bluuebunny/crossref_metadata_2025 huggingface dataset:
What Do Language Disorders Reveal about Brain–Language Relationships? From Classic Models to Network Approaches
Authors: Dronkers Nina F. , Ivanova Maria V. , Baldo Juliana V.
Published: December 2017

Studies of language disorders have shaped our understanding of brain–language relationships over the last two centuries. This article provides a review of this research and how our thinking has changed over the years regarding how the brain processes language. In the 19th century, a series of famous case studies linked distinct speech and language functions to specific portions of the left hemisphere of the brain, regions that later came to be known as Broca’s and Wernicke’s areas. One hundred years later, the emergence of new brain imaging tools allowed for the visualization of brain injuriesin vivothat ushered in a new era of brain-behavior research and greatly expanded our understanding of the neural processes of language. Toward the end of the 20th century, sophisticated neuroimaging approaches allowed for the visualization of both structural and functional brain activity associated with language processing in both healthy individuals and in those with language disturbance. More recently, language is thought to be mediated by a much broader expanse of neural networks that covers a large number of cortical and subcortical regions and their interconnecting fiber pathways. Injury to both grey and white matter has been seen to affect the complexities of language in unique ways that have altered how we think about brain–language relationships. The findings that support this paradigm shift are described here along with the methodologies that helped to discover them, with some final thoughts on future directions, techniques, and treatment interventions for those with communication impairments. (JINS, 2017,23, 741–754)
Current nut recommendation practices differ between health professionals in New Zealand
Authors: Brown Rachel C , Gray Andrew R , Yong Lee Ching , Chisholm Alex , Leong Sook Ling , Tey Siew Ling
Published: December 2017

Objective

Despite evidence linking regular nut consumption with reduced chronic disease risk, population-level intakes remain low. Research suggests nut-promoting advice from doctors facilitates regular nut consumption. However, there is no information on current nut recommendation practices of health professionals. The aim of the present study was to examine the advice provided by health professionals regarding nut consumption.

Design

In this cross-sectional study, participants were invited to complete a survey including questions about their nut recommendation practices.

Setting

New Zealand (NZ).

Subjects

The NZ Electoral Roll was used to identify dietitians, general practitioners and practice nurses.

Results

In total 318 dietitians, 292 general practitioners and 149 practice nurses responded. Dietitians were more likely (82·7 %) to recommend patients increase consumption of nuts than general practitioners (55·5 %) and practice nurses (63·1 %; both P<0·001). The most popular nuts recommended were almonds, Brazil nuts and walnuts, with most health professionals recommending raw nuts. The most common recommendation for frequency of consumption by dietitians and practice nurses was to eat nuts every day, while general practitioners most frequently recommended 2–4 times weekly, although not statistically significantly different between professions. Dietitians recommended a significantly greater amount of nuts (median 30 g/d) than both general practitioners and practice nurses (20 g/d; both P<0·001).

Conclusions

Dietitians were most likely to recommend consumption of nuts in accordance with current guidelines, but there are opportunities to improve the adoption of nut consumption recommendations for all professions. This may be a viable strategy for increasing population-level nut intakes to reduce chronic disease.
Optimism and quality of life in patients with heart failure
Authors: Kraai I.H. , Vermeulen K.M. , Hillege H.L. , Jaarsma T. , Hoekstra T.
Published: December 2017

Objectives

Health-related quality of life (HR-QoL) of patients with heart failure (HF) is low despite the aim of HF treatment to improve HR-QoL. To date, most studies have focused on medical and physical factors in relation to HR-QoL, few data are available on the role of emotional factors such as dispositional optimism. This study examines the prevalence of optimism and pessimism in HF patients and investigates how optimism and pessimism are associated with different patient characteristics and HR-QoL.

Methods

Dispositional optimism was assessed in 86 HF patients (mean age 70 ± 9 years, 28% female, mean left ventricular ejection fraction 33%) with the Revised Life Orientation Test (LOT-R). HR-QoL was assessed with the Minnesota Living with Heart Failure Questionnaire and the EuroQol.

Results

The (mean ± SD) total score on the LOT-R was 14.6 ± 2.9 (theoretical range 0–24) and the scores on the subscales optimism and pessimism were 8.1 ± 1.9 and 5.5 ± 2.5, respectively. Higher age was related to more optimism (r = 0.22, p < 0.05), and optimism was associated with higher generic HR-QoL (B = 0.04, p < 0.05).

Significance of results

The association found between optimism and generic HR-QoL of HF patients can lead to promising strategies to improve HF patients’ HR-QoL, particularly because the literature has indicated that optimism is a modifiable condition.
Managing grazing lands to improve soils and promote climate change adaptation and mitigation: a global synthesis
Authors: DeLonge Marcia , Basche Andrea
Published: December 2017

The potential to improve soils to help farmers and ranchers adapt to and mitigate climate change has generated significant enthusiasm. Within this discussion, grasslands have surfaced as being particularly important, due to their geographic range, their capacity to store substantial quantities of carbon relative to cultivated croplands and their potential role in mitigating droughts and floods. However, leveraging grasslands for climate change mitigation and adaptation will require a better understanding of how farmers and ranchers who rely on them for their livelihoods can improve management and related outcomes. To investigate opportunities for such improvements, we conducted a meta-analysis of field experiments that investigated how soil water infiltration rates are affected by a range of management options: adding complexity to grazing patterns, reducing stocking rates or extended rest from grazing. Further, to explore the relationships between observed changes in soil water infiltration and soil carbon, we identified papers that reported data on both metrics. We found that in 81.9% of all cases, responses of infiltration rates to identified management treatments (response ratios) were above zero, with infiltration rates increasing by 59.3 ± 7.3%. Mean response ratios from unique management categories were not significantly different, although the effect of extended rest (67.9 ± 8.5%,n= 140 from 31 experiments) was slightly higher than from reducing stocking rates (42.0 ± 10.8%;n= 63 from 17 experiments) or adding complexity (34.0 ± 14.1%,n= 17 from 11 experiments). We did not find a significant effect of several other variables, including treatment duration, mean annual precipitation or soil texture; however, analysis of aridity indices suggested that grazing management may have a slightly larger effect in more humid environments. Within our database, we found that 42% of complexity studies, 41% of stocking rate studies and 29% of extended rest studies also reported at least some measure of soil carbon. Within the subset of cases where both infiltration rates and carbon were reported, response ratios were largely positive for both variables (at least 64% of cases had positive mean response ratios in all management categories). Overall, our findings reveal that a variety of management strategies have the potential to improve soil water infiltration rates, with possible benefits for soil carbon as well. However, we identified a shortage of well-replicated and detailed experiments in all grazing management categories, and call for additional research of both soil water and soil carbon properties for these critical agroecosystems.
Prisoners’ objects: The collection of the International Red Cross and Red Crescent Museum
Authors: Mayou Roger
Published: December 2017

The International Red Cross and Red Crescent Museum has a unique collection of prisoners’ objects – items made by conflict-related detainees and given to International Committee of the Red Cross (ICRC) delegates who, in keeping with the ICRC's mandate under the Geneva Conventions, were visiting the prisons.
The Empathic Process and Misconceptions that Lead to Burnout in Healthcare Professionals
Authors: Villacieros Marta , Olmos Ricardo , Bermejo José Carlos
Published: December 2017

Empathy has been identified as a relevant variable in order to predict burnout in healthcare professionals. In addition, assertiveness and self-esteem have been considered relevant variables to develop empathic capacity. In the other hand, misconceptions surrounding empathy constitute a risk factor for burnout. Two adult samples (N = 252 and N = 275) were used to explore and confirm the underlying structure of two questionnaires. The Exercise of Process of Empathy (EPE) scale (18 items) confirmatory factor analysis including 5 dimensions (cognitive and emotional comprehension, attention, clarity and assertiveness), showed reasonable goodness- of-fit indices χ2(130) = 269.63, p < .001; RMSEA = .069 90% CI [0.058 – 0.079]; CFI = .965; TLI = .959. Alpha coefficient resulted .848. Common Misconceptions (EH) of empathy scale (16 items) confirmatory factor analysis, including 3 dimensions (feeling, confluence and character misconceptions) also obtained reasonable goodness-of-fit indices χ2(101) = 250.59, p < .001; RMSEA = .075 90% CI [0.063 – 0.087]; CFI = .952; TLI = .943. Alpha coefficient for Character resulted .727 (5 items), for Confluence .764 (5 items) and for Feeling .822 (6 items). The SEM model’s R2 resulted .303, being EH (misconceptions) a risk factor (b* = .171), EPE (empathy process) a protection factor (b* = –.183). The model partially explains how misconceptions empathy process and self-esteem (b* = –.334) relate to burnout syndrome in healthcare professionals; what is more, it heralds a potential means to prevent it.
Teachers’ Perceived Disruption at School and Related Variables from Teachers and School Functioning
Authors: Martínez Fernández María Belén , Chacón Gómez José C. , Martín Babarro Javier , Díaz-Aguado Jalón María José , Martínez Arias Rosario
Published: December 2017

This study explores variables related to teachers’ perception of disruption at school as a function of teachers (sense of personal accomplishment, professional disengagement and depersonalization and emotional exhaustion) and school (overall school management and quality of school rules) factors. Using a questionnaire regarding school climate, data from 4,055 teachers across 187 high schools were analyzed. Hierarchical linear modeling was applied and the results indicate that, taken separately, significant individual teacher predictors (Model 1) explain 26% (95% CI [.23, .29]) of the variability of the perceived disruption, especially depersonalization and emotional exhaustion. Contextual school variables (Model 2) explained 15% (95% CI [.12, .18]) of variance in teachers’ perceived disruption, with a significant negative relationship with the quality of rules. Model 3 included the above factors plus interactions between the emotional exhaustion and depersonalization variables and school indicators (30% of variance explained; 95% CI [.26, .33]). The results indicated the existence of a moderating effect for the quality of school rules, so that fair and properly-applied rules in the school context may be associated with a decrease in the relationship between depersonalization and emotional exhaustion and perceived disruption.
Reliability and Validity of Nonsymbolic and Symbolic Comparison Tasks in School-Aged Children
Authors: Castro Danilka , Estévez Nancy , Gómez David , Dartnell Pablo Ricardo
Published: December 2017

Basic numerical processing has been regularly assessed using numerical nonsymbolic and symbolic comparison tasks. It has been assumed that these tasks index similar underlying processes. However, the evidence concerning the reliability and convergent validity across different versions of these tasks is inconclusive. We explored the reliability and convergent validity between two numerical comparison tasks (nonsymbolic vs. symbolic) in school-aged children. The relations between performance in both tasks and mental arithmetic were described and a developmental trajectories’ analysis was also conducted. The influence of verbal and visuospatial working memory processes and age was controlled for in the analyses. Results show significant reliability (p < .001) between Block 1 and 2 for nonsymbolic task (global adjusted RT (adjRT): r = .78, global efficiency measures (EMs): r = .74) and, for symbolic task (adjRT: r = .86, EMs: r = .86). Also, significant convergent validity between tasks (p < .001) for both adjRT (r = .71) and EMs (r = .70) were found after controlling for working memory and age. Finally, it was found the relationship between nonsymbolic and symbolic efficiencies varies across the sample’s age range. Overall, these findings suggest both tasks index the same underlying cognitive architecture and are appropriate to explore the Approximate Number System (ANS) characteristics. The evidence supports the central role of ANS in arithmetic efficiency and suggests there are differences across the age range assessed, concerning the extent to which efficiency in nonsymbolic and symbolic tasks reflects ANS acuity.
Cajal, Psychologist of Science
Authors: Anaya-Reig Nuria , Romo Manuela
Published: December 2017

This paper presents abundant empirical evidence to support the view that Santiago Ramón y Cajal was a pioneer of the emerging Psychology of Science discipline. Narrative analysis of his autobiography (Recollections of my Life) and some of his unspecialized works (Advice for a Young Investigator, The World from an Eighty-Year-Old’s Point of View, and Café Chats) revealed that the Spanish histologist’s interest in the psychology of scientists was part and parcel of a high-level, intellectual self-regulation strategy he applied on his path to success. This research led him to document various psychological conclusions about scientists in writing, so as to encourage, guide, and facilitate the work of junior researchers. Current knowledge of the Psychology of Science has confirmed many of the Nobel laureate’s observations about psychosocial aspects of scientists, scientific reasoning, and creativity.
Insecticide Seed Treatments as Safeners to Drift Rates of Herbicides in Soybean and Grain Sorghum
Authors: Steppig Nicholas R. , Norsworthy Jason K. , Scott Robert C. , Lorenz Gus M.
Published: December 2017

Previous research has shown that some insecticide seed treatments provide safening effects in rice following exposure to low rates of the herbicides glyphosate and imazethapyr. However, no research has been conducted to determine whether a similar effect may be seen in soybean or grain sorghum, two important rotational crops across the Midsouth. To evaluate the potential safening effects of insecticide seed treatments in these two crops, field trials were conducted in Marianna, AR, in 2015 and 2016, and near Colt, AR, in 2016. In soybean, glyphosate, glufosinate, 2,4-D, dicamba, halosulfuron, mesotrione, tembotrione, and propanil were applied at low rates to simulate drift events, in combination with the insecticide seed treatments thiamethoxam and clothianidin at labeled rates. In grain sorghum, glyphosate, imazethapyr, and quizalofop were applied at low rates in combination with the insecticide seed treatments thiamethoxam, clothianidin, and imidacloprid at labeled rates. Injury reduction was seen at 1 site-year for glyphosate, glufosinate, 2,4-D, dicamba, mesotrione, and tembotrione, and at 2 of 3 site-years for halosulfuron. At 1 site-year, the safening in halosulfuron resulted in increases in both crop height and yield. In grain sorghum, reducing injury via seed treatments was generally more successful. All three herbicides applied in sorghum displayed instances of injury reduction when seed treatments were used at 1 or more site-years, including reducing injury upward of 40% in the case of quizalofop+clothianidin at Marianna in 2016. For 2 site-years, injury reduction through the use of insecticides resulted in increases in crop height and grain yield in grain sorghum compared with no insecticide use. Although the degree of safening seen varied depending on site-year in both crops, growers who use insecticide seed treatments on an annual basis may expect to see a safening effect from drift events of most herbicides evaluated in both soybean and grain sorghum.
HIV-1-associated inflammation and antiretroviral therapy regulate astrocyte endoplasmic reticulum stress responses
Authors: Nooka Shruthi , Ghorpade Anuja
Published: December 2017

Antiretroviral (ARV) therapy (ART) has effectively suppressed the incidence of human immunodeficiency virus (HIV)-associated dementia in HIV-1 positive individuals. However, the prevalence of more subtle forms of neurocognitive dysfunction continues to escalate. Recently, endoplasmic reticulum (ER) stress has been linked to many neurological diseases; yet, its role in HIV/neuroAIDS remains largely unexplored. Furthermore, upregulation of astrocyte elevated gene-1 (AEG-1), a novel HIV-1 inducible gene, along with ER stress markers in a Huntington’s disease model, suggests a possible role in HIV-associated ER stress. The current study is focused on unfolded protein responses (UPRs) and AEG-1 regulation in primary human astrocytes exposed to HIV-associated neurocognitive disorders (HAND)-relevant stimuli (HIV-1 virions, inflammation and ARV drugs). Interleukin (IL)-1β and the nucleoside reverse transcriptase inhibitor abacavir upregulated expression of ER stress markers in human astrocytes, including binding immunoglobulin protein (BiP), C/EBP homologous protein (CHOP), and calnexin. In addition, IL-1β activated all three well-known UPR pathways: protein kinase RNA-like ER kinase (PERK); activating transcription factor 6 (ATF-6); and inositol-requiring enzyme 1α (IRE1α). AEG-1 upregulation correlated to ER stress and demonstrated astrocyte AEG-1 interaction with the calcium-binding chaperone, calnexin. IL-1β and abacavir enhanced intracellular calcium signaling in astrocytes in the absence of extracellular calcium, illustrating ER-associated calcium release. Alternatively, calcium evoked in response to HAND-relevant stimuli led to mitochondrial permeability transition pore (mPTP) opening in human astrocytes. Importantly, IL-1β- and abacavir-induced UPR and mPTP opening were inhibited by the intracellular calcium chelation, indicating the critical role of calcium signaling in HAND-relevant ER stress in astrocytes. In summary, our study highlights that ARV drugs and IL-1β induced UPR, AEG-1 expression, intracellular calcium, and mitochondrial depolarization in astrocytes. This study uncovers astrocyte ER stress as a novel therapeutic target in the management of HIV-1-associated neurotoxicity and possibly in the treatment of neuroAIDS.
Soft electrostatic trapping in nanofluidics
Authors: Gerspach Michael A. , Mojarad Nassir , Sharma Deepika , Pfohl Thomas , Ekinci Yasin
Published: December 2017

Trapping and manipulation of nano-objects in solution are of great interest and have emerged in a plethora of fields spanning from soft condensed matter to biophysics and medical diagnostics. We report on establishing a nanofluidic system for reliable and contact-free trapping as well as manipulation of charged nano-objects using elastic polydimethylsiloxane (PDMS)-based materials. This trapping principle is based on electrostatic repulsion between charged nanofluidic walls and confined charged objects, called geometry-induced electrostatic (GIE) trapping. With gold nanoparticles as probes, we study the performance of the devices by measuring the stiffness and potential depths of the implemented traps, and compare the results with numerical simulations. When trapping 100 nm particles, we observe potential depths of up to Q≅24 kBT that provide stable trapping for many days. Taking advantage of the soft material properties of PDMS, we actively tune the trapping strength and potential depth by elastically reducing the device channel height, which boosts the potential depth up to Q~200 kBT, providing practically permanent contact-free trapping. Due to a high-throughput and low-cost fabrication process, ease of use, and excellent trapping performance, our method provides a reliable platform for research and applications in study and manipulation of single nano-objects in fluids.
The Kalanchoë genome provides insights into convergent evolution and building blocks of crassulacean acid metabolism
Authors: Yang Xiaohan , Hu Rongbin , Yin Hengfu , Jenkins Jerry , Shu Shengqiang , Tang Haibao , Liu Degao , Weighill Deborah A. , Cheol Yim Won , Ha Jungmin , Heyduk Karolina , Goodstein David M. , Guo Hao-Bo , Moseley Robert C. , Fitzek Elisabeth , Jawdy Sara , Zhang Zhihao , Xie Meng , Hartwell James , Grimwood Jane , Abraham Paul E. , Mewalal Ritesh , Beltrán Juan D. , Boxall Susanna F. , Dever Louisa V. , Palla Kaitlin J. , Albion Rebecca , Garcia Travis , Mayer Jesse A. , Don Lim Sung , Man Wai Ching , Peluso Paul , Van Buren Robert , De Paoli Henrique Cestari , Borland Anne M. , Guo Hong , Chen Jin-Gui , Muchero Wellington , Yin Yanbin , Jacobson Daniel A. , Tschaplinski Timothy J. , Hettich Robert L. , Ming Ray , Winter Klaus , Leebens-Mack James H. , Smith J. Andrew C. , Cushman John C. , Schmutz Jeremy , Tuskan Gerald A.
Published: December 2017

Crassulacean acid metabolism (CAM) is a water-use efficient adaptation of photosynthesis that has evolved independently many times in diverse lineages of flowering plants. We hypothesize that convergent evolution of protein sequence and temporal gene expression underpins the independent emergences of CAM from C3 photosynthesis. To test this hypothesis, we generate a de novo genome assembly and genome-wide transcript expression data for Kalanchoë fedtschenkoi, an obligate CAM species within the core eudicots with a relatively small genome (~260 Mb). Our comparative analyses identify signatures of convergence in protein sequence and re-scheduling of diel transcript expression of genes involved in nocturnal CO2 fixation, stomatal movement, heat tolerance, circadian clock, and carbohydrate metabolism in K. fedtschenkoi and other CAM species in comparison with non-CAM species. These findings provide new insights into molecular convergence and building blocks of CAM and will facilitate CAM-into-C3 photosynthesis engineering to enhance water-use efficiency in crops.
Spatial competition constrains resistance to targeted cancer therapy
Authors: Bacevic Katarina , Noble Robert , Soffar Ahmed , Wael Ammar Orchid , Boszonyik Benjamin , Prieto Susana , Vincent Charles , Hochberg Michael E. , Krasinska Liliana , Fisher Daniel
Published: December 2017

Adaptive therapy (AT) aims to control tumour burden by maintaining therapy-sensitive cells to exploit their competition with resistant cells. This relies on the assumption that resistant cells have impaired cellular fitness. Here, using a model of resistance to a pharmacological cyclin-dependent kinase inhibitor (CDKi), we show that this assumption is valid when competition between cells is spatially structured. We generate CDKi-resistant cancer cells and find that they have reduced proliferative fitness and stably rewired cell cycle control pathways. Low-dose CDKi outperforms high-dose CDKi in controlling tumour burden and resistance in tumour spheroids, but not in monolayer culture. Mathematical modelling indicates that tumour spatial structure amplifies the fitness penalty of resistant cells, and identifies their relative fitness as a critical determinant of the clinical benefit of AT. Our results justify further investigation of AT with kinase inhibitors.
CRISPR-Cpf1 mediates efficient homology-directed repair and temperature-controlled genome editing
Authors: Moreno-Mateos Miguel A. , Fernandez Juan P. , Rouet Romain , Vejnar Charles E. , Lane Maura A. , Mis Emily , Khokha Mustafa K. , Doudna Jennifer A. , Giraldez Antonio J.
Published: December 2017

Cpf1 is a novel class of CRISPR-Cas DNA endonucleases, with a wide range of activity across different eukaryotic systems. Yet, the underlying determinants of this variability are poorly understood. Here, we demonstrate that LbCpf1, but not AsCpf1, ribonucleoprotein complexes allow efficient mutagenesis in zebrafish and Xenopus. We show that temperature modulates Cpf1 activity by controlling its ability to access genomic DNA. This effect is stronger on AsCpf1, explaining its lower efficiency in ectothermic organisms. We capitalize on this property to show that temporal control of the temperature allows post-translational modulation of Cpf1-mediated genome editing. Finally, we determine that LbCpf1 significantly increases homology-directed repair in zebrafish, improving current approaches for targeted DNA integration in the genome. Together, we provide a molecular understanding of Cpf1 activity in vivo and establish Cpf1 as an efficient and inducible genome engineering tool across ectothermic species.
Atlantic deep water provenance decoupled from atmospheric CO2 concentration during the lukewarm interglacials
Authors: Howe Jacob N. W. , Piotrowski Alexander M.
Published: December 2017

Ice core records show that atmospheric CO2 concentrations and Antarctic temperature were lower during the ‘lukewarm interglacials’ from 800 to 430 ka than the subsequent five interglacials. These different interglacial ‘strengths’ have been hypothesised to be controlled by Antarctic overturning circulation. How these variations in Antarctic overturning relate to Northern Atlantic overturning circulation, a major driver of Northern Hemisphere climate, is uncertain. Here we present a high-resolution record of authigenic neodymium isotopes—a water mass tracer that is independent of biological processes—and use it to reconstruct Atlantic overturning circulation during the last 800 kyr. This record reveals a similar proportion of North Atlantic Deep Water during the ‘lukewarm interglacials’ and the more recent interglacials. This observation suggests that the provenance of deep water in the Atlantic Ocean can be decoupled from ventilation state of the Southern Ocean and consequently the atmospheric concentration of carbon dioxide.
Spectroscopic identification of active sites for the oxygen evolution reaction on iron-cobalt oxides
Authors: Smith Rodney D. L. , Pasquini Chiara , Loos Stefan , Chernev Petko , Klingan Katharina , Kubella Paul , Mohammadi Mohammad Reza , Gonzalez-Flores Diego , Dau Holger
Published: December 2017

The emergence of disordered metal oxides as electrocatalysts for the oxygen evolution reaction and reports of amorphization of crystalline materials during electrocatalysis reveal a need for robust structural models for this class of materials. Here we apply a combination of low-temperature X-ray absorption spectroscopy and time-resolved in situ X-ray absorption spectroelectrochemistry to analyze the structure and electrochemical properties of a series of disordered iron-cobalt oxides. We identify a composition-dependent distribution of di-μ-oxo bridged cobalt–cobalt, di-μ-oxo bridged cobalt–iron and corner-sharing cobalt structural motifs in the composition series. Comparison of the structural model with (spectro)electrochemical data reveals relationships across the composition series that enable unprecedented assignment of voltammetric redox processes to specific structural motifs. We confirm that oxygen evolution occurs at two distinct reaction sites, di-μ-oxo bridged cobalt–cobalt and di-μ-oxo bridged iron–cobalt sites, and identify direct and indirect modes-of-action for iron ions in the mixed-metal compositions.
Exceptional increase in the creep life of magnesium rare-earth alloys due to localized bond stiffening
Authors: Choudhuri Deep , Srinivasan Srivilliputhur G. , Gibson Mark A. , Zheng Yufeng , Jaeger David L. , Fraser Hamish L. , Banerjee Rajarshi
Published: December 2017

Several recent papers report spectacular, and unexpected, order of magnitude improvement in creep life of alloys upon adding small amounts of elements like zinc. This microalloying effect raises fundamental questions regarding creep deformation mechanisms. Here, using atomic-scale characterization and first principles calculations, we attribute the 600% increase in creep life in a prototypical Mg–rare earth (RE)–Zn alloy to multiple mechanisms caused by RE–Zn bonding—stabilization of a large volume fraction of strengthening precipitates on slip planes, increase in vacancy diffusion barrier, reduction in activated cross-slip, and enhancement of covalent character and bond strength around Zn solutes along the c-axis of Mg. We report that increased vacancy diffusion barrier, which correlates with the observed 25% increase in interplanar bond stiffness, primarily enhances the high-temperature creep life. Thus, we demonstrate that an approach of local, randomized tailoring of bond stiffness via microalloying enhances creep performance of alloys.
Author Correction: Tyrosine dephosphorylated cortactin downregulates contractility at the epithelial zonula adherens through SRGAP1
Authors: Liang Xuan , Budnar Srikanth , Gupta Shafali , Verma Suzie , Han Siew-Ping , Hill Michelle M. , Daly Roger J. , Parton Robert G. , Hamilton Nicholas A. , Gomez Guillermo A. , Yap Alpha S.
Published: December 2017

A correction to this article has been published and is linked from the HTML version of this article.
Author Correction: Identification of functional tetramolecular RNA G-quadruplexes derived from transfer RNAs
Authors: Lyons Shawn M. , Gudanis Dorota , Coyne Steven M. , Gdaniec Zofia , Ivanov Pavel
Published: December 2017

The original version of this Article contained an error in the spelling of the author Steven M. Coyne, which was incorrectly given as Stephen M. Coyne. This has now been corrected in both the PDF and HTML versions of the Article.
An assessment of the global impact of 21st century land use change on soil erosion
Authors: Borrelli Pasquale , Robinson David A. , Fleischer Larissa R. , Lugato Emanuele , Ballabio Cristiano , Alewell Christine , Meusburger Katrin , Modugno Sirio , Schütt Brigitta , Ferro Vito , Bagarello Vincenzo , Oost Kristof Van , Montanarella Luca , Panagos Panos
Published: December 2017

Human activity and related land use change are the primary cause of accelerated soil erosion, which has substantial implications for nutrient and carbon cycling, land productivity and in turn, worldwide socio-economic conditions. Here we present an unprecedentedly high resolution (250 × 250 m) global potential soil erosion model, using a combination of remote sensing, GIS modelling and census data. We challenge the previous annual soil erosion reference values as our estimate, of 35.9 Pg yr−1 of soil eroded in 2012, is at least two times lower. Moreover, we estimate the spatial and temporal effects of land use change between 2001 and 2012 and the potential offset of the global application of conservation practices. Our findings indicate a potential overall increase in global soil erosion driven by cropland expansion. The greatest increases are predicted to occur in Sub-Saharan Africa, South America and Southeast Asia. The least developed economies have been found to experience the highest estimates of soil erosion rates.
Semiconductor SERS enhancement enabled by oxygen incorporation
Authors: Zheng Zuhui , Cong Shan , Gong Wenbin , Xuan Jinnan , Li Guohui , Lu Weibang , Geng Fengxia , Zhao Zhigang
Published: December 2017

Semiconductor-based surface-enhanced Raman spectroscopy (SERS) substrates represent a new frontier in the field of SERS. However, the application of semiconductor materials as SERS substrates is still seriously impeded by their low SERS enhancement and inferior detection sensitivity, especially for non-metal-oxide semiconductor materials. Herein, we demonstrate a general oxygen incorporation-assisted strategy to magnify the semiconductor substrate–analyte molecule interaction, leading to significant increase in SERS enhancement for non-metal-oxide semiconductor materials. Oxygen incorporation in MoS2 even with trace concentrations can not only increase enhancement factors by up to 100,000-fold compared with oxygen-unincorporated samples but also endow MoS2 with low limit of detection below 10−7 M. Intriguingly, combined with the findings in previous studies, our present results indicate that both oxygen incorporation and extraction processes can result in SERS enhancement, probably due to the enhanced charge-transfer resonance as well as exciton resonance arising from the judicious control of oxygen admission in semiconductor substrate.
Hippocampal oxytocin receptors are necessary for discrimination of social stimuli
Authors: Raam Tara , McAvoy Kathleen M. , Besnard Antoine , Veenema Alexa H. , Sahay Amar
Published: December 2017

Oxytocin receptor (Oxtr) signaling in neural circuits mediating discrimination of social stimuli and affiliation or avoidance behavior is thought to guide social recognition. Remarkably, the physiological functions of Oxtrs in the hippocampus are not known. Here we demonstrate using genetic and pharmacological approaches that Oxtrs in the anterior dentate gyrus (aDG) and anterior CA2/CA3 (aCA2/CA3) of mice are necessary for discrimination of social, but not non-social, stimuli. Further, Oxtrs in aCA2/CA3 neurons recruit a population-based coding mechanism to mediate social stimuli discrimination. Optogenetic terminal-specific attenuation revealed a critical role for aCA2/CA3 outputs to posterior CA1 for discrimination of social stimuli. In contrast, aCA2/CA3 projections to aCA1 mediate discrimination of non-social stimuli. These studies identify a role for an aDG-CA2/CA3 axis of Oxtr expressing cells in discrimination of social stimuli and delineate a pathway relaying social memory computations in the anterior hippocampus to the posterior hippocampus to guide social recognition.
Crystal structure of an RNA-cleaving DNAzyme
Authors: Liu Hehua , Yu Xiang , Chen Yiqing , Zhang Jing , Wu Baixing , Zheng Lina , Haruehanroengra Phensinee , Wang Rui , Li Suhua , Lin Jinzhong , Li Jixi , Sheng Jia , Huang Zhen , Ma Jinbiao , Gan Jianhua
Published: December 2017

In addition to storage of genetic information, DNA can also catalyze various reactions. RNA-cleaving DNAzymes are the catalytic DNAs discovered the earliest, and they can cleave RNAs in a sequence-specific manner. Owing to their great potential in medical therapeutics, virus control, and gene silencing for disease treatments, RNA-cleaving DNAzymes have been extensively studied; however, the mechanistic understandings of their substrate recognition and catalysis remain elusive. Here, we report three catalytic form 8–17 DNAzyme crystal structures. 8–17 DNAzyme adopts a V-shape fold, and the Pb2+ cofactor is bound at the pre-organized pocket. The structures with Pb2+ and the modification at the cleavage site captured the pre-catalytic state of the RNA cleavage reaction, illustrating the unexpected Pb2+-accelerated catalysis, intrinsic tertiary interactions, and molecular kink at the active site. Our studies reveal that DNA is capable of forming a compacted structure and that the functionality-limited bio-polymer can have a novel solution for a functional need in catalysis.
Brain insulin resistance impairs hippocampal synaptic plasticity and memory by increasing GluA1 palmitoylation through FoxO3a
Authors: Spinelli Matteo , Fusco Salvatore , Mainardi Marco , Scala Federico , Natale Francesca , Lapenta Rosita , Mattera Andrea , Rinaudo Marco , Li Puma Domenica Donatella , Ripoli Cristian , Grassi Alfonso , D’Ascenzo Marcello , Grassi Claudio
Published: December 2017

High-fat diet (HFD) and metabolic diseases cause detrimental effects on hippocampal synaptic plasticity, learning, and memory through molecular mechanisms still poorly understood. Here, we demonstrate that HFD increases palmitic acid deposition in the hippocampus and induces hippocampal insulin resistance leading to FoxO3a-mediated overexpression of the palmitoyltransferase zDHHC3. The excess of palmitic acid along with higher zDHHC3 levels causes hyper-palmitoylation of AMPA glutamate receptor subunit GluA1, hindering its activity-dependent trafficking to the plasma membrane. Accordingly, AMPAR current amplitudes and, more importantly, their potentiation underlying synaptic plasticity were inhibited, as well as hippocampal-dependent memory. Hippocampus-specific silencing of Zdhhc3 and, interestingly enough, intranasal injection of the palmitoyltransferase inhibitor, 2-bromopalmitate, counteract GluA1 hyper-palmitoylation and restore synaptic plasticity and memory in HFD mice. Our data reveal a key role of FoxO3a/Zdhhc3/GluA1 axis in the HFD-dependent impairment of cognitive function and identify a novel mechanism underlying the cross talk between metabolic and cognitive disorders.
Immune stealth-driven O2 serotype prevalence and potential for therapeutic antibodies against multidrug resistant Klebsiella pneumoniae
Authors: Pennini Meghan E. , De Marco Anna , Pelletier Mark , Bonnell Jessica , Cvitkovic Romana , Beltramello Martina , Cameroni Elisabetta , Bianchi Siro , Zatta Fabrizia , Zhao Wei , Xiao Xiaodong , Camara Maria M. , DiGiandomenico Antonio , Semenova Elena , Lanzavecchia Antonio , Warrener Paul , Suzich JoAnn , Wang Qun , Corti Davide , Stover C. Kendall
Published: December 2017

Emerging multidrug-resistant bacteria are a challenge for modern medicine, but how these pathogens are so successful is not fully understood. Robust antibacterial vaccines have prevented and reduced resistance suggesting a pivotal role for immunity in deterring antibiotic resistance. Here, we show the increased prevalence ofKlebsiella pneumoniaelipopolysaccharide O2 serotype strains in all major drug resistance groups correlating with a paucity of anti-O2 antibodies in human B cell repertoires. We identify human monoclonal antibodies to O-antigens that are highly protective in mouse models of infection, even against heavily encapsulated strains. These antibodies, including a rare anti-O2 specific antibody, synergistically protect against drug-resistant strains in adjunctive therapy with meropenem, a standard-of-care antibiotic, confirming the importance of immune assistance in antibiotic therapy. These findings support an antibody-based immunotherapeutic strategy even for highly resistantK. pneumoniaeinfections, and underscore the effect humoral immunity has on evolving drug resistance.
HEB is required for the specification of fetal IL-17-producing γδ T cells
Authors: In Tracy S. H. , Trotman-Grant Ashton , Fahl Shawn , Chen Edward L. Y. , Zarin Payam , Moore Amanda J. , Wiest David L. , Zúñiga-Pflücker Juan Carlos , Anderson Michele K.
Published: December 2017

IL-17-producing γδ T (γδT17) cells are critical components of the innate immune system. However, the gene networks that control their development are unclear. Here we show that HEB (HeLa E-box binding protein, encoded byTcf12) is required for the generation of a newly defined subset of fetal-derived CD73−γδT17 cells. HEB is required in immature CD24+CD73−γδ T cells for the expression ofSox4,Sox13, andRorc, and these genes are repressed by acute expression of the HEB antagonist Id3. HEB-deficiency also affects mature CD73+γδ T cells, which are defective in RORγt expression and IL-17 production. Additionally, the fetal TCRγ chain repertoire is altered, and peripheral Vγ4 γδ T cells are mostly restricted to the IFNγ-producing phenotype in HEB-deficient mice. Therefore, our work identifies HEB-dependent pathways for the development of CD73+and CD73−γδT17 cells, and provides mechanistic evidence for control of the γδT17 gene network by HEB.
Different carotenoid conformations have distinct functions in light-harvesting regulation in plants
Authors: Liguori Nicoletta , Xu Pengqi , van Stokkum Ivo H.M. , van Oort Bart , Lu Yinghong , Karcher Daniel , Bock Ralph , Croce Roberta
Published: December 2017

To avoid photodamage plants regulate the amount of excitation energy in the membrane at the level of the light-harvesting complexes (LHCs). It has been proposed that the energy absorbed in excess is dissipated via protein conformational changes of individual LHCs. However, the exact quenching mechanism remains unclear. Here we study the mechanism of quenching in LHCs that bind a single carotenoid species and are constitutively in a dissipative conformation. Via femtosecond spectroscopy we resolve a number of carotenoid dark states, demonstrating that the carotenoid is bound to the complex in different conformations. Some of those states act as excitation energy donors for the chlorophylls, whereas others act as quenchers. Via in silico analysis we show that structural changes of carotenoids are expected in the LHC protein domains exposed to the chloroplast lumen, where acidification triggers photoprotection in vivo. We propose that structural changes of LHCs control the conformation of the carotenoids, thus permitting access to different dark states responsible for either light harvesting or photoprotection.
Redox-switchable breathing behavior in tetrathiafulvalene-based metal–organic frameworks
Authors: Su Jian , Yuan Shuai , Wang Hai-Ying , Huang Lan , Ge Jing-Yuan , Joseph Elizabeth , Qin Junsheng , Cagin Tahir , Zuo Jing-Lin , Zhou Hong-Cai
Published: December 2017

Metal–organic frameworks (MOFs) that respond to external stimuli such as guest molecules, temperature, or redox conditions are highly desirable. Herein, we coupled redox-switchable properties with breathing behavior induced by guest molecules in a single framework. Guided by topology, two flexible isomeric MOFs, compounds 1 and 2, with a formula of In(Me2NH2)(TTFTB), were constructed via a combination of [In(COO)4]− metal nodes and tetratopic tetrathiafulvalene-based linkers (TTFTB). The two compounds show different breathing behaviors upon the introduction of N2. Single-crystal X-ray diffraction, accompanied by molecular simulations, reveals that the breathing mechanism of 1 involves the bending of metal–ligand bonds and the sliding of interpenetrated frameworks, while 2 undergoes simple distortion of linkers. Reversible oxidation and reduction of TTF moieties changes the linker flexibility, which in turn switches the breathing behavior of 2. The redox-switchable breathing behavior can potentially be applied to the design of stimuli-responsive MOFs.
Viscosity jump in the lower mantle inferred from melting curves of ferropericlase
Authors: Deng Jie , Lee Kanani K. M.
Published: December 2017

Convection provides the mechanism behind plate tectonics, which allows oceanic lithosphere to be subducted into the mantle as “slabs” and new rock to be generated by volcanism. Stagnation of subducting slabs and deflection of rising plumes in Earth’s shallow lower mantle have been suggested to result from a viscosity increase at those depths. However, the mechanism for this increase remains elusive. Here, we examine the melting behavior in the MgO–FeO binary system at high pressures using the laser-heated diamond-anvil cell and show that the liquidus and solidus of (Mg
x
Fe1−x
)O ferropericlase (x = ~0.52–0.98), exhibit a local maximum at ~40 GPa, likely caused by the spin transition of iron. We calculate the relative viscosity profiles of ferropericlase using homologous temperature scaling and find that viscosity increases 10–100 times from ~750 km to ~1000–1250 km, with a smaller decrease at deeper depths, pointing to a single mechanism for slab stagnation and plume deflection.
Robust RNA-based in situ mutation detection delineates colorectal cancer subclonal evolution
Authors: Baker Ann-Marie , Huang Weini , Wang Xiao-Ming Mindy , Jansen Marnix , Ma Xiao-Jun , Kim Jeffrey , Anderson Courtney M. , Wu Xingyong , Pan Liuliu , Su Nan , Luo Yuling , Domingo Enric , Heide Timon , Sottoriva Andrea , Lewis Annabelle , Beggs Andrew D. , Wright Nicholas A. , Rodriguez-Justo Manuel , Park Emily , Tomlinson Ian , Graham Trevor A.
Published: December 2017

Intra-tumor heterogeneity (ITH) is a major underlying cause of therapy resistance and disease recurrence, and is a read-out of tumor growth. Current genetic ITH analysis methods do not preserve spatial context and may not detect rare subclones. Here, we address these shortfalls by developing and validating BaseScope—a novel mutation-specific RNA in situ hybridization assay. We target common point mutations in the BRAF, KRAS and PIK3CA oncogenes in archival colorectal cancer samples to precisely map the spatial and morphological context of mutant subclones. Computational modeling suggests that subclones must arise sufficiently early, or carry a considerable fitness advantage, to form large or spatially disparate subclones. Examples of putative treatment-resistant cells isolated in small topographical areas are observed. The BaseScope assay represents a significant technical advance for in situ mutation detection that provides new insight into tumor evolution, and could have ramifications for selecting patients for treatment.
Weekly self-measurement of FEV1 and PEF and its impact on ACQ (asthma control questionnaire)-scores: 12-week observational study with 76 patients
Authors: Werner Christoph Ulrich , Linde Klaus , Schäffner Julia , Storr Constanze , Schneider Antonius
Published: December 2017

The “Asthma Control Questionnaire” (ACQ) is a very common questionnaire for assessing asthma control. This study compares different ACQ versions in a self-monitoring program over a 12-week period combining them with patients' self-measurements of peak expiratory flow (PEF) and forced expiratory volume in one second (FEV1). The objective was to test the feasibility of FEV1-self-measurements and to compare ACQ versions regarding possible additional information given by lung function. In this prospective multicenter observational study 100 adult asthma patients, recruited at six family practices and two pulmologists' private practices in Germany, completed the ACQ weekly, performing self-measurements of PEF and FEV1. Seventy-six patients were included into final analysis with only 3% missing values. Scores for all ACQ versions improved significantly (all P-values < 0.05) with reductions of 32% for ACQ5, 31% for ACQ6, 22% for ACQ7-FEV1, and 21% for ACQ7-PEF with high Pearson’s correlation coefficients of all scores (r between 0.96 and 0.99). ACQ7-FEV1 scores were significantly higher than others. Separated courses of lung function parameters showed nearly no change, but ACQ5 and ACQ6 as scores for symptoms and reliever medication improved constantly. ACQ5 and ACQ6 revealed higher percentages of patients classified as “controlled” than ACQ7-scores. In conclusion, with only a few missing data points, our results suggest feasibility of FEV1-self-measurements. Courses of symptom-related and lung function-related ACQ items differ clearly. Our results support the GINA recommendations to consider symptoms and lung function separately. FEV1-self-measurements for research purposes may be included with the ACQ, but in clinical practice seem to measure a different domain to symptomatic asthma control.
Publisher Correction: Population scale data reveals the antidepressant effects of ketamine and other therapeutics approved for non-psychiatric indications
Authors: Cohen Isaac V. , Makunts Tigran , Atayee Rabia , Abagyan Ruben
Published: December 2017

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