bluuebunny/crossref_metadata_2025_split huggingface dataset:
Arabidopsis RAV1 transcription factor, phosphorylated by SnRK2 kinases, regulates the expression of ABI3,ABI4, and ABI5 during seed germination and early seedling development
Authors: Feng Cui‐Zhu , Chen Yun , Wang Cun , Kong You‐Han , Wu Wei‐Hua , Chen Yi‐Fang 
Published: September 2014

SummaryThe phytohormone abscisic acid (ABA) modulates a number of processes during plant growth and development. In this study, the molecular mechanism of Arabidopsis RAV (Related to ABI3/VP1) transcription factor RAV1 involving ABA signaling was investigated. RAV1‐underexpressing lines were more sensitive to ABA than wild‐type plants during seed germination and early seedling development, whereas RAV1‐overexpressing lines showed strong ABA‐insensitive phenotypes. Overexpression of RAV1 repressed ABI3, ABI4, and ABI5 expression, and RAV1 bound to the ABI3, ABI4, and ABI5 promoters in vitro and in vivo, indicating that RAV1 directly down‐regulates the expression of ABI3, ABI4, and ABI5. The interruption of ABI5 function in RAV1‐U abi5 plants abolished the ABA‐hypersensitive phenotype of RAV1‐U plants, demonstrating that ABI5 is epistatic to RAV1. RAV1 interacted with SNF1‐RELATED PROTEIN KINASE SnRK2.2, SnRK2.3 and SnRK2.6 in the nucleus. In vitro kinase assays showed that SnRK2.2, SnRK2.3 and SnRK2.6 phosphorylated RAV1. Transient expression assays revealed that SnRK2.2, SnRK2.3 and SnRK2.6 reduced the RAV1‐dependent repression of ABI5, and the ABA‐insensitive phenotype of the RAV1‐overexpressing line was impaired by overexpression of SnRK2.3 in the RAV1 OE3 plants. Together, these results demonstrated that the Arabidopsis RAV1 transcription factor plays an important role in ABA signaling by modulating the expression of ABI3, ABI4, and ABI5, and that its activity is negatively affected by SnRK2s.
Bounding Lagrangian widths via geodesic paths
Authors: Borman Matthew Strom , McLean Mark 
Published: September 2014

AbstractThe width of a Lagrangian is the largest capacity of a ball that can be symplectically embedded into the ambient manifold such that the ball intersects the Lagrangian exactly along the real part of the ball. Due to Dimitroglou Rizell, finite width is an obstruction to a Lagrangian admitting an exact Lagrangian cap in the sense of Eliashberg–Murphy. In this paper we introduce a new method for bounding the width of a Lagrangian$Q$by considering the Lagrangian Floer cohomology of an auxiliary Lagrangian$L$with respect to a Hamiltonian whose chords correspond to geodesic paths in$Q$. This is formalized as a wrapped version of the Floer–Hofer–Wysocki capacity and we establish an associated energy–capacity inequality with the help of a closed–open map. For any orientable Lagrangian$Q$admitting a metric of non-positive sectional curvature in a Liouville manifold, we show the width of$Q$is bounded above by four times its displacement energy.
Spectral theory for the -Boson particle system
Authors: Borodin Alexei , Corwin Ivan , Petrov Leonid , Sasamoto Tomohiro 
Published: September 2014

AbstractWe develop spectral theory for the generator of the $q$-Boson (stochastic) particle system. Our central result is a Plancherel type isomorphism theorem for this system. This theorem has various implications. It proves the completeness of the Bethe ansatz for the $q$-Boson generator and consequently enables us to solve the Kolmogorov forward and backward equations for general initial data. Owing to a Markov duality with $q$-TASEP ($q$-deformed totally asymmetric simple exclusion process), this leads to moment formulas which characterize the fixed time distribution of $q$-TASEP started from general initial conditions. The theorem also implies the biorthogonality of the left and right eigenfunctions. We consider limits of our $q$-Boson results to a discrete delta Bose gas considered previously by van Diejen, as well as to another discrete delta Bose gas that describes the evolution of moments of the semi-discrete stochastic heat equation (or equivalently, the O’Connell–Yor semi-discrete directed polymer partition function). A further limit takes us to the delta Bose gas which arises in studying moments of the stochastic heat equation/Kardar–Parisi–Zhang equation.
Jordan property for groups of birational selfmaps
Authors: Prokhorov Yuri , Shramov Constantin 
Published: September 2014

AbstractAssuming a particular case of the Borisov–Alexeev–Borisov conjecture, we prove that finite subgroups of the automorphism group of a finitely generated field over $\mathbb{Q}$ have bounded orders. Further, we investigate which algebraic varieties have groups of birational selfmaps satisfying the Jordan property. Unless explicitly stated otherwise, all varieties are assumed to be algebraic, geometrically irreducible and defined over an arbitrary field $\Bbbk$ of characteristic zero.
Impact of the Steepness of the Slope on the Biomechanics of World Cup Slalom Skiers
Authors: Supej Matej , Hébert-Losier Kim , Holmberg Hans-Christer 
Published: September 2014

Purpose:Numerous environmental factors can affect alpine-ski-racing performance, including the steepness of the slope. However, little research has focused on this factor. Accordingly, the authors’ aim was to determine the impact of the steepness of the slope on the biomechanics of World Cup slalom ski racers.Methods:The authors collected 3-dimensional kinematic data during a World Cup race from 10 male slalom skiers throughout turns performed on a relatively flat (19.8°) and steep (25.2°) slope under otherwise similar course conditions.Results:Kinematic data revealed differences between the 2 slopes regarding the turn radii of the skis and center of gravity, velocity, acceleration, and differential specific mechanical energy (all P < .001). Ground-reaction forces (GRFs) also tended toward differences (P = .06). Examining the time-course behaviors of variables during turn cycles indicated that steeper slopes were associated with slower velocities but greater accelerations during turn initiation, narrower turns with peak GRFs concentrated at the midpoint of steering, more pronounced lateral angulations of the knees and hips at the start of steering that later became less pronounced, and overall slower turns that involved deceleration at completion. Consequently, distinct energy-dissipation-patterns were apparent on the 2 slope inclines, with greater pregate and lesser postgate dissipation on the steeper slope. The steepness of the slope also affected the relationships between mechanical skiing variables.Conclusions:The findings suggest that specific considerations during training and preparation would benefit the race performance of slalom skiers on courses involving sections of varying steepness.
Acute Effects of Static Active or Dynamic Active Stretching on Eccentric-Exercise-Induced Hamstring Muscle Damage
Authors: Chen Che-Hsiu , Chen Trevor C. , Jan Mei-Hwa , Lin Jiu-Jenq 
Published: September 2014

Objectives:To examine whether an acute bout of active or dynamic hamstring-stretching exercises would reduce the amount of muscle damage observed after a strenuous eccentric task and to determine whether the stretching protocols elicit similar responses.Design:A randomized controlled clinical trial.Methods:Thirty-six young male students performed 5 min of jogging as a warm-up and were allocated to 1 of 3 groups: 3 min of static active stretching (SAS), 3 min of dynamic active stretching (DAS), or control (CON). All subjects performed eccentric exercise immediately after stretching. Heart rate, core temperature, maximal voluntary isometric contraction, passive hip flexion, passive hamstring stiffness (PHS), plasma creatine kinase activity, and myoglobin were recorded at prestretching, at poststretching, and every day after the eccentric exercises for 5 d.Results:After stretching, the change in hip flexion was significantly higher in the SAS (5°) and DAS (10.8°) groups than in the CON (–4.1°) group. The change in PHS was significantly higher in the DAS (5.6%) group than in the CON (–5.7%) and SAS (–6.7%) groups. Furthermore, changes in muscle-damage markers were smaller in the SAS group than in the DAS and CON groups.Conclusions:Prior active stretching could be useful for attenuating the symptoms of muscle damage after eccentric exercise. SAS is recommended over DAS as a stretching protocol in terms of strength, hamstring range of motion, and damage markers.
Susceptibility to
Campylobacter
Infection Is Associated with the Species Composition of the Human Fecal Microbiota
Authors: Dicksved Johan , Ellström Patrik , Engstrand Lars , Rautelin Hilpi 
Published: September 2014

ABSTRACT

The gut microbiota is essential for human health, but very little is known about how the composition of this ecosystem can influence and respond to bacterial infections. Here we address this by prospectively studying the gut microbiota composition before, during, and after natural
Campylobacter
infection in exposed poultry abattoir workers. The gut microbiota composition was analyzed with 16S amplicon sequencing of fecal samples from poultry abattoir workers during the peak season of
Campylobacter
infection in Sweden. The gut microbiota compositions were compared between individuals who became culture positive for
Campylobacter
and those who remained negative. Individuals who became
Campylobacter
positive had a significantly higher abundance of
Bacteroides
(
P
= 0.007) and
Escherichia
(
P
= 0.002) species than those who remained culture negative. Furthermore, this group had a significantly higher abundance of
Phascolarctobacterium
(
P
= 0.017) and
Streptococcus
(
P
= 0.034) sequences than the
Campylobacter
-negative group, which had an overrepresentation of
Clostridiales
(
P
= 0.017), unclassified
Lachnospiraceae
(
P
= 0.008), and
Anaerovorax
(
P
= 0.015) sequences. Intraindividual comparisons of the fecal microbiota compositions yielded small differences over time in
Campylobacter
-negative participants, but significant long-term changes were found in the
Campylobacter
-positive group (
P
< 0.005). The results suggest that the abundance of specific genera in the microbiota reduces resistance to
Campylobacter
colonization in humans and that
Campylobacter
infection can have long-term effects on the composition of the human fecal microbiota.

IMPORTANCE
Studies using mouse models have made important contributions to our understanding of the role of the gut microbiota in resistance to bacterial enteropathogen colonization. The relative abundances of
Escherichia coli
and
Bacteroides
species have been pointed out as important determinants of susceptibility to Gram-negative pathogens in general and
Campylobacter
infection in particular. In this study, we assessed the role of the human gut microbiota in resistance to
Campylobacter
colonization by studying abattoir workers that are heavily exposed to these bacteria. Individuals with a certain composition of the gut microbiota became culture positive for
Campylobacter
. As their microbiotas were characterized by high abundances of
Bacteroides
spp. and
E. coli
, well in line with the findings with mouse models, these bacterial species likely play an important role in colonization resistance also in humans.
Streptolysin O and NAD-Glycohydrolase Prevent Phagolysosome Acidification and Promote Group A
Streptococcus
Survival in Macrophages
Authors: Bastiat-Sempe Benedicte , Love John F. , Lomayesva Natalie , Wessels Michael R. 
Published: September 2014

ABSTRACT

Group A
Streptococcus
(GAS,
Streptococcus pyogenes
) is an ongoing threat to human health as the agent of streptococcal pharyngitis, skin and soft tissue infections, and life-threatening conditions such as necrotizing fasciitis and streptococcal toxic shock syndrome. In animal models of infection, macrophages have been shown to contribute to host defense against GAS infection. However, as GAS can resist killing by macrophages
in vitro
and induce macrophage cell death, it has been suggested that GAS intracellular survival in macrophages may enable persistent infection. Using isogenic mutants, we now show that the GAS pore-forming toxin streptolysin O (SLO) and its cotoxin NAD-glycohydrolase (NADase) mediate GAS intracellular survival and cytotoxicity for macrophages. Unexpectedly, the two toxins did not inhibit fusion of GAS-containing phagosomes with lysosomes but rather prevented phagolysosome acidification. SLO served two essential functions, poration of the phagolysosomal membrane and translocation of NADase into the macrophage cytosol, both of which were necessary for maximal GAS intracellular survival. Whereas NADase delivery to epithelial cells is mediated by SLO secreted from GAS bound to the cell surface, in macrophages, the source of SLO and NADase is GAS contained within phagolysosomes. We found that transfer of NADase from the phagolysosome to the macrophage cytosol occurs not by simple diffusion through SLO pores but rather by a specific translocation mechanism that requires the N-terminal translocation domain of NADase. These results illuminate the mechanisms through which SLO and NADase enable GAS to defeat macrophage-mediated killing and provide new insight into the virulence of a major human pathogen.

IMPORTANCE
Macrophages constitute an important element of the innate immune response to mucosal pathogens. They ingest and kill microbes by phagocytosis and secrete inflammatory cytokines to recruit and activate other effector cells. Group A
Streptococcus
(GAS,
Streptococcus pyogenes
), an important cause of pharyngitis and invasive infections, has been shown to resist killing by macrophages. We find that GAS resistance to macrophage killing depends on the GAS pore-forming toxin streptolysin O (SLO) and its cotoxin NAD-glycohydrolase (NADase). GAS bacteria are internalized by macrophage phagocytosis but resist killing by secreting SLO, which damages the phagolysosome membrane, prevents phagolysosome acidification, and translocates NADase from the phagolysosome into the macrophage cytosol. NADase augments SLO-mediated cytotoxicity by depleting cellular energy stores. These findings may explain the nearly universal production of SLO by GAS clinical isolates and the association of NADase with the global spread of a GAS clone implicated in invasive infections.
Synthetic Lethality Reveals Mechanisms of Mycobacterium tuberculosis Resistance to β-Lactams
Authors: Lun Shichun , Miranda David , Kubler Andre , Guo Haidan , Maiga Mariama C. , Winglee Kathryn , Pelly Shaaretha , Bishai William R. 
Published: September 2014

ABSTRACT

Most β-lactam antibiotics are ineffective against
Mycobacterium tuberculosis
due to the microbe’s innate resistance. The emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains has prompted interest to repurpose this class of drugs. To identify the genetic determinants of innate β-lactam resistance, we carried out a synthetic lethality screen on a transposon mutant library for susceptibility to imipenem, a carbapenem β-lactam antibiotic. Mutations in 74 unique genes demonstrated synthetic lethality. The majority of mutations were in genes associated with cell wall biosynthesis. A second quantitative real-time PCR (qPCR)-based synthetic lethality screen of randomly selected mutants confirmed the role of cell wall biosynthesis in β-lactam resistance. The global transcriptional response of the bacterium to β-lactams was investigated, and changes in levels of expression of cell wall biosynthetic genes were identified. Finally, we validated these screens
in vivo
using the
MT1616
transposon mutant, which lacks a functional acyl-transferase gene. Mice infected with the mutant responded to β-lactam treatment with a 100-fold decrease in bacillary lung burden over 4 weeks, while the numbers of organisms in the lungs of mice infected with wild-type bacilli proliferated. These findings reveal a road map of genes required for β-lactam resistance and validate synthetic lethality screening as a promising tool for repurposing existing classes of licensed, safe, well-characterized antimicrobials against tuberculosis.

IMPORTANCE
The global emergence of multidrug-resistant and extensively drug-resistant
M. tuberculosis
strains has threatened public health worldwide, yet the pipeline of new tuberculosis drugs under development remains limited. One strategy to cope with the urgent need for new antituberculosis agents is to repurpose existing, approved antibiotics. The carbapenem class of β-lactam antibiotics has been proposed as one such class of drugs. Our study identifies molecular determinants of innate resistance to β-lactam drugs in
M. tuberculosis
, and we demonstrate that functional loss of one of these genes enables successful treatment of
M. tuberculosis
with β-lactams in the mouse model.
Vesicular Trafficking of Incoming Human Papillomavirus 16 to the Golgi Apparatus and Endoplasmic Reticulum Requires γ-Secretase Activity
Authors: Zhang Wei , Kazakov Teymur , Popa Andreea , DiMaio Daniel 
Published: September 2014

ABSTRACT
The route taken by papillomaviruses from the cell surface to the nucleus during infection is incompletely understood. Here, we developed a novel human papillomavirus 16 (HPV16) pseudovirus in which the carboxy terminus of the minor capsid protein L2 is exposed on the exterior of the intact capsid prior to cell binding. With this pseudovirus, we used the proximity ligation assay immune detection technique to demonstrate that during entry HPV16 L2 traffics into and out of the early endosome prior to Golgi localization, and we demonstrated that L2 enters the endoplasmic reticulum during entry. The cellular membrane-associated protease, γ-secretase, is required for infection by HPV16 pseudovirus and authentic HPV16. We also showed that inhibition of γ-secretase does not interfere substantively with virus internalization, initiation of capsid disassembly, entry into the early endosome, or exit from this compartment, but γ-secretase is required for localization of L2 and viral DNA to the Golgi apparatus and the endoplasmic reticulum. These results show that incoming HPV16 traffics sequentially from the cell surface to the endosome and then to the Golgi apparatus and the endoplasmic reticulum prior to nuclear entry.

IMPORTANCE
The human papillomaviruses are small nonenveloped DNA viruses responsible for approximately 5% of all human cancer deaths, but little is known about the process by which these viruses transit from the cell surface to the nucleus. Here we show that incoming HPV16, the most common high-risk HPV, traffics though a series of vesicular compartments during infectious entry, including the endosome, Golgi apparatus, and endoplasmic reticulum. Furthermore, we show that γ-secretase, a cellular membrane-associated protease, is required for entry of the L2 minor capsid protein and viral DNA into the Golgi apparatus and endoplasmic reticulum. These studies reveal a new pathway of cell entry by DNA viruses and suggest that components of this pathway are candidate antiviral targets.
Paracetamol-associated acute liver failure in Australian and New Zealand children: high rate of medication errors
Authors: Rajanayagam J , Bishop J R , Lewindon P J , Evans Helen M 
Published: September 2014

BackgroundIn children, paracetamol overdose due to deliberate self-poisoning, accidental exposure or medication errors can lead to paediatric acute liver failure and death. In Australia and New Zealand, the nature of ingestion and outcomes of paracetamol-associated paediatric acute liver failure have not been described.ObjectiveTo describe the nature and outcomes of paracetamol-associated paediatric acute liver failure.DesignRetrospective analysis of paracetamol-associated paediatric acute liver failure cases presenting 2002–2012.SettingNew Zealand and Queensland Paediatric Liver Transplant Services.Results14 of 54 cases of paediatric acute liver failure were attributed to paracetamol, the majority were secondary to medication errors. 12 of the 14 children were under the age of 5 years. Seven children received doses in excess of 120 mg/kg/day. Many of the other children received either a double dose, too frequent administration, coadministration of other medicines containing paracetamol or regular paracetamol for up to 24 days. Three children underwent transplant. One of these and one other child died.ConclusionsIn Australia and New Zealand, paracetamol overdose secondary to medication errors is the leading cause of paediatric acute liver failure. A review of regional safety practices surrounding paracetamol use in children is indicated.
The cost-effectiveness and public health benefit of nalmefene added to psychosocial support for the reduction of alcohol consumption in alcohol-dependent patients with high/very high drinking risk levels: a Markov model
Authors: Laramée Philippe , Brodtkorb Thor-Henrik , Rahhali Nora , Knight Chris , Barbosa Carolina , François Clément , Toumi Mondher , Daeppen Jean-Bernard , Rehm Jürgen 
Published: September 2014

ObjectivesTo determine whether nalmefene combined with psychosocial support is cost-effective compared with psychosocial support alone for reducing alcohol consumption in alcohol-dependent patients with high/very high drinking risk levels (DRLs) as defined by the WHO, and to evaluate the public health benefit of reducing harmful alcohol-attributable diseases, injuries and deaths.DesignDecision modelling using Markov chains compared costs and effects over 5 years.SettingThe analysis was from the perspective of the National Health Service (NHS) in England and Wales.ParticipantsThe model considered the licensed population for nalmefene, specifically adults with both alcohol dependence and high/very high DRLs, who do not require immediate detoxification and who continue to have high/very high DRLs after initial assessment.Data sourcesWe modelled treatment effect using data from three clinical trials for nalmefene (ESENSE 1 (NCT00811720), ESENSE 2 (NCT00812461) and SENSE (NCT00811941)). Baseline characteristics of the model population, treatment resource utilisation and utilities were from these trials. We estimated the number of alcohol-attributable events occurring at different levels of alcohol consumption based on published epidemiological risk-relation studies. Health-related costs were from UK sources.Main outcome measuresWe measured incremental cost per quality-adjusted life year (QALY) gained and number of alcohol-attributable harmful events avoided.ResultsNalmefene in combination with psychosocial support had an incremental cost-effectiveness ratio (ICER) of £5204 per QALY gained, and was therefore cost-effective at the £20 000 per QALY gained decision threshold. Sensitivity analyses showed that the conclusion was robust. Nalmefene plus psychosocial support led to the avoidance of 7179 alcohol-attributable diseases/injuries and 309 deaths per 100 000 patients compared to psychosocial support alone over the course of 5 years.ConclusionsNalmefene can be seen as a cost-effective treatment for alcohol dependence, with substantial public health benefits.Trial registration numbersThis cost-effectiveness analysis was developed based on data from three randomised clinical trials: ESENSE 1 (NCT00811720), ESENSE 2 (NCT00812461) and SENSE (NCT00811941).