bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing virulence of Varroa destructor mites from different honey bee management regimes
Authors: Dynes Travis L. , Berry Jennifer A. , Delaplane Keith S. , de Roode Jacobus C. , Brosi Berry J.
Published: December 2019

The mite Varroa destructor is an important honey bee parasite that causes substantial losses of honey bee colonies worldwide. Evolutionary theory suggests that the high densities at which honey bees are managed in large-scale beekeeping settings will likely select for mites with greater growth and virulence, thereby potentially explaining the major damage done by these mites. We tested this hypothesis by collecting mites from feral bee colonies, “lightly” managed colonies (those from small-scale sedentary operations), and “heavily” managed colonies (those from large-scale operations that move thousands of colonies across the US on a yearly basis). We established 8 apiaries, each consisting of 11 colonies from a standardized lightly managed bee background that were cleared of mites, and artificially infested each apiary with controlled numbers of mites from feral, lightly managed, or heavily managed bees or left uninoculated as negative control. We monitored the colonies for more than 2 years for mite levels, colony strength (adult bee population, brood coverage, and honey storage), and survival. As predicted by evolutionary theory, we found that colonies inoculated with mites from managed backgrounds had increased V. destructor mite levels relative to those with mites from feral colonies or negative controls. However, we did not see a difference between heavily and lightly managed colonies, and these higher mite burdens did not translate into greater virulence, as measured by reductions in colony strength and survival. Our results suggest that human management of honey bee colonies may favor the increased population growth rate of V. destructor, but that a range of potential confounders (including viral infections and genotype-by-genotype interactions) likely contribute to the relationship between mite reproduction and virulence.
Varroa destructor reproduction and cell re-capping in mite-resistant Apis mellifera populations
Authors: Martin Stephen J. , Hawkins George P. , Brettell Laura E. , Reece Natasha , Correia-Oliveira Maria E. , Allsopp Michael H.
Published: December 2019

Globalization has facilitated the spread of emerging pests such as the Varroa destructor mite, resulting in the near global distribution of the pest. In South African and Brazilian honey bees, mite-resistant colonies appeared within a decade; in Europe, mite-resistant colonies are rare, but several of these exhibited high levels of “re-capping” behavior. We studied re-capping in Varroa-naïve (UK/Australia) and Varroa-resistant (South Africa and Brazil) populations and found very low and very high levels, respectively, with the resistant populations targeting mite-infested cells. Furthermore, 54% of artificially infested A. m. capensis worker cells were removed after 10 days and 83% of the remaining infested cells were re-capped. Such targeted re-capping of drone cells did not occur. We propose that cell opening is a fundamental trait in mite-resistant populations and that re-capping is an accurate proxy for this behavior.
Legume-based rotations have clear economic advantages over cereal monocropping in dry areas
Authors: Yigezu Yigezu A. , El-Shater Tamer , Boughlala Mohamed , Bishaw Zewdie , Niane Abdul Aziz , Maalouf Fouad , Degu Wuletaw Tadesse , Wery Jacques , Boutfiras Mohamed , Aw-Hassan Aden
Published: December 2019

Current land use trends show an increasing preference for monocropping – mostly a consequence of policies and incentives aimed at enhancing the intensification of cereals. This shift has caused some to question whether legume–cereal rotations can remain economically viable options for farmers, particularly in the dry areas. In this paper, we present the results of an endogenous switching regression model which suggests, for the first time, that legume–cereal rotations have clear economic advantages over cereal monocropping. Rotations provide higher yields, gross margins, and consumption of wheat and faba beans. Most past economic analyses on rotation used data from experimental stations or small-sized farmer surveys covering only one season and variety. This study makes an important improvement by employing two-year data from a large sample of 1230 farm households and their 2643 fields cultivated with different varieties of wheat and faba beans in the wheat-based production system of Morocco. Assuming a biennial rotation – the fastest cycle possible in a rainfed dryland system, this paper is also the first to demonstrate that joint adoption of rotations and improved faba bean varieties leads to a two-year average gross margin that is US$537/ha (48%) higher than wheat monocropping. This is the highest economic benefit of all available cropping options. A striking result of the study is that, contrary to common expectations, adopters of rotation did not use lesser amounts of nitrogen fertilizer than those monocropping wheat, thereby undermining the ecological benefits of faba bean–wheat rotations. Given that current average applications are below marginal product-maximizing levels, higher marginal yields of nitrogen fertilizers after rotation help explain farmers’ current behavior. Our results suggest that: 1) promoting improved legume varieties may enhance adoption of rotation; and 2) an economic rationale should be used as the main driver of the rotation agenda in the dry areas.
Contributions of bark and tension wood and role of the G-layer lignification in the gravitropic movements of 21 tropical tree species
Authors: Ghislain Barbara , Alméras Tancrède , Prunier Jonathan , Clair Bruno
Published: December 2019

Key message

Gravitropic movements in angiosperm woody stems are achieved through the action of bark and/or wood motor, depending on the bark and wood fibre anatomy (with trellis structure or not; with G-layers or not). Bark motor is as efficient as wood motor to recover from tilting in young trees of 21 tropical species.

Context

Angiosperm trees produce tension wood to control their orientation through changes in stem curvature. Tension wood is classified into 3 anatomical groups: with unlignified G-layer, with lignified G-layer and without G-layer.

Aims

This study aimed at assessing whether this anatomical diversity reflects a diversity in efficiency of gravitropic movement.

Methods

The study was conducted on tropical seedling from the three anatomical groups. Seedlings were staked and grown tilted. At the end of the experiment, changes in curvature when releasing the stem from the stake and when removing bark were measured. Three parameters were computed to compare the global efficiency of gravitropism (stem gravitropic efficiency) and the specific efficiency of motor mechanism based on wood (maturation strain of tension wood) and bark (standardized debarking curvature).

Results

The maturation strain of tension wood was similar between species with unlignified and lignified G-layer. Species without G-layer exhibited low maturation strain and large debarking curvature, showing they rely on bark for gravitropism. Bark and wood achieved similar motor efficiency.

Conclusion

Lignin does not affect the generation of tensile stress in the G-layer. Bark can be as efficient as wood as a motor of gravitropic movements.
Empowering medical students as agents of curricular change: a value-added approach to student engagement in medical education
Authors: Geraghty Joseph R. , Young Alexandria N. , Berkel Tiffani D.M. , Wallbruch Eric , Mann Julie , Park Yoon Soo , Hirshfield Laura E. , Hyderi Abbas
Published: December 2019

One area in which medical students can add significant value is medical education, and involving them as key stakeholders in their education can have a profound impact on students and the institutions that serve them. However, detailed descriptions of the structure, implementation and quality of programs facilitating student engagement are lacking. We describe the structure of a novel student engagement program at the University of Illinois College of Medicine-Chicago (UICOM-Chicago) known as the Student Curricular Board (SCB). We surveyed 563 medical students across all levels of training at our institution in order to examine the impact of this program, including its strengths and potential areas of improvement. The SCB serves as a highly structured and collaborative student group that has far-reaching involvement from course-level program evaluation to longitudinal curriculum design. Medical students overwhelmingly valued opportunities to be involved in their curriculum. Students with the greatest exposure to the SCB were more aware of specific program initiatives and expressed increased interest in academic medicine as a career. By highlighting this innovative student engagement program, we aim to share best practices for a highly structured, value-added approach to medical student engagement in medical education that is applicable to other medical schools and student leaders.
Measuring nanoscale friction at graphene step edges
Authors: Chen Zhe , Kim Seong H.
Published: December 2019

Although graphene is well known for super-lubricity on its basal plane, friction at its step edge is not well understood and contradictory friction behaviors have been reported. In this study, friction of mono-layer thick graphene step edges was studied using atomic force microscopy (AFM) with a Si tip in dry nitrogen atmosphere. It is found that, when the tip slides over a ‘buried’ graphene step edge, there is a resistive force during the step-up motion and an assistive force during the step-down motion due to the topographic height change. The magnitude of these two forces is small and the same in both step-up and step-down motions. As for the ‘exposed’ graphene step edge, friction increases in magnitude and exhibits more complicated behaviors. During the step-down motion of the tip over the exposed step edge, both resistive and assistive components can be detected in the lateral force signal of AFM if the scan resolution is sufficiently high. The resistive component is attributed to chemical interactions between the functional groups at the tip and step-edge surfaces, and the assistive component is due to the topographic effect, same as the case of buried step edge. If a blunt tip is used, the distinct effects of these two components become more prominent. In the step-up scan direction, the blunt tip appears to have two separate topographic effects elastic deformation of the contact region at the bottom of the tip due to the substrate height change at the step edge and tilting of the tip while the vertical position of the cantilever (the end of the tip) ascends from the lower terrace to the upper terrace. The high-resolution measurement of friction behaviors at graphene step edges will further enrich understanding of interfacial friction behaviors on graphene-covered surfaces.
EuGMS survey on structures of geriatric rehabilitation across Europe
Authors: Grund Stefan , van Wijngaarden Janneke P. , Gordon Adam L. , Schols Jos M.G.A. , Bauer Jürgen M.
Published: December 2019

Purpose

Geriatric rehabilitation provides effective multidisciplinary treatment for older people who show symptoms of relevant and potentially reversible functional decline. The aim of this study is to provide an overview on structures of geriatric rehabilitation across Europe.

Methods

All European Geriatric Medicine Society (EuGMS) Full board members, each representing one member state of the society, were asked to complete an online questionnaire about the current structure of geriatric rehabilitation in their country.

Results

Thirty-one out of 33 EuGMS Full Board members participated in this questionnaire. Geriatric rehabilitation was officially recognized in 65% (20/31) of participating countries while 29% (9/31) had no geriatric rehabilitation services in their country. In countries with geriatric rehabilitation, the number of available beds varied widely (0–70/100,000 inhabitants). Average length of stay varied from 7 to 65 days. The estimated mean age of the patients in geriatric rehabilitation was 80 years, with most patients being older than 70 years. Six countries had no specified lower age limit and no country had an upper age limit. 42% (13/31) of countries reported having national or local guidelines and 35% (11/31) had a benchmarking or audit system established. Most participants responded positively about the prospects for improvement in the field.

Conclusion

We observed major differences among EuGMS member countries with regard to the availability of geriatric rehabilitation and how it was organized. Despite various barriers in most countries, future improvement in geriatric rehabilitation services is anticipated.
“What matters to you?”: A randomized controlled effectiveness trial, Using Systematic Idiographic Assessment as an intervention to Increase Adolescents’ perceived control of their mental health
Authors: Tollefsen Thomas Kristian , Neumer Simon‐Peter , Berg‐Nielsen Turid Suzanne
Published: December 2019

Introduction

Over the last decades, many Western countries have seen an increase in mental health difficulties in the adolescent population. Among Norwegian adolescents, internalizing symptoms are most prevalent, and 10%–38% of adolescents seek out primary health care services for mental health problems. This study examined whether an idiographic measure designed for adolescents called Assert, which uses variables individually selected by the adolescents, could improve user involvement, locus of control, mental health, and quality of life.

Methods

This study conducted a randomized controlled effectiveness trial using Assert in primary healthcare. A community sample of 150 Norwegian adolescents aged 12–23 years (M = 16.2; SD = 2.2) were randomized to the Assert or control group. Of the participants 27 (18%) were male. The adolescents and 52 counsellors from primary healthcare services responded to online questionnaires. Of the counselors, 92.8% were female and trained in the use of systematic idiographic assessment.

Results

Adolescents who used Assert scored significantly lower on external LoC, attributing less of their mental health improvement to chance, fate, or luck. However, the intervention showed no effect on the symptoms of mental health, QoL, or user involvement.

Conclusions

Using Assert in primary healthcare may enhance adolescents’ sense of being able to influence their life circumstances and mental health by allowing them more control of their treatment. However, this approach might not be successful in reducing symptoms.
Essential tremor: genetic update
Authors: Deng Hao , Wu Shan , Jankovic Joseph
Published: December 2019

Essential tremor (ET) is a neurological movement disorder characterised by bilateral limb kinetic/postural tremor, with or without tremor in other body parts including head, voice and lower limbs. Since no causative genes for ET have been identified, it is likely that the disorder occurs as a result of complex genetic factors interacting with various cellular and environmental factors that can result in abnormal function of circuitry involving the cerebello–thalamo–cortical pathway. Genetic analyses have uncovered at least 14 loci and 11 genes that are related to ET, as well as various risk or protective genetic factors. Limitations in ET genetic analyses include inconsistent disease definition, small sample size, varied ethnic backgrounds and many other factors that may contribute to paucity of relevant genetic data in ET. Genetic analyses, coupled with functional and animal studies, have led to better insights into possible pathogenic mechanisms underlying ET. These genetic studies may guide the future development of genetic testing and counselling, and specific, pathogenesis-targeted, therapeutic strategies.
Implementation of a phase plate for the generation of homogeneous focal-spot intensity distributions at the high-energy short-pulse laser facility PHELIX
Authors: Bagnoud V. , Hornung J. , Afshari M. , Eisenbarth U. , Brabetz C. , Major Z. , Zielbauer B.
Published: December 2019

We propose and demonstrate the use of random phase plates (RPPs) for high-energy sub-picosecond lasers. Contrarily to previous work related to nanosecond lasers, an RPP poses technical challenges with ultrashort-pulse lasers. Here, we implement the RPP near the beginning of the amplifier and image-relay it throughout the laser amplifier. With this, we obtain a uniform intensity distribution in the focus over an area 1600 times the diffraction limit. This method shows no significant drawbacks for the laser and it has been implemented at the PHELIX laser facility where it is now available for users.
Effects of daily treatment with acid suppressants for stress ulcer prophylaxis on risk of ventilator-associated events
Authors: Li Xiaojuan , Klompas Michael , Menchaca John T. , Young Jessica G.
Published: December 2019

Objective:

To estimate the effects of continuous daily treatment with different acid suppressants on the risk of ventilator-associated events in critically ill patients.

Design:

Retrospective cohort study.

Patients:

Adult critically ill patients who underwent mechanical ventilation for ≥3 days during an inpatient admission between January 2006 and December 2014.

Methods:

We estimated the 30-day cumulative risk ratios (RRs) for ventilator-associated events comparing daily proton pump inhibitor (PPI) versus daily histamine-2-receptor antagonist (H2RA) strategies while controlling for time-fixed and time-varying confounding and accounting for competing events.

Results:

Of 6,133 patients, on ventilation day 3, 58.8% received H2RAs, 26.1% received PPIs, and 4.1% received sucralfate. Patients frequently changed treatment throughout follow-up. Among 4,595 patients receiving PPIs or H2RAs on day 3, we found no differences in risk estimates for ventilator mortality and extubation alive comparing daily PPI versus daily H2RA strategies: RR, mortality, 1.03 (95% CI, 0.89–1.22); extubation alive, 1.00 (95% CI, 0.96–1.03). We found similar results after accounting for PPI dose. For possible ventilator-associated pneumonia (PVAP) and infection-related ventilator-associated complication (IVAC), point estimates were larger, but the 95% CIs crossed 1.0: RR PVAP, 1.25 (95% CI, 0.80–1.94); IVAC, 0.89 (95% CI, 0.64–1.17). The magnitude of effect estimates depended on PPI dose. The RR for PVAP, high-dose PPI versus H2RA, was 1.53 (95% CI, 0.82–2.51), and for low-dose PPI versus H2RA, the RR was 0.97 (95% CI, 0.47–1.63). For IVAC, high-dose PPI versus H2RA, the RR was 1.01 (95% CI, 0.66–1.42), and for low-dose PPI versus H2RA, the RR was 0.78 (95% CI, 0.50–1.11).

Conclusions:

We estimated no effect of daily PPI versus daily H2RA on risk of mortality or extubation alive in critically ill patients. Further investigation with larger samples is warranted for PVAP and IVAC.
Accuracy and reliability of electronic versus CDC surveillance criteria for non-ventilator hospital-acquired pneumonia
Authors: Batlle Haiyan Ramirez , Klompas Michael ,   for the CDC Prevention Epicenters Program
Published: December 2019

Nonventilator hospital-acquired pneumonia (NV-HAP) is one of the most common healthcare-associated infections, but most hospitals do not track it. We created a pilot electronic definition for NV-HAP and compared its accuracy to Centers for Disease Control and Prevention (CDC) criteria. Kappa values for the electronic definition and CDC criteria versus “true” pneumonia were similar: 0.40 and 0.47, respectively.
Dynamic simulations of Vatnajökull ice cap from 1980 to 2300
Authors: Schmidt Louise Steffensen , Ađalgeirsdóttir Guðfinna , Pálsson Finnur , Langen Peter L. , Guđmundsson Sverrir , Björnsson Helgi
Published: December 2019

Like most ice caps and glaciers worldwide, Icelandic glaciers are retreating in a warming climate. Here, the evolution of Vatnajökull ice cap, Iceland, from 1980 to 2300 is simulated by forcing the Parallel Ice Sheet Model (PISM) with output from Regional Climate Models (RCMs). For climate simulations of the recent past, HARMONIE-AROME reanalysis-forced simulations are used, while for future climate conditions, high-resolution (5.5 km) simulations from the RCM HIRHAM5 are used in addition to available CORDEX simulations (12 km). The glacier evolution is modelled using the RCP 4.5 and RCP 8.5 scenarios until 2100. To extend the time series, the 2081–2100 climate forcing is repeated until 2300. For RCP 4.5, the ice cap loses 31–64% of its volume and 13–37% of its area by 2300 depending on the used model forcing. For RCP 8.5, the volume decrease is 51–94% and the area decrease is 24–80% by 2300. In addition, the effect of elevation feedbacks is investigated by adding a precipitation and temperature lapse rate to the HIRHAM5 simulations. By 2300, the lapse rate runs have a 9–14% smaller volume and a 9–20% smaller area than the runs without a lapse rate correction.
EHRENFEUCHT-FRAÏSSÉ GAMES ON A CLASS OF SCATTERED LINEAR ORDERS
Authors: MWESIGYE FERESIANO , TRUSS JOHN KENNETH
Published: December 2019

Two structures A and B are n-equivalent if Player II has a winning strategy in the n-move Ehrenfeucht-Fraïssé game on A and B. In earlier articles we studied n-equivalence classes of ordinals and coloured ordinals. In this article we similarly treat a class of scattered order-types, focussing on monomials and sums of monomials in ω and its reverse ω*.
“Just Like AIDS”: Latinx Identity, HIV/AIDS, and the Problems and Possibilities of Analogy
Authors: CARROLL VICTORIA
Published: December 2019

In 2009, Residente, the lead singer of a well-known Latinx music group and newly appointed international ambassador for the Latino Commission on AIDS, likened Latinxs in the US to HIV/AIDS. Taking this fertile equivalence as a conceptual point of departure, this article tracks the pitfalls and possibilities of aligning these two positions, touching on the performativity of disgust, the transmission of brown affect, and economies of racialization and deracination via the exchange of viral matter. Building upon the reparative labour of critical mestizaje, which came to the fore of Latinx studies in the 1980s, I reimagine the potentiality of a “viral mestizaje,” a form of relatedness that allows for networks of intimacy, multiplicity, and reproduction that extend beyond heternormative coupling. What is at stake in the positioning of Latinxs as “just like AIDS”? What are the possibilities and problems of analogy?
POPLMark reloaded: Mechanizing proofs by logical relations
Authors: ABEL ANDREAS , ALLAIS GUILLAUME , HAMEER ALIYA , PIENTKA BRIGITTE , MOMIGLIANO ALBERTO , SCHÄFER STEVEN , STARK KATHRIN
Published: December 2019

We propose a new collection of benchmark problems in mechanizing the metatheory of programming languages, in order to compare and push the state of the art of proof assistants. In particular, we focus on proofs using logical relations (LRs) and propose establishing strong normalization of a simply typed calculus with a proof by Kripke-style LRs as a benchmark. We give a modern view of this well-understood problem by formulating our LR on well-typed terms. Using this case study, we share some of the lessons learned tackling this problem in different dependently typed proof environments. In particular, we consider the mechanization in Beluga, a proof environment that supports higher-order abstract syntax encodings and contrast it to the development and strategies used in general-purpose proof assistants such as Coq and Agda. The goal of this paper is to engage the community in discussions on what support in proof environments is needed to truly bring mechanized metatheory to the masses and engage said community in the crafting of future benchmarks.
Herbicide-resistant weeds in the Canadian prairies: 2012 to 2017
Authors: Beckie Hugh J. , Shirriff Scott W. , Leeson Julia Y. , Hall Linda M. , Harker K. Neil , Dokken-Bouchard Faye , Brenzil Clark A.
Published: December 2019

This report updates the incidence of herbicide-resistant (HR) weeds across western Canada from the last report covering 2007 to 2011. This third round of preharvest surveys was conducted in Saskatchewan in 2014 and 2015, Manitoba in 2016, and Alberta in 2017, totaling 798 randomly selected cropped fields across 28 million ha. In addition, we screened 1,108 weed seed samples submitted by prairie growers or industry between 2012 and 2016. Of 578 fields where wild oat seed was collected, 398 (69%) had an HR biotype: 62% acetyl-CoA carboxylase inhibitor (WSSA Group 1) resistant, 34% acetolactate synthase inhibitor (Group 2) resistant, and 27% Group 1+2 resistant (vs. 41%, 12%, and 8%, respectively, in the previous second-round surveys from 2007 to 2009). The sharp increase in Group 2 resistance is the result of reliance on this site of action to manage Group 1 resistance and the resultant increased selection pressure. There are no POST options to control Group 1+2–HR wild oat in wheat or barley. The rise of Group 2 resistance in green foxtail (11% of sampled fields) and yellow foxtail (17% of Manitoba fields), which was not detected in the previous survey round, parallels the results for wild oat resistance. Various Group 2–HR populations of broadleaf weeds were confirmed, with cleavers and field pennycress being most abundant. Results of submission-sample testing reflected survey results. Although not included in this study, a postharvest survey in Alberta in 2017 indicated widespread Groups 2, 4 (dicamba), and 9 (glyphosate) resistance in kochia and Group 2 resistance in Russian thistle. These surveys bring greater awareness of HR weeds to growers and land managers at local and regional levels, and highlight the urgency to preserve herbicide susceptibility in our key economic weed species.
How Personal and Social Selves Influence the Development of Children and Adolescents at School
Authors: Hannover Bettina , Zander Lysann
Published: December 2019

Abstract. How do different aspects of students' self-relate to their development at school? In educational psychology, this question has been examined essentially only in terms of the influence of the ability self-concept, a central part of the personal self. Starting with a literature review on why and how the ability self-concept impacts motivation and student outcomes, we argue that social selves – learners' knowledge about their group memberships and associated evaluations – have an impact, too. Students are more intrinsically motivated and more successful if they experience fit between learning environment and important self-aspects. Accordingly, we suggest a model according to which students try to increase fit by exerting primary control, i. e., by proactively changing the environment, with the self as agent. To that end (i) they mentally project the self as different from the actual self, with the mental self-projection serving as a self-evaluative standard and motiving behaviors aiming at its attainment, (ii) they choose behavioral options that allow for the enactment of important self-aspects, (iii) they choose interaction partners who share important self-aspects or are supportive of their behavioral enactment, and (iv) they switch between or prioritize different values, to best match affordances and constraints of the learning environment. If a student repeatedly fails to achieve fit through primary control, secondary control strategies are deployed, i. e., internal processes aimed at minimizing losses and saving resources for the pursuit of more attainable goals. To that end, students either disidentify with the learning environment or redefine their selves in a reactive manner, with, in many cases, detrimental effects on their academic outcomes. We hope to inspire educational psychologists to more systematically investigate the different self-aspects' impact on social and academic development of learners at school.
Sensitivity of Marine Heatwave Metrics to Ocean Model Resolution
Authors: Pilo Gabriela S. , Holbrook Neil J. , Kiss Andrew E. , Hogg Andrew McC.
Published: December 2019

Sustained extreme temperature events in the ocean, referred to as marine heatwaves (MHWs), generate substantial ecological, social, and economic impacts. Ocean models provide insights to the drivers, persistence, and dissipation of MHWs. However, the sensitivity of MHW metrics to ocean model resolution is unknown. Here, we analyze global MHW metrics in three configurations of a global ocean‐sea ice model at coarse (1°), eddy‐permitting (0.25°), and eddy‐rich (0.1°) resolutions. We show that all configurations qualitatively represent broad‐scale global patterns of MHWs. These simulated MHWs are, however, weaker, longer‐lasting, and less frequent than in observations. The 0.1° configuration, despite local biases, performs best both globally and regionally. Based on these results, model projections of future MHW metrics using coarse‐resolution models are expected to be biased toward weaker and less frequent MHWs, when compared with results using an eddy‐rich model.
Applying Information Theory and Bayesian Inference to Paleoenvironmental Interpretation
Authors: Li Haipeng , Plink‐Björklund Piret
Published: December 2019

Gathering and analyzing data in the most unbiased and reproducible fashion is crucial for successful scientific research. However, scientists are influenced by prior experiences and tend to introduce biases in data interpretation when solutions are nonunique. In Earth science, a key task is the reconstruction of paleoenvironmental conditions, which relies on measurable changes in certain attributes of the resultant landscapes or the sedimentary record. The attributes in use commonly have multiple explanations, which may result in biased interpretation. To mitigate the problem, we propose a general conceptual framework for linking the observed attribute changes to their possible causes based on Shannon's information theory. This framework further serves as a hypothesis generator. We then present a rigorous procedure for paleoenvironmental interpretation based on the multiple‐hypotheses method and Bayesian inference. Application examples illustrate the benefits of this procedure in paleoenvironmental reconstructions and in understanding environmental signal propagation through sediment routing systems.
Evidence of Overtone Interference in Fundamental‐Mode Rayleigh Wave Phase and Amplitude Measurements
Authors: Hariharan Anant , Dalton Colleen A. , Ma Zhitu , Ekström Göran
Published: December 2019

We present evidence that measurements of minor‐arc fundamental‐mode (FM) Rayleigh waves experience interference from major‐arc overtones, resulting in travel‐time and amplitude measurements oscillating along a ray path. The oscillations are present in synthetic seismograms generated in a 3‐D Earth model via SPECFEM3D_GLOBE and in a 1‐D Earth model by mode summation. The absence of oscillations in synthetics containing only the FM indicates that the oscillations originate from higher‐mode interference. This interference is present across multiple measurement techniques, including multi‐channel cross correlation, phase‐matched filtering, and cluster analysis. Experiments with 1‐D synthetics suggest that contamination from interference is largest at epicentral distances greater than around 120 degrees, where record sections of seismograms show the major‐arc overtones intersecting the minor‐arc FM Rayleigh wave. The short wavelength of the interference pattern means it is only observable with dense station spacing and high data quality, which may explain why it has not, to our knowledge, been previously recognized. We show the interference is visible in real data. Its overall impact on phase‐velocity maps is probably minor due to many measurements from shorter path lengths less prone to interference bias. However, phase‐velocity maps constructed only from measurements at epicentral distances prone to interference exhibit significant noise and poor agreement with maps from measurements that include all path lengths; the issue is especially problematic for approaches that use differential travel times between nearby stations. Accounting for interference may diminish noise in measurements and improve the accuracy of images of the upper mantle.
Alternate Trait‐Based Leaf Respiration Schemes Evaluated at Ecosystem‐Scale Through Carbon Optimization Modeling and Canopy Property Data
Authors: Thomas R.Q. , Williams M. , Cavaleri M.A. , Exbrayat J.‐F. , Smallman T.L. , Street L.E.
Published: December 2019

Leaf maintenance respiration (Rleaf,m) is a major but poorly understood component of the terrestrial carbon cycle (C). Earth systems models (ESMs) use simple sub‐models relating Rleaf,m to leaf traits, applied at canopy scale. Rleaf,m models vary depending on which leaf N traits they incorporate (e.g., mass or area based) and the form of relationship (linear or nonlinear). To simulate vegetation responses to global change, some ESMs include ecological optimization to identify canopy structures that maximize net C accumulation. However, the implications for optimization of using alternate leaf‐scale empirical Rleaf,m models are undetermined. Here we combine alternate well‐known empirical models of Rleaf,m with a process model of canopy photosynthesis. We quantify how net canopy exports of C vary with leaf area index (LAI) and total canopy N (TCN). Using data from tropical and arctic canopies, we show that estimates of canopy Rleaf,m vary widely among the three models. Using an optimization framework, we show that the LAI and TCN values maximizing C export depends strongly on the Rleaf,m model used. No single model could match observed arctic and tropical LAI‐TCN patterns with predictions of optimal LAI‐TCN. We recommend caution in using leaf‐scale empirical models for components of ESMs at canopy‐scale. Rleaf,m models may produce reasonable results for a specified LAI, but, due to their varied representations of Rleaf,mfoliar N sensitivity, are associated with different and potentially unrealistic optimization dynamics at canopy scale. We recommend ESMs to be evaluated using response surfaces of canopy C export in LAI‐TCN space to understand and mitigate these risks.
Brain-age in midlife is associated with accelerated biological aging and cognitive decline in a longitudinal birth cohort
Authors: Elliott Maxwell L. , Belsky Daniel W. , Knodt Annchen R. , Ireland David , Melzer Tracy R. , Poulton Richie , Ramrakha Sandhya , Caspi Avshalom , Moffitt Terrie E. , Hariri Ahmad R.
Published: December 2019

An individual’s brainAGE is the difference between chronological age and age predicted from machine-learning models of brain-imaging data. BrainAGE has been proposed as a biomarker of age-related deterioration of the brain. Having an older brainAGE has been linked to Alzheimer’s, dementia, and mortality. However, these findings are largely based on cross-sectional associations which can confuse age differences with cohort differences. To illuminate the validity of brainAGE as a biomarker of accelerated brain aging, a study is needed of a large cohort all born in the same year who nevertheless vary on brainAGE. In the Dunedin Study, a population-representative 1972–73 birth cohort, we measured brainAGE at age 45 years, as well as the pace of biological aging and cognitive decline in longitudinal data from childhood to midlife (N = 869). In this cohort, all chronological age 45 years, brainAGE was measured reliably (ICC = 0.81) and ranged from 24 to 72 years. Those with older midlife brainAGEs tended to have poorer cognitive function in both adulthood and childhood, as well as impaired brain health at age 3. Furthermore, those with older brainAGEs had an accelerated pace of biological aging, older facial appearance, and early signs of cognitive decline from childhood to midlife. These findings help to validate brainAGE as a potential surrogate biomarker for midlife intervention studies that seek to measure dementia-prevention efforts in midlife. However, the findings also caution against the assumption that brainAGE scores represent only age-related deterioration of the brain as they may also index central nervous system variation present since childhood.
Disease-specific alteration of karyopherin-α subtype establishes feed-forward oncogenic signaling in head and neck squamous cell carcinoma
Authors: Hazawa Masaharu , Sakai Kie , Kobayashi Akiko , Yoshino Hironori , Iga Yoshihiro , Iwashima Yuki , Lim Kee Sing , Chih-Cheng Voon Dominic , Jiang Yan-Yi , Horike Shin-ichi , Lin De-Chen , Wong Richard W.
Published: December 2019

Nuclear import, mediated in part by karyopherin-α (KPNA)/importin-α subtypes, regulates transcription factor access to the genome and determines cell fate. However, the cancer-specific changes of KPNA subtypes and the relevancy in cancer biology remain largely unknown. Here, we report that KPNA4, encoding karyopherin-α4 (KPNA4), is exclusively amplified and overexpressed in head and neck of squamous cell carcinoma (HNSCC). Depletion of KPNA4 attenuated nuclear localization signal-dependent transport activity and suppressed malignant phenotypes and induced epidermal differentiation. Mechanistically, KPNA4-mediated nuclear transport of Ras-responsive element-binding protein (RREB1), which sustains Ras/ERK pathway signaling through repressing miR-143/145 expression. Notably, MAPK signaling enhanced trafficking activity of KPNA4 via phosphorylation of KPNA4 at Ser60. These data reveal that KPNA4 establishes a feed-forward cascade that potentiates Ras/ERK signaling in HNSCC.
Performance in delayed non-matching to sample task predicts the diagnosis of obsessive–compulsive disorder
Authors: Maatoug Redwan , Goff Benoît Le , Rotge Jean-Yves , Jaafari Nemat , Guillin Olivier , Millet Bruno
Published: December 2019

Electrical stimulation studies have recently evidenced the involvement of orbitofrontal cortex (OFC) in obsessive–compulsive disorder (OCD). In addition, lateral OFC is activated in healthy subjects during delayed non-matching-to-sample task (DNMS). In the present study, we hypothesized that OCD results from a specific defect of lateral OFC processing that can be evidenced via a DNMS task. To this end, we compared the DNMS performances of 20 OCD patients vs 20 demographically matched healthy controls. As predicted, our results showed that OCD patients performed worse than healthy controls at DNMS task. To test for the specificity of this behavioral impairment, we furthermore compared OCD patients and healthy subjects on a different task not involving directly the lateral OFC: the delayed match-to-sample task (DMS). As expected, OCD patients are more impaired for both the DNMS and the DMS task, compared with healthy subjects. Moreover, OCD patients tend statistically to perform worse for the DNMS task than for DMS task. Our results suggest the DNMS task specifically target the malfunctioning areas in OCD, such as the lateral OFC. In light of these results, lateral OFC should therefore be the focus of future therapeutic interventions.
New aspects of amino acid metabolism in cancer
Authors: Vettore Lisa , Westbrook Rebecca L. , Tennant Daniel A.
Published: December 2019

An abundant supply of amino acids is important for cancers to sustain their proliferative drive. Alongside their direct role as substrates for protein synthesis, they can have roles in energy generation, driving the synthesis of nucleosides and maintenance of cellular redox homoeostasis. As cancer cells exist within a complex and often nutrient-poor microenvironment, they sometimes exist as part of a metabolic community, forming relationships that can be both symbiotic and parasitic. Indeed, this is particularly evident in cancers that are auxotrophic for particular amino acids. This review discusses the stromal/cancer cell relationship, by using examples to illustrate a number of different ways in which cancer cells can rely on and contribute to their microenvironment – both as a stable network and in response to therapy. In addition, it examines situations when amino acid synthesis is driven through metabolic coupling to other reactions, and synthesis is in excess of the cancer cell’s proliferative demand. Finally, it highlights the understudied area of non-proteinogenic amino acids in cancer metabolism and their potential role.
Hypoxia and hyperglycaemia determine why some endometrial tumours fail to respond to metformin
Authors: Sivalingam Vanitha N. , Latif Ayşe , Kitson Sarah , McVey Rhona , Finegan Katherine G. , Marshall Kay , Lisanti Michael P. , Sotgia Federica , Stratford Ian J. , Crosbie Emma J.
Published: December 2019

Background

High expression of Ki67, a proliferation marker, is associated with reduced endometrial cancer-specific survival. Pre-surgical metformin reduces tumour Ki-67 expression in some women with endometrial cancer. Metformin’s anti-cancer activity may relate to effects on cellular energy metabolism. Since tumour hypoxia and glucose availability are major cellular redox determinants, we evaluated their role in endometrial cancer response to metformin.

Methods

Endometrial cancer biopsies from women treated with pre-surgical metformin were tested for the hypoxia markers, HIF-1α and CA-9. Endometrial cancer cell lines were treated with metformin in variable glucose concentrations in normoxia or hypoxia and cell viability, mitochondrial biogenesis, function and energy metabolism were assessed.

Results

In women treated with metformin (n = 28), Ki-67 response was lower in hypoxic tumours. Metformin showed minimal cytostatic effects towards Ishikawa and HEC1A cells in conventional medium (25 mM glucose). In low glucose (5.5 mM), a dose-dependent cytostatic effect was observed in normoxia but attenuated in hypoxia. Tumours treated with metformin showed increased mitochondrial mass (n = 25), while in cultured cells metformin decreased mitochondrial function. Metformin targets mitochondrial respiration, however, in hypoxic, high glucose conditions, there was a switch to glycolytic metabolism and decreased metformin response.

Conclusions

Understanding the metabolic adaptations of endometrial tumours may identify patients likely to derive clinical benefit from metformin.
ASCT2 (SLC1A5)-dependent glutamine uptake is involved in the progression of head and neck squamous cell carcinoma
Authors: Zhang Ze , Liu Ruoyan , Shuai Yanjie , Huang Yuting , Jin Rui , Wang Xudong , Luo Jingtao
Published: December 2019

Background

Glutamine is an abundant and versatile nutrient in cancer cells. Head and neck squamous cell carcinoma (HNSCC) was reported to be dependent on mainly glucose, not glutamine, for producing the energy required for survival and proliferation.

Methods

The roles of ASCT2 (SLC1A5) and associated glutamine metabolism were determined by the MTT, colony formation, glutamine uptake, intracellular glutathione, ROS detection, immunofluorescence, immunohistochemistry, and apoptosis enzyme-linked immunosorbent assays as well as animal studies.

Results

We found that glutamine is also critical for HNSCC. In this study, ASCT2, an amino acid transporter responsible for glutamine transport, in addition to LAT1 and GLS, is overexpressed in HNSCC and associated with poor survival. Using both in vivo and in vitro models, we found that knocking down ASCT2 by shRNAs or miR-137 or the combination of silencing ASCT2 and pharmacologically inhibiting SNAT2 via a small-molecule antagonist called V-9302 significantly suppressed intracellular glutamine levels and downstream glutamine metabolism, including glutathione production; these effects attenuated growth and proliferation, increased apoptosis and autophagy, and increased oxidative stress and mTORC1 pathway suppression in HNSCC. Additionally, silencing ASCT2 improved the response to cetuximab in HNSCC.

Conclusions

In summary, ASCT2-dependent glutamine uptake and subsequent glutamine metabolism are essential for HNSCC tumorigenesis, and the combination of glutamine uptake inhibitors and cetuximab presents a promising strategy for improving the outcomes of HNSCC patients.
Targeting aerobic glycolysis by dichloroacetate improves Newcastle disease virus-mediated viro-immunotherapy in hepatocellular carcinoma
Authors: Meng Gang , Li Binghua , Chen Anxian , Zheng Meihong , Xu Tiancheng , Zhang Hailin , Dong Jie , Wu Junhua , Yu Decai , Wei Jiwu
Published: December 2019

Background

Oncolytic viro-immunotherapy holds promise for cancer treatment. While immune activation can be robustly triggered by oncolytic viruses, negative feedback is often upregulated in the tumour microenvironment (TME). Lactate accumulation, signal transducer and activator of transcription 3 (STAT3) activation, indoleamine 2,3-dioxygenase 1 (IDO1) expression, and myeloid-derived suppressor cell (MDSC) infiltration coordinate to shape the immunosuppressive TME.

Methods

Representative hepatocellular carcinoma (HCC) cell lines and HCC-bearing mice were treated with oncolytic Newcastle disease virus (NDV), alone or in combination with dichloroacetate (DCA, a pyruvate dehydrogenase kinase (PDK) inhibitor).

Results

We found that infection with oncolytic NDV led to significant induction of the aforementioned suppressive factors. Interestingly, DCA significantly reduced lactate release, STAT3 activation, IDO1 upregulation, and MDSC infiltration in NDV-treated HCC. Consequently, DCA significantly enhanced the antitumour immune responses, leading to improved antitumour efficacy and prolonged survival in mouse models of ascitic and subcutaneous HCC. Furthermore, DCA increased NDV replication in a PDK-1-dependent manner in HCC.

Conclusions

Targeting aerobic glycolysis by DCA improves NDV-mediated viro-immunotherapy in HCC by mitigating immune negative feedback and promoting viral replication. These findings provide a rationale for targeting reprogrammed metabolism together with oncolytic virus-mediated viro-immunotherapy for HCC treatment.
Aconitase 2 inhibits the proliferation of MCF-7 cells promoting mitochondrial oxidative metabolism and ROS/FoxO1-mediated autophagic response
Authors: Ciccarone Fabio , Di Leo Luca , Lazzarino Giacomo , Maulucci Giuseppe , Di Giacinto Flavio , Tavazzi Barbara , Ciriolo Maria Rosa
Published: December 2019

Background

Deregulation of the tricarboxylic acid cycle (TCA) due to mutations in specific enzymes or defective aerobic metabolism is associated with tumour growth. Aconitase 2 (ACO2) participates in the TCA cycle by converting citrate to isocitrate, but no evident demonstrations of its involvement in cancer metabolism have been provided so far.

Methods

Biochemical assays coupled with molecular biology, in silico, and cellular tools were applied to circumstantiate the impact of ACO2 in the breast cancer cell line MCF-7 metabolism. Fluorescence lifetime imaging microscopy (FLIM) of NADH was used to corroborate the changes in bioenergetics.

Results

We showed that ACO2 levels are decreased in breast cancer cell lines and human tumour biopsies. We generated ACO2- overexpressing MCF-7 cells and employed comparative analyses to identify metabolic adaptations. We found that increased ACO2 expression impairs cell proliferation and commits cells to redirect pyruvate to mitochondria, which weakens Warburg-like bioenergetic features. We also demonstrated that the enhancement of oxidative metabolism was supported by mitochondrial biogenesis and FoxO1-mediated autophagy/mitophagy that sustains the increased ROS burst.

Conclusions

This work identifies ACO2 as a relevant gene in cancer metabolic rewiring of MCF-7 cells, promoting a different utilisation of pyruvate and revealing the potential metabolic vulnerability of ACO2-associated malignancies.