bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantification of the zygotic barrier between interbreeding taxa using gene flow data
Authors: Bialozyt Ronald , Niggemann Marc , Ziegenhagen Birgit 
Published: November 2016

Hybridization and introgression via interspecific gene flow are common processes in the plant kingdom. The effectiveness of these processes is governed by the strengths of multiple zygotic barriers. These barriers have often been quantified in artificial settings using laborious and time‐consuming hand‐pollination experiments, but their quantification is nonexistent in the landscape. In this study, we utilized gene flow data within a spatially explicit simulation to assess the strengths of zygotic barriers.Our model system consisted of Populus nigra and its hybrid, P. × canadensis, which interbreed under natural conditions. The study population was located in the floodplain of the Eder River in central Germany. Pollen‐mediated introgression rates from hybrid males into the seeds of individual female trees were used as the target pattern using an inverse modeling approach. Simulations that treated pollen from both taxa equally revealed a large discrepancy between the observed and modeled rates of introgression for both taxa. The discrepancy was reduced by introducing a zygotic barrier against the pollen from the hybrid males. The best model outcome values indicated comparably strong zygotic barriers acting against pollen‐mediated introgressive gene flow into the two parental taxa, P. nigra and P. × canadensis.The sensitivity of our model was tested by applying different dispersal functions. Four common probability density functions were used along with a pollen dispersal function that had previously been fitted to gene flow data from the same dataset. The best barrier value was almost independent of the dispersal functions used here. Moreover, it was within the range previously determined in hand‐pollination‐based investigations, validating our model.These data indicate that the inverse modeling approach is a powerful method for quantifying hidden processes, and we discuss its use as a valuable tool for generating new insights into plant mating systems that are relevant to evolutionary biology and risk analyses in conservation efforts.
Conflicting demands on angiosperm xylem: Tradeoffs among storage, transport and biomechanics
Authors: Pratt R. Brandon , Jacobsen Anna L. 
Published: November 2016

AbstractThe secondary xylem of woody plants transports water mechanically supports the plant body and stores resources. These three functions are interdependent giving rise to tradeoffs in function. Understanding the relationships among these functions and their structural basis forms the context in which to interpret xylem evolution. The tradeoff between xylem transport efficiency and safety from cavitation has been carefully examined with less focus on other functions, particularly storage. Here, we synthesize data on all three xylem functions in angiosperm branch xylem in the context of tradeoffs. Species that have low safety and efficiency, examined from a resource economics perspective, are predicted to be adapted for slow resource acquisition and turnover as characterizes some environments. Tradeoffs with water storage primarily arise because of differences in fibre traits, while tradeoffs in carbohydrate storage are driven by parenchyma content of tissue. We find support for a tradeoff between safety from cavitation and storage of both water and starch in branch xylem tissue and between water storage capacity and mechanical strength. Living fibres may facilitate carbohydrate storage without compromising mechanical strength. The division of labour between different xylem cell types allows for considerable functional and structural diversity at multiple scales.
Impact of childhood asthma on growth trajectories in early adolescence: Findings from the Childhood Asthma Prevention Study (CAPS)
Authors: Movin Maria , Garden Frances L. , Protudjer Jennifer L.P. , Ullemar Vilhelmina , Svensdotter Frida , Andersson David , Kruse Andreas , Cowell Chris T. , Toelle Brett G. , Marks Guy B. , Almqvist Catarina ,   for the Childhood Asthma Prevention Team
Published: November 2016

ABSTRACT
Background and objectiveUnderstanding the associations between childhood asthma and growth in early adolescence by accounting for the heterogeneity of growth during puberty has been largely unexplored. The objective was to identify sex‐specific classes of growth trajectories during early adolescence, using a method which takes the heterogeneity of growth into account and to evaluate the association between childhood asthma and different classes of growth trajectories in adolescence.MethodsOur longitudinal study included participants with a family history of asthma born during 1997–1999 in Sydney, Australia. Hence, all participants were at high risk for asthma. Asthma status was ascertained at 8 years of age using data from questionnaires and lung function tests. Growth trajectories between 11 and 14 years of age were classified using a latent basis growth mixture model. Multinomial regression analyses were used to evaluate the association between asthma and the categorized classes of growth trajectories.ResultsIn total, 316 participants (51.6% boys), representing 51.3% of the entire cohort, were included. Sex‐specific classes of growth trajectories were defined. Among boys, asthma was not associated with the classes of growth trajectories. Girls with asthma were more likely than girls without asthma to belong to a class with later growth (OR: 3.79, 95% CI: 1.33, 10.84). Excluding participants using inhaled corticosteroids or adjusting for confounders did not significantly change the results for either sex.ConclusionWe identified sex‐specific heterogeneous classes of growth using growth mixture modelling. Associations between childhood asthma and different classes of growth trajectories were found for girls only.
Clinical relevance of necrotizing change in patients with community‐acquired pneumonia
Authors: Seo Hyewon , Cha Seung‐Ick , Shin Kyung‐Min , Lim Jae‐Kwang , Yoo Seung‐Soo , Lee Jaehee , Lee Shin‐Yup , Kim Chang‐Ho , Park Jae‐Yong , Lee Won‐Kee 
Published: November 2016

ABSTRACT
Background and objectiveFew studies have analysed a large number of patients with necrotizing pneumonia (NP) diagnosed based on computed tomography (CT) scans. The aim of the present study was to document the incidence and clinical features of NP in patients with community‐acquired pneumonia (CAP).MethodsThis retrospective study was conducted on CAP patients who had been admitted to a tertiary referral centre and who had available enhanced CT scan images. Patients were allocated into NP and non‐NP groups, and they were compared with respect to various clinical variables.ResultsOf the 830 patients included in the present study, necrotizing change was observed in 103 patients (12%). Patients with NP experienced more symptoms of pneumonia, had higher blood levels of inflammatory markers and more often required pleural drainage compared to patients with non‐NP. Although the use of mechanical ventilation, vasopressor infusion, 30‐day mortality, in‐hospital mortality and clinical deterioration did not differ between the NP and non‐NP groups, the median length of hospital stay (LOS) was significantly longer in the NP group. Multivariate analysis using Cox proportional hazards model showed that necrotizing change independently predicted LOS in patients with CAP.Conclusion
NP affects approximately one‐tenth of hospitalized CAP patients. It may be associated with more severe clinical manifestations and may increase the need for pleural drainage. NP was found to be an independent predictor of LOS, but not of mortality in CAP patients.
Social identity and psychosis: Explaining elevated rates of psychosis in migrant populations
Authors: McIntyre Jason C. , Elahi Anam , Bentall Richard P. 
Published: November 2016

AbstractA substantial body of literature suggests that migrants are at greater risk of developing psychotic symptoms, such as paranoia, compared to non‐migrants. To date, researchers have been unable to identify the primary cause of this effect, finding scarce support for biological, diagnostic, and economic explanations. Social determinants have received little empirical attention in this domain, which we assert is a critical gap in the literature. Here, we propose that the social identity approach offers a framework to help explain the elevated rates of psychosis among migrants, and in turn inform policies and interventions to address this important mental health issue. We propose that cultural identities play a central role in mitigating the psychological precursors of psychosis and that disidentification and social disconnection subsequent to migration could initiate or exacerbate psychosis for multiple generations. We draw together research from social and clinical psychology to detail a social identity approach to psychosis in migrant populations, and make recommendations for future research.
Numerical Study in a Mini Trochoidal-Gear Pump With Multi-Meshing Contact Points
Authors: Gamez-Montero P. J. , Castilla R. , Buza A. , Khamashta M. , Codina E. 
Published: November 2016

A numerical study in a mini trochoidal-gear pump based on an ingenious strategy to adapt the background mesh to the profiles shape and a new boundary condition is presented. The strategy achieves a final background mesh better adapted to the geometries and, additionally, the cells are more homogenous and less distorted when the trochodial-profiles are moved. The new boundary condition to simulate the multi-meshing contact points is applied at every time step by means of the viscous wall approach, a home-made ad-hoc code, which has been integrated in an OpenFOAM solver that also includes the dynamic mesh functionality by deforming the mesh following the trochoidal-gear rotation.
The presented numerical study establishes the basis that will allow simulating more realistic aspects of a new design of a mini trochoidal-gear pump once the need for a continuous fluid domain is overcome reproducing actual contacts between the rotors and will guide to a better understanding of the new design.
Investigation of Steady-State Flow Forces in Spool Valves of Different Geometries and at Different Oil Temperatures With the Help of Measurements and CFD Simulations
Authors: Bordovsky Patrik , Murrenhoff Hubertus 
Published: November 2016

When designing an actuator for a spool type directional control valve, axial forces acting on the spool have to be estimated. The steady-state flow force is the dominant axial force, which usually acts in the closing direction of the valve. However, many factors such as the valve geometry and the oil properties influence the flow force characteristics. Investigations regarding their effects on steady-state flow forces are described within this paper.
Different spool geometries of a test 2/2-way spool valve are used for steady-state flow force measurements at different oil temperatures. The measurement data are used for validation of CFD simulations, which are carried out to scrutinise the flow inside the valve. Besides the steady-state flow forces, the fluid flow angles at the inlet and the outlet of the spool chamber are analysed.
The results show that the spool geometry has a significant influence both on the flow rate and the steady-state flow force characteristics. Especially, the shape of the control edge has an impact on the flow patterns and on the magnitudes of steady-state flow forces. Moreover, the inlet and outlet fluid flow angles do not correlate with the expected values, which are commonly used for an analytical estimation of the flow forces. Furthermore, the oil temperature leads to quantitative deviations of the steady-state flow forces.
Reducing Friction and Wear in Common-Rail Pumps by Grooved and Contoured Pistons
Authors: Rückert Marcel , Heitzig Stefan , Murrenhoff Hubertus 
Published: November 2016

Within the cluster of excellence “Tailor-made Fuels from Biomass” at RWTH Aachen University new biofuels are developed and investigated. Because common-rail injection pumps are generally lubricated by the fuel itself, the tribological characteristics of the fuel candidates is of interest. The lubricity and viscosity of the alternative fuels differ from diesel. Hence, a reliable function of the tribological contacts, which are designed for the operation with diesel, cannot be guaranteed. To achieve a reliable operation even for fuels with, for instance, a lower viscosity or worse lubricity an optimisation of the tribological contacts is necessary.
The focus of the investigations presented in this paper lies on the piston-cylinder-contact. Prior to the simulative study the losses in a pump operating with various fuel candidates are quantified by means of efficiency measurements. By these measurements the great impact of the fuel’s rheology on the pump performance is clarified.
Based on detailed EHD-simulations with various fuels under typical operating conditions, an optimisation of the piston-cylinder-contact is presented. The optimisation aims for the reduction of solid friction by changing the pressure field on the piston. The approaches can basically be separated into grooved and contoured pistons. The potential of the different approaches is discussed based on simulation results and effects, which occur in the lubricating film of the optimised contacts.
An Enhanced Emtricitabine-Loaded Long-Acting Nanoformulation for Prevention or Treatment of HIV Infection
Authors: Mandal Subhra , Belshan Michael , Holec Ashley , Zhou You , Destache Christopher J. 
Published: November 2016

ABSTRACT

Among various FDA-approved combination antiretroviral drugs (cARVs), emtricitabine (FTC) has been a very effective nucleoside reverse transcriptase inhibitor. Thus far, FTC is the only deoxycytidine nucleoside analog. However, a major drawback of FTC is its large volume distribution (averaging 1.4 liters/kg) and short plasma half-life (8 to 10 h), necessitating a high daily dosage. Thus, we propose an innovative fabrication method of loading FTC in poly(lactic-co-glycolic acid) polymeric nanoparticles (FTC-NPs), potentially overcoming these drawbacks. Our nanoformulation demonstrated enhanced FTC loading (size of <200 nm and surface charge of −23 mV) and no to low cytotoxicity with improved biocompatibility compared to those with FTC solution. An
ex vivo
endosomal release assay illustrated that NP entrapment prolongs FTC release over a month. Intracellular retention studies demonstrate sustained FTC retention over time, with approximately 8% (24 h) to 68% (96 h) release with a mean retention of ∼0.74 μg of FTC/10
5
cells after 4 days. An
in vitro
HIV-1 inhibition study demonstrated that FTC-NP treatment results in a 50% inhibitory concentration (IC
50
) ∼43 times lower in TZM-bl cells (0.00043 μg/ml) and ∼3.7 times lower (0.009 μg/ml) in peripheral blood mononuclear cells (PBMCs) than with FTC solution (TZM-bl cells, 0.01861, and PBMCs, 0.033 μg/ml). Further, on primary PBMCs, FTC-NPs also illustrate an HIV-1 infection blocking efficacy comparable to that of FTC solution. All the above-described studies substantiate that FTC nanoformulation prolongs intracellular FTC concentration and inhibition of HIV infection. Therefore, FTC-NPs potentially could be a long-acting, stable formulation to ensure once-biweekly dosing to prevent or treat HIV infection.
Penicillin-Binding Protein 3 Is Essential for Growth of Pseudomonas aeruginosa
Authors: Chen Wei , Zhang Yong-Mei , Davies Christopher 
Published: November 2016

ABSTRACT

Penicillin-binding proteins (PBPs) function as transpeptidases, carboxypeptidases, or endopeptidases during peptidoglycan synthesis in bacteria. As the well-known drug targets for β-lactam antibiotics, the physiological functions of PBPs and whether they are essential for growth are of significant interest. The pathogen
Pseudomonas aeruginosa
poses a particular risk to immunocompromised and cystic fibrosis patients, and infections caused by this pathogen are difficult to treat due to antibiotic resistance. To identify potential drug targets among the PBPs in
P. aeruginosa
, we performed gene knockouts of all the high-molecular-mass (HMM) PBPs and determined the impacts on cell growth and morphology, susceptibility to β-lactams, peptidoglycan structure, virulence, and pathogenicity. Disruptions of the transpeptidase domains of most HMM PBPs, including double disruptions, had only minimal effects on cell growth. The exception was PBP3, where cell growth occurred only when the protein was conditionally expressed on an integrated plasmid. Conditional deletion of PBP3 also caused a defect in cell division and increased susceptibility to β-lactams. Knockout of PBP1a led to impaired motility, and this observation, together with its localization at the cell poles, suggests its involvement in flagellar function. Overall, these findings reveal that PBP3 represents the most promising target for drug discovery against
P. aeruginosa
, whereas other HMM PBPs have less potential.
Pharmacokinetics, Distribution, Metabolism, and Excretion of Omadacycline following a Single Intravenous or Oral Dose of
14
C-Omadacycline in Rats
Authors: Lin Wen , Flarakos Jimmy , Du Yancy , Hu Wenyu , He Handan , Mangold James , Tanaka S. Ken , Villano Stephen 
Published: November 2016

ABSTRACT
The absorption, distribution, metabolism, and excretion (ADME) of omadacycline, a first-in-class aminomethylcycline antibiotic with a broad spectrum of activity against Gram-positive, Gram-negative, anaerobic, and atypical bacteria, were evaluated in rats. Tissue distribution was investigated by quantitative whole-body autoradiography in male Long-Evans Hooded (LEH) rats. Following an intravenous (i.v.) dose of 5 mg/kg of body weight, radioactivity widely and rapidly distributed into most tissues. The highest tissue-to-blood concentration ratios (t/b) were observed in bone mineral, thyroid gland, and Harderian gland at 24 h post-i.v. dose. There was no evidence of stable accumulation in uveal tract tissue, suggesting the absence of a stable binding interaction with melanin. Following a 90 mg/kg oral dose in LEH rats, the highest t/b were observed in bone mineral, Harderian gland, liver, spleen, and salivary gland. The plasma protein binding levels were 26% in the rat and 15% to 21% in other species. Omadacycline plasma clearance was 1.2 liters/h/kg, and its half-life was 4.6 h; the steady-state volume of distribution (Vss) was 6.89 liters/kg. Major circulating components in plasma were intact omadacycline and its epimer. Consistent with observations in human, approximately 80% of the dose was excreted into the feces as unchanged omadacycline after i.v. administration. Fecal excretion was primarily the result of biliary excretion (∼40%) and direct gastrointestinal secretion (∼30%). However, urinary excretion (∼30%) was equally prominent after i.v. dosing.
Altered Plasmodium falciparum Sensitivity to the Antiretroviral Protease Inhibitor Lopinavir Associated with Polymorphisms in
pfmdr1
Authors: Sonoiki Ebere , Nsanzabana Christian , Legac Jennifer , Sindhe Kirthana M. V. , DeRisi Joseph , Rosenthal Philip J. 
Published: November 2016

ABSTRACT

The HIV protease inhibitor lopinavir inhibits
Plasmodium falciparum
aspartic proteases (plasmepsins) and parasite development, and children receiving lopinavir-ritonavir experienced fewer episodes of malaria than those receiving other antiretroviral regimens. Resistance to lopinavir was selected
in vitro
over ∼9 months, with ∼4-fold decreased sensitivity. Whole-genome sequencing of resistant parasites showed a mutation and increased copy number in
pfmdr1
and a mutation in a protein of unknown function, but no polymorphisms in plasmepsin genes.
Differential Penicillin-Binding Protein 5 (PBP5) Levels in the Enterococcus faecium Clades with Different Levels of Ampicillin Resistance
Authors: Montealegre Maria Camila , Roh Jung Hyeob , Rae Meredith , Davlieva Milya G. , Singh Kavindra V. , Shamoo Yousif , Murray Barbara E. 
Published: November 2016

ABSTRACT

Ampicillin resistance in
Enterococcus faecium
is a serious concern worldwide, complicating the treatment of
E. faecium
infections. Penicillin-binding protein 5 (PBP5) is considered the main ampicillin resistance determinant in
E. faecium
. The three known
E. faecium
clades showed sequence variations in the
pbp5
gene that are associated with their ampicillin resistance phenotype; however, these changes alone do not explain the array of resistance levels observed among
E. faecium
clinical strains. We aimed to determine if the levels of PBP5 are differentially regulated between the
E. faecium
clades, with the hypothesis that variations in PBP5 levels could help account for the spectrum of ampicillin MICs seen in
E. faecium
. We studied
pbp5
mRNA levels and PBP5 protein levels as well as the genetic environment upstream of
pbp5
in 16
E. faecium
strains that belong to the different
E. faecium
clades and for which the ampicillin MICs covered a wide range. Our results found that
pbp5
and PBP5 levels are increased in subclade A1 and A2 ampicillin-resistant strains compared to those in clade B and subclade A2 ampicillin-susceptible strains. Furthermore, we found evidence of major clade-associated rearrangements in the region upstream of
pbp5
, including large DNA fragment insertions, deletions, and single nucleotide polymorphisms, that may be associated with the differential regulation of PBP5 levels between the
E. faecium
clades. Overall, these findings highlight the contribution of the clade background to the regulation of PBP5 abundance and point to differences in the region upstream of
pbp5
as likely contributors to the differential expression of ampicillin resistance.
Listeria monocytogenes-Induced Cell Death Inhibits the Generation of Cell-Mediated Immunity
Authors: Theisen Erin , Sauer John-Demian 
Published: November 2016

ABSTRACTThe influence of cell death on adaptive immunity has been studied for decades. Despite these efforts, the intricacies of how various cell death pathways shape immune responses in the context of infection remain unclear, particularly with regard to more recently discovered pathways such as pyroptosis. The emergence ofListeria monocytogenesas a promising immunotherapeutic platform demands a thorough understanding of how cell death induced in the context of infection influences the generation of CD8+T-cell-mediated immune responses. To begin to address this question, we designed strains ofL. monocytogenesthat robustly activate necrosis, apoptosis, or pyroptosis. We hypothesized that proinflammatory cell death such as necrosis would be proimmunogenic while apoptosis would be detrimental, as has previously been reported in the context of sterile cell death. Surprisingly, we found that the activation of any host cell death in the context ofL. monocytogenesinfection inhibited the generation of protective immunity and specifically the activation of antigen-specific CD8+T cells. Importantly, the mechanism of attenuation was unique for each type of cell death, ranging from deficits in costimulation in the context of necrosis to a suboptimal inflammatory milieu in the case of pyroptosis. Our results suggest that cell death in the context of infection is different from sterile-environment-induced cell death and that inhibition of cell death or its downstream consequences is necessary for developing effective cell-mediated immune responses usingL. monocytogenes-based immunotherapeutic platforms.