bluuebunny/crossref_metadata_2025 huggingface dataset:
Invasive green algae in a western Mediterranean Marine Protected Area: interaction of photophilous sponges with Caulerpa cylindracea
Authors: Manconi R. , Padiglia A. , Padedda B. M. , Pronzato R.
Published: March 2020

We report on the relationships between some conspicuous Mediterranean photophilous sponge species and Caulerpa cylindracea, a non-indigenous species. A diversification of defence strategies and behaviour is highlighted in target species belonging to different orders of Demospongiae from a western Mediterranean Marine Protected Area (NW Sardinian Sea). Caulerpa cylindracea displays a strongly invasive behaviour during body colonization of the Irciniidae Sarcotragus spinosulus and Ircinia retidermata (order Dictyoceratida). These sponges possess pre-adaptive defensive morpho-functional and physiological traits enabling them to partly withstand algal invasion. Also Aplysina aerophoba (order Verongiida) seems to be able to control colonization. Successful anti-Caulerpa strategies characterize the rarely affected Crambe crambe (order Poecilosclerida). Species-specific competitive strategies are displayed at different levels of body architecture, behaviour and physiology by native sponge species. The invasion patterns on sponges, the invasion dynamics in 2016–2017 and topographic distribution of C. cylindracea on S. spinosulus confirm this algal species as a threat, with potential long-term effects on sponge assemblages. Data suggest other kinds of poorly investigated synergic stressors affecting these habitat-forming species. Defence strategies of sponge species take the form of: (1) passive deterrence by morpho-functional pre-adaptive traits as growth form, biomass amount, surface traits, and microhabitat within the sponges' aquiferous system; (2) active physiological defence, whereby the morphology/anatomy of the sponge body is adapted to control invaders, by body remodelling and regenerative processes within the aquiferous system and at the sponge surface; (3) presumed active chemical defence by exudation processes of bioactive compounds.
Assessing anthelmintic resistance risk in the post-genomic era: a proof-of-concept study assessing the potential for widespread benzimidazole-resistant gastrointestinal nematodes in North American cattle and bison
Authors: Avramenko Russell W. , Redman Elizabeth M. , Windeyer Claire , Gilleard John S.
Published: March 2020

As genomic research continues to improve our understanding of the genetics of anthelmintic drug resistance, the revolution in DNA sequencing technologies will provide increasing opportunities for large-scale surveillance for the emergence of drug resistance. In most countries, parasite control in cattle and bison has mainly depended on pour-on macrocyclic lactone formulations resulting in widespread ivermectin resistance. Consequently, there is an increased interest in using benzimidazole drugs which have been used comparatively little in cattle and bison in recent years. This situation, together with our understanding of benzimidazole resistance genetics, provides a practical opportunity to use deep-amplicon sequencing to assess the risk of drug resistance emergence. In this paper, we use deep-amplicon sequencing to scan for those mutations in the isotype-1 β-tubulin gene previously associated with benzimidazole resistance in many trichostrongylid nematode species. We found that several of these mutations occur at low frequency in many cattle and bison parasite populations in North America, suggesting increased use of benzimidazole drugs in cattle has the potential to result in widespread emergence of resistance in multiple parasite species. This work illustrates a post-genomic approach to large-scale surveillance of early emergence of anthelmintic resistance in the field.
Why heaven doesn't make earth absolutely meaningless, just relatively
Authors: MAWSON T. J.
Published: March 2020

In this article, I seek charitably to develop an argument suggested by Thaddeus Metz. This is an argument against the view that it is consistent to hold that, while our lives may have some meaningfulness even if there is no heavenly afterlife awaiting us, if there is such an afterlife, they are even more meaningful, because heaven adds a potential infinity of meaningfulness. Having developed this argument on Metz's behalf, I criticize it. I conclude that – while throwing out a number of interesting ideas and possibilities along the way – no argument along Metz's lines can finally reach the conclusion aimed for.
CONTENT TARGETS WORK: A PRACTICAL EXAMPLE OF CHANGING BEHAVIOURS AND PROCESSES IN PROGRAMMING WOMEN COMPOSERS
Authors: Johnson Naomi , Dewey Matthew
Published: March 2020

In September 2015, ABC Classic set a target of 5 per cent women composers on air as the beginning of a push to combat serious gender imbalance in the works broadcast on the network. This target has gradually changed broadcast culture, encouraging content makers to champion women's music and allowing for major programming events and goals, and it has led to an increase of women composers broadcast from 2.2 per cent in 2015 to 9.9 per cent in the 2018/19 reporting cycle. This article examines our journey over this time, arguing for targets as a means to enact change and establish concrete outcomes. It explores the ways in which a target has encouraged us to consider gaps in the content offered along with new opportunities to present music by hitherto under-represented composers. It also reflects on the work ahead, acknowledging the ongoing importance of targets in moving towards better gender representation in classical music programming.
Biomarkers of appetite: is there a potential role for metabolomics?
Authors: Horner Katy , Hopkins Mark , Finlayson Graham , Gibbons Catherine , Brennan Lorraine
Published: March 2020

Knowing the biological signals associated with appetite control is crucial for understanding the regulation of food intake. Biomarkers of appetite have been defined as physiological measures that relate to subjective appetite ratings, measured food intake, or both. Several metabolites including amino acids, lipids and glucose were proposed as key molecules associated with appetite control over 60 years ago, and along with bile acids are all among possible appetite biomarker candidates. Additional metabolites that have been associated with appetite include endocannabinoids, lactate, cortisol and β-hydroxybutyrate. However, although appetite is a complex integrative process, studies often investigated a limited number of markers in isolation. Metabolomics involves the study of small molecules or metabolites present in biological samples such as urine or blood, and may present a powerful approach to further the understanding of appetite control. Using multiple analytical techniques allows the characterisation of molecules, such as carbohydrates, lipids, amino acids, bile acids and fatty acids. Metabolomics has proven successful in identifying markers of consumption of certain foods and biomarkers implicated in several diseases. However, it has been underexploited in appetite control or obesity. The aim of the present narrative review is to: (1) provide an overview of existing metabolites that have been identified in human biofluids and associated with appetite control; and (2) discuss the potential of metabolomics to deepen understanding of appetite control in humans.
Nonuniform language in technical writing: Detection and correction
Authors: Wang Weibo , Islam Aminul , Moh’d Abidalrahman , Soto Axel J. , Milios Evangelos E.
Published: March 2020

Technical writing in professional environments, such as user manual authoring, requires the use of uniform language. Nonuniform language refers to sentences in a technical document that are intended to have the same meaning within a similar context, but use different words or writing style. Addressing this nonuniformity problem requires the performance of two tasks. The first task, which we named nonuniform language detection (NLD), is detecting such sentences. We propose an NLD method that utilizes different similarity algorithms at lexical, syntactic, semantic and pragmatic levels. Different features are extracted and integrated by applying a machine learning classification method. The second task, which we named nonuniform language correction (NLC), is deciding which sentence among the detected ones is more appropriate for that context. To address this problem, we propose an NLC method that combines contraction removal, near-synonym choice, and text readability comparison. We tested our methods using smartphone user manuals. We finally compared our methods against state-of-the-art methods in paraphrase detection (for NLD) and against expert annotators (for both NLD and NLC). The experiments demonstrate that the proposed methods achieve performance that matches expert annotators.
Collaborative innovation blocs and antifragility
Authors: Elert Niklas , Henrekson Magnus
Published: March 2020

We present the theory of the collaborative innovation bloc (CIB), an evolving system of innovation within which activity takes place over time. We show how the application of the CIB perspective can help make institutional and evolutionary economics more concrete, relevant, and persuasive, especially regarding policy prescriptions. Such policy actions should strive to improve theantifragilityof CIBs and the economic system as a whole, thus enabling individual CIBs and the broader economic system to thrive when faced with adversity. With this in mind, we develop heuristics to evaluate CIB antifragility before using Sweden's economic and institutional evolution since the 1970s as a backdrop for identifying a set of institutional areas where reform can be undertaken to move in this direction.
Tea catechin role in decreasing the oxidation of dairy beverages containing linseed oil
Authors: Boroski Marcela , Giroux Hélène J. , Visentainer Jesui V. , Dubé Pascal , Desjardins Yves , Britten Michel
Published: March 2020

Abstract. Dairy beverages containing emulsified linseed oil is a suitable vehicle for delivering polyunsaturated fatty acids to consumers. However, these beverages are prone to oxidation. The purpose of this study was to evaluate the effect of adding various concentrations (0, 0.001, 0.01 and 0.1% (w/w)) of green tea extract (GTE) to dairy beverages (DB) containing linseed oil (2.0%, w/w), in order to inhibit lipid oxidation during storage at high temperature (50 °C) or under fluorescent light exposure. During storage, the concentration of catechin (C), epicatechin (EC) and epicatechin gallate (ECG) were significantly reduced ( P ≤ 0.05) and degradation rate was greater when the DB were exposed to light (C 35%, EC 74% and ECG 68%) as compared to high temperature (C 34%, EC 45% and ECG 49%). In DB without GTE, the conjugated dienes (CD) hydroperoxides concentration increased significantly ( P ≤ 0.05) from 23 mmol kg−1fat to 243 mmol kg−1fat under 6-day-light exposition, and to 83 mmol kg−1fat under 6-day-heat temperature. The addition of GTE significantly increased the antioxidant capacity of DB and reduced the formation of CD, propanal and hexanal, induced by light exposure or high temperature. GTE at 0.10% completely inhibited CD formation during the storage period and reduced propanal and hexanal concentrations below the threshold.
Adherence to healthy dietary pattern and risk of kidney disease: a systematic review and meta-analysis of observational studies
Authors: Soltani Sepideh , Jayedi Ahmad
Published: March 2020

Abstract. Epidemiological studies show that adherence to healthy dietary patterns may be associated with a lower risk of decline in kidney function. However, existing evidence has not been quantitatively gathered. Pertinent observational studies investigating the association of adherence to a healthy dietary pattern, either priori-defined dietary pattern/indices or data-driven dietary patterns, with risk of kidney disease in the general population were identified by searching Medline and Scopus databases to May 28, 2018. A random-effects meta-analysis was applied. The analysis included eight prospective cohorts (5734 cases among 569,688 participants) and five cross-sectional studies (1955 cases among 16,614 participants). Higher adherence to a healthy dietary pattern (either priori-defined or data-driven dietary patterns) was associated with a 28% lower risk of kidney disease in the analysis of prospective cohort studies (RR = 0.72, 95 % CI = 0.58, 0.86; I2 = 71%, n = 8). A subgroup analysis based on definition of healthy dietary pattern resulted in significant inverse association only in the subgroup of Dietary Approaches to Stop Hypertension dietary pattern (RR: 0.74, 95 % CI: 0.54, 0.93; I2 = 73%, n = 5). A dose-response analysis indicated a monotonic inverse association between adherence to the Dietary Approaches to Stop Hypertension dietary pattern with risk of kidney disease. A 32% lower risk was observed in the analysis of cross-sectional studies (OR: 0.68, 95 % CI: 0.53, 0.83, I2 = 0%, n = 5). The findings suggest that higher adherence to a healthy dietary pattern is associated with a lower risk of kidney disease.
A Comparison of Self-Harm Presentations to Emergency Services
Authors: Chartrand Hayley , Tefft Bruce , Sareen Jitender , Hiebert-Murphy Diane , Katz Laurence Y. , Kim Huntae , Bolton James M.
Published: March 2020

Abstract. Background: In the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, the distinction between nonsuicidal self-injury (NSSI) and suicide attempts (SA) is highlighted in the section of conditions for further study. Aims: The objective of this study was to examine the correlates of people who presented to emergency departments (ED) with NSSI compared with those who presented with SA and no self-harm or suicidal ideation (no SH or SI). Method: Data came from 4,772 presentations to ED of tertiary care hospitals in Manitoba, Canada, between January 2009 and June 2012. Chart reviews were conducted for presentations with NSSI ( n = 158), and a sample of SA ( n = 172) and no SH or SI ( n = 173). Results: NSSI was associated with borderline personality traits/disorders, previous history of SH, and aggression/impulsivity compared with no SH or SI. SA was associated with a lower likelihood of adjustment disorder ( OR = 0.58; 95 % CI [0.34, 0.99]) and previous history of NSSI ( OR = 0.30; 95 % CI [0.17, 0.53]) compared with NSSI. Limitations: A limitation of this study is its cross-sectional design. Conclusion: Given the distress associated with NSSI, the findings highlight the need for treatment plans that address all those who present to ED with SH regardless of intent.
A Sensitivity Study of Arctic Air‐Mass Transformation Using Large Eddy Simulation
Authors: Dimitrelos Antonios , Ekman Annica M.L. , Caballero Rodrigo , Savre Julien
Published: March 2020

Arctic air mass transformation is linked to the evolution of low‐level mixed‐phase clouds. These clouds can alter the structure of the boundary layer and modify the surface energy budget. In this study, we use three‐dimensional large eddy simulation and a bulk sea ice model to examine the lifecycle of clouds formed during wintertime advection of moist and warm air over sea ice, following a Lagrangian perspective. We investigate the stages of cloud formation, evolution, and decay. The results show that radiative cooling at the surface gives rise to fog formation which subsequently rises and transforms into a mixed‐phase cloud. In our baseline simulation, the cloud persists for about 5 days and increases the surface temperature by on average 17 °C. Sensitivity tests show that the lifetime of the cloud is sensitive to changes in the vapor supply at cloud top. This flux is mainly impacted by changes in the divergence rate; an imposed convergence decreases the lifetime to 2 days while an imposed large‐scale divergence increases the lifetime to more than 6 days. The largest difference in cloud radiative properties is found in the experiment with increased ice crystal number concentrations. In this case, the lifetime of the cloud is similar compared to baseline but the amount of liquid water is clearly depleted throughout the whole cloud sequence and the surface temperature is on average 6 °C cooler. The cloud condensation nuclei concentration has a weaker effect on the radiative properties and lifetime of the cloud.
Performance of Radiative Transfer Models in the Microwave Region
Authors: Moradi Isaac , Goldberg Mitchell , Brath Manfred , Ferraro Ralph , Buehler Stefan A. , Saunders Roger , Sun Ninghai
Published: March 2020

We compared two fast radiative transfer models, Community Radiative Transfer Model (CRTM) and Radiative Transfer for TIROS Operational Vertical Sounder (RTTOV), with the LBL model Atmospheric Radiative Transfer Simulator (ARTS). We used the measurements from Advanced Technology Microwave Sounder (ATMS) and the Global Precipitation Measurement Microwave Imager (GMI) for evaluation of the radiative transfer models. The models in comparison with the observations and each other performed very well with a mean difference less than 0.5 K for the temperature sounding channels operating near the oxygen absorption band at 60 GHz. There was a difference of up to 1 K among the models as well as compared with the observations for humidity sounding channels operating around water vapor absorption line at 183 GHz. The mean difference between the simulations and observations was up to 6 K for surface sensitive channels. Water vapor and surface sensitive channels also showed to be more sensitive than the temperature sounding channels to the spectroscopy models used to calculate the absorption coefficients. There was a small difference, less than 0.1 K, between brightness temperatures calculated using traditional boxcar and actual Sensor or Spectral Response Functions, except for a difference of 0.25 K for ATMS Channel 6. Double difference technique showed about 1 K difference between water vapor channels from ATMS instruments onboard N20 and National Polar‐orbiting Partnership (NPP). However, comparison of a new version of ATMS/NPP observations recently generated using an enhanced calibration algorithm with ATMS/N20 observations showed that the differences between the two instruments are less than 0.5 K after improving the ATMS/NPP calibration.
Study of SO2 Pollution in the Middle East Using MERRA‐2, CAMS Data Assimilation Products, and High‐Resolution WRF‐Chem Simulations
Authors: Ukhov A. , Mostamandi S. , Krotkov N. , Flemming J. , da Silva A. , Li C. , Fioletov V. , McLinden C. , Anisimov A. , Alshehri Y. M. , Stenchikov G.
Published: March 2020

Oil recovery, power generation, water desalination, gas flaring, and traffic are the main contributors to SO emissions in the Middle East (ME). Satellite observations suggest that the traditional emission inventories do not account for multiple SO emission sources in the ME. This study aims to evaluate the most frequently used SO emission data sets over the ME by comparing high‐resolution regional model simulations and meteorology/chemistry assimilation products, MERRA‐2 and CAMS, with satellite and available ground‐based air‐quality observations. Here, we employ the WRF‐Chem‐3.7.1 regional meteorology‐chemistry model and conduct simulations for the period 2015–2016 with 10 km grid spacing using HTAP‐2.2 emission data sets and the new OMI‐HTAP data, which is based on the combination of the near‐surface SO emissions taken from the HTAP‐2.2 inventory with strong (>30 kt/year) SO point sources obtained from the satellite Ozone Monitoring Instrument (OMI) observations. We find that conventional emission inventories (EDGAR‐4.2, MACCity, and HTAP‐2.2) have uncertainties in the location and magnitude of SO sources in the ME and significantly underestimate SO emissions in the Arabian Gulf. The WRF‐Chem, run in conjunction with the new OMI‐HTAP emissions, improves comparisons between the satellite and ground‐based SO observations. Our simulations show that SO surface concentrations in Jeddah and Riyadh frequently exceed European air‐quality limits. The ME generates about 10% of global anthropogenic SO emissions, on par with India. Therefore, the development of effective emission controls and improvement of air‐quality monitoring in the ME are urgently needed.
Evidence for Late Quaternary Deformation Along Crowleys Ridge, New Madrid Seismic Zone
Authors: Thompson Jobe Jessica A. , Gold Ryan D. , Briggs Richard W. , Williams Robert A. , Stephenson William J. , Delano Jaime E. , Shah Anjana , Minsley Burke
Published: March 2020

The New Madrid seismic zone has been the source of multiple major (M ~7.0–7.5) earthquakes in the past 2 ka, yet the surface expression of recent deformation remains ambiguous. Crowleys Ridge, a linear ridge trending north‐south for 300+ km through the Mississippi Embayment, has been interpreted as either a fault‐bounded uplift or a nontectonic erosional remnant. New and previously published seismic reflection and shallow resistivity data show discontinuities at the ridge margins in Plio‐Pleistocene strata, yet the timing of most recent faulting and the lateral extent of these faults remain unknown. To assess Pleistocene‐to‐recent tectonic activity of Crowleys Ridge, we perform landscape‐scale geomorphic analyses, such as relief, slope, hypsometry, and drainage basin shape, on a 10‐m digital elevation model (DEM). North‐to‐south variations in geomorphic indices indicate Pleistocene‐to‐recent tectonic uplift of the southern ridge. Moreover, mapping on a <1‐m lidar‐derived DEM reveals scarps on late Pleistocene geomorphic surfaces. The scarps are primarily located along the southern ridge, trend parallel to the ridge margin discontinuously for 0.1–1 km, and vertically offset <56 ka surfaces 0.4 m with up to 6 m of tilting. These landscape‐scale patterns and scarps, integrated with discontinuities in the seismic reflection and resistivity data, provide evidence of low‐rate (<0.2 mm/year) late Quaternary tectonic activity along the southern segment of Crowleys Ridge. The interpretations agree with recent tectonic models suggesting southern Crowleys Ridge is a compressional step over in a right‐lateral fault system within the Reelfoot Rift.
Deformational Temperatures Across the Lesser Himalayan Sequence in Eastern Bhutan and Their Implications for the Deformation History of the Main Central Thrust
Authors: Grujic Djordje , Ashley Kyle T. , Coble Matthew A. , Coutand Isabelle , Kellett Dawn A. , Larson Kyle P. , Whipp David M. , Gao Min , Whynot Nicholas
Published: March 2020

We postulate that the inverted metamorphic sequence in the Lesser Himalayan Sequence of the Himalayan orogen is a finite product of its deformation and temperature history. To explain the formation of this inverted metamorphic sequence across the Lesser Himalayan Sequence with a focus on the Main Central Thrust (MCT) in eastern Bhutan, we determined the metamorphic peak temperatures by Raman spectroscopy of carbonaceous material and established the deformation temperatures by Ti‐in‐quartz thermobarometry and quartz c axis textures. These data were combined with thermochronology, including new and published 40Ar/39Ar ages of muscovite and published apatite fission track, and apatite and zircon (U‐Th)/He ages. To obtain accurate metamorphic, deformation, and closure temperatures of thermochronological systems, pressures and cooling rates for the period of interest were derived by inverse modeling of multiple thermochronological data sets, and temperatures were determined by iterative calculations. The Raman spectroscopy of carbonaceous material results indicate two temperature sequences separated by a thrust. In the external sequence, peak temperatures are constant across the structural strike, consistent with the observed hinterland‐dipping duplex system. In the internal temperature sequence associated with the MCT shear zone, each geothermometer yields an apparent inverted temperature gradient although with different temperature ranges, and all temperatures appear to be retrograde. These observations are consistent with the quartz microfabrics. Further, all thermochronometers indicate upward younging across the MCT. We interpret our data as a composite peak and deformation temperature sequence that formed successively and reflects the broadening and narrowing of the MCT shear zone in which the ductile deformation lasted until ~11 Ma.
Advances in targeted therapy for malignant lymphoma
Authors: Wang Li , Qin Wei , Huo Yu-Jia , Li Xiao , Shi Qing , Rasko John E. J. , Janin Anne , Zhao Wei-Li
Published: March 2020

The incidence of lymphoma has gradually increased over previous decades, and it ranks among the ten most prevalent cancers worldwide. With the development of targeted therapeutic strategies, though a subset of lymphoma patients has become curable, the treatment of refractory and relapsed diseases remains challenging. Many efforts have been made to explore new targets and to develop corresponding therapies. In addition to novel antibodies targeting surface antigens and small molecular inhibitors targeting oncogenic signaling pathways and tumor suppressors, immune checkpoint inhibitors and chimeric antigen receptor T-cells have been rapidly developed to target the tumor microenvironment. Although these targeted agents have shown great success in treating lymphoma patients, adverse events should be noted. The selection of the most suitable candidates, optimal dosage, and effective combinations warrant further investigation. In this review, we systematically outlined the advances in targeted therapy for malignant lymphoma, providing a clinical rationale for mechanism-based lymphoma treatment in the era of precision medicine.
Regulation of cancer stem cell properties, angiogenesis, and vasculogenic mimicry by miR-450a-5p/SOX2 axis in colorectal cancer
Authors: Chen Jiaxuan , Chen Shengyuan , Zhuo Linghao , Zhu Yin , Zheng Haoxuan
Published: March 2020

Growing evidence indicates that a small number of cancer cells express stem cell markers and possess stem cell-like properties that promote malignant progression. Sex-determining region Y-box2 (SOX2) is a stem cell transcription factor essential for maintaining the properties of cancer stem cell (CSC). As CSC properties have been associated with angiogenesis and vasculogenic mimicry (VM), we aimed to comprehensively investigate whether SOX2 regulates CSC properties, angiogenesis, and VM in colorectal carcinoma (CRC) and its potential mechanism in this study. For this study, sphere formation assay, flow cytometry, cell survival analysis, tube formation, 3D culture, immunoblot, mouse model, and luciferase reporter assay were performed in vivo and in vitro. Expressions of SOX2 and miR-450a-5p in CRC tissue samples were examined through immunohistochemistry. First, the expression of SOX2 was not only associated with poor differentiation and prognosis but also promoted angiogenesis and VM. Knockdown of SOX2 ceased stemness properties, angiogenesis, and VM, along with decreased expression of CD133, CD31, and VE-cadherin as observed in functional experiments. Downregulation of SOX2 was found to inhibit tumorigenesis in vivo. Second, miR-450a-5p suppressed the expression of SOX2 by targeting its 3’UTR region directly and hence restrained SOX2-induced CSC properties, angiogenesis, and VM. Moreover, SOX2 overexpression preserved the miR-450a-5p-induced inhibition of CRC properties, angiogenesis, and VM. Finally, clinical samples exhibited a negative correlation between miR-450a-5p and SOX2. Patients with higher SOX2 and lower miR-450a-5p expressions had a poorer prognosis than patients with inverse expressions. Conclusively, we elucidated a unique mechanism of miR-450a-5p-SOX2 axis in the regulation of stemness, angiogenesis, and VM, which may act as a potential therapeutic practice in CRC.
Evolution and function of interleukin-4 receptor signaling in adaptive immunity and neutrophils
Authors: Heeb Lukas E. M. , Egholm Cecilie , Boyman Onur
Published: March 2020

The cytokines interleukin (IL)-4 and IL-13, signaling via the IL-4 receptor (IL-4R), orchestrate type 2 immunity to helminth infections and toxins. Activation of epithelial and myeloid cells, and a transient neutrophils influx initiates type 2 immune responses, which are dominated by basophils, eosinophils, mast cells, B cell immunoglobulin E production, and type 2 T helper and T follicular helper cells. Interestingly, IL-4 and IL-13 can curtail chemotaxis and several effector functions of neutrophils in mice and humans. This inhibitory role of IL-4 and IL-13 probably developed to limit tissue damage by neutrophils during type 2 immunity where a “weep and sweep” response aims at expulsion and decreased fecundity, instead of killing, of macroparasites. Here, we review when IL-4R signaling cytokines appeared during evolution relative to neutrophils and adaptive immunity. Neutrophil-like granular phagocytes were present in invertebrates throughout the bilaterian clade, but we were unable to find data on IL-4, IL-13, or their receptors in invertebrates. Conversely, vertebrates had both adaptive immunity and IL-4, IL-13, and IL-4Rs, suggesting that type 2 cytokines evolved together with adaptive immunity. Further studies are necessary to determine whether IL-4R signaling in neutrophils was established simultaneously with the appearance of adaptive immunity or later.
An andesitic source for Jack Hills zircon supports onset of plate tectonics in the Hadean
Authors: Turner Simon , Wilde Simon , Wörner Gerhard , Schaefer Bruce , Lai Yi-Jen
Published: March 2020

The composition and origin of Earth’s early crust remains hotly debated. Here we use partition coefficients to invert the trace element composition of 4.3–3.3 Gyr Jack Hills zircons to calculate the composition of the melts from which they crystallised. Using this approach, the average SiO2 content of these melts was 59 ± 6 wt. % with Th/Nb, Dy/Yb and Sr/Y ratios of 2.7 ± 1.9, 0.9 ± 0.2 and 1.6 ± 0.7, respectively. Such features strongly indicate that the protolith for the Jack Hills zircons was not an intra-plate mafic rock, nor a TTG (tondjhemite-tonalite-granodiorite) or a Sudbury-like impact melt. Instead, the inferred equilibrium melts are much more similar to andesites formed in modern subduction settings. We find no evidence for any secular variation between 4.3 and 3.3 Gyr implying little change in the composition or tectonic affinity of the Earth’s early crust from the Hadean to Mesoarchaean.
Heterogeneous photoredox flow chemistry for the scalable organosynthesis of fine chemicals
Authors: Yang Can , Li Run , Zhang Kai A. I. , Lin Wei , Landfester Katharina , Wang Xinchen
Published: March 2020

Large-scale photochemical synthesis of high value chemicals under mild conditions is an ideal method of green chemical production. However, a scalable photocatalytic process has been barely reported due to the costly preparation, low stability of photosensitizers and critical reaction conditions required for classical photocatalysts. Here, we report the merging of flow chemistry with heterogeneous photoredox catalysis for the facile production of high value compounds in a continuous flow reactor with visible light at room temperature in air. In the flow reactor system, polymeric carbon nitrides, which are cheap, sustainable and stable heterogeneous photocatalysts, are immobilized onto glass beads and fibers, demonstrating a highly flexible construction possibility for devices of the photocatalytic materials. As an example of the production of high value chemicals, important chemical structures such as cyclobutanes, which are basic building blocks for many pharmaceutical compounds, like magnosalin, are synthesized in flow with high catalytic efficiency and stability.
Polymer brush hypersurface photolithography
Authors: Carbonell Carlos , Valles Daniel , Wong Alexa M. , Carlini Andrea S. , Touve Mollie A. , Korpanty Joanna , Gianneschi Nathan C. , Braunschweig Adam B.
Published: March 2020

Polymer brush patterns have a central role in established and emerging research disciplines, from microarrays and smart surfaces to tissue engineering. The properties of these patterned surfaces are dependent on monomer composition, polymer height, and brush distribution across the surface. No current lithographic method, however, is capable of adjusting each of these variables independently and with micrometer-scale resolution. Here we report a technique termed Polymer Brush Hypersurface Photolithography, which produces polymeric pixels by combining a digital micromirror device (DMD), an air-free reaction chamber, and microfluidics to independently control monomer composition and polymer height of each pixel. The printer capabilities are demonstrated by preparing patterns from combinatorial polymer and block copolymer brushes. Images from polymeric pixels are created using the light reflected from a DMD to photochemically initiate atom-transfer radical polymerization from initiators immobilized on Si/SiO2 wafers. Patterning is combined with high-throughput analysis of grafted-from polymerization kinetics, accelerating reaction discovery, and optimization of polymer coatings.
Liquid-liquid phase separation and extracellular multivalent interactions in the tale of galectin-3
Authors: Chiu Yi-Ping , Sun Yung-Chen , Qiu De-Chen , Lin Yu-Hao , Chen Yin-Quan , Kuo Jean-Cheng , Huang Jie-rong
Published: March 2020

Liquid-liquid phase separation (LLPS) explains many intracellular activities, but its role in extracellular functions has not been studied to the same extent. Here we report how LLPS mediates the extracellular function of galectin-3, the only monomeric member of the galectin family. The mechanism through which galectin-3 agglutinates (acting as a “bridge” to aggregate glycosylated molecules) is largely unknown. Our data show that its N-terminal domain (NTD) undergoes LLPS driven by interactions between its aromatic residues (two tryptophans and 10 tyrosines). Our lipopolysaccharide (LPS) micelle model shows that the NTDs form multiple weak interactions to other galectin-3 and then aggregate LPS micelles. Aggregation is reversed when interactions between the LPS and the carbohydrate recognition domains are blocked by lactose. The proposed mechanism explains many of galectin-3’s functions and suggests that the aromatic residues in the NTD are interesting drug design targets.
Prioritizing disease and trait causal variants at the TNFAIP3 locus using functional and genomic features
Authors: Ray John P. , de Boer Carl G. , Fulco Charles P. , Lareau Caleb A. , Kanai Masahiro , Ulirsch Jacob C. , Tewhey Ryan , Ludwig Leif S. , Reilly Steven K. , Bergman Drew T. , Engreitz Jesse M. , Issner Robbyn , Finucane Hilary K. , Lander Eric S. , Regev Aviv , Hacohen Nir
Published: March 2020

Genome-wide association studies have associated thousands of genetic variants with complex traits and diseases, but pinpointing the causal variant(s) among those in tight linkage disequilibrium with each associated variant remains a major challenge. Here, we use seven experimental assays to characterize all common variants at the multiple disease-associated TNFAIP3 locus in five disease-relevant immune cell lines, based on a set of features related to regulatory potential. Trait/disease-associated variants are enriched among SNPs prioritized based on either: (1) residing within CRISPRi-sensitive regulatory regions, or (2) localizing in a chromatin accessible region while displaying allele-specific reporter activity. Of the 15 trait/disease-associated haplotypes at TNFAIP3, 9 have at least one variant meeting one or both of these criteria, 5 of which are further supported by genetic fine-mapping. Our work provides a comprehensive strategy to characterize genetic variation at important disease-associated loci, and aids in the effort to identify trait causal genetic variants.
Transforming solid-state precipitates via excess vacancies
Authors: Bourgeois Laure , Zhang Yong , Zhang Zezhong , Chen Yiqiang , Medhekar Nikhil V.
Published: March 2020

Many phase transformations associated with solid-state precipitation look structurally simple, yet, inexplicably, take place with great difficulty. A classic case of difficult phase transformations is the nucleation of strengthening precipitates in high-strength lightweight aluminium alloys. Here, using a combination of atomic-scale imaging, simulations and classical nucleation theory calculations, we investigate the nucleation of the strengthening phase θ′ onto a template structure in the aluminium-copper alloy system. We show that this transformation can be promoted in samples exhibiting at least one nanoscale dimension, with extremely high nucleation rates for the strengthening phase as well as for an unexpected phase. This template-directed solid-state nucleation pathway is enabled by the large influx of surface vacancies that results from heating a nanoscale solid. Template-directed nucleation is replicated in a bulk alloy as well as under electron irradiation, implying that this difficult transformation can be facilitated under the general condition of sustained excess vacancy concentrations.
Major antigenic site B of human influenza H3N2 viruses has an evolving local fitness landscape
Authors: Wu Nicholas C. , Otwinowski Jakub , Thompson Andrew J. , Nycholat Corwin M. , Nourmohammad Armita , Wilson Ian A.
Published: March 2020

Antigenic drift of influenza virus hemagglutinin (HA) is enabled by facile evolvability. However, HA antigenic site B, which has become immunodominant in recent human H3N2 influenza viruses, is also evolutionarily constrained by its involvement in receptor binding. Here, we employ deep mutational scanning to probe the local fitness landscape of HA antigenic site B in six different human H3N2 strains spanning from 1968 to 2016. We observe that the fitness landscape of HA antigenic site B can be very different between strains. Sequence variants that exhibit high fitness in one strain can be deleterious in another, indicating that the evolutionary constraints of antigenic site B have changed over time. Structural analysis suggests that the local fitness landscape of antigenic site B can be reshaped by natural mutations via modulation of the receptor-binding mode. Overall, these findings elucidate how influenza virus continues to explore new antigenic space despite strong functional constraints.
Global lake thermal regions shift under climate change
Authors: Maberly Stephen C. , O’Donnell Ruth A. , Woolway R. Iestyn , Cutler Mark E. J. , Gong Mengyi , Jones Ian D. , Merchant Christopher J. , Miller Claire A. , Politi Eirini , Scott E. Marian , Thackeray Stephen J. , Tyler Andrew N.
Published: March 2020

Water temperature is critical for the ecology of lakes. However, the ability to predict its spatial and seasonal variation is constrained by the lack of a thermal classification system. Here we define lake thermal regions using objective analysis of seasonal surface temperature dynamics from satellite observations. Nine lake thermal regions are identified that mapped robustly and largely contiguously globally, even for small lakes. The regions differed from other global patterns, and so provide unique information. Using a lake model forced by 21st century climate projections, we found that 12%, 27% and 66% of lakes will change to a lower latitude thermal region by 2080–2099 for low, medium and high greenhouse gas concentration trajectories (Representative Concentration Pathways 2.6, 6.0 and 8.5) respectively. Under the worst-case scenario, a 79% reduction in the number of lakes in the northernmost thermal region is projected. This thermal region framework can facilitate the global scaling of lake-research.
Organotypic human skin culture models constructed with senescent fibroblasts show hallmarks of skin aging
Authors: Weinmüllner Regina , Zbiral Barbara , Becirovic Adnan , Stelzer Elena Maria , Nagelreiter Fabian , Schosserer Markus , Lämmermann Ingo , Liendl Lisa , Lang Magdalena , Terlecki-Zaniewicz Lucia , Andriotis Orestis , Mildner Michael , Golabi Bahar , Waidhofer-Söllner Petra , Schedle Karl , Emsenhuber Gerhard , Thurner Philipp J. , Tschachler Erwin , Gruber Florian , Grillari Johannes
Published: March 2020

Skin aging is driven by intrinsic and extrinsic factors impacting on skin functionality with progressive age. One factor of this multifaceted process is cellular senescence, as it has recently been identified to contribute to a declining tissue functionality in old age. In the skin, senescent cells have been found to markedly accumulate with age, and thus might impact directly on skin characteristics. Especially the switch from young, extracellular matrix-building fibroblasts to a senescence-associated secretory phenotype (SASP) could alter the microenvironment in the skin drastically and therefore promote skin aging. In order to study the influence of senescence in human skin, 3D organotypic cultures are a well-suited model system. However, only few “aged” skin- equivalent (SE) models are available, requiring complex and long-term experimental setups. Here, we adapted a previously published full-thickness SE model by seeding increasing ratios of stress-induced premature senescent versus normal fibroblasts into the collagen matrix, terming these SE “senoskin”. Immunohistochemistry stainings revealed a shift in the balance between proliferation (Ki67) and differentiation (Keratin 10 and Filaggrin) of keratinocytes within our senoskin equivalents, as well as partial impairment of skin barrier function and changed surface properties. Monitoring of cytokine levels of known SASP factors confirmedly showed an upregulation in 2D cultures of senescent cells and at the time of seeding into the skin equivalent. Surprisingly, we find a blunted response of cytokines in the senoskin equivalent over time during 3D differentiation.
Melting of charge order in the low-temperature state of an electronic ferroelectric-like system
Authors: Hassan Nora M. , Thirunavukkuarasu Komalavalli , Lu Zhengguang , Smirnov Dmitry , Zhilyaeva Elena I. , Torunova Svetlana , Lyubovskaya Rimma N. , Drichko Natalia
Published: March 2020

Strong electronic interactions can drive a system into a state with a symmetry breaking. Lattice frustration or competing interactions tend to prevent symmetry breaking, leading to quantum disordered phases. In spin systems frustration can produce a spin liquid state. Frustration of a charge degree of freedom also can result in various exotic states, however, experimental data on these effects is scarce. In this work we demonstrate how in a Mott insulator on a weakly anisotropic triangular lattice a charge ordered state melts on cooling down to low temperatures. Raman scattering spectroscopy finds that $$\kappa$$
κ
-(BEDT-TTF)$${}_{2}$$

2

Hg(SCN)$${}_{2}$$

2

Cl enters an insulating “dipole solid” state at $$T=30\,{\mathrm{K}}$$

T
=
30

K

, but below $$T=15\,{\mathrm{K}}$$

T
=
15

K

the order melts, while preserving the insulating energy gap. Based on these observations, we suggest a phase diagram relevant to other quantum paraelectric materials.
Manipulating long-lived topological surface photovoltage in bulk-insulating topological insulators Bi2Se3 and Bi2Te3
Authors: Ciocys Samuel , Morimoto Takahiro , Mori Ryo , Gotlieb Kenneth , Hussain Zahid , Analytis James G. , Moore Joel E. , Lanzara Alessandra
Published: March 2020

The appearance of topologically protected spin-momentum locked surface states in topological insulators gives rise to robust room temperature spin currents making them ideal candidates for the realization of spintronic devices. New methods are needed to access and manipulate such currents with timescales that are compatible with modern electronics. Here we reveal that an optically induced long-lived (~10 ns), spin-polarized surface state excitation in topological insulators can be easily tuned in both magnitude and duration. Time-resolved angle-resolved photoemission spectroscopy, together with a quantitative model, reveals the ideal conditions for a surface photovoltage in two different topological insulators. Our model predicts that the reported effects are an intrinsic property of topological insulators, as long as the chemical potential falls within the band gap. This work demonstrates that persistent excited topological surface states are photon-accessible and easily tuned in both magnitude and duration, merging photonics- and spintronics-based devices in the same material.
Impact of cardiac interoception cues and confidence on voluntary decisions to make or withhold action in an intentional inhibition task
Authors: Rae Charlotte L. , Ahmad Aysha , Larsson Dennis E. O. , Silva Marta , Praag Cassandra D. Gould van , Garfinkel Sarah N. , Critchley Hugo D.
Published: March 2020

Interoceptive signals concerning the internal physiological state of the body influence motivational feelings and action decisions. Cardiovascular arousal may facilitate inhibition to mitigate risks of impulsive actions. Baroreceptor discharge at ventricular systole underpins afferent signalling of cardiovascular arousal. In a modified Go/NoGo task, decisions to make or withhold actions on ‘Choose’ trials were not influenced by cardiac phase, nor individual differences in heart rate variability. However, cardiac interoceptive awareness and insight predicted how frequently participants chose to act, and their speed of action: Participants with better awareness and insight tended to withhold actions and respond slower, while those with poorer awareness and insight tended to execute actions and respond faster. Moreover, self-reported trait urgency correlated negatively with intentional inhibition rates. These findings suggest that lower insight into bodily signals is linked to urges to move the body, putatively by engendering noisier sensory input into motor decision processes eliciting reactive behaviour.
Author Correction: Vision-related quality of life and symptom perception change over time in newly-diagnosed primary open angle glaucoma patients
Authors: Riva Ivano , Legramandi Lorenzo , Rulli Eliana , Konstas Anastasios G. , Katsanos Andreas , Oddone Francesco , Weinreb Robert N. , Quaranta Luciano ,   The Italian Study Group on QoL in Glaucoma*, Varano L. , Carchedi T. , Talarico S. , Frezzotti P. , Parravano F. , Motolese I. , Bagaglia S. A. , Rossi G. C. M. , Lateri S. , Bossolesi L. , Carmassi L. , Rolle T. , Piccini R. , Ratiglia R. , Rossi A. , Gandolfi S. , Tagliavini V. , Ungaro N. , Fossarello M. , Cuccu A. , Zucca I. , Uva M. , Bonacci E. , Cardarella G. , Tognetto D. , Vattovani O. , Vallon P. , Iannacone F. , Fontana L. , Marchi S. , Manni G. L. , Jannetta D. , Roberti G. , Rossetti L. , Maggiolo E. , Oneta O. , Sborgia C. , Cantatore F. , Mastropasqua L. , Agnifili L. , Campos E. , Gizzi C. , Giannaccare G. , Pucci V. , Cassamali M. , Costagliola C. , Traverso C. , Scotto R. , Musolino M. , Landi L. , Bagnis A.
Published: March 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.