, and that they do not rely on an extracellular matrix for antimicrobial tolerance. However, we show here that biofilm matrix overexpression, as displayed by various clinical isolates, significantly protects
P. aeruginosa
aggregates against antimicrobial treatment. Alginate-overproducing
mucA
mutant bacteria growing in aggregates showed highly increased antibiotic tolerance compared to wild-type bacteria in aggregates. Deletion of
algD
in the
mucA
mutant strain abrogated alginate production and reversed the antibiotic tolerance displayed by the aggregates to a level similar to that observed for aggregates formed by the wild type. The
P. aeruginosa
Δ
wspF
and Δ
yfiR
mutant strains both overproduce Pel and Psl exopolysaccharide, and when these bacteria grew in aggregates, they showed highly increased antibiotic tolerance compared to wild-type bacteria growing in aggregates. However, the Δ
wspF
and Δ
yfiR
mutant strains, deficient in Pel/Psl production due to additional Δ
pelA
Δ
pslBCD
deletions, formed aggregates that displayed antibiotic tolerance levels close to those of wild-type aggregates. These results suggest that biofilm matrix components, such as alginate, Pel, and Psl, do play a role in the tolerance toward antimicrobials when bacteria grow as aggregates.
Activity of the Pore-Forming Virulence Factor Listeriolysin O Is Reversibly Inhibited by Naturally Occurring S-Glutathionylation
Authors: Portman Jonathan L. , Huang Qiongying , Reniere Michelle L. , Iavarone Anthony T. , Portnoy Daniel A. 
Published: January 2017

ABSTRACT

Cholesterol-dependent cytolysins (CDCs) represent a family of homologous pore-forming proteins secreted by many Gram-positive bacterial pathogens. CDCs mediate membrane binding partly through a conserved C-terminal undecapeptide, which contains a single cysteine residue. While mutational changes to other residues in the undecapeptide typically have severe effects, mutation of the cysteine residue to alanine has minor effects on overall protein function. Thus, the role of this highly conserved reactive cysteine residue remains largely unknown. We report here that the CDC listeriolysin O (LLO), secreted by the facultative intracellular pathogen
Listeria monocytogenes
, was posttranslationally modified by S-glutathionylation at this conserved cysteine residue and that either endogenously synthesized or exogenously added glutathione was sufficient to form this modification. When recapitulated with purified protein
in vitro
, this modification completely ablated the activity of LLO, and this inhibitory effect was fully reversible by treatment with reducing agents. A cysteine-to-alanine mutation in LLO rendered the protein completely resistant to inactivation by S-glutathionylation, and a mutant expressing this mutation retained full hemolytic activity. A mutant strain of
L. monocytogenes
expressing the cysteine-to-alanine variant of LLO was able to infect and replicate within bone marrow-derived macrophages indistinguishably from the wild type
in vitro
, yet it was attenuated 4- to 6-fold in a competitive murine infection model
in vivo
. This study suggests that S-glutathionylation may represent a mechanism by which CDC-family proteins are posttranslationally modified and regulated and help explain an evolutionary pressure to retain the highly conserved undecapeptide cysteine.
Correlates of non-technical skills in surgery: a prospective study
Authors: Gillespie Brigid M , Harbeck Emma , Kang Evelyn , Steel Catherine , Fairweather Nicole , Chaboyer Wendy 
Published: January 2017

BackgroundCommunication and teamwork failures have frequently been identified as the root cause of adverse events and complications in surgery. Few studies have examined contextual factors that influence teams’ non-technical skills (NTS) in surgery. The purpose of this prospective study was to identify and describe correlates of NTS.MethodsWe assessed NTS of teams and professional role at 2 hospitals using the revised 23-item Non-TECHnical Skills (NOTECHS) and its subscales (communication, situational awareness, team skills, leadership and decision-making). Over 6 months, 2 trained observers evaluated teams’ NTS using a structured form. Interobserver agreement across hospitals ranged from 86% to 95%. Multiple regression models were developed to describe associations between operative time, team membership, miscommunications, interruptions, and total NOTECHS and subscale scores.ResultsWe observed 161 surgical procedures across 8 teams. The total amount of explained variance in NOTECHS and its 5 subscales ranged from 14% (adjusted R20.12, p<0.001) to 24% (adjusted R20.22, p<0.001). In all models, inverse relationships between thetotal number of miscommunicationsandtotal number of interruptionsand teams’ NTS were observed.ConclusionsMiscommunications and interruptions impact on team NTS performance.
Effects of different early rehabilitation techniques on haemodynamic and metabolic parameters in sedated patients: protocol for a randomised, single-bind, cross-over trial
Authors: Medrinal Clément , Combret Yann , Prieur Guillaume , Robledo Quesada Aurora , Bonnevie Tristan , Gravier Francis Edouard , Frenoy Éric , Contal Olivier , Lamia Bouchra 
Published: January 2017

IntroductionEarly rehabilitation has become widespread practice for patients in intensive care; however, the prevalence of intensive care unit-acquired weakness remains high and the majority of physiotherapy is carried out in bed. Several inbed rehabilitation methods exist, but we hypothesise that techniques that provoke muscle contractions are more effective than passive techniques.MethodsA randomised, controlled cross-over study will be carried out to evaluate and compare the effectiveness of early rehabilitation techniques on cardiac output (CO) in sedated patients in intensive care. 20 intubated and sedated patients will undergo 4 10 min rehabilitation sessions. 2 sessions will involve ‘passive’ techniques based on mobilisations and inbed cycle ergometry and 2 involving electrostimulation of the quadriceps muscle and Functional Electrical Stimulation-cycling (FES-cycling). The primary outcome is CO measured by Doppler ultrasound. The secondary outcomes are right ventricular function, pulmonary systolic arterial pressure, muscle oxygenation and minute ventilation during exercise.Results and conclusionApproval has been granted by our Institutional Review Board (Comité de Protection des Personnes Nord-Ouest 3). The results of the trial will be presented at national and international meetings and published in peer-reviewed journals.Trial registration numberNCT02920684.
DAS28-CRP and DAS28-ESR cut-offs for high disease activity in rheumatoid arthritis are not interchangeable
Authors: Fleischmann Roy M , van der Heijde Désirée , Gardiner Philip V , Szumski Annette , Marshall Lisa , Bananis Eustratios 
Published: January 2017

BackgroundIn most patients with rheumatoid arthritis (RA), Disease Activity Score 28-joint count C reactive protein (DAS28-CRP) is lower than DAS28 erythrocyte sedimentation rate (DAS28-ESR), suggesting that use of the DAS28-ESR cut-off to assess high disease activity (HDA) with DAS28-CRP may underestimate the number of patients with HDA. We determined the DAS28-CRP value corresponding to the validated DAS28-ESR cut-off for HDA.MethodsBaseline data were pooled from 2 clinical studies evaluating etanercept (ETN) plus methotrexate (MTX) or MTX in early RA; DAS28-CRP and DAS28-ESR were obtained, allowing the determination of the DAS28-CRP HDA value best corresponding to the DAS28-ESR cut-off of >5.1.ResultsAt baseline, as expected, fewer patients had HDA by DAS28-CRP than DAS28-ESR; DAS28-CRP>5.1 and DAS28-ESR>5.1 had only modest agreement (κ coefficients 0.45–0.54). Mean DAS28-CRP and DAS28-ESR were 5.7 and 6.2, respectively, in the ETN+MTX group (n=571), and 6.0 and 6.5 in the MTX group (n=262). A DAS28-CRP cut-off of 4.6 corresponded to a DAS28-ESR cut-off of 5.1.ConclusionsWe have shown that a DAS28-CRP of 4.6 corresponds to 5.1 for DAS28-ESR. Since this is substantially lower than the DAS28-ESR cut-off of 5.1, using 5.1 as the cut-off for DAS28-CRP underestimates disease activity in RA.Trial registration numberNCT00195494;NCT00913458.
Global economic cost of smoking-attributable diseases
Authors: Goodchild Mark , Nargis Nigar , Tursan d'Espaignet Edouard 
Published: January 2017

BackgroundThe detrimental impact of smoking on health has been widely documented since the 1960s. Numerous studies have also quantified the economic cost that smoking imposes on society. However, these studies have mostly been in high income countries, with limited documentation from developing countries. The aim of this paper is to measure the economic cost of smoking-attributable diseases in countries throughout the world, including in low- and middle-income settings.MethodsThe Cost of Illness approach is used to estimate the economic cost of smoking attributable-diseases in 2012. Under this approach, economic costs are defined as either ‘direct costs' such as hospital fees or ‘indirect costs’ representing the productivity loss from morbidity and mortality. The same method was applied to 152 countries, which had all the necessary data, representing 97% of the world's smokers.FindingsThe amount of healthcare expenditure due to smoking-attributable diseases totalled purchasing power parity (PPP) $467 billion (US$422 billion) in 2012, or 5.7% of global health expenditure. The total economic cost of smoking (from health expenditures and productivity losses together) totalled PPP $1852 billion (US$1436 billion) in 2012, equivalent in magnitude to 1.8% of the world's annual gross domestic product (GDP). Almost 40% of this cost occurred in developing countries, highlighting the substantial burden these countries suffer.ConclusionsSmoking imposes a heavy economic burden throughout the world, particularly in Europe and North America, where the tobacco epidemic is most advanced. These findings highlight the urgent need for countries to implement stronger tobacco control measures to address these costs.
AZD6738, A Novel Oral Inhibitor of ATR, Induces Synthetic Lethality with ATM Deficiency in Gastric Cancer Cells
Authors: Min Ahrum , Im Seock-Ah , Jang Hyemin , Kim Seongyeong , Lee Miso , Kim Debora Keunyoung , Yang Yaewon , Kim Hee-Jun , Lee Kyung-Hun , Kim Jin Won , Kim Tae-Yong , Oh Do-Youn , Brown Jeff , Lau Alan , O'Connor Mark J. , Bang Yung-Jue 
Published: January 2017

Abstract
Ataxia telangiectasia and Rad3-related (ATR) can be considered an attractive target for cancer treatment due to its deleterious effect on cancer cells harboring a homologous recombination defect. The aim of this study was to investigate the potential use of the ATR inhibitor, AZD6738, to treat gastric cancer.
In SNU-601 cells with dysfunctional ATM, AZD6738 treatment led to an accumulation of DNA damage due to dysfunctional RAD51 foci formation, S phase arrest, and caspase 3–dependent apoptosis. In contrast, SNU-484 cells with functional ATM were not sensitive to AZD6738. Inhibition of ATM in SNU-484 cells enhanced AZD6738 sensitivity to a level comparable with that observed in SNU-601 cells, showing that activation of the ATM-Chk2 signaling pathway attenuates AZD6738 sensitivity. In addition, decreased HDAC1 expression was found to be associated with ATM inactivation in SNU-601 cells, demonstrating the interaction between HDAC1 and ATM can affect sensitivity to AZD6738. Furthermore, in an in vivo tumor xenograft mouse model, AZD6738 significantly suppressed tumor growth and increased apoptosis.
These findings suggest synthetic lethality between ATR inhibition and ATM deficiency in gastric cancer cells. Further clinical studies on the interaction between AZD 6738 and ATM deficiency are warranted to develop novel treatment strategies for gastric cancer. Mol Cancer Ther; 16(4); 566–77. ©2017 AACR.