bluuebunny/crossref_metadata_2025 huggingface dataset:
The Personal Antipsychotic Choice Index
Authors: van Dijk Floor , de Wit Iris , Blankers Matthijs , Sommer Iris , de Haan Lieuwe
Published: August 2017

Introduction We present an online decision aid to involve patients with a psychotic disorder in shared decision-making concerning the selection of antipsychotic medication.

Method Patients selected effectiveness and adverse effects criteria from the Subject’s Response to Antipsychotics-34 questionnaire. Numerical data from meta-analyses, clinical trial data, receptor affinities and expert opinions were used to rank antipsychotics on each criterion. When using the the tool, patients indicate on a 5-point Likert scale how they value each (adverse) effect. The Likert scale values are combined in an algorithm with the rank orders of antipsychotics to create a personalized ranking.

Results Criteria used were: effectiveness concerning psychotic, depressive and cognitive symptoms, weight gain, sexual dysfunction, drowsiness, hypersomnia, extrapyramidal symptoms, anticholinergic adverse effects, hypersalivation, nausea, dizziness, energy loss, blunted affect/less need for companionship. High-level evidence was available for ranking weight gain, sexual dysfunction, menstrual disorders, extrapyramidal symptoms and effectiveness on psychotic symptoms. We used lower level evidence ranking the remaining criteria.

Discussion A transparent procedure has resulted in an updateable tool to produce individual ranking of antipsychotics based on the patients’ input.
Unique, but still best practice? The Research Excellence Framework (REF) from an international perspective
Authors: Sivertsen Gunnar
Published: August 2017

Inspired by The Metric Tide report (2015) on the role of metrics in research assessment and management, and Lord Nicholas Stern’s report Building on Success and Learning from Experience (2016), which deals with criticisms of REF2014 and gives advice for a redesign of REF2021, this article discusses the possible implications for other countries. It also contributes to the discussion of the future of the REF by taking an international perspective. The article offers a framework for understanding differences in the motivations and designs of performance-based research funding systems (PRFS) across countries. It also shows that a basis for mutual learning among countries is more needed than a formulation of best practice, thereby both contributing to and correcting the international outlook in The Metric Tide report and its supplementary Literature Review.
Effect of vortex inlet mode on low-power cylindrical Hall thruster
Authors: Ding Yongjie , Jia Boyang , Xu Yu , Wei Liqiu , Su Hongbo , Li Peng , Sun Hezhi , Peng Wuji , Cao Yong , Yu Daren
Published: August 2017

This paper examines a new propellant inlet mode for a low-power cylindrical Hall thruster called the vortex inlet mode. This new mode makes propellant gas diffuse in the form of a circumferential vortex in the discharge channel of the thruster. Simulation and experimental results show that the neutral gas density in the discharge channel increases upon the application of the vortex inlet mode, effectively extending the dwell time of the propellant gas in the channel. According to the experimental results, the vortex inlet increases the propellant utilization of the thruster by 3.12%–8.81%, thrust by 1.1%–53.5%, specific impulse by 1.1%–53.5%, thrust-to-power ratio by 10%–63%, and anode efficiency by 1.6%–7.3%, greatly improving the thruster performance.
H4: A model system for assessing the performance of diffusion Monte Carlo calculations using a single Slater determinant trial function
Authors: Gasperich Kevin , Deible Michael , Jordan Kenneth D.
Published: August 2017

A model H4 system is used to investigate the accuracy of diffusion Monte Carlo (DMC) calculations employing a single Slater determinant to fix the nodal surface. The lowest energy singlet state of square H4 is a diradical which is poorly described by DMC calculations using a single determinant (SD) trial function. Here we consider distortions to rectangular structures, which decrease the amount of diradical character. The falloff of the error in the SD-DMC energy with increasing separation between the two H2 molecules is found to be much more rapid for small distortions away from square than for large distortions. This behavior is shown to be correlated with the extent of mixing between the two configurations needed to properly describe the diradical character. The error in the SD-DMC energy is found to be sizeable (∼0.1 eV) even for separations at which the coefficient of the dominant configuration in a four-electron, four-orbital complete active space self-consistent-field wave function is as large as 0.9.
Broadband non-polarizing terahertz beam splitters with variable split ratio
Authors: Wei Minggui , Xu Quan , Wang Qiu , Zhang Xueqian , Li Yanfeng , Gu Jianqiang , Tian Zhen , Zhang Xixiang , Han Jiaguang , Zhang Weili
Published: August 2017

Seeking effective terahertz functional devices has always aroused extensive attention. Of particular interest is the terahertz beam splitter. Here, we have proposed, designed, manufactured, and tested a broadband non-polarizing terahertz beam splitter with a variable split ratio based on an all-dielectric metasurface. The metasurface was created by patterning a dielectric surface of the N-step phase gradient and etching to a few hundred micrometers. The conversion efficiency as high as 81% under the normal incidence at 0.7 THz was achieved. Meanwhile, such a splitter works well over a broad frequency range. The split ratio of the proposed design can be continuously tuned by simply shifting the metasurface, and the angle of emergences can also be easily adjusted by choosing the step of phase gradients. The proposed design is non-polarizing, and its performance is kept under different polarizations.
Secondary cavitation in a rigid tube
Authors: Ji Chen , Li Bo , Zou Jun
Published: August 2017

The oscillation of a single spark-generated bubble in a rigid tube is studied experimentally, with the help of a high-speed camera and a hydrophone. The non-dimensional collapse position XF is divided into three regimes, according to the various phenomena after the first oscillation period T1. In an asymmetric regime, secondary cavitation is observed. Both the axial position and the oscillation period of the secondary cavitation show a linear correlation with the first bubble. The period ratio k is independent of the relative bubble size L1* but is affected by the tube diameter Dt. In a symmetric regime, the secondary cavitation is much weaker and unrepeatable. The rebound bubble is strengthened in this regime, and the rebound ratio kr is independent of both L1* and Dt. A mechanism of reflected rarefaction wave is proposed to explain the position relation between the first and secondary cavities, and the energy partition in different regimes is discussed.
Magnetically-tunable cutoff in asymmetric thin metal film plasmonic waveguide
Authors: Im Song-Jin , Ri Chol-Song , Pae Ji-Song , Han Yong-Ha , Herrmann Joachim
Published: August 2017

We theoretically investigated the magnetically tunable cutoff of long-range surface plasmon polariton along thin metal film surrounded by a magneto-optic material on one side and by a nonmagnetic dielectric on the other. The analytically derived cutoff condition predicts that a magnetic field bias can induce a novel degenerate cutoff-state near which the beyond-cutoff radiation on one side can be switched to that on the other by a minor variation of the magnetic field from the bias. The magnetization bias needed for the degeneracy is proportional to the metal film thickness and inversely proportional to the wavelength.
Generalized Einstein relation for the mutual diffusion coefficient of a binary fluid mixture
Authors: Felderhof B. U.
Published: August 2017

The method employed by Einstein to derive his famous relation between the diffusion coefficient and the friction coefficient of a Brownian particle is used to derive a generalized Einstein relation for the mutual diffusion coefficient of a binary fluid mixture. The expression is compared with the one derived by de Groot and Mazur from irreversible thermodynamics and later by Batchelor for a Brownian suspension. A different result was derived by several other workers in irreversible thermodynamics. For a nearly incompressible solution, the generalized Einstein relation agrees with the expression derived by de Groot and Mazur. The two expressions also agree to first order in solute density. For a Brownian suspension, the result derived from the generalized Smoluchowski equation agrees with both expressions.
Transition state theory for activated systems with driven anharmonic barriers
Authors: Revuelta F. , Craven Galen T. , Bartsch Thomas , Borondo F. , Benito R. M. , Hernandez Rigoberto
Published: August 2017

Classical transition state theory has been extended to address chemical reactions across barriers that are driven and anharmonic. This resolves a challenge to the naive theory that necessarily leads to recrossings and approximate rates because it relies on a fixed dividing surface. We develop both perturbative and numerical methods for the computation of a time-dependent recrossing-free dividing surface for a model anharmonic system in a solvated environment that interacts strongly with an oscillatory external field. We extend our previous work, which relied either on a harmonic approximation or on periodic force driving. We demonstrate that the reaction rate, expressed as the long-time flux of reactive trajectories, can be extracted directly from the stability exponents, namely, Lyapunov exponents, of the moving dividing surface. Comparison to numerical results demonstrates the accuracy and robustness of this approach for the computation of optimal (recrossing-free) dividing surfaces and reaction rates in systems with Markovian solvation forces. The resulting reaction rates are in strong agreement with those determined from the long-time flux of reactive trajectories.
Distinguishability notion based on Wootters statistical distance: Application to discrete maps
Authors: Gomez Ignacio S. , Portesi M. , Lamberti P. W.
Published: August 2017

We study the distinguishability notion given by Wootters for states represented by probability density functions. This presents the particularity that it can also be used for defining a statistical distance in chaotic unidimensional maps. Based on that definition, we provide a metric d¯ for an arbitrary discrete map. Moreover, from d¯, we associate a metric space with each invariant density of a given map, which results to be the set of all distinguished points when the number of iterations of the map tends to infinity. Also, we give a characterization of the wandering set of a map in terms of the metric d¯, which allows us to identify the dissipative regions in the phase space. We illustrate the results in the case of the logistic and the circle maps numerically and analytically, and we obtain d¯ and the wandering set for some characteristic values of their parameters. Finally, an extension of the metric space associated for arbitrary probability distributions (not necessarily invariant densities) is given along with some consequences. The statistical properties of distributions given by histograms are characterized in terms of the cardinal of the associated metric space. For two conjugate variables, the uncertainty principle is expressed in terms of the diameters of the associated metric space with those variables.
Soliton dynamics for trapped Bose-Einstein condensate with higher-order interaction
Authors: Wang Ying , Zhou Shuyu
Published: August 2017

We model the three-dimensional (3D) trapped Bose-Einstein condensate with the Gross-Pitaevskii equation (GPE) incorporating higher-order nonlinear interaction effects. Based on the F-expansion method and self-similar approach, we analytically derive the exact soliton solutions of the 3D GPE, identifying the oscillatory mode under certain experimental settings. The oscillatory kinetic parameter values we obtained coincide very well with those reported in previous work, which is based on the variational approach, showing the applicability of the theoretical treatment presented in this work.
Scale-dependent habitat analysis and implications for climate change risk for the southern hairy-nosed wombat
Authors: Marshall Victoria M. , Taggart David A. , Ostendorf Bertram
Published: August 2017

Understanding factors determining the distribution of a species is critical for developing strategies and policies in natural resources management. The southern hairy-nosed wombat (Lasiorhinus latifrons) is an excellent model species to examine species distribution patterns because of its conspicuous burrowing behaviour, making it possible to obtain highly accurate distribution maps. The aim of this study was to evaluate the relative importance of biophysical factors impacting on the species’ distribution at regional and continental scales. At the fine scale, we digitised the distribution of individual warrens within a population, whereas at the continental scale we utilised the entire species’ distribution. At the regional level, the strongest predictors of burrowing activity were soil characteristics and geology with little influence of climate. In contrast, at the continental scale, species distribution was most strongly influenced by climatic variables, with most of the distribution located in regions with narrow ranges of mean annual maximum temperature (23−25°C) and mean annual rainfall (200–300 mm). This discrepancy suggests that the species’ distribution is limited to small geographic areas where both a suitable climate and appropriate soil and geology exist and, consequently, that conservation strategies need to adopt a long-term view considering the combined effect of both regional and continental factors.
Understanding practitioner professionalism in Aboriginal and Torres Strait Islander health: lessons from student and registrar placements at an urban Aboriginal and Torres Strait Islander primary healthcare service
Authors: Askew Deborah A. , Lyall Vivian J. , Ewen Shaun C. , Paul David , Wheeler Melissa
Published: August 2017

Aboriginal and Torres Strait Islander peoples continue to be pathologised in medical curriculum, leaving graduates feeling unequipped to effectively work cross-culturally. These factors create barriers to culturally safe health care for Aboriginal and Torres Strait Islander peoples. In this pilot pre-post study, the learning experiences of seven medical students and four medical registrars undertaking clinical placements at an urban Aboriginal and Torres Strait Islander primary healthcare service in 2014 were followed. Through analysis and comparison of pre- and post-placement responses to a paper-based case study of a fictitious Aboriginal patient, four learning principles for medical professionalism were identified: student exposure to nuanced, complex and positive representations of Aboriginal peoples; positive practitioner role modelling; interpersonal skills that build trust and minimise patient–practitioner relational power imbalances; and knowledge, understanding and skills for providing patient-centred, holistic care. Though not exhaustive, these principles can increase the capacity of practitioners to foster culturally safe and optimal health care for Aboriginal peoples. Furthermore, competence and effectiveness in Aboriginal health care is an essential component of medical professionalism.
Genomic evidence reveals a radiation of placental mammals uninterrupted by the KPg boundary
Authors: Liu Liang , Zhang Jin , Rheindt Frank E. , Lei Fumin , Qu Yanhua , Wang Yu , Zhang Yu , Sullivan Corwin , Nie Wenhui , Wang Jinhuan , Yang Fengtang , Chen Jinping , Edwards Scott V. , Meng Jin , Wu Shaoyuan
Published: August 2017

Significance

We produced a genome-scale dataset from representatives of all placental mammal orders to infer diversification timing relative to the Cretaceous–Paleogene (KPg) boundary. Our sensitivity analyses show that divergence time estimates within placentals are considerably biased by the specific way in which a given dataset is processed. We examined the performance of various dating approaches using a comprehensive scheme of likelihood analyses and computational simulations, allowing us to identify the optimal molecular clock parameters, gene sets, and gene partitioning schemes for reliable dating. Based on the optimal methodology, we present a hypothesis of mammalian divergence timing that is more consistent with the fossil record than previous molecular clock reconstructions, suggesting that placental mammals underwent a continuous radiation across the KPg boundary.
Early photosynthetic eukaryotes inhabited low-salinity habitats
Authors: Sánchez-Baracaldo Patricia , Raven John A. , Pisani Davide , Knoll Andrew H.
Published: August 2017

Significance

Although it is widely accepted that the chrloroplasts in photosynthetic eukaryotes can be traced back to a single cyanobacterial ancestor, the nature of that ancestor remains debated. Chloroplasts have been proposed to derive from either early- or late-branching cyanobacterial lineages, and similarly, the timing and ecological setting of this event remain uncertain. Phylogenomic and Bayesian relaxed molecular clock analyses show that the chloroplast lineage branched deep within the cyanobacterial tree of life ∼2.1 billion y ago, and ancestral trait reconstruction places this event in low-salinity environments. The chloroplast took another 200 My to become established, with most extant groups originating much later. Our analyses help to illuminate the little known evolutionary history of early life on land.
Behavioral responses to annual temperature variation alter the dominant energy pathway, growth, and condition of a cold-water predator
Authors: Guzzo Matthew M. , Blanchfield Paul J. , Rennie Michael D.
Published: August 2017

Significance

Climate warming is having wide-ranging effects on aquatic ecosystems. Fish are believed to adapt their feeding behavior as temperatures change, but empirical evidence of this behavior in nature and its impacts on individual fitness are lacking. We monitored the feeding behavior and growth of a temperature-sensitive fish population in a pristine lake for 11 y. Fish adjusted their feeding behavior annually in response to differences in temperature. In cooler years, fish ate more large prey from shallow nearshore regions, resulting in higher growth and condition than in warmer years, when fish ate more small prey from deep offshore regions. This suggests that the impacts of warming on aquatic ecosystems can scale from the individual to the food web level.
Kinetic and high-throughput profiling of epigenetic interactions by 3D-carbene chip-based surface plasmon resonance imaging technology
Authors: Zhao Shuai , Yang Mo , Zhou Wenfei , Zhang Baichao , Cheng Zhiqiang , Huang Jiaxin , Zhang Min , Wang Zhiyou , Wang Rui , Chen Zhonglei , Zhu Jinsong , Li Haitao
Published: August 2017

Significance

In the era of functional proteomics, a myriad of new interactions, notably those modification-dependent ones, are widely suggested by advanced proteomic approaches and bioinformatic analysis. Therefore, there exists an urgent need to develop a technology for high-throughput mapping and quantitative characterization of biomolecular binding events. This study achieved the immobilization and kinetic detection of various biomacromolecules (including modified peptides and modified nucleic acids) in high throughput through the 3D-carbene chip-based surface plasmon resonance imaging (SPRi) technology. Modified histone peptides and nucleic acids, which are key epigenetic marks, could be efficiently probed by this platform. We envision that the 3D-carbene SPRi technology described here will have wide appeal in profiling and discovering biological recognitions in and beyond epigenetics.
Immune evasion by a staphylococcal inhibitor of myeloperoxidase
Authors: de Jong Nienke W. M. , Ramyar Kasra X. , Guerra Fermin E. , Nijland Reindert , Fevre Cindy , Voyich Jovanka M. , McCarthy Alex J. , Garcia Brandon L. , van Kessel Kok P. M. , van Strijp Jos A. G. , Geisbrecht Brian V. , Haas Pieter-Jan A.
Published: August 2017

Significance

Staphylococcus aureussecretes numerous proteins to evade our innate immune system, for example to evade opsonization and phagocytosis by neutrophils. Here we describe the discovery thatS. aureushas evolved a protein, called SPIN, that specifically binds and inhibits the human myeloperoxidase enzyme (MPO). MPO is located inside the granules of neutrophils and is important in the oxidative burst against pathogens. We identify the molecular mode of action of SPIN inhibiting MPO, illustrate this with the cocrystal structure, and show that SPIN is important for bacterial survival by MPO-dependent killing. Our study shows thatS. aureusfights back after it is engulfed by neutrophils, which will help our understanding of the complex nature ofS. aureusinfections.
Mechanical constraint from growing jaw facilitates mammalian dental diversity
Authors: Renvoisé Elodie , Kavanagh Kathryn D. , Lazzari Vincent , Häkkinen Teemu J. , Rice Ritva , Pantalacci Sophie , Salazar-Ciudad Isaac , Jernvall Jukka
Published: August 2017

Significance

Good examples of the relative autonomy of organ development are teeth, and for decades researchers have cultured isolated mouse teeth on a petri dish by starting from the earliest recognizable stage. We have cultured cheek teeth of voles, another species of rodent, and show how the cultured vole teeth lack their species-specific morphology. Based on computational modeling, 3D imaging, and experiments in which we culture mouse and vole teeth between microscopic braces, we suggest that the development of vole tooth shape requires the lateral support of the jaw. Because mice lack the vole-specific morphology, the requirement of the jaw for tooth shape has not been possible to uncover previously. Comparative studies are required for the understanding of organogenesis.
Next step in the ongoing arms race between myxoma virus and wild rabbits in Australia is a novel disease phenotype
Authors: Kerr Peter J. , Cattadori Isabella M. , Liu June , Sim Derek G. , Dodds Jeff W. , Brooks Jason W. , Kennett Mary J. , Holmes Edward C. , Read Andrew F.
Published: August 2017

Significance

When a pathogen emerges in a host population, will it evolve to do more or less harm to its host? A single strain of myxoma virus was released as a biocontrol agent against Australian rabbit populations in 1950. The subsequent coevolution has become a textbook classic, although there has been little experimental work on this topic since the early 1980s. Here, we show that the host–pathogen arms race continued with the evolution of highly lethal viruses that cause immune collapse. The possibility that pathogens can become highly immunosuppressive in response to increases in host resistance needs to be considered where genetic and immunologic manipulations are used to enhance host resistance, as, for instance, in agriculture.
Vibrio cholerae
type 6 secretion system effector trafficking in target bacterial cells
Authors: Ho Brian T. , Fu Yang , Dong Tao G. , Mekalanos John J.
Published: August 2017

Significance

This work demonstrates that it is possible to alter the prey target range of the antibacterial activity of the type 6 secretion system (T6SS). Being able to change the T6SS target specificity is the first step toward using the T6SS as an antipathogen or commensal therapeutic, prophylactic, or probiotic. This work also uncovers a cryptic secretion mechanism(s) for delivering protein substrates from the bacterial cytosol to the periplasm. This mechanism is exploited by some T6SS effectors as an alternative pathway for reaching periplasmic targets when they are by chance delivered into the cytosol of target cells.
Charge mobility modification of semiconducting carbon nanotubes by intrinsic defects
Authors: Bai Hongcun , Ma Yujia , Ma Jinsuo , Mei Jingnan , Tong Yan , Ji Yongqiang
Published: August 2017

Charge carrier mobility is a central transport property in nanoscale electronics. Carbon nanotubes (CNTs) are supposed to have high carrier mobility. The preparation methods of CNTs have been greatly improved, but the defects always exist. This work presented first-principle investigations on the charge carrier mobility of carbon nanotubes containing several intrinsic defects. The charge carrier mobilities of zigzag (10, 0) tubes with Stone–Wales, mono vacant and 5/8/5 defects were studied as an example to explore the role of defects. Most carrier mobilities were decreased, but several values of mobility are unexpectedly increased upon the appearance of the defects. This interesting result is discussed based on the changes of the stretching modulus, the effective mass of the carrier and deformation potential constant induced by the defects.
Genome-wide association studies using a penalized moving-window regression
Authors: Bao Minli , Wang Kai
Published: August 2017

Motivation

Genome-wide association studies (GWAS) have played an important role in identifying genetic variants underlying human complex traits. However, its success is hindered by weak effect at causal variants and presence of noise at non-causal variants. In an effort to overcome these difficulties, a previous study proposed a regularized regression method that penalizes on the difference of signal strength between two consecutive single-nucleotide polymorphisms (SNPs).

Results

We provide a generalization to the afore-mentioned method so that more adjacent SNPs can be incorporated. The choice of optimal number of SNPs is studied. Simulation studies indicate that when consecutive SNPs have similar absolute coefficients our method performs better than using LASSO penalty. In other situations, our method is still comparable to using LASSO penalty. The practical utility of the proposed method is demonstrated by applying it to Genetic Analysis Workshop 16 rheumatoid arthritis GWAS data.

Availability and implementation

An implementation of the proposed method is provided in R package MWLasso.
ReMILO: reference assisted misassembly detection algorithm using short and long reads
Authors: Bao Ergude , Song Changjin , Lan Lingxiao
Published: August 2017

Motivation

Contigs assembled from the second generation sequencing short reads may contain misassemblies, and thus complicate downstream analysis or even lead to incorrect analysis results. Fortunately, with more and more sequenced species available, it becomes possible to use the reference genome of a closely related species to detect misassemblies. In addition, long reads of the third generation sequencing technology have been more and more widely used, and can also help detect misassemblies.

Results

Here, we introduce ReMILO, a reference assisted misassembly detection algorithm that uses both short reads and PacBio SMRT long reads. ReMILO aligns the initial short reads to both the contigs and reference genome, and then constructs a novel data structure called red-black multipositional de Bruijn graph to detect misassemblies. In addition, ReMILO also aligns the contigs to long reads and find their differences from the long reads to detect more misassemblies. In our performance test on short read assemblies of human chromosome 14 data, ReMILO can detect 41.8–77.9% extensive misassemblies and 33.6–54.5% local misassemblies. On hybrid short and long read assemblies of S.pastorianus data, ReMILO can also detect 60.6–70.9% extensive misassemblies and 28.6–54.0% local misassemblies.

Availability and implementation

The ReMILO software can be downloaded for free under Artistic License 2.0 from this site: https://github.com/songc001/remilo.

Supplementary information

Supplementary data are available at Bioinformatics online.
Lineage specification of early embryos and embryonic stem cells at the dawn of enabling technologies
Authors: Peng Guangdun , Tam Patrick P. L. , Jing Naihe
Published: August 2017

Establishment of progenitor cell populations and lineage diversity during embryogenesis and the differentiation of pluripotent stem cells is a fascinating and intricate biological process. Conceptually, an understanding of this developmental process provides a framework to integrate stem-cell pluripotency, cell competence and differentiating potential with the activity of extrinsic and intrinsic molecular determinants. The recent advent of enabling technologies of high-resolution transcriptome analysis at the cellular, population and spatial levels proffers the capability of gaining deeper insights into the attributes of the gene regulatory network and molecular signaling in lineage specification and differentiation. In this review, we provide a snapshot of the emerging enabling genomic technologies that contribute to the study of development and stem-cell biology.
Nutritional and smoking advice recalled by patients attending a UK age-related macular degeneration clinic
Authors: Bott Deborah , Huntjens Byki , Binns Alison
Published: August 2017

Background

Age-related macular degeneration (AMD) is responsible for half of registered visual impairment in the UK. The Royal College of Ophthalmologists recommends providing guidance to people with AMD regarding smoking, diet, and nutritional supplements. The aim of this study was to investigate lifestyle advice recalled by patients with neovascular AMD (nAMD).

Methods

The study took place at a UK hospital outpatients’ clinic. Eligible patients with unilateral nAMD were presented with a survey about lifestyle advice provision.

Results

Of 248 respondents, only 39.9% remembered receiving advice regarding diet at the hospital. Only 24.2% of respondents recalled receiving advice regarding nutritional supplements, and only 19.8% of respondents started taking daily supplements as a result of their AMD. The most prevalent reason for not taking supplements amongst those advised to do so was lack of understanding of how it would help their eyes. Nearly 13% of the sample reported currently smoking, 53.1% of which reported that they were advised to stop smoking when diagnosed with AMD.

Conclusion

The findings suggest that it would be beneficial to review the provision of lifestyle advice to patients attending AMD outpatients’ clinics, and to consider whether advice is being provided in an optimal format for later recall.
Structure of Psb29/Thf1 and its association with the FtsH protease complex involved in photosystem II repair in cyanobacteria
Authors: Bec̆ková Martina , Yu Jianfeng , Krynická Vendula , Kozlo Amanda , Shao Shengxi , Koník Peter , Komenda Josef , Murray James W. , Nixon Peter J.
Published: August 2017

One strategy for enhancing photosynthesis in crop plants is to improve their ability to repair photosystem II (PSII) in response to irreversible damage by light. Despite the pivotal role of thylakoid-embedded FtsH protease complexes in the selective degradation of PSII subunits during repair, little is known about the factors involved in regulating FtsH expression. Here we show using the cyanobacterium
Synechocystis
sp. PCC 6803 that the Psb29 subunit, originally identified as a minor component of His-tagged PSII preparations, physically interacts with FtsH complexes
in vivo
and is required for normal accumulation of the FtsH2/FtsH3 hetero-oligomeric complex involved in PSII repair. We show using X-ray crystallography that Psb29 from
Thermosynechococcus elongatus
has a unique fold consisting of a helical bundle and an extended C-terminal helix and contains a highly conserved region that might be involved in binding to FtsH. A similar interaction is likely to occur in Arabidopsis chloroplasts between the Psb29 homologue, termed THF1, and the FTSH2/FTSH5 complex. The direct involvement of Psb29/THF1 in FtsH accumulation helps explain why THF1 is a target during the hypersensitive response in plants induced by pathogen infection. Downregulating FtsH function and the PSII repair cycle via THF1 would contribute to the production of reactive oxygen species, the loss of chloroplast function and cell death.

This article is part of the themed issue ‘Enhancing photosynthesis in crop plants: targets for improvement’.
Chloroplast thioredoxin systems: prospects for improving photosynthesis
Authors: Nikkanen Lauri , Toivola Jouni , Diaz Manuel Guinea , Rintamäki Eevi
Published: August 2017

Thioredoxins (TRXs) are protein oxidoreductases that control the structure and function of cellular proteins by cleavage of a disulphide bond between the side chains of two cysteine residues. Oxidized thioredoxins are reactivated by thioredoxin reductases (TR) and a TR-dependent reduction of TRXs is called a thioredoxin system. Thiol-based redox regulation is an especially important mechanism to control chloroplast proteins involved in biogenesis, in regulation of light harvesting and distribution of light energy between photosystems, in photosynthetic carbon fixation and other biosynthetic pathways, and in stress responses of plants. Of the two plant plastid thioredoxin systems, the ferredoxin-dependent system relays reducing equivalents from photosystem I via ferredoxin and ferredoxin-thioredoxin reductase (FTR) to chloroplast proteins, while NADPH-dependent thioredoxin reductase (NTRC) forms a complete thioredoxin system including both reductase and thioredoxin domains in a single polypeptide. Chloroplast thioredoxins transmit environmental light signals to biochemical reactions, which allows fine tuning of photosynthetic processes in response to changing environmental conditions. In this paper we focus on the recent reports on specificity and networking of chloroplast thioredoxin systems and evaluate the prospect of improving photosynthetic performance by modifying the activity of thiol regulators in plants.

This article is part of the themed issue ‘Enhancing photosynthesis in crop plants: targets for improvement'.
Microbe Profile: Candida albicans: a shape-changing, opportunistic pathogenic fungus of humans
Authors: Gow Neil A. R. , Yadav Bhawna
Published: August 2017

Candida albicans is normally a harmless commensal of human beings, but it can cause superficial infections of the mucosa (oral/vaginal thrush) in healthy individuals and (rarely) infections of the skin or nails. It can also become invasive, causing life-threatening systemic and bloodstream infections in immunocompromised hosts, where the mortality rate can be as high as 50 %. It is the most common cause of serious fungal infection and is a common cause of nosocomial infections in hospitals. Some strains have been recognized that are resistant to azoles or echinocandins, which are the first-line antifungals for treatment of C. albicans infections.
The Novel Monocomponent FAD-dependent Monooxygenase HpaM Catalyzes the 2-Decarboxylative Hydroxylation of 5-Hydroxypicolinic Acid inAlcaligenes faecalisJQ135
Authors: Qiu Jiguo , Liu Bin , Zhao Lingling , Zhang Yanting , Cheng Dan , Yan Xin , Jiang Jiandong , Hong Qing , He Jian
Published: August 2017

5-hydroxypicolinic acid (5HPA) is a natural pyridine derivative that can be microbially degraded. However, the physiological, biochemical, and genetic foundation of the microbial catabolism of 5HPA remains unknown. In this study, a gene clusterhpa(which is involved in degradation of 5HPA inAlcaligenes faecalisJQ135) was cloned and HpaM was identified as a novel monocomponent FAD-dependent monooxygenase. HpaM shared a sequence only 31% similarity with the most related protein 6-hydroxynicotinate 3-monooxygenase (NicC) ofPseudomonas putidaKT2440.hpaMwas heterologously expressed inE. coliBL21(DE3), and the recombinant HpaM was purified via Ni-affinity chromatography. HpaM catalyzed the 2-decarboxylative hydroxylation of 5-HPA, thus generating 2,5-dihydroxypyridine (2,5-DPH). Monooxygenase activity was only detected in the presence of FAD and NADH, but not of FMN and NADPH. The apparentKmvalues of HpaM toward 5HPA and NADH were 45.4 μ and 37.8 μ, respectively. Results of gene deletion and complementation showed thathpaMwas essential for 5HPA degradation inAlcaligenes faecalisJQ135.

Importance

Pyridine derivatives are ubiquitous in nature and important chemical materials that are currently widely used in agriculture, pharmaceutical, and chemical industries. Thus, the microbial degradation and transformation mechanisms of pyridine derivatives received considerable attention. Decarboxylative hydroxylation was an important degradation process in pyridine derivatives, and previously reported decarboxylative hydroxylations happened in the C3 of the pyridine ring. In this study, we cloned the gene clusterhpa, which is responsible for 5HPA degradation inAlcaligenes faecalisJQ135, thus identifying a novel monocomponent FAD-dependent monooxygenase HpaM. Unlike 3-decarboxylative monooxygenases, HpaM catalyzed decarboxylative hydroxylation in the C2 of the pyridine ring in 5-hydroxypicolinic acid. These findings deepen our understanding of the molecular mechanism of microbial degradation of pyridine derivatives. Furthermore, HpaM offers potential for applications to transform useful pyridine derivatives.
Revealing unidentified heterogeneity in different epithelial cancers using heterocellular subtype classification
Authors: Poudel Pawan , Nyamundanda Gift , Ragulan Chanthirika , Lawlor Rita T. , Das Kakoli , Tan Patrick , Scarpa Aldo , Sadanandam Anguraj
Published: August 2017

Cancers are currently diagnosed, categorised, and treated based on their tissue of origin. However, how different cellular compartments of tissues (e.g., epithelial, immune and stem cells) are similar across cancer types is unknown. Here we used colorectal cancer subtypes and their signatures representing different colonic crypt cell types as surrogates to classify different epithelial cancers into five heterotypic cellular (heterocellular) subtypes. The stem-like and inflammatory heterocellular subtypes are ubiquitous across epithelial cancers so capture intrinsic, tissue-independent properties. Conversely, well-differentiated/specialized goblet-like/enterocyte heterocellular subtypes differ across cancer types due to their colorectum-specific genes. The transit-amplifying heterocellular subtype shows a dynamic range of cellular differentiation with shared common pathways (Wnt, FGFR) in certain cancer types. Importantly, this approach revealed previously unrecognised heterogeneity in pancreatic, breast, microsatellite-instability enriched andKRASmutation-dependent cancers. Immune cell-type differences are common and useful for patient stratification for immunotherapy. This unique approach identifies cell type-dependent but tissue-independent heterogeneity in different cancers for precision medicine.
A retrieved context model of the emotional modulation of memory
Authors: Talmi Deborah , Lohnas Lynn J. , Daw Nathaniel D.
Published: August 2017

Emotion enhances episodic memory, an effect thought to be an adaptation to prioritise the memories that best serve evolutionary fitness. But viewing this effect largely in terms of prioritising what to encode or consolidate neglects broader rational considerations about what sorts of associations should be formed at encoding, and which should be retrieved later. Although neurobiological investigations have provided many mechanistic clues about how emotional arousal modulates item memory, these effects have not been wholly integrated with the cognitive and computational neuroscience of memory more generally.

Here we apply the Context Maintenance and Retrieval Model (CMR, Polyn, Norman & Kahana, 2009) to this problem by extending it to describe the way people may represent and process emotional information. A number of ways to operationalise the effect of emotion were tested. The winning emotional CMR (eCMR) model reconceptualises emotional memory effects as arising from the modulation of a process by which memories become bound to ever-changing temporal and emotional contexts. eCMR provides a good qualitative fit for the emotional list-composition effect and the emotional oddball effect, illuminating how these effects are jointly determined by the interplay of encoding and retrieval processes. eCMR explains the increased advantage of emotional memories in delayed memory tests through the limited ability of retrieval to reinstate the temporal context of encoding.

By leveraging the rich tradition of temporal context models, eCMR helps integrate existing effects of emotion and provides a powerful tool to test mechanisms by which emotion affects memory in a broad range of paradigms.
Real-time genomic and epidemiological investigation of a multi-institution outbreak of KPC-producing Enterobacteriaceae: a translational study
Authors: Kwong JC , Lane C , Romanes F , Gonçalves da Silva A , Easton M , Cronin K , Waters MJ , Tomita T , Stevens K , Schultz MB , Baines SL , Sherry NL , Carter G , Mu A , Sait M , Ballard SA , Seemann T , Stinear TP , Howden BP
Published: August 2017

Background

Until recently, KPC-producing Enterobacteriaceae were rarely identified in Australia. Following an increase in the number of incident cases across the state of Victoria, we undertook a real-time combined genomic and epidemiological investigation. The scope of this study included identifying risk factors and routes of transmission, and investigating the utility of genomics to enhance traditional field epidemiology for informing management of established widespread outbreaks.

Methods and Findings

All KPC-producing Enterobacteriaceae isolates referred to the state reference laboratory from 2012 onwards were included. Whole-genome sequencing (WGS) was performed in parallel with a detailed descriptive epidemiological investigation of each case, using Illumina sequencing on each isolate. This was complemented with PacBio long-read sequencing on selected isolates to establish high-quality reference sequences and interrogate characteristics of KPC-encoding plasmids. Initial investigations indicated the outbreak was widespread, with 86 KPC-producing Enterobacteriaceae isolates (K. pneumoniae92%) identified from 35 different locations across metropolitan and rural Victoria between 2012-2015. Initial combined analyses of the epidemiological and genomic data resolved the outbreak into distinct nosocomial transmission networks, and identified healthcare facilities at the epicentre of KPC transmission. New cases were assigned to transmission networks in real-time, allowing focussed infection control efforts. PacBio sequencing confirmed a secondary transmission network arising from inter-species plasmid transmission. Insights from Bayesian transmission inference and analyses of within-host diversity informed the development of state-wide public health and infection control guidelines, including interventions such as an intensive approach to screening contacts following new case detection to minimise unrecognised colonisation.

Conclusions

A real-time combined epidemiological and genomic investigation proved critical to identifying and defining multiple transmission networks of KPC Enterobacteriaceae, while data from either investigation alone were inconclusive. The investigation was fundamental to informing infection control measures in real-time and the development of state-wide public health guidelines on carbapenemase producing Enterobacteriaceae management.
Environmental fluctuations accelerate molecular evolution of thermal tolerance in a marine diatom
Authors: Schaum C.-Elisa , Buckling A. , Smirnoff N. , Studholme D. J. , Yvon-Durocher G.
Published: August 2017

Diatoms contribute roughly 20% of global primary production, but the factors determining their ability to adapt to global warming are unknown. Here we quantify the capacity for adaptation to warming in the marine diatomThalassiosira pseudonana. We found that evolutionary rescue under severe warming was slow but adaptation to more realistic scenarios, where temperature increases were moderate or where they fluctuated between benign and severe conditions, was rapid. Adaption to warming was linked to major phenotypic changes in metabolism and elemental composition. Whole genome re-sequencing identified significant genetic divergence both among populations adapted to the different warming regimes and between the evolved and ancestral lineages. Consistent with the phenotypic changes, the most rapidly evolving genes were associated with transcriptional regulation, cellular response to oxidative stress and redox homeostasis. These results demonstrate that evolution of thermal tolerance in marine diatoms can be rapid, particularly in fluctuating environments, and is underpinned by major genomic and phenotypic divergence.
The effect of the thin body ideal in a media-naïve population
Authors: Jucker Jean-Luc , Thornborrow Tracey , Tovee Martin J. , Boothroyd Lynda G.
Published: August 2017

The thin ideal is the western concept of an ideally slim or underweight female body1, and its omnipresence in the mass media has a negative impact on women’s health2-5. Media consumption is associated with a drive for thinness, body dissatisfaction, low self-esteem, and disordered eating in women of western and/or industrialised societies4. Furthermore, cross-cultural research suggests that the media have similar effects when they are introduced into non-western or non-industrialised societies2,6,7. No study, however, has attempted to induce a change in female body size ideals in a population that is not exposed to the thin ideal and that has currently no access to the media. Here we show experimentally that a short exposure to the thin ideal can change body size ideals in a media-naïve population. 80 rural Nicaraguan men and women with very low to non-existent media access created their ideal female body before and after seeing photographs of either thin or plus size fashion models. Analyses revealed a significant interaction between time and group, meaning that exposure to media images shifted the subjects’ ideal female body size. We discuss problems posed by the pervasiveness of the thin body ideal in the context of the global obesity pandemic.
A network modeling approach to elucidate drug resistance mechanisms and predict combinatorial drug treatments in breast cancer
Authors: Zañudo Jorge G. T. , Albert Réka
Published: August 2017

Background

Mechanistic models of within-cell signal transduction networks can explain how these networks integrate internal and external inputs to give rise to the appropriate cellular response. These models can be fruitfully used in cancer cells, whose aberrant decision-making regarding their survival or death, proliferation or quiescence can be connected to errors in the state of nodes or edges of the signal transduction network.

Results

Here we present a comprehensive network, and discrete dynamic model, of signal transduction in breast cancer based on the literature of ER+, HER2+, and PIK3CA-mutant breast cancers. The network model recapitulates known resistance mechanisms to PI3K inhibitors and suggests other possibilities for resistance. The model also reveals known and novel combinatorial interventions that are more effective than PI3K inhibition alone.

Conclusions

The use of a logic-based, discrete dynamic model enables the identification of results that are mainly due to the organization of the signaling network, and those that also depend on the kinetics of individual events. Network-based models such as this will play an increasing role in the rational design of high-order therapeutic combinations.