bluuebunny/crossref_metadata_2025 huggingface dataset:
Correlations of methane and carbon dioxide concentrations from feedlot cattle as a predictor of methane emissions
Authors: Bai Mei , Griffith David W. T. , Phillips Frances A. , Naylor Travis , Muir Stephanie K. , McGinn Sean M. , Chen Deli
Published: December 2014

Accurate measurements of methane (CH4) emissions from feedlot cattle are required for verifying greenhouse gas (GHG) accounting and mitigation strategies. We investigate a new method for estimating CH4 emissions by examining the correlation between CH4 and carbon dioxide (CO2) concentrations from two beef cattle feedlots in Australia representing southern temperate and northern subtropical locations. Concentrations of CH4 and CO2 were measured at the two feedlots during summer and winter, using open-path Fourier transform infrared spectroscopy. There was a strong correlation for the concentrations above background of CH4 and CO2 with concentration ratios of 0.008 to 0.044 ppm/ppm (R2 >0.90). The CH4/CO2 concentration ratio varied with animal diet and ambient temperature. The CH4/CO2 concentration ratio provides an alternative method to estimate CH4 emissions from feedlots when combined with CO2 production derived from metabolisable energy or heat production.
Speciation with gene flow in equids despite extensive chromosomal plasticity
Authors: Jónsson Hákon , Schubert Mikkel , Seguin-Orlando Andaine , Ginolhac Aurélien , Petersen Lillian , Fumagalli Matteo , Albrechtsen Anders , Petersen Bent , Korneliussen Thorfinn S. , Vilstrup Julia T. , Lear Teri , Myka Jennifer Leigh , Lundquist Judith , Miller Donald C. , Alfarhan Ahmed H. , Alquraishi Saleh A. , Al-Rasheid Khaled A. S. , Stagegaard Julia , Strauss Günter , Bertelsen Mads Frost , Sicheritz-Ponten Thomas , Antczak Douglas F. , Bailey Ernest , Nielsen Rasmus , Willerslev Eske , Orlando Ludovic
Published: December 2014

Significance

Thirty years after the first DNA fragment from the extinct quagga zebra was sequenced, we set another milestone in equine genomics by sequencing its entire genome, along with the genomes of the surviving equine species. This extensive dataset allows us to decipher the genetic makeup underlying lineage-specific adaptations and reveal the complex history of equine speciation. We find that
Equus
first diverged in the New World, spread across the Old World 2.1–3.4 Mya, and finally experienced major demographic expansions and collapses coinciding with past climate changes. Strikingly, we find multiple instances of hybridization throughout the equine tree, despite extremely divergent chromosomal structures. This contrasts with theories promoting chromosomal incompatibilities as drivers for the origin of equine species.
Silencing urease: A key evolutionary step that facilitated the adaptation of
Yersinia pestis
to the flea-borne transmission route
Authors: Chouikha Iman , Hinnebusch B. Joseph
Published: December 2014

Significance

The plague bacillus
Yersinia pestis
is transmitted by fleas but evolved very recently from
Yersinia pseudotuberculosis
, a closely related food- and water-borne enteric pathogen. Identifying the specific genetic changes underlying the switch to arthropod-borne transmission is essential to understanding the evolution of
Y. pestis
and the emergence of plague. We have identified an important early step in this process. The urease enzyme, beneficial for an enteric bacterium, causes acute oral toxicity and significant mortality to fleas.
Y. pestis
is not toxic to fleas because of a loss-of-function mutation in one of the genes essential for urease activity. Epidemiologic modeling suggests that this mutation was positively selected during evolution because it resulted in a significantly higher probability of
Y. pestis
transmission.
Impact of HLA-driven HIV adaptation on virulence in populations of high HIV seroprevalence
Authors: Payne Rebecca , Muenchhoff Maximilian , Mann Jaclyn , Roberts Hannah E. , Matthews Philippa , Adland Emily , Hempenstall Allison , Huang Kuan-Hsiang , Brockman Mark , Brumme Zabrina , Sinclair Marc , Miura Toshiyuki , Frater John , Essex Myron , Shapiro Roger , Walker Bruce D. , Ndung’u Thumbi , McLean Angela R. , Carlson Jonathan M. , Goulder Philip J. R.
Published: December 2014

Significance

Factors that influence the virulence of HIV are of direct relevance to ongoing efforts to contain, and ultimately eradicate, the HIV epidemic. We here investigate in Botswana and South Africa, countries severely affected by HIV, the impact on HIV virulence of adaptation of HIV to protective HLA alleles such as HLA-B*57. In Botswana, where the epidemic started earlier and reached higher adult seroprevalence than in South Africa, HIV replication capacity is lower. HIV is also better adapted to HLA-B*57, which in Botswana has no protective effect, in contrast to its impact in South Africa. Modelling studies indicate that increasing antiretroviral therapy access may also contribute to accelerated declines in HIV virulence over the coming decades.
Erythritol feeds the pentose phosphate pathway via three new isomerases leading to D-erythrose-4-phosphate in
Brucella
Authors: Barbier Thibault , Collard François , Zúñiga-Ripa Amaia , Moriyón Ignacio , Godard Thibault , Becker Judith , Wittmann Christoph , Van Schaftingen Emile , Letesson Jean-Jacques
Published: December 2014

Significance

Erythritol is a preferential substrate for
Brucella
, a common zoonotic bacterial pathogen. This four-carbon polyol is found in the reproductive organs of several affected species, a feature that may account for the characteristic viscerotropism of
Brucella
that leads to sterility and abortion. Although described previously as feeding glycolysis via dihydroxyacetone-phosphate, we show here that erythritol is actually converted into D-erythrose-4-phosphate through a hitherto undescribed set of reactions that involves three isomerases and that allows hexose-monophosphate synthesis and growth by feeding the pentose phosphate shunt. Elucidation of this unique carbohydrate pathway, which also applies to the
Rhizobiales
plant endosymbionts, opens the way for further research on the metabolic adaptation of an important facultative intracellular pathogen to target organs.
Carnivorous leaves from Baltic amber
Authors: Sadowski Eva-Maria , Seyfullah Leyla J. , Sadowski Friederike , Fleischmann Andreas , Behling Hermann , Schmidt Alexander R.
Published: December 2014

Significance

Amber, fossil tree resin, preserves organisms in microscopic fidelity, and frequently fossils preserved in amber are otherwise absent in the entire fossil record. Plant remains, however, are rarely entrapped in amber, compared with the vast amount of insects and other animals. Our newly discovered fossils from Eocene Baltic amber are the only documented case of fossilized carnivorous plant traps and represent the first fossil evidence of the carnivorous plant family Roridulaceae, which is today a narrow endemic of South Africa. Hence, our results shed light onto the paleobiogeography of the Roridulaceae, indicating a wide Eocene distribution of the roridulid ancestors and challenging previous notions about a Gondwanan origin of this plant family.
Escherichia coli
dihydrofolate reductase catalyzed proton and hydride transfers: Temporal order and the roles of Asp27 and Tyr100
Authors: Liu C. Tony , Francis Kevin , Layfield Joshua P. , Huang Xinyi , Hammes-Schiffer Sharon , Kohen Amnon , Benkovic Stephen J.
Published: December 2014

Significance

Dihydrofolate reductase is a classic drug target because it promotes the NADPH-dependent reduction of 7,8-dihydrofolate (DHF) to yield 5,6,7,8-tetrahydrofolate (THF), which is involved in the biosynthesis of purines, thymidylate, and several amino acids. It is also a popular model system for various biochemical/biophysical studies. However, there are many unresolved mechanistic issues regarding the mechanism of catalysis. We combined primary, solvent, and multiple kinetic isotope effects; their temperature dependence; theoretical calculations; and site-specific mutagenesis to elucidate the reaction mechanism, which involves stepwise protonation of DHF by a water molecule prior to the hydride transfer. These two events are facilitated by two active site residues (D27 and Y100) that operate synergistically to ensure catalysis and to enable efficient DHF protonation over a wide pH range.
Recessive cardiac phenotypes in induced pluripotent stem cell models of Jervell and Lange-Nielsen syndrome: Disease mechanisms and pharmacological rescue
Authors: Zhang Miao , D’Aniello Cristina , Verkerk Arie O. , Wrobel Eva , Frank Stefan , Ward-van Oostwaard Dorien , Piccini Ilaria , Freund Christian , Rao Jyoti , Seebohm Guiscard , Atsma Douwe E. , Schulze-Bahr Eric , Mummery Christine L. , Greber Boris , Bellin Milena
Published: December 2014

Significance

There are few laboratory models that recapitulate human cardiac disease. Here, we created human cell models for Jervell and Lange-Nielsen syndrome (JLNS) in vitro, based on human induced pluripotent stem cells (hiPSCs). JLNS is one of the most severe disorders of heart rhythm and can cause sudden death in young patients. JLNS is inherited recessively and is caused by homozygous mutations in the slow component of the delayed rectifier potassium current, I
Ks
. Cardiomyocytes (CMs) from two independent sets of patient-derived and engineered hiPSCs showed electrophysiological defects that reflect the severity of the condition in patients. Our work allowed better understanding of the mechanisms of recessive inheritance. Furthermore, JLNS-CMs showed increased sensitivity to proarrhythmic drugs, which could be rescued pharmacologically, demonstrating the potential of hiPSC-CMs in drug testing.
Communication between oocytes and somatic cells regulates volatile pheromone production in
Caenorhabditis elegans
Authors: Leighton Daniel H. W. , Choe Andrea , Wu Shannon Y , Sternberg Paul W.
Published: December 2014

Significance

It has been shown that males of
Caenorhabditis elegans
are more likely to be attracted to females and hermaphrodites that do not harbor sperm, and that females and hermaphrodites behave differently depending on whether or not they harbor mature sperm, but the mechanism that links sperm status to behavior and attraction remains unknown. In this paper, we show that oocyte–somatic communication is responsible for controlling the production of a mate-attracting pheromone by
C. elegans
hermaphrodites. This volatile pheromone, whose production is suppressed by oocyte–somatic communication, is the first volatile pheromone described in
C. elegans
. Our study of its control provides a detailed description of pheromone regulation in a nematode.
The second demographic transition: A concise overview of its development
Authors: Lesthaeghe Ron
Published: December 2014

Significance

At the end of the historical declines in both mortality and fertility (the “first demographic transition”), new demographic phenomena developed in the Western World. Therefore, new theoretical frameworks were needed to explain features such as the baby bust, the systematic postponement of marriage and parenthood, subreplacement fertility, the rise of alternative forms of partnerships, and parenthood outside marriage. The “second demographic transition” (SDT) theory is such an attempt. Although it accepts the major tenets of bounded rational economic choice, it also allows for autonomous preference drift by relying on Maslow’s theory of shifting needs. As such, an essentially cultural component is being added.
Repurposing of bisphosphonates for the prevention and therapy of nonsmall cell lung and breast cancer
Authors: Stachnik Agnes , Yuen Tony , Iqbal Jameel , Sgobba Miriam , Gupta Yogesh , Lu Ping , Colaianni Graziana , Ji Yaoting , Zhu Ling-Ling , Kim Se-Min , Li Jianhua , Liu Peng , Izadmehr Sudeh , Sangodkar Jaya , Scherer Thomas , Mujtaba Shiraz , Galsky Matthew , Gomez Jorge , Epstein Solomon , Buettner Christoph , Bian Zhuan , Zallone Alberta , Aggarwal Aneel K. , Haider Shozeb , New Maria I. , Sun Li , Narla Goutham , Zaidi Mone
Published: December 2014

Significance

Small molecules to target oncogenic signaling cascades in cancer have achieved success in molecularly defined patient subsets. The path to approval is often protracted and plagued with failures. Repositioning Food and Drug Administration-approved drugs with known side effects has become a major focus. Bisphosphonates are a commonly prescribed therapy for osteoporosis and skeletal metastases. The drugs have also been associated with reduced tumor burden in some patients, but the mechanism is unknown. Here we provide evidence that bisphosphonates inhibit the human EGFR (HER) receptor tyrosine kinase, including the commonly mutated forms that drive nonsmall cell lung cancer, as well as a resistance mutation. This new mechanism lays the basis for the future use of bisphosphonates for the prevention and therapy of HER family-driven cancers.
Bmi1 enhances skeletal muscle regeneration through MT1-mediated oxidative stress protection in a mouse model of dystrophinopathy
Authors: Di Foggia Valentina , Zhang Xinyu , Licastro Danilo , Gerli Mattia F.M. , Phadke Rahul , Muntoni Francesco , Mourikis Philippos , Tajbakhsh Shahragim , Ellis Matthew , Greaves Laura C. , Taylor Robert W. , Cossu Giulio , Robson Lesley G. , Marino Silvia
Published: December 2014

The Polycomb group (PcG) protein Bmi1 is an essential epigenetic regulator of stem cell function during normal development and in adult organ systems. We show that mild up-regulation of Bmi1 expression in the adult stem cells of the skeletal muscle leads to a remarkable improvement of muscle function in a mouse model of Duchenne muscular dystrophy. The molecular mechanism underlying enhanced physiological function of Bmi1 depends on the injury context and it is mediated by metallothionein 1 (MT1)–driven modulation of resistance to oxidative stress in the satellite cell population. These results lay the basis for developing Bmi1 pharmacological activators, which either alone or in combination with MT1 agonists could be a powerful novel therapeutic approach to improve regeneration in muscle wasting conditions.
Effect of three-dimensional conducting structures on vertical stability in EAST
Authors: Chen S.L. , Villone F. , Barbato L. , Mastrostefano S. , Xiao B.J. , Luo Z.P.
Published: December 2014

The vertical stability of the Experimental Advanced Superconducting Tokamak (EAST) is studied in detail in the present paper. It is found that correct modelling of the detailed three-dimensional (3D) features of the conducting structures surrounding the plasma is essential in order to get reliable estimates of the growth rate of vertical displacement events. The numerical model developed, based on the CarMa0 code, can take 3D effects into account, and provides results very close to experimental values for a wide range of plasma configurations. A deep insight about the current density patterns induced in passive structures is gained.
Suppression of energetic particle driven instabilities with HHFW heating
Authors: Fredrickson E.D. , Taylor G. , Bertelli N. , Darrow D.S. , Gorelenkov N. , Kramer G. , Liu D. , Crocker N.A. , Kubota S. , White R.
Published: December 2014

In plasmas in the National Spherical Torus Experiment (NSTX) (Ono et al 2000 Nucl. Fusion
40 557) heated with neutral beams, the beam ions typically excite energetic particle modes (or fishbones), and toroidal, global or compressional Alfvén eigenmodes. These modes can redistribute the energetic beam ions, altering the beam driven current profile and the plasma heating profile, or they may affect electron thermal transport or cause losses of the beam ions. In this paper we present experimental results where these instabilities, driven by the super-thermal beam ions, are suppressed with the application of high harmonic fast wave heating.
Impact of Te and ne on edge current density profiles in ELM mitigated regimes on ASDEX Upgrade
Authors: Dunne M.G. , Rathgeber S. , Burckhart A. , Fischer R. , Giannone L. , McCarthy P.J. , Schneider P.A. , Wolfrum E.
Published: December 2014

ELM resolved edge current density profiles are reconstructed using the CLISTE equilibrium code. As input, highly spatially and temporally resolved edge electron temperature and density profiles are used in addition to data from the extensive set of external poloidal field measurements available at ASDEX Upgrade, flux loop difference measurements, and current measurements in the scrape-off layer. Both the local and flux surface averaged current density profiles are analysed for several ELM mitigation regimes. The focus throughout is on the impact of altered temperature and density profiles on the current density. In particular, many ELM mitigation regimes rely on operation at high density. Two reference plasmas with type-I ELMs are analysed, one with a deuterium gas puff and one without, in order to provide a reference for the behaviour in type-II ELMy regimes and high density ELM mitigation with external magnetic perturbations at ASDEX Upgrade. For type-II ELMs it is found that while a similar pedestal top pressure is sustained at the higher density, the temperature gradient decreases in the pedestal. This results in lower local and flux surface averaged current densities in these phases, which reduces the drive for the peeling mode. No significant differences between the current density measured in the type-I phase and ELM mitigated phase is seen when external perturbations are applied, though the pedestal top density was increased. Finally, ELMs during the nitrogen seeded phase of a high performance discharge are analysed and compared to ELMs in the reference phase. An increased pedestal pressure gradient, which is the source of confinement improvement in impurity seeded discharges, causes a local current density increase. However, the increased Z
eff in the pedestal acts to reduce the flux surface averaged current density. This dichotomy, which is not observed in other mitigation regimes, could act to stabilize both the ballooning mode and the peeling mode at the same time.
The Yield of Plant Variety Protection
Authors: Thomson Russell
Published: December 2014

The prospects for plant variety protection to deliver improved varieties of self‐pollinating crops is assessed using the experience of the Australian wheat breeding sector as a natural experiment. The analysis is based on detailed new data on the agronomic performance of all wheat varieties released by Australian breeders between 1976 and 2011. The results indicate that plant variety protection, and associated reforms, led to a substantial fall in breeder output. Qualitative evidence indicates that this was caused by a combination of fewer research spillovers, lower release standards, and a possible fall in total investment in breeding.
Should Blood Pressure Targets After Lacunar Stroke Vary by Body Size? The SPS3 Trial
Authors: Field Thalia S. , McClure Leslie A. , White Carole L. , Pergola Pablo E. , Hart Robert G. , Benavente Oscar R. , Hill Michael D.
Published: December 2014

BACKGROUND

It is unknown whether the physiological impact of a given blood pressure (BP) varies by body size. We explored interactions between higher vs. lower systolic BP (SBP) targets and anthropometric measures (body mass index (BMI), body surface area (BSA), height, weight) and recurrent stroke and death in the Secondary Prevention of Small Subcortical Strokes (SPS3) Trial.

METHODS

Patients with recent magnetic resonance imaging-proven lacunar infarcts were randomized to 2 BP targets (130–149mm Hg vs. <130) in a prospective, open-label, blinded end-point design. Time to outcome was evaluated with Cox proportional hazard models and compared between targets. We examined multiplicative interactions between each anthropometric measure and target and mean difference in achieved BP 1 year after randomization between BP groups by quartile. We also computed rates of recurrent stroke and death by quartiles of anthropometrics.

RESULTS

Three thousand and twenty patients were followed over a mean of 3.7 (SD 2.0) years. Mean age was 63; 63% were male. Mean height was 167 (SD 11) cm, weight 81 (18) kg, BMI 29 (5.9) kg/m2, and BSA 1.9 (0.25) m2. Achieved BP at 1 year was comparable between quartiles for each anthropometric measurement. We found no consistent interactions between BP target and anthropometrics for either outcome, nor were there any significant associations between hazard of stroke or death when assessed by BMI, BSA, height, or weight.

CONCLUSIONS

We found no interactions between BP target groups and quartiles of anthropometrics for rates of stroke and death in SPS3. There is no evidence at this time supporting body size-based modifications to current BP targets for secondary prevention after lacunar stroke.

CLINICAL TRIALS REGISTRATION

Trial Number NCT00059306
Crystal structure of 6,9-dimethyl-7H-[1,2,4]triazolo[4,3-b][1,2,4]triazepin-8(9H)-one 0.40-hydrate
Authors: Harmaoui Abdellah , Bouhfid Rachid , Essassi El Mokhtar , Saadi Mohamed , El Ammari Lahcen
Published: December 2014

In the molecule of the title compound, C7H9N5O·0.40H2O, the seven-membered heterocyclic ring exhibits a boat conformation, whereas the five-membered triazole ring is almost planar (r.m.s. deviation = 0.005 Å). In the crystal, centrosymmetric dimers are linked by pairs of C—H...O hydrogen bonds into dimers, which are further connectedviaO—H...N and C—H...N hydrogen bonds, forming a three-dimensional network. The structure contains a partially occupied water molecule lying on a twofold axis with an occupancy factor of 0.4.
Crystal structure of 1,3-bis(4-methylbenzyl)-1H-1,3-benzimidazol-3-ium bromide monohydrate
Authors: Çelikesir Sevim Türktekin , Çelik Ömer , Akkoç Senem , İlhan İlhan Özer , Gök Yetkin , Akkurt Mehmet
Published: December 2014

In the title hydrated symetrically substituted 1,3-bis(4-methylbenzyl)benzimidazolium salt, C23H23N2+·Br−·H2O, the dihedral angles between the benzimidazole ring system (r.m.s. deviation = 0.003 Å) and the pendant benzene rings are 73.18 (16) and 77.52 (16)°. Both benzene rings lie to the same side of the benzimidazole ring system, giving the cation an overall U-shape. In the crystal, the cation is linked to the water molecule by a short C—H...O hydrogen bond and the water molecule forms O—H...Br hydrogen bonds. Together, these interactions lead to [010] chains. The packing is consolidated by C—H...Br hydrogen bonds and aromatic π–π stacking interactions [centroid–centroid distances = 3.5401 (17) and 3.8815 (18) Å], generating a three-dimensional network.
Crystal structures of 2-benzylamino-4-(4-bromophenyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridine-3-carbonitrile and 2-benzylamino-4-(4-chlorophenyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridine-3-carbonitrile
Authors: Nagalakshmi R. A. , Suresh J. , Maharani S. , Kumar R. Ranjith , Lakshman P. L. Nilantha
Published: December 2014

In the title compounds, C24H22BrN3, (I), and C24H22ClN3, (II), the 2-aminopyridine ring is fused with a cycloheptane ring, which adopts a half-chair conformation. The planes of the phenyl and benzene rings are inclined to that of the central pyridine ring [r.m.s. deviations = 0.0083 (1) and 0.0093 (1) Å for (I) and (II), respectively] by 62.47 (17) and 72.51 (14)°, respectively, in (I), and by 71.44 (9) and 54.90 (8)°, respectively, in (II). The planes of the aromatic rings are inclined to one another by 53.82 (17)° in (I) and by 58.04 (9)° in (II). In the crystals of both (I) and (II), pairs of N—H...Nnitrilehydrogen bonds link the molecules, forming inversion dimers withR22(12) ring motifs. In (I), the resulting dimers are connected through C—H...Br hydrogen bonds, forming sheets parallel to (10-1), and π–π interactions [inter-centroid distance = 3.7821 (16) Å] involving inversion-related pyridine rings, forming a three-dimensional network. In (II), the resulting dimers are connected through π–π interactions [inter-centroid distance = 3.771 (2) Å] involving inversion-related pyridine rings, forming a two-dimensional network lying parallel to (001).
Linkage and trade‐off in trophic morphology and behavioural performance of birds
Authors: Corbin Clay E. , Lowenberger Lauren K. , Gray Brandan L.
Published: December 2014

Bill closing behaviour involves a complex suite of tissue types, kinematics, morphological states and muscle architectural arrangements that has been under the scrutiny of natural selection for millions of years. Hence, an evolutionary shift to specialize in closing force may come at a cost to closing velocity and vice versa.

Using field measurements on behavioural performance and morphological data from museum specimens, we tested predictions of the force–velocity trade‐off hypothesis in 18 species of North American birds with diverse phylogenetic and ecological backgrounds.

Linear models revealed that size and shape are excellent predictors of both bite force and closing velocity. However, taken one at a time, they each have a somewhat unique set of morphological predictors. In‐lever length, mandibular depth and bill width comprise the best model of prediction for force, while a combination of out‐lever length and total skull length provides the best prediction of closing velocity. Additionally, in our sample, only force is size‐dependent. Hence, the predicted trade‐off is revealed only after correcting bite force for head size.

Various modes of predation and decoupled morphological prediction models for performance suggest that specialization towards one strategy (e.g. increase force) may not necessarily come at a cost to the other.
Food Policy in 2013: Ending Hunger and Undernutrition Sustainably by 2025
Authors: Fan Shenggen
Published: December 2014

The challenge of ensuring future food and nutrition security received widespread attention in 2013. The Millennium Development Goal (MDG) to halve global hunger by 2015 has not yet been met. Although progress has been made, one in eight people still suffer from hunger, and nearly 2 billion are affected by hidden hunger, or micronutrient deficiencies. Hunger and undernutrition can be eliminated sustainably by 2025. The experiences of successful countries in substantially reducing hunger and undernutrition suggest that it is realistic to strive for this goal by accelerating the pace of progress. But to achieve this goal, governments and donors must devote sufficient resources and implement appropriate policies and investments. Discussions of a post‐2015 development agenda, including a set of Sustainable Development Goals, which will advance what began with the MDGs are now well underway. Environmental sustainability is certainly integral to the post‐2015 agenda, but it should be pursued in ways that do not undermine the food and nutrition security and well‐being of poor and hungry people. The agenda must be grounded in a multisectoral, sustainable, people‐focused approach that (1) focuses on clear goals and targets, (2) uses comprehensive data and indicators to monitor and measure the goals and targets accurately, (3) supports partnerships among all stakeholders, and (4) promotes accountability.
Estimating pairwise relatedness between individuals with different levels of ploidy
Authors: Huang Kang , Ritland Kermit , Guo Songtao , Dunn Derek W. , Chen Dan , Ren Yi , Qi Xiaoguang , Zhang Pei , He Gang , Li Baoguo
Published: December 2014

Estimates of relatedness coefficients, based on genetic marker data, are often necessary for studies of genetics and ecology. Whilst many estimates based on method‐of‐moment or maximum‐likelihood methods exist for diploid organisms, no such estimators exist for organisms with multiple ploidy levels, which occur in some insect and plant species. Here, we extend five estimators to account for different levels of ploidy: one relatedness coefficient estimator, three coefficients of coancestry estimators and one maximum‐likelihood estimator. We use arrhenotoky (when unfertilized eggs develop into haploid males) as an example in evaluations of estimator performance by Monte Carlo simulation. Also, three virtual sex‐determination systems are simulated to evaluate their performances for higher levels of ploidy. Additionally, we used two real data sets to test the robustness of these estimators under actual conditions. We make available a software package, PolyRelatedness, for other researchers to apply to organisms that have various levels of ploidy.
Universal and blocking primer mismatches limit the use of high‐throughput DNA sequencing for the quantitative metabarcoding of arthropods
Authors: Piñol J. , Mir G. , Gomez‐Polo P. , Agustí N.
Published: December 2014

The quantification of the biological diversity in environmental samples using high‐throughput DNA sequencing is hindered by the PCR bias caused by variable primer–template mismatches of the individual species. In some dietary studies, there is the added problem that samples are enriched with predator DNA, so often a predator‐specific blocking oligonucleotide is used to alleviate the problem. However, specific blocking oligonucleotides could coblock nontarget species to some degree. Here, we accurately estimate the extent of the PCR biases induced by universal and blocking primers on a mock community prepared with DNA of twelve species of terrestrial arthropods. We also compare universal and blocking primer biases with those induced by variable annealing temperature and number of PCR cycles. The results show that reads of all species were recovered after PCR enrichment at our control conditions (no blocking oligonucleotide, 45 °C annealing temperature and 40 cycles) and high‐throughput sequencing. They also show that the four factors considered biased the final proportions of the species to some degree. Among these factors, the number of primer–template mismatches of each species had a disproportionate effect (up to five orders of magnitude) on the amplification efficiency. In particular, the number of primer–template mismatches explained most of the variation (~3/4) in the amplification efficiency of the species. The effect of blocking oligonucleotide concentration on nontarget species relative abundance was also significant, but less important (below one order of magnitude). Considering the results reported here, the quantitative potential of the technique is limited, and only qualitative results (the species list) are reliable, at least when targeting the barcoding COI region.
Exercise augmentation compared with usual care for post‐traumatic stress disorder: a randomized controlled trial
Authors: Rosenbaum S. , Sherrington C. , Tiedemann A.
Published: December 2014

Objective

To investigate the impact of a 12‐week exercise programme in addition to usual care for post‐traumatic stress disorder (PTSD).

Method

An assessor‐blinded randomized controlled trial was conducted among 81 participants with a DSM‐IV‐TR diagnosis of primary PTSD. Participants were recruited after admission to an in‐patient programme at a private hospital. Participants were randomized to receive either usual care (n = 42), or exercise in addition to usual care (n = 39). The exercise intervention involved three, 30‐min resistance‐training sessions/week and a pedometer‐based walking programme. Usual care involved psychotherapy, pharmaceutical interventions, and group therapy. Primary outcome was PTSD symptoms assessed via the PTSD checklist–civilian version (PCL‐C). Secondary outcomes included symptoms of depression, anthropometry, physical activity, mobility, strength, and sleep quality.

Results

Participants had a mean (SD) age of 47.8 years (12.1), 84% male. PTSD symptoms in the intervention group significantly reduced compared with the usual care group (mean difference = −5.4, 95% CI −10.5 to −0.3, P = 0.04, n = 58). There were significant between‐group differences at follow‐up for depressive symptoms, waist circumference, sleep quality, and sedentary time.

Conclusion

This study provides the first evidence that an exercise intervention is associated with reduced PTSD and depressive symptoms, reduced waist circumference, and improved sleep quality.
The Benefit Corporation: Corporate Governance and the For‐profit Social Entrepreneur
Authors: Hemphill Thomas A. , Cullari Francine
Published: December 2014

The adoption by 19 states and the District of Columbia of a new variant of the business corporation form—known as the benefit corporation—presents several issues for legislatures, for entrepreneurs electing to organize as benefit corporations, for existing corporations that are converting to the new form, and for the stakeholders (other than shareholders) who are intended to be considered in benefit corporation governance. The article presents the history and structure of the new business form and a discussion of what has become its predecessor—the constituency statute. The model benefit corporation statute provisions are reviewed, which many states have adopted in toto. The authors address the obstacles that should be overcome by legislatures, businesses, and stakeholders before further legislative adoptions occur, as well as considerations for effective implementation by government, corporations, and stakeholders under existing and proposed variations of the statute.
Testing the bi‐dimensional effects of attitudes on behavioural intentions and subsequent behaviour
Authors: Elliott Mark A. , Brewster Sarah E. , Thomson James A. , Malcolm Carly , Rasmussen Susan
Published: November 2014

Attitudes are typically treated as unidimensional predictors of both behavioural intentions and subsequent behaviour. On the basis of previous research showing that attitudes comprise two independent, positive and negative dimensions, we hypothesized that attitudes would be bi‐dimensional predictors of both behavioural intentions and subsequent behaviour. We focused on health‐risk behaviours. We therefore also hypothesized that the positive dimension of attitude (evaluations of positive behavioural outcomes) would better predict both behavioural intentions and subsequent behaviour than would the negative dimension, consistent with the positivity bias/offset principle. In Study 1 (cross sectional design), N = 109 university students completed questionnaire measures of their intentions to binge‐drink and the positive and negative dimensions of attitude. Consistent with the hypotheses, both attitude dimensions independently predicted behavioural intentions and the positive dimension was a significantly better predictor than was the negative dimension. The same pattern of findings emerged in Study 2 (cross sectional design; N = 186 university students) when we predicted intentions to binge‐drink, smoke and consume a high‐fat diet. Similarly, in Study 3 (prospective design; N = 1,232 speed limit offenders), both the positive and negative dimensions of attitude predicted subsequent (6‐month post‐baseline) speeding behaviour on two different road types and the positive dimension was the better predictor. The implications for understanding the motivation of behaviour and the development of behaviour‐change interventions are discussed.
The peroxisome proliferator‐activated receptors in cardiovascular diseases: experimental benefits and clinical challenges
Authors: Cheang Wai San , Tian Xiao Yu , Wong Wing Tak , Huang Yu
Published: December 2014

The peroxisome proliferator‐activated receptors, PPARα, PPARβ/δ and PPARγ, are ligand‐activated transcriptional factors belonging to the nuclear receptors superfamily and they are known to play important roles in glucose and lipid metabolism. Experimental studies in animal models of metabolic diseases have also revealed that activation of PPARs protects against the vascular complications of diabetes, hypertension, atherosclerosis, myocardial infarction and stroke, through exerting their anti‐inflammatory, anti‐atherogenic and antioxidant effects. In clinical trials and post‐market surveillance, agonists of PPARs have been shown to effectively prevent cardiovascular events. However, adverse effects, particularly for PPARγ agonists, are also observed with the use of investigational PPAR agonists and even some approved drugs. Further exploration of underlying mechanisms is needed to develop novel ways of PPAR activation without causing serious side effects. This article reviews the cardiovascular effects of PPARs, with emphasis on the therapeutic potential of PPAR agonists in combating metabolic vascular diseases.

Linked Articles

This article is part of a themed section on Chinese Innovation in Cardiovascular Drug Discovery. To view the other articles in
this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-23
S1P‐induced airway smooth muscle hyperresponsiveness and lung inflammation in vivo: molecular and cellular mechanisms
Authors: Roviezzo F , Sorrentino R , Bertolino A , De Gruttola L , Terlizzi M , Pinto A , Napolitano M , Castello G , D'Agostino B , Ianaro A , Sorrentino R , Cirino G
Published: December 2014

Background and Purpose

Sphingosine‐1‐phosphate (S1P) has been shown to be involved in the asthmatic disease as well in preclinical mouse experimental models of this disease. The aim of this study was to understand the mechanism(s) underlying S1P effects on the lung.

Experimental Approach

BALB/c, mast cell‐deficient and Nude mice were injected with S1P (s.c.) on days 0 and 7. Functional, molecular and cellular studies were performed.

Key Results

S1P administration to BALB/c mice increased airway smooth muscle reactivity, mucus production, PGD2, IgE, IL‐4 and IL‐13 release. These features were associated to a higher recruitment of mast cells to the lung. Mast cell‐deficient Kit W‐sh/W‐sh mice injected with S1P did not display airway smooth muscle hyper‐reactivity. However, lung inflammation and IgE production were still present. Treatment in vivo with the anti‐CD23 antibody B3B4, which blocks IgE production, inhibited both S1P‐induced airway smooth muscle reactivity in vitro and lung inflammation. S1P administration to Nude mice did not elicit airway smooth muscle hyper‐reactivity and lung inflammation. Naïve (untreated) mice subjected to the adoptive transfer of CD4+ T‐cells harvested from S1P‐treated mice presented all the features elicited by S1P in the lung.

Conclusions and Implications

S1P triggers a cascade of events that sequentially involves T‐cells, IgE and mast cells reproducing several asthma‐like features. This model may represent a useful tool for defining the role of S1P in the mechanism of action of currently‐used drugs as well as in the development of new therapeutic approaches for asthma‐like diseases.
AT‐1001: a high‐affinity α3β4 nAChR ligand with novel nicotine‐suppressive pharmacology
Authors: Cippitelli Andrea , Wu Jinhua , Gaiolini Kelly A , Mercatelli Daniela , Schoch Jennifer , Gorman Michelle , Ramirez Alejandra , Ciccocioppo Roberto , Khroyan Taline V , Yasuda Dennis , Zaveri Nurulain T , Pascual Conrado , Xie Xinmin (Simon) , Toll Lawrence
Published: December 2014

Background and Purpose

The α3β4 subtype of nicotinic acetylcholine receptors (nAChRs) has been implicated in mediating nicotine reinforcement processes. AT‐1001 has been recently described as a high‐affinity and selective α3β4 nAChR antagonist that blocks nicotine self‐administration in rats. The aim of this study was to investigate the mechanism of action underlying the nicotine‐suppressive effects of AT‐1001.

Experimental Approach

Effects of AT‐1001 were determined using in vitro assays and rat models of nicotine addiction, and compared with varenicline.

Key Results

AT‐1001 and its analogue AT‐1012 were functionally selective as antagonists for α3β4 over α4β2 nAChRs, but not to the same extent as the binding selectivity, and had partial agonist activity at α3β4 nAChRs. In contrast, varenicline was a partial agonist at α4β2, a weak agonist at α3β4 and inhibited α4β2 at a much lower concentration than it inhibited α3β4 nAChRs. AT‐1001 and varenicline also had very different in vivo properties. Firstly, AT‐1001 did not exhibit reinforcing properties per se while varenicline was self‐administered. Secondly, systemic treatment with AT‐1001 did not induce reinstatement of nicotine seeking but rather attenuated reinstatement induced by varenicline, as well as nicotine. Finally, unlike varenicline, AT‐1001 selectively blocked nicotine self‐administration without altering alcohol lever pressing as assessed in an operant co‐administration paradigm.

Conclusions and Implications

These findings describe a more complex AT‐1001 in vitro profile than previously appreciated and provide further support for the potential of AT‐1001 and congeners as clinically useful compounds for smoking cessation, with a mechanism of action distinct from currently available medications.
Immunohistochemical analysis of RTKs expression identified HER3 as a prognostic indicator of gastric cancer
Authors: Ema Akira , Yamashita Keishi , Ushiku Hideki , Kojo Ken , Minatani Naoko , Kikuchi Mariko , Mieno Hiroaki , Moriya Hiromitsu , Hosoda Kei , Katada Natsuya , Kikuchi Shiro , Watanabe Masahiko
Published: December 2014

Standard treatment in Japan for the 13th Japanese Gastric Cancer Association stage II/III advanced gastric cancer is postoperative adjuvant S‐1 administration after curative surgery. High expression of receptor type tyrosine kinases (RTKs) has repeatedly represented poor prognosis for cancers. However it has not been demonstrated whether RTKs have prognostic relevance for stage II/III gastric cancer with standard treatment. Tumor tissues were obtained from 167 stage II/III advanced gastric cancer patients who underwent curative surgery and received postoperative S‐1 chemotherapy from 2000 to 2010. Expression of the RTKs including EGFR, HER2, HER3, IGF‐1R, and EphA2 was analyzed using immunohistochemistry (IHC). Analysis using a multivariate proportional hazard model identified the most significant RTKs that represented independent prognostic relevance. When tumor HER3 expression was classified into IHC 1+/2+ (n = 98) and IHC 0 (n = 69), the cumulative 5‐year Relapse Free Survival (5y‐RFS) was 56.5 and 82.9%, respectively (P = 0.0034). Significant prognostic relevance was similarly confirmed for IGF‐1R (P = 0.014), and EGFR (P = 0.030), but not for EphA2 or HER2 expression. Intriguingly, HER3 expression was closely correlated with IGF‐1R (P < 0.0001, R = 0.41), and EphA2 (P < 0.0001, R = 0.34) expression. Multivariate proportional hazard model analysis identified HER3 (IHC 1+/2+) (HR; 1.53, 95% CI, 1.11–2.16, P = 0.0078) as the sole RTK that was a poor prognostic factor independent of stage. Of the 53 patients who recurred, 40 patients (75.5%) were HER3‐positive. Thus, of the RTKs studied, HER3 was the only RTK identified as an independent prognostic indicator of stage II/III advanced gastric cancer with standard treatment.
Determinants of participation in prostate cancer screening: A simple analytical framework to account for healthy‐user bias
Authors: Tabuchi Takahiro , Nakayama Tomio , Fukushima Wakaba , Matsunaga Ichiro , Ohfuji Satoko , Kondo Kyoko , Kawano Eiji , Fukuhara Hiroyuki , Ito Yuri , Oshima Akira
Published: December 2014

In Japan at present, fecal occult blood testing (FOBT) is recommended for cancer screening while routine population‐based prostate‐specific antigen (PSA) screening is not. In future it may be necessary to increase participation in the former and decrease it in the latter. Our objectives were to explore determinants of PSA‐screening participation while simultaneously taking into account factors associated with FOBT. Data were gathered from a cross‐sectional study conducted with random sampling of 6191 adults in Osaka city in 2011. Of 3244 subjects (return rate 52.4%), 936 men aged 40–64 years were analyzed using log‐binomial regression to explore factors related to PSA‐screening participation within 1 year. Only responders for cancer screening, defined as men who participated in either FOBT or PSA‐testing, were used as main study subjects. Men who were older (prevalence ratio [PR] [95% confidence interval (CI)] = 2.17 [1.43, 3.28] for 60–64 years compared with 40–49 years), had technical or junior college education (PR [95% CI] = 1.76 [1.19, 2.59] compared with men with high school or less) and followed doctors' recommendations (PR [95% CI] = 1.50 [1.00, 2.26]) were significantly more likely to have PSA‐screening after multiple variable adjustment among cancer‐screening responders. Attenuation in PR of hypothesized common factors was observed among cancer‐screening responders compared with the usual approach (among total subjects). Using the analytical framework to account for healthy‐user bias, we found three factors related to participation in PSA‐screening with attenuated association of common factors. This approach may provide a more sophisticated interpretation of participation in various screenings with different levels of recommendation.
The Identity‐Location Binding Problem
Authors: Howe Piers D. L. , Ferguson Adam
Published: December 2014

The binding problem is fundamental to visual perception. It is the problem of associating an object's visual properties with itself and not with some other object. The problem is made particular difficult because different properties of an object, such as its color, shape, size, and motion, are often processed independently, sometimes in different cortical areas. The results of these separate analyses have to be combined before the object can be seen as a single coherent entity as opposed to a collection of unconnected features. Visual bindings are typically initiated and updated in a serial fashion, one object at a time. Here, we show that one type of binding, location‐identity bindings, can be updated in parallel. We do this by using two complementary techniques, the simultaneous‐sequential paradigm and systems factorial technology. These techniques make different assumptions and rely on different behavioral measures, yet both came to the same conclusion.
MOR1 Expression in Gastric Cancer: A Biomarker Associated With Poor Outcome
Authors: Yao Ya‐sai , Yao Ru‐yong , Zhuang Li‐kun , Qi Wei‐wei , Lv Jing , Zhou Fei , Qiu Wen‐sheng , Yue Lu
Published: December 2014

Background

At present, the expression of MOR1 and its function in gastric cancer remains unclear with evidence suggesting that it is to be involved in tumor progression and metastasis. The study was to assess the clinicopathologic relevance and prognostic value of MOR1 expression in gastric cancer.

Methods

Real‐time quantitative RT‐PCR and immunohistochemical staining were used to detect MOR1 expression in primary gastric cancerous surgical specimens and adjacent nontumorous tissues.

Results

High MOR1 expression was detected in cancerous tumor compared with their adjacent nontumorous tissues. In addition, the chi‐square test revealed that high MOR1 expression was significantly correlated with depth of invasion (p = 0.006), lymph node metastasis (p = 0.001), distant metastasis (p = 0.017), and TNM staging (p = 0.027). Moreover, Kaplan–Meier analysis revealed a significant association between MOR1 expression and overall survival. High expression of MOR1 was identified as an independent and significant predictor gene of reduced postoperative survival.

Conclusion

We conclude that MOR1 expression may be a useful biomarker for better prediction of the clinical outcome and management of gastric cancer patients.
TheNativeAmerican Organic Garden: Using Service Learning as a Site of Resistance
Authors: Chollett Donna L.
Published: December 2014

As educators, we owe it to our students to enable them to transgress structural impediments and to create sustainable alternatives from the margins of the industrial agro‐food system. Policies of assimilation, allotment, and enclosure of theNativeAmerican commons and ecosystems brought devastation toNative cultures. Dependence on government commodities replacedNative food sovereignty and contributed to malnutrition, obesity, and diabetes as diets responded to corporately produced and processed foods. Young people often feel disempowered and ask how they might confront such formidable forces as corporate control of our agro‐food system, destruction of natural resources, and threats to human health. Service learning at a formerNativeAmerican boarding school, now a university campus, empowered students to create a community of learning and practice that resulted in aNativeAmericanOrganicGarden. Based onNative values, the garden serves the community's needs for healthy, locally produced food.