bluuebunny/crossref_metadata_2025 huggingface dataset:
Benefits of phenotypic plasticity for population growth in varying environments
Authors: Xue BingKan , Leibler Stanislas
Published: November 2018

Significance

Biological organisms show amazing abilities to change their forms and behavior according to their surroundings. For example, some caterpillars mimic flowers or twigs of the tree depending on their diet, freshwater snails grow thickened and deformed shells on sensing predator cues, and female aphids develop wings for migration if their habitat is crowded. Such flexibility in developing distinct external characteristics is known as “phenotypic plasticity,” often considered an adaptation strategy for surviving in variable environmental conditions. The prevalence of this phenomenon calls for a theoretical quantitative understanding of its evolutionary benefits. We use a simple model to illustrate how such benefits can be defined in terms of population growth rate and classify different contributions and limitations to those benefits.
Argumentation in Prime Minister’s Question Time
Authors: Mohammed Dima
Published: November 2018

When political actors respond to criticism by pointing at an inconsistency in the critic’s position, a tricky political practice emerges. Turning the criticism back to the critic can be a constructive move that restores coherence, but it may also be a disruptive move that silences the critical voice and obstructs accountability. What distinguishes constructive cases from disruptive ones? This is the question this book sets out to answer.
The question is addressed by adopting an argumentative perspective. Argumentation in Prime Minister’s Question Time focuses on the turnabout employed by the British Prime Minister in response to the Leader of the Opposition. The turnabout is characterised as a particular way of strategic manoeuvring. The manoeuvring is analysed and evaluated by combining pragmatic, dialectical and rhetorical insights with considerations from the realm of politics. The outcome is an account of the turnabout’s strategic functions and an assessment guide for evaluating its reasonableness.
The book will be of interest to advanced students and researchers of argumentation, discourse analysis, communication and rhetoric.
Translation quality research
Authors: Akbari Alireza
Published: November 2018

Recently, there is a growing interest in the development of translation quality research programmes at different stages worldwide. Scholars and researchers have paid much attention to the quality of translation; however, there is a dearth of meta-analyses of studies and research in the field of translation quality research. In fact there has been no systematic review since 2000. The purpose of the current research paper is to design translation quality research through the construction of a database of 14 peer-reviewed journal publications during the period 2000 to 2017. A combination of thematic and methodological analyses, scientometric methods, and corpus tool were applied to analyse the extracted database. Also, top-down and bottom-up procedures were conducted to minimise the subjectivity of thematic analysis. The present research scrutinised the extracted database on the basis of four main criteria, namely theoretical importance, pertinence to empirical and non-empirical research, the size of readership, and geographical coverage including institutions and countries. Finally, this database aims at serving as a resource for researchers and scholars to become familiar with the most cutting edge information on developments in translation quality research, challenges within this field, and the possible trajectories for future research.
Negation in Singapore English
Authors: Cao Luwen , Bao Zhiming
Published: November 2018

Singapore English is a new variety of English that has developed unique grammatical characteristics due to contact with the heritage languages of Singapore, especially Chinese. In this paper, we document the morphosyntax of negation in Singapore English, using data culled from available databases, including the Singaporean component of the International Corpus of English. There is little doubt that the negation system is inherited from English, but there is strong Chinese influence in the interaction between negation and aspect, and between negation and quantification. Other features of negation will also be described, including the novel use of no and no need, also due to Chinese influence.
Cross-linguistic negation contrasts in co-convergent contact languages
Authors: Slomanson Peter
Published: November 2018

Sri Lankan contact Malay (SLM) and Portuguese (SLP) share sprachbund-discordant features, including pre-verbal functional markers for TMA and negation. Yet their negation strategies also differ. In SLM, negation morphology is a diagnostic for the finiteness status of verbs. SLP verbs are contrastively negated, based on aspectual (not tense/finiteness) contrasts, and participles in adjunct clauses have distinctive non-finite negation. SLM marks finiteness status on matrix auxiliaries in a biclausal periphrastic construction. In the SLP construction, auxiliary and participle cannot be independently negated and the auxiliary cannot be separated from the verbal complex, arguing against biclausal status. SLM marks negative polarity in quantified nominal constituents, but has no negative concord, whereas SLP has negative concord, but relatively little negative polarity marking.
Modes of analysis
Authors: Krishnamurthy Ramesh
Published: November 2018

Throughout history, the study of language has involved looking for units, their patterns of combination, the functions they serve, and the processes involved; and construing the relationships between these features and the meanings which arise from them. Developments in technology inevitably revolutionise ideas, innovate methods, and transform the fields in which they are implemented. So, just as the invention and development of writing systems, and the advent of printing, did in the distant past, computers have had a similarly revolutionary effect on linguistics in recent decades. This paper looks at some of the ways in which corpus linguistics has used the latest technologies to embark on a substantial re-investigation and re-appraisal of the elements of language, their roles within the language system, and their relationships within the wider social context of human beings, their environments, and their activities. The structuring of the paper owes much to recent retrospection, but the pieces of research consist mainly of my early explorations of corpus linguistics, hence ‘auto (self) + ergo (work) + graphy (description)’ in the title.
Keywords
Authors: Baker Paul
Published: November 2018

This chapter focuses on describing, illustrating and critiquing the keywords technique, which is used to automatically identify lexical salience when comparing multiple corpora. Arguably, keywords present researchers with words that they may not have chosen to analyse in advance, thus helping to reduce researcher subjectivity.1 I illustrate how the identification of keywords enables researchers to embark on interesting research journeys, through examples taken from an analysis of the representation of Islam and Muslims in a corpus of British newspaper articles. However, when using large corpora, even with high cut-off points for statistical salience, hundreds of keywords may be produced, meaning that researchers need to make decisions regarding which words are worthy of detailed focus. The chapter ends with an illustrative analysis where I revisit six of my own keyword studies, arguing that researchers should consider the benefits of giving a more reflexive account of their own decision making procedures around keywords.
Tracking the third code
Authors: Granger Sylviane
Published: November 2018

Corpus-driven methods are a powerful heuristic for identifying features of translated language, particularly phraseological features, which have been largely neglected in crosslinguistic studies. This chapter presents the results of an n-gram based study of metadiscursive markers in original and translated English. Automatic comparison of three- to four-word recurrent sequences in the two corpora reveals a series of markers that are significantly overused or underused in translated language. One category of overused bundles, i.e. markers of contrast, is analysed in the light of translation universals and source language effects. In a wider perspective, the study highlights the benefits of a multi-corpus empirical basis for corpus-based crosslinguistic studies and draws the preliminary contours of a methodological framework, ‘Contrastive Translation Analysis’, which integrates comparable, translation and learner corpus data.
Central Southern Guangxi as a grammaticalization area
Authors: Huang Yang , Wu Fuxiang
Published: November 2018

This paper investigates contact-induced grammatical changes that are observed among the Zhuang Tai-Kadai and Sinitic languages in the Central Southern Guangxi Region. Following recent advances in the theoretical analysis of grammaticalization, this paper describes four uncommon grammaticalization processes that represent diffusion from Zhuang into several Sinitic languages. On this basis, we argue that the Central Southern Guangxi Region constitutes a micro-grammaticalization area.
Cross-varietal diversity in constructional entrenchment
Authors: Izutsu Mitsuko Narita , Izutsu Katsunobu
Published: November 2018

The present study analyzes clauses with final tags as a construction, i.e., a symbolic form-meaning pairing, which is formulated as [[ANCHi FTj] ↔ [S conclude verbalization of propositioni with attitudej]] (ANCH: Anchor, FT: Final Tag, S: Speaker). The final-tag construction is observed in most varieties of English. However, a comparison of two spoken corpora of English (SPICE-Ireland and the Santa Barbara Corpus) reveals that the degree of the constructional entrenchment of this symbolic unit differs markedly between Irish and American English. Our analysis illustrates that both type and token frequencies of final tags are higher in Irish English than American English. Interpreting the results in terms of the three characteristics of grammatical constructionalization: increase in schematicity, increase in productivity, and decrease in compositionality (Traugott & Trousdale 2013), our study concludes that the final-tag construction is more entrenched in the minds of Irish English speakers than American English speakers. This observation points to a greater development of the construction in Irish English, where the final position has become a more accommodating slot of broader versatility in which the speakers can put a wider variety of expressions for emotive and/or interactive purposes. In addition to conceivable motivations (sub- and superstrate influences) responsible for the development, the constructional approach can also illustrate the impact of a well-entrenched schema on incremental language use.
Our Drinking Problem: Recovery and Bad Aesthetics
Authors: Travis Trysh
Published: November 2018

Both the lived experience and the literature of twelve-step recovery resist the ethics and aesthetics of distance, irony, and authorial agency that hallmark modernism and postmodernism. As a result, authors (and sophisticated readers) with substance abuse problems have often struggled to align their ideas of literary value with recovery’s focus on simplicity and earnestness. Neil Steinberg and Sara Bader’s Out of this Wreck I Rise: A Literary Companion to Recovery (2016) is a compendium of inspiring quotations that acknowledges and seeks to offer a way around this problem. Leslie Jamison’s The Recovering: Life after Intoxication (2018) blends the author’s personal recovery narrative with a literary historical attempt to explain it.
Estimation of high-dimensional directed acyclic graphs with surrogate intervention
Authors: Ha Min Jin , Sun Wei
Published: November 2018

Directed acyclic graphs (DAGs) have been used to describe causal relationships between variables. The standard method for determining such relations uses interventional data. For complex systems with high-dimensional data, however, such interventional data are often not available. Therefore, it is desirable to estimate causal structure from observational data without subjecting variables to interventions. Observational data can be used to estimate the skeleton of a DAG and the directions of a limited number of edges. We develop a Bayesian framework to estimate a DAG using surrogate interventional data, where the interventions are applied to a set of external variables, and thus such interventions are considered to be surrogate interventions on the variables of interest. Our work is motivated by expression quantitative trait locus (eQTL) studies, where the variables of interest are the expression of genes, the external variables are DNA variations, and interventions are applied to DNA variants during the process of a randomly selected DNA allele being passed to a child from either parent. Our method, surrogate intervention recovery of a DAG ($\texttt{sirDAG}$), first constructs a DAG skeleton using penalized regressions and the subsequent partial correlation tests, and then estimates the posterior probabilities of all the edge directions after incorporating DNA variant data. We demonstrate the utilities of $\texttt{sirDAG}$ by simulation and an application to an eQTL study for 550 breast cancer patients.
The Effect of Preexisting Immunity on Virus Detection and Immune Responses in a Phase II, Randomized Trial of a Russian-Backbone, Live, Attenuated Influenza Vaccine in Bangladeshi Children
Authors: Brickley Elizabeth B , Wright Peter F , Khalenkov Alexey , Neuzil Kathleen M , Ortiz Justin R , Rudenko Larisa , Levine Min Z , Katz Jacqueline M , Brooks W Abdullah
Published: November 2018

Background

In a 2012 Phase II clinical trial, 300 Bangladeshi children aged 24 to 59 months with no prior influenza vaccine exposure were randomized to receive a single intranasally-administered dose of either trivalent, Russian-backbone, live, attenuated influenza vaccine (LAIV) or placebo. Protocol-defined analyses, presented in the companion manuscript, demonstrate decreased viral detection and immunogenicity for A/H1N1pdm09, relative to the A/H3N2 and B strains. This post hoc analysis of the trial data aims to investigate the LAIV strain differences by testing the hypothesis that preexisting humoral and mucosal immunity may influence viral recovery and immune responses after LAIV receipt.

Methods

We used logistic regressions to evaluate the relations between markers of preexisting immunity (ie, hemagglutination inhibition [HAI], microneutralization, and immunoglobulin G and immunoglobulin A (both serum and mucosal antibodies) and LAIV viral recovery in the week post-vaccination. We then tested for potential effect modification by baseline HAI titers (ie, <10 versus ≥10) and week 1 viral recovery on the LAIV-induced serum and mucosal immune responses, measured between days 0 and 21 post-vaccination.

Results

Higher levels of preexisting immunity to influenza A/H3N2 and B were strongly associated with strain-specific prevention of viral shedding upon LAIV receipt. While evidence of LAIV immunogenicity was observed for all 3 strains, the magnitudes of immune responses were most pronounced in children with no evidence of preexisting HAI and in those with detectable virus.

Conclusions

The results provide evidence for a bidirectional association between viral replication and immunity, and underscore the importance of accounting for preexisting immunity when evaluating virologic and immunologic responses to LAIVs.

Clinical Trials Registration

NCT01625689.
Respiratory Syncytial Virus Prophylaxis in Infants With Congenital Diaphragmatic Hernia in the Canadian Respiratory Syncytial Virus Evaluation Study of Palivizumab, 2005–2017
Authors: Kim Doyoung , Saleem Mahwesh , Paes Bosco , Mitchell Ian , Lanctôt Krista L
Published: November 2018

Background

Infants with congenital diaphragmatic hernia (CDH) are at an increased risk of respiratory morbidity from recurrent respiratory tract infections including those from respiratory syncytial virus (RSV). Prospective studies on RSV prophylaxis in CDH infants are limited. We determined the risk of respiratory illness– and RSV-related hospitalizations (RIH and RSVH, respectively) among infants prophylaxed for CDH, standard indications (SIs) and those without increased risk (NR).

Methods

The prospective Canadian Respiratory Syncytial Virus Evaluation Study of Palivizumab (CARESS) registry was searched for infants who received palivizumab during 12 RSV seasons (2005–2017) in Canada. Cox proportional hazards analyses were conducted to compare RIH and RSVH risks across the groups adjusted for potential confounders.

Results

In total, 21 107 infants (201 CDH, 389 NR, and 20 517 SI) were included. RIH incidences were 10.0% (CDH), 2.1% (NR), and 6.2% (SI). CDH patients had a significantly higher RIH hazard compared with NR (hazard ratio [HR], 3.6 [95% confidence interval {CI}, 1.5–8.8]; P = .005) but not SI (HR, 1.2 [95% CI, .8–2.0]; P = .379). RSVH incidences were 0.6%, 0.3%, and 1.5% for CDH, NR, and SI, respectively. RSVH risk was similar across groups (SI: HR, 0.0, P = .922; NR: HR, 0.0, P = .934).

Conclusions

CDH infants had a 3-fold increased risk of RIH compared to NR but not SI infants. RSVH risk was similar with low RSVH incidences across all groups, implying that CDH infants may benefit from palivizumab during the RSV season, similar to other high-risk groups.

Clinical Trials Registration

NCT00420966.
Efficacy and Safety of Ascending Dosages of Tribendimidine Against Hookworm Infections in Children: A Randomized Controlled Trial
Authors: Coulibaly Jean T , Hiroshige Noemi , N’Gbesso Yves K , Hattendorf Jan , Keiser Jennifer
Published: November 2018

Background

The global strategy to control soil-transmitted helminthiasis is mainly focused on preventive chemotherapy with albendazole and mebendazole. We assessed the efficacy and safety of ascending tribendimidine doses against hookworm infections in African school-aged children, key information for the development of tribendimidine.

Methods

We performed a single blind, randomized, controlled trial in Côte d’Ivoire between June and August 2017. Eligible participants were randomly assigned to placebo, 100, 200, or 400 mg tribendimidine. Cure rates (CRs, primary outcome) and egg reduction rates (ERRs) were determined 14–21 days after treatment. Clinical symptoms were assessed before treatment and adverse events monitored 3 and 24 hours posttreatment.

Results

CRs calculated for 130 children dose-dependently increased. The observed CRs were 20.6% (7/34), 21.2% (7/33), 38.7% (12/31), and 53.1% (17/32) for placebo, 100, 200, and 400 mg of tribendimidine, respectively. The Emax model predicted a placebo corrected net effect of 34.3 percentage points (95% confidence interval [CI], 13.3–54.4) for the 400-mg tribendimidine dose. The ERRs (geometric mean) were 30.6% (95% CI, −24.7 to 64.1), 65.4% (95% CI, 24.5–85.9), 82.1% (95% CI, 58.4–92.5) and 92.2% (95% CI, 81.0–97.1) for placebo, 100, 200, and 400 mg tribendimidine, respectively. The Emax model predicted an ERR of 95% at 500 mg. Only mild adverse events and no abnormal biochemical parameters were observed.

Conclusion

A 400-mg dose of tribendimidine yielded the highest efficacy and was well tolerated. Because children were mostly lightly infected, further investigations with tribendimidine against moderate/heavy hookworm infection are needed.

Clinical Trials Registration

The trial is registered at www.isrctn.com number ISRCTN81391471.
A Genome-wide Association Study Identifying RAP1A as a Novel Susceptibility Gene for Crohn’s Disease in Japanese Individuals
Authors: Kakuta Yoichi , Kawai Yosuke , Naito Takeo , Hirano Atsushi , Umeno Junji , Fuyuno Yuta , Liu Zhenqiu , Li Dalin , Nakano Takeru , Izumiyama Yasuhiro , Ichikawa Ryo , Okamoto Daisuke , Nagai Hiroshi , Matsumoto Shin , Yamamoto Katsutoshi , Yokoyama Naonobu , Chiba Hirofumi , Shimoyama Yusuke , Onodera Motoyuki , Moroi Rintaro , Kuroha Masatake , Kanazawa Yoshitake , Kimura Tomoya , Shiga Hisashi , Endo Katsuya , Negoro Kenichi , Yasuda Jun , Esaki Motohiro , Tokunaga Katsushi , Nakamura Minoru , Matsumoto Takayuki , McGovern Dermot P B , Nagasaki Masao , Kinouchi Yoshitaka , Shimosegawa Tooru , Masamune Atsushi
Published: November 2018

Background and Aims

Genome-wide association studies [GWASs] of European populations have identified numerous susceptibility loci for Crohn’s disease [CD]. Susceptibility genes differ by ethnicity, however, so GWASs specific for Asian populations are required. This study aimed to clarify the Japanese-specific genetic background for CD by a GWAS using the Japonica array [JPA] and subsequent imputation with the 1KJPN reference panel.

Methods

Two independent Japanese case/control sets (Tohoku region [379 CD patients, 1621 controls] and Kyushu region [334 CD patients, 462 controls]) were included. GWASs were performed separately for each population, followed by a meta-analysis. Two additional replication sets [254 + 516 CD patients and 287 + 565 controls] were analysed for top hit single nucleotide polymorphisms [SNPs] from novel genomic regions.

Results

Genotype data of 4 335 144 SNPs from 713 Japanese CD patients and 2083 controls were analysed. SNPs located in TNFSF15 (rs78898421, Pmeta = 2.59 × 10−26, odds ratio [OR] = 2.10), HLA-DQB1 [rs184950714, pmeta = 3.56 × 10−19, OR = 2.05], ZNF365, and 4p14 loci were significantly associated with CD in Japanese individuals. Replication analyses were performed for four novel candidate loci [p <1 × 10−6], and rs488200 located upstream of RAP1A was significantly associated with CD [pcombined = 4.36 × 10−8, OR = 1.31]. Transcriptome analysis of CD4+ effector memory T cells from lamina propria mononuclear cells of CD patients revealed a significant association of rs488200 with RAP1A expression.

Conclusions

RAP1A is a novel susceptibility locus for CD in the Japanese population.
Prediction of individual life-years gained without cardiovascular events from lipid, blood pressure, glucose, and aspirin treatment based on data of more than 500 000 patients with Type 2 diabetes mellitus
Authors: Berkelmans Gijs F N , Gudbjörnsdottir Soffia , Visseren Frank L J , Wild Sarah H , Franzen Stefan , Chalmers John , Davis Barry R , Poulter Neil R , Spijkerman Annemieke M , Woodward Mark , Pressel Sara L , Gupta Ajay K , van der Schouw Yvonne T , Svensson Ann-Marie , van der Graaf Yolanda , Read Stephanie H , Eliasson Bjorn , Dorresteijn Jannick A N
Published: November 2018

Aims

Although group-level effectiveness of lipid, blood pressure, glucose, and aspirin treatment for prevention of cardiovascular disease (CVD) has been proven by trials, important differences in absolute effectiveness exist between individuals. We aim to develop and validate a prediction tool for individualizing lifelong CVD prevention in people with Type 2 diabetes mellitus (T2DM) predicting life-years gained without myocardial infarction or stroke.

Methods and results

We developed and validated the Diabetes Lifetime-perspective prediction (DIAL) model, consisting of two complementary competing risk adjusted Cox proportional hazards functions using data from people with T2DM registered in the Swedish National Diabetes Registry (n = 389 366). Competing outcomes were (i) CVD events (vascular mortality, myocardial infarction, or stroke) and (ii) non-vascular mortality. Predictors were age, sex, smoking, systolic blood pressure, body mass index, haemoglobin A1c, estimated glomerular filtration rate, non- high-density lipoprotein cholesterol, albuminuria, T2DM duration, insulin treatment, and history of CVD. External validation was performed using data from the ADVANCE, ACCORD, ASCOT and ALLHAT-LLT-trials, the SMART and EPIC-NL cohorts, and the Scottish diabetes register (total n = 197 785). Predicted and observed CVD-free survival showed good agreement in all validation sets. C-statistics for prediction of CVD were 0.83 (95% confidence interval: 0.83–0.84) and 0.64–0.65 for internal and external validation, respectively. We provide an interactive calculator at www.U-Prevent.com that combines model predictions with relative treatment effects from trials to predict individual benefit from preventive treatment.

Conclusion

Cardiovascular disease-free life expectancy and effects of lifelong prevention in terms of CVD-free life-years gained can be estimated for people with T2DM using readily available clinical characteristics. Predictions of individual-level treatment effects facilitate translation of trial results to individual patients.
Risk of hospital readmission and associated factors after a positive sample for a multidrug-resistant microorganism
Authors: Sentís Alexis , González Cristina , Montero Maria , Herranz Milagros , Hidalgo Carlota , Campà Cristina , Sala Maria , Macià Francesc , Román Marta , Prats-Uribe Albert , Horcajada Juan Pablo , Castells Xavier
Published: November 2018

Background

To determine the risk of hospital readmission and associated factors in patients with a positive sample for multidrug-resistant microorganisms (MRM) and to analyze whether there is a higher risk of hospital readmission with some of the more common MRM.

Methods

Retrospective cohort study (2012–16) performed in a tertiary-care teaching hospital in Barcelona. Patients were divided into two groups, depending on the presence or absence of an MRM-positive sample during hospital admission. Logistic regression models were used to estimate the risk of hospital readmission in the first 30 and 90 days, and the first year for patients with an MRM-positive sample compared with those without. The models were stratified by the presence or absence of an MRM-positive sample and by grouped Charlson comorbidity index.

Results

We included 983 patients with an MRM-positive sample and 39 323 patients without. The risk of hospital readmission in the first 30 days was 41% higher in admitted patients with an MRM-positive sample (95%CI=1.17 to 1.69) than in those without. Stratified models showed similar results to the overall results for all Charlson comorbidity index groups. When the models were stratified by the presence of an MRM-positive sample, methicillin-resistant Staphylococcus aureus showed the highest risk of readmissions within the more common MRM [103% (95%CI=1.10 to 3.75)].

Conclusion

MRMs seem to be an important risk factor for hospital readmissions both among patients with and without comorbidities. Specific types of MRM may represent a higher risk for hospital readmissions than other MRMs, depending on the particular environment or hospital.
Exploring diversity in expert knowledge: variation in local ecological knowledge of Alaskan recreational and subsistence fishers
Authors: Chan Maggie N , Beaudreau Anne H , Loring Philip A
Published: November 2018

Local ecological knowledge (LEK) of resource users is a valuable source of information about environmental trends and conditions. However, many factors influence how people perceive their environment and it may be important to identify sources of variation in LEK when using it to understand ecological change. This study examined variation in LEK arising from differences in people’s experience in the environment. From 2014 to 2016, we conducted 98 semi-structured interviews with subsistence fishers and recreational charter captains in four Alaskan coastal communities to document LEK of seven fish species. Fishers observed declines in fish abundance and body size, though the patterns varied among species, regions, and fishery sectors. Overall, subsistence harvesters provided a longer-term view of abundance changes compared with charter captains. Regression analyses indicated that the extent of people’s fishing areas and their years of fishing experience were relatively important factors in explaining variation in fishers’ perceptions of fish abundance. When taken together, perspectives from fishers in multiple regions and sectors can provide a more complete picture of changes in nearshore fish populations than any source alone. These findings underscore the importance of including people with different types of expertise in local knowledge studies designed to document environmental change.
Simple bespoke preservation of two conservation laws
Authors: Frasca-Caccia Gianluca , Hydon Peter Ellsworth
Published: November 2018

Conservation laws are among the most fundamental geometric properties of a partial differential equation (PDE), but few known finite difference methods preserve more than one conservation law. All conservation laws belong to the kernel of the Euler operator, an observation that was first used recently to construct approximations symbolically that preserve two conservation laws of a given PDE. However, the complexity of the symbolic computations has limited the effectiveness of this approach. The current paper introduces some key simplifications that make the symbolic–numeric approach feasible. To illustrate the simplified approach we derive bespoke finite difference schemes that preserve two discrete conservation laws for the Korteweg–de Vries equation and for a nonlinear heat equation. Numerical tests show that these schemes are robust and highly accurate compared with others in the literature.
Contribution of Asymptomatic Plasmodium Infections to the Transmission of Malaria in Kayin State, Myanmar
Authors: Chaumeau Victor , Kajeechiwa Ladda , Fustec Bénédicte , Landier Jordi , Naw Nyo Saw , Nay Hsel Saw , Phatharakokordbun Phabele , Kittiphanakun Prapan , Nosten Suphak , Thwin May Myo , Win Tun Saw , Wiladphaingern Jacher , Cottrell Gilles , Parker Daniel M , Minh Myo Chit , Kwansomboon Nittpha , Metaane Selma , Montazeau Céline , Kunjanwong Kitti , Sawasdichai Sunisa , Andolina Chiara , Ling Clare , Haohankhunnatham Warat , Christiensen Peter , Wanyatip Sunaree , Konghahong Kamonchanok , Cerqueira Dominique , Imwong Mallika , Dondorp Arjen M , Chareonviriyaphap Theeraphap , White Nicholas J , Nosten François H , Corbel Vincent
Published: November 2018

Background

The objective of mass antimalarial drug administration (MDA) is to eliminate malaria rapidly by eliminating the asymptomatic malaria parasite reservoirs and interrupting transmission. In the Greater Mekong Subregion, where artemisinin-resistant Plasmodium falciparum is now widespread, MDA has been proposed as an elimination accelerator, but the contribution of asymptomatic infections to malaria transmission has been questioned. The impact of MDA on entomological indices has not been characterized previously.

Methods

MDA was conducted in 4 villages in Kayin State (Myanmar). Malaria mosquito vectors were captured 3 months before, during, and 3 months after MDA, and their Plasmodium infections were detected by polymerase chain reaction (PCR) analysis. The relationship between the entomological inoculation rate, the malaria prevalence in humans determined by ultrasensitive PCR, and MDA was characterized by generalized estimating equation regression.

Results

Asymptomatic P. falciparum and Plasmodium vivax infections were cleared by MDA. The P. vivax entomological inoculation rate was reduced by 12.5-fold (95% confidence interval [CI], 1.6–100-fold), but the reservoir of asymptomatic P. vivax infections was reconstituted within 3 months, presumably because of relapses. This was coincident with a 5.3-fold (95% CI, 4.8–6.0-fold) increase in the vector infection rate.

Conclusion

Asymptomatic infections are a major source of malaria transmission in Southeast Asia.
Emerging threat of triazole-resistant Aspergillus fumigatus
Authors: Rybak Jeffrey M , Fortwendel Jarrod R , Rogers P David
Published: November 2018

Invasive aspergillosis is a leading cause of morbidity and mortality among immunocompromised populations and is predicted to cause more than 200 000 life-threatening infections each year. Aspergillus fumigatus is the most prevalent pathogen isolated from patients with invasive aspergillosis, accounting for more than 60% of all cases. Currently, the only antifungal agents available with consistent activity against A. fumigatus are the mould-active triazoles and amphotericin B, of which the triazoles commonly represent both front-line and salvage therapeutic options. Unfortunately, the treatment of infections caused by A. fumigatus has recently been further complicated by the global emergence of triazole resistance among both clinical and environmental isolates. Mutations in the A. fumigatus sterol-demethylase gene cyp51A, overexpression of cyp51A and overexpression of efflux pump genes are all known to contribute to resistance, yet much of the triazole resistance among A. fumigatus still remains unexplained. Also lacking is clinical experience with therapeutic options for the treatment of triazole-resistant A. fumigatus infections and mortality associated with these infections remains unacceptably high. Thus, further research is greatly needed to both better understand the emerging threat of triazole-resistant A. fumigatus and to develop novel therapeutic strategies to combat these resistant infections.
Tfp, News, and “Sentiments”: the International Transmission of Business Cycles
Authors: Levchenko Andrei A , Pandalai-Nayar Nitya
Published: November 2018

We propose a novel identification scheme for a nontechnology business cycle shock, which we label “sentiment”. This is a shock orthogonal to identified surprise and news TFP shocks that maximize the short-run forecast error variance of an expectational variable, alternatively a GDP forecast or a consumer confidence index. We then estimate the international transmission of three identified shocks—surprise TFP, news of future TFP, and sentiment—from the United States to Canada. The US sentiment shock produces a business cycle in the United States, with output, hours, and consumption rising following a positive shock, and accounts for the bulk of the US short-run business cycle fluctuations. The sentiment shock also has a significant impact on Canadian macroaggregates. In the short run, it is more important than either the surprise or the news TFP shocks in generating business cycle comovement between the United States and Canada, accounting for over 40% of the forecast error variance of Canadian GDP and over one-third of Canadian hours, imports, and exports. The news shock is responsible for some comovement at 5–10 years, and surprise TFP innovations do not generate synchronization. We provide a simple theoretical framework to illustrate how the US sentiment shocks can transmit to Canada.
Large tumor suppressor 2, LATS2, activates JNK in a kinase-independent mechanism through ASK1
Authors: Rusnak Lauren , Tang Cong , Qi Qi , Mo Xiulei , Fu Haian
Published: November 2018

Apoptosis signal-regulating kinase 1 (ASK1) is an important mediator of the cell stress response pathways. Because of its central role in regulating cell death, the activity of ASK1 is tightly regulated by protein–protein interactions and post-translational modifications. Deregulation of ASK1 activity has been linked to human diseases, such as neurological disorders and cancer. Here we describe the identification and characterization of large tumor suppressor 2 (LATS2) as a novel binding partner for ASK1. LATS2 is a core kinase in the Hippo signaling pathway and is commonly downregulated in cancer. We found that LATS2 interacts with ASK1 and increases ASK1-mediated signaling to promote apoptosis and activate the JNK mitogen-activated protein kinase (MAPK). This change in MAPK signaling is dependent on the catalytic activity of ASK1 but does not require LATS2 kinase activity. This work identifies a novel role for LATS2 as a positive regulator of the ASK1–MKK–JNK signaling pathway and establishes a kinase-independent function of LATS2 that may be part of the intricate regulatory system for cellular response to diverse stress signals.
Overexpression of ubiquitin-specific peptidase 15 in systemic sclerosis fibroblasts increases response to transforming growth factor β
Authors: Galant Christine , Marchandise Joel , Stoenoiu Maria S , Ducreux Julie , De Groof Aurélie , Pirenne Sophie , Van den Eynde Benoit , Houssiau Frédéric A , Lauwerys Bernard R
Published: November 2018

Objective

Ubiquitination of proteins leads to their degradation by the proteasome, and is regulated by ubiquitin ligases and substrate-specific ubiquitin-specific peptidases (USPs). The ubiquitination process also plays important roles in the regulation of cell metabolism and cell cycle. Here, we found that the expression of several USPs is increased in SSc tenosynovial and skin biopsies, and we demonstrated that USP inhibition decreases TGF-β signalling in primary fibroblast cell lines.

Methods

High-density transcriptomic studies were performed using total RNA obtained from SSc tenosynovial samples. Confirmatory immunostaining experiments were performed on tenosynovial and skin samples. In vitro experiments were conducted in order to study the influence of USP modulation on responses to TGF-β stimulation.

Results

Tenosynovial biopsies from SSc patients overexpressed known disease-associated gene pathways: fibrosis, cytokines and chemokines, and Wnt/TGF-β signalling, but also several USPs. Immunohistochemistry experiments confirmed the detection of USPs in the same samples, and in SSc skin biopsies. Exposure of primary fibroblast cell lines to TGF-β induced USP gene expression. The use of a pan-USP inhibitor decreased SMAD3 phosphorylation, and expression of COL1A1, COL3A1 and fibronectin gene expression in TGF-β-stimulated fibroblasts. The effect of the USP inhibitor resulted in increased SMAD3 ubiquitination, and was blocked by a proteasome inhibitor, thereby confirming the specificity of its action.

Conclusion

Overexpression of several USPs, including USP15, amplifies fibrotic responses induced by TGF-β, and is a potential therapeutic target in SSc.
Phylogeny and molecular species delimitation of long-nosed armadillos (Dasypus: Cingulata) supports morphology-based taxonomy
Authors: Feijó Anderson , Vilela Júlio F , Cheng Jilong , Schetino Marco Antônio A , Coimbra Raphael T F , Bonvicino Cibele R , Santos Fabrício R , Patterson Bruce D , Cordeiro-Estrela Pedro
Published: November 2018

The armadillo genus Dasypus is the most species-rich and widely distributed genus of the order Cingulata and it has a dynamic taxonomic history. Recent morphology-based studies have proposed new taxonomic arrangements, but these were not yet assessed with molecular data. The two comprehensive phylogenetic hypotheses available for the genus are conflicting and were each based on a subset of taxa, hampering a proper evaluation of species boundaries. Using a multilocus molecular dataset, based on the broadest geographic sampling of Dasypus to date, we inferred the phylogenetic relationships of all species of the genus, including the recently reinstated D. beniensis and D. pastasae. We tested recent taxonomic hypotheses using several species-delimitation approaches. Our phylogeny recovered three main lineages of long-nosed armadillos that we treat as subgenera (Hyperoambon, Muletia and Dasypus) and identified the majority of its diversification as having occurred during the Pliocene. Molecular species delimitation supported morphological evidence in assigning D. hybridus as a subspecies of D. septemcinctus and confirming the split of the D. kappleri complex into three species. Our results strongly support the recognition of Guiana Shield populations formerly assigned to D. novemcinctus as a distinct species. The phylogenetic positions of D. mazzai and D. sabanicola remain uncertain. Further investigation using faster-evolving genes and additional samples may help to clarify the relationships of these young species.
Direct Regulation of the EFR-Dependent Immune Response by Arabidopsis TCP Transcription Factors
Authors: Spears Benjamin J. , Howton T. C. , Gao Fei , Garner Christopher M. , Mukhtar M. Shahid , Gassmann Walter
Published: November 2018

One layer of the innate immune system allows plants to recognize pathogen-associated molecular patterns (PAMPS), activating a defense response known as PAMP-triggered immunity (PTI). Maintaining an active immune response, however, comes at the cost of plant growth and development; accordingly, optimization of the balance between defense and development is critical to plant fitness. The TEOSINTE BRANCHED1/CYCLOIDEA/PROLIFERATING CELL FACTOR (TCP) transcription factor family consists of well-characterized transcriptional regulators of plant development and morphogenesis. The three closely related class I TCP transcription factors TCP8, TCP14, and TCP15 have also been implicated in the regulation of effector-triggered immunity, but there has been no previous characterization of PTI-related phenotypes. To identify TCP targets involved in PTI, we screened a PAMP-induced gene promoter library in a yeast one-hybrid assay and identified interactions of these three TCPs with the EF-Tu RECEPTOR (EFR) promoter. The direct interactions between TCP8 and EFR were confirmed to require an intact TCP binding site in planta. A tcp8 tcp14 tcp15 triple mutant was impaired in EFR-dependent PTI and exhibited reduced levels of PATHOGENESIS-RELATED PROTEIN 2 and induction of EFR expression after elicitation with elf18 but also increased production of reactive oxygen species relative to Col-0. Our data support an increasingly complex role for TCPs at the nexus of plant development and defense.
Phytophthora infestansSporangia Produced in Culture and on Tomato Leaflet Lesions Show Marked Differences in Indirect Germination Rates, Aggressiveness, and Global Transcription Profiles
Authors: Fry William E. , Patev Sean P. , Myers Kevin L. , Bao Kan , Fei Zhangjun
Published: November 2018

Sporangia of Phytophthora infestans from pure cultures on agar plates are typically used in lab studies, whereas sporangia from leaflet lesions drive natural infections and epidemics. Multiple assays were performed to determine if sporangia from these two sources are equivalent. Sporangia from plate cultures showed much lower rates of indirect germination and produced much less disease in field and moist-chamber tests. This difference in aggressiveness was observed whether the sporangia had been previously incubated at 4°C (to induce indirect germination) or at 21°C (to prevent indirect germination). Furthermore, lesions caused by sporangia from plates produced much less sporulation. RNA-Seq analysis revealed that thousands of the >17,000 P. infestans genes with a RPKM (reads per kilobase of exon model per million mapped reads) >1 were differentially expressed in sporangia obtained from plate cultures of two independent field isolates compared with sporangia of those isolates from leaflet lesions. Among the significant differentially expressed genes (DEGs), putative RxLR effectors were overrepresented, with almost half of the 355 effectors with RPKM >1 being up- or downregulated. DEGs of both isolates include nine flagellar-associated genes, and all were down-regulated in plate sporangia. Ten elicitin genes were also detected as DEGs in both isolates, and nine (including INF1) were up-regulated in plate sporangia. These results corroborate previous observations that sporangia produced from plates and leaflets sometimes yield different experimental results and suggest hypotheses for potential mechanisms. We caution that use of plate sporangia in assays may not always produce results reflective of natural infections and epidemics.
A New Disease of Epimedium Caused by Carnation Ringspot Virus
Authors: Kiambi Roy G. , Baumann Mattie M. , Lockhart Benham E.
Published: November 2018

Epimediums (Epimedium grandiflorum) are popular perennial groundcovers and are known to produce a wide range of medicinal effects. Extracts have long been used in traditional Chinese medicine. Carnation ringspot virus (CRSV) has a wide host range. In 2018, symptoms were observed on epimedium in three different landscape settings across St. Paul, MN. Leaf symptoms consisted of conspicuous mottling, chlorotic ringspots, and distortion of leaf margins. CRSV was confirmed by reverse transcription polymerase chain reaction. The CRSV host range now includes epimedium, which is the first species of the Berberidaceae family shown to be susceptible to CRSV. The potential risk of infection in other ornamental plant species in the family should be evaluated.
The human secretome – the proteins secreted from human cells
Authors: Uhlen Mathias , Tegel Hanna , Sivertsson Åsa , Kuo Chih-Chung , Gutierrez Jahir M. , Lewis Nathan E. , Forsström Björn , Dannemeyer Melanie , Fagerberg Linn , Malm Magdalena , Vunk Helian , Edfors Fredrik , Hober Andreas , Sjöstedt Evelina , Kotol David , Mulder Jan , Mardinoglu Adil , Schwenk Jochen M. , Nilsson Peter , Zwahlen Martin , Takanen Jenny Ottosson , von Feilitzen Kalle , Stadler Charlotte , Lindskog Cecilia , Ponten Fredrik , Nielsen Jens , Palsson Bernhard O. , Volk Anna-Luisa , Lundqvist Magnus , Berling Anna , Svensson Anne-Sophie , Kanje Sara , Enstedt Henric , Afshari Delaram , Ekblad Siri , Scheffel Julia , Katona Borbala , Vuu Jimmy , Lindström Emil , Xu LanLan , Mihai Roxana , Bremer Lucas , Westin Malin , Muse Muna , Mayr Lorenz M. , Knight Sinead , Göpel Sven , Davies Rick , Varley Paul , Hatton Diane , Fields Ray , Voldborg Bjørn G. , Rockberg Johan , Schiavone Lovisa Holmberg , Hober Sophia
Published: November 2018

The proteins secreted by human tissues (the secretome) are important for the basic understanding of human biology, but also for identification of potential targets for future diagnosis and therapy. Here, we present an annotation of all predicted secreted proteins (n=2,623) with information about their spatial distribution in the human body. A high-throughput mammalian cell factory was established to create a resource of recombinant full-length proteins. This resource was used for phenotypic assays involving β-cell dedifferentiation and for development of targeted proteomics assays. A comparison between host cells, including omics analysis, shows that many of the proteins that failed to be generated in CHO cells could be rescued in human HEK293 cells. In conclusion, the human secretome has been mapped and characterized to facilitate further exploration of the human secretome.
Hepatocyte Membrane Potential Regulates Serum Insulin and Insulin Sensitivity by Altering Hepatic GABA Release
Authors: Geisler Caroline. E. , Ghimire Susma. , Hepler Chelsea. , Miller Kendra E. , Higgins Mark. R. , Yoshino Jun. , Klein Samuel. , Renquist Benjamin. J.
Published: November 2018

The degree of hepatic lipid accumulation in obesity correlates with the severity of hyperinsulinemia and systemic insulin resistance. Here, we propose a mechanism that explains this associative link, whereby, hepatic steatosis dysregulates glucose and insulin homeostasis. Obesity-induced hepatocellular lipid accumulation results in hepatocyte depolarization. We have established that hepatocyte depolarization depresses hepatic afferent vagal nerve firing, increases GABA release from liver slices, and causes hyperinsulinemia. Preventing hepatic GABA release or eliminating the ability of the liver to communicate to the hepatic vagal nerve ameliorates the hyperinsulinemia and insulin resistance associated with diet-induced obesity. In people with obesity hepatic expression of GABA transporters is associated with glucose infusion and disposal rates during a hyperinsulinemic euglycemic clamp. Single nucleotide polymorphisms in hepatic GABA re-uptake transporters are associated with an increased incidence of type II diabetes mellitus. Herein, we identify GABA as a novel hepatokine that is dysregulated in obesity and whose release can be manipulated to mute or exacerbate the glucoregulatory dysfunction common to obesity.