bluuebunny/crossref_metadata_2025 huggingface dataset:
Dose–response relationship between dietary choline and lipid accumulation in pyloric enterocytes of Atlantic salmon (Salmo salar L.) in seawater
Authors: Hansen Anne K. G. , Kortner Trond M. , Denstadli Vegard , Måsøval Kjell , Björkhem Ingemar , Grav Hans J. , Krogdahl Åshild
Published: February 2020

Foamy, whitish appearance of the pyloric caeca, reflecting elevated lipid content, histologically visible as hypervacuolation, is frequently observed in Atlantic salmon fed high-plant diets. Lipid malabsorption syndrome (LMS) is suggested as term for the phenomenon. Earlier studies have shown that insufficient supply of phospholipids may cause similar symptoms. The objective of the present study was to strengthen knowledge on the role of choline, the key component of phosphatidylcholine, in development of LMS as well as finding the dietary required choline level in Atlantic salmon. A regression design was chosen to be able to estimate the dietary requirement level of choline, if found essential for the prevention of LMS. Atlantic salmon (456 g) were fed diets supplemented with 0, 392, 785, 1177, 1569, 1962, 2354, 2746 and 3139 mg/kg choline chloride. Fish fed the lowest-choline diet had pyloric caeca with whitish foamy surface, elevated relative weight, and the enterocytes were hypervacuolated. These characteristics diminished with increasing choline level and levelled off at levels of 2850, 3593 and 2310 mg/kg, respectively. The concomitant alterations in expression of genes related to phosphatidylcholine synthesis, cholesterol biosynthesis, lipid transport and storage confirmed the importance of choline in lipid turnover in the intestine and ability to prevent LMS. Based on the observations of the present study, the lowest level of choline which prevents LMS and intestinal lipid hypervacuolation in post-smolt Atlantic salmon is 3·4 g/kg. However, the optimal level most likely depends on the feed intake and dietary lipid level.
Richard Misrach and Kate Orrf's Petrochemical America: Cartographies of the Picturesque
Authors: BLINDER CAROLINE
Published: February 2020

This article looks at the landscape photographer Richard Misrach's collaboration with the architect Kate Orff in Petrochemical America (2012), a prizewinning examination of the effects of the oil industry in the Mississippi delta. Whilst situating its critique of the oil industry in the twentieth and twenty-first centuries, Petrochemical America nonetheless uses a variety of aesthetic devices from previous centuries and traditions, in particular the use of the picturesque in landscapes of the nineteenth century. Through this and other mechanisms, the images in Petrochemical America become potential allegories for the paradoxical coexistence of a picturesque nature visibly affected by industrial transformation.
Haematologic malignancies associated with clozapine v. all other antipsychotic agents: a pharmacovigilance study in VigiBase®
Authors: Chrétien Basile , Lelong-Boulouard Véronique , Chantepie Sylvain , Sassier Marion , Bertho Mickael , Brazo Perrine , Humbert Xavier , Alexandre Joachim , Fedrizzi Sophie , Dolladille Charles
Published: February 2020

Background

Clozapine is mainly used in patients with treatment-resistant schizophrenia and may lead to potentially severe haematologic adverse events, such as agranulocytosis. Whether clozapine might be associated with haematologic malignancies is unknown. We aimed to assess the association between haematologic malignancies and clozapine using Vigibase®, the WHO pharmacovigilance database.

Methods

We performed a disproportionality analysis to compute reporting odds-ratio adjusted for age, sex and concurrent reporting of antineoplastic/immunomodulating agents (aROR) for clozapine and structurally related drugs (loxapine, olanzapine and quetiapine) compared with other antipsychotic drugs. Cases were malignant lymphoma and leukaemia reports. Non-cases were all other reports including at least one antipsychotic report.

Results

Of the 140 226 clozapine-associated reports, 493 were malignant lymphoma cases, and 275 were leukaemia cases. Clozapine was significantly associated with malignant lymphoma (aROR 9.14, 95% CI 7.75–10.77) and leukaemia (aROR 3.54, 95% CI 2.97–4.22). Patients suffering from those haematologic malignancies were significantly younger in the clozapine treatment group than patients treated with other medicines (p < 0.001). The median time to onset (available for 212 cases) was 5.1 years (IQR 2.2–9.9) for malignant lymphoma and 2.5 years (IQR 0.6–7.4) for leukaemia. The aROR by quartile of dose of clozapine in patients with haematologic malignancies suggested a dose-dependent association.

Conclusions

Clozapine was significantly associated with a pharmacovigilance signal of haematologic malignancies. The risk-benefit balance of clozapine should be carefully assessed in patients with risk factors of haematologic malignancies. Clozapine should be used at the lowest effective posology.
Comparison of Kane’s and Lagrange’s Methods in Analysis of Constrained Dynamical Systems
Authors: Talaeizadeh Amin , Forootan Mahmoodreza , Zabihi Mehdi , Nejat Pishkenari Hossein
Published: February 2020

Dynamic modeling is a fundamental step in analyzing the movement of any mechanical system. Methods for dynamical modeling of constrained systems have been widely developed to improve the accuracy and minimize computational cost during simulations. The necessity to satisfy constraint equations as well as the equations of motion makes it more critical to use numerical techniques that are successful in decreasing the number of computational operations and numerical errors for complex dynamical systems. In this study, performance of a variant of Kane’s method compared to six different techniques based on the Lagrange’s equations is shown. To evaluate the performance of the mentioned methods, snake-like robot dynamics is considered and different aspects such as the number of the most time-consuming computational operations, constraint error, energy error, and CPU time assigned to each method are compared. The simulation results demonstrate the superiority of the variant of Kane’s method concerning the other ones.
SELF-OWNERSHIP AND AGENT-CENTERED OPTIONS
Authors: Lazar Seth
Published: February 2020

I argue that agent-centered options to favor and sacrifice one’s own interests are grounded in a particular aspect of self-ownership. Because you own your interests, you are entitled to a say over how they are used. That is, whether those interests count for or against some action is, at least in part, to be determined by your choice. This is not the only plausible argument for agent-centered options. But it has some virtues that other arguments lack.
OWNERSHIP AND THE MORAL SIGNIFICANCE OF THE SELF
Authors: Tadros Victor
Published: February 2020

The idea of self-ownership has played a prominent role in justifying normative conclusions in moral and political philosophy. I argue that whether or not we are self-owners, there is no such role for it to play. Self-ownership is better thought a conclusion of moral and political arguments rather than their source. I then begin to explore an alternative idea—that the self is morally significant—that provides what those who rely on self-ownership ought to be looking for.
Experiential Learning Revisited: Lessons from a Student-Led Public Opinion Polling Class
Authors: Rinfret Sara R. , Angle Justin , Scott Samuel , Ward Daisy , Yang Kaixuan , Copeland Emily , Power Rebecca , Ray Thomas , Hiett Thomas
Published: February 2020

For decades, political and private polling operations have informed about the public’s perceptions regarding a range of topics. In particular, universities (e.g., Marist and Quinnipiac) provide noteworthy research to inform and predict the outcomes of US elections. Yet, what role do our classrooms play in advancing the public opinion polling skills of our students? This article uses experiential learning as a descriptive framework to illustrate how a yearlong, immersive, and student-led public opinion polling experience, the Big Sky Poll, advances students’ social-science and data-fluency skills. Our findings suggest important insights into the future of public opinion polling from the vantage point of a rural Western state, which can be replicated in other academic institutions.
HETEROGENEOUS EXPECTATIONS AND ASSET PRICE DYNAMICS
Authors: Schmitt Noemi
Published: February 2020

Within the seminal asset-pricing model by Brock and Hommes (Journal of Economic Dynamics Control 22, 1235–1274, 1998), heterogeneous boundedly rational agents choose between a fixed number of expectation rules to forecast asset prices. However, agents’ heterogeneity is limited in the sense that they typically switch between a representative technical and a representative fundamental expectation rule. Here, we generalize their framework by considering that all agents follow their own time-varying technical and fundamental expectation rules. Estimating our model using the method of simulated moments reveals that it is able to explain the statistical properties of the daily and monthly behavior of the S&P500 quite well. Moreover, our analysis reveals that heterogeneity is not only a realistic model property but clearly helps to explain the intricate dynamics of financial markets.
Must antidepressants be avoided in patients with neuroendocrine tumors? Results of a systematic review
Authors: Isenberg-Grzeda Elie , MacGregor Meredith , Matsoukas Konstantina , Chow Ngai , Reidy-Lagunes Diane , Alici Yesne
Published: February 2020

Objective

Symptoms of depression and anxiety are common in neuroendocrine tumor (NET), yet controversy exists over whether serotonin-mediated antidepressants (SAs) are safe in this population. We sought to address this knowledge gap.

Method

Following PRISMA guidelines, we conducted a systematic review to identify NET patients who were prescribed SA.

Results

We identified 15 articles, reporting on 161 unique patients, 72 with carcinoid syndrome (CS) and 89 without. There was substantial agreement between reviewers at the full-text stage (κ = 0.69). Three of the articles, all with low risk of bias, accounted for most of the cases (149/161; 93%). Among the 72 NET patients with CS prior to antidepressant usage, CS was exacerbated in 6 cases (8%), only 3 (4%) of whom chose to discontinue the antidepressant. The remaining 89 patients had no prior CS symptoms, and none developed CS following antidepressant usage. Overall, no instances of carcinoid crisis or death were reported.

Conclusions

We found no evidence for serious adverse outcomes related to SA usage in NET patients. Previous authors have recommended avoiding antidepressants in NET, but our findings do not support those recommendations. Oncologists should nonetheless monitor for symptom exacerbation when prescribing SA to patients with NET.
Multicriteria decision-support system to assess the potential of exclosure-based conservation in Ethiopia
Authors: Kibret Kefyalew Sahle , Haileslassie Amare , Mekuria Bori Wolde , Schmitter Petra
Published: February 2020

Land degradation is a global challenge that affects lives and livelihoods in many communities. Since 1950, about 65% of Africa's cropland, on which millions of people depend, has been affected by land degradation caused by mining, poor farming practices and illegal logging. One-quarter of the land area of Ethiopia is severely degraded. As part of interventions to restore ecosystem services, exclosures have been implemented in Ethiopia since the 1980s. But the lack of tools to support prioritization and more efficient targeting of areas for large-scale exclosure-based interventions remains a challenge. Within that perspective, the overarching objectives of the current study were: (i) to develop a Geographic Information System-based multicriteria decision-support tool that would help in the identification of suitable areas for exclosure initiatives; (ii) to provide spatially explicit information, aggregated by river basin and agroecology, on potential areas for exclosure interventions and (iii) to conduct ex-ante analysis of the potential of exclosure areas for improving ecosystem services in terms of increase in above-ground biomass (AGB) production and carbon storage. The results of this study demonstrated that as much as 10% of Ethiopia's land area is suitable for establishing exclosures. This amounts to 11 million hectares (ha) of land depending on the criteria used to define suitability for exclosure. Of this total, a significant proportion (0.5–0.6 million ha) is currently under agricultural land-use systems. In terms of propriety river basins, we found that the largest amount of suitable area for exclosures falls in the Abay (2.6 million ha) and Tekeze (2.2 million ha) river basins, which are hosts to water infrastructure such as hydropower dams and are threatened by siltation. Ex-ante analysis of ecosystem services indicated that about 418 million tons of carbon can be stored in the AGB through exclosure land use. Ethiopia has voluntarily committed to the Bonn Challenge to restore 15 million ha of degraded land by 2025. The decision-support tool developed by the current study and the information so generated go toward supporting the planning, implementation and monitoring of these kinds of local and regional initiatives.
Across‐Arc Diversity in Rhyolites From an Intra‐oceanic Arc: Evidence From IODP Site U1437, Izu‐Bonin Rear Arc, and Surrounding Area
Authors: Heywood Luan J. , DeBari Susan M. , Gill James B. , Straub Susanne M. , Schindlbeck‐Belo Julie C. , Escobar‐Burciaga Ricardo D. , Woodhead Jon
Published: February 2020

Felsic magmas from the Izu‐Bonin rear arc have compositions that resemble average continental crust in some respects. In order to understand their origin, we studied 1.1–4.4 Ma tephras in a rear‐arc drill core from International Ocean Discovery Program Expedition 350, Site U1437. They provide a well‐dated record of changing magmatic compositions during the early stages of the most recent episode of Izu‐Bonin arc rifting. Based on our comprehensive recontextualization of published analyses of <7 Ma regional dredged rocks across the arc, basalts to rhyolites are shown to vary in coherent chronological and spatial trends and can be classified into three series: light rare earth element‐depleted volcanic front series; a rift‐related series with nearly flat rare earth element patterns; and light rare earth element‐enriched rear‐arc seamount chain‐type (RASC‐type) series, which are abundant in the studied Site U1437 tephra record. All three series erupted simultaneously between 4.4 and 1.1 Ma, including the RASC‐type rhyolites which erupted until 1.1 Ma in significant quantities. Remarkably, trace element and radiogenic isotope ratios are similar between rhyolites and basalts from the same region. This recontextualization of rhyolite affinity represents a significant departure from existing frameworks. Geochemical modeling shows that fractional crystallization can largely explain <4.4 Ma RASC‐type rhyolites with some additional open system processing evident in rhyolites with >73% SiO2. However, trace element and Hf isotope ratios preclude rear‐arc rhyolite derivation by partial melting of the Oligocene‐Eocene arc basement. Thus, we favor a model where fractional crystallization is more important than crustal melting in producing intra‐oceanic arc rhyolites in this region.
Mineralogy and Origin of Aerosol From an Arc Basaltic Eruption: Case Study of Tolbachik Volcano, Kamchatka
Authors: Zelenski M. , Kamenetsky V. S. , Taran Yu. , Kovalskii A. M.
Published: February 2020

Intense emission of volcanic aerosol accompanied the 2012–2013 basaltic effusive eruption of Tolbachik volcano, Kamchatka. The aerosols sampled contain sulfuric acid droplets, glassy particles, and 70 mineral phases. All aerosol particles may be classified by their origin. The fragmentation aerosol includes magma fragments: silicate glass clasts, silicate microspheres, and small phenocrysts (olivine, pyroxene, and magnetite). The alteration aerosol comprises particles of quenched silicate melt covered with secondary minerals (fluorides, sulfates, and oxides/hydroxides of rock‐forming elements) and fragments of altered rocks composed solely of secondary minerals. The condensation aerosol dominated the mass during the later stages of the eruption when the explosive activity had ceased, and was characterized by the greatest variety of particle compositions. Na‐K sulfate and Fe (III) oxide comprised more than 95% of the solid fraction of the condensation aerosol. The remaining 5% was represented by native elements (Au, Ag‐Pt alloy, and Pt); sulfides of Fe, Cu, Ag, and Re; oxides and hydroxides of Al, Fe, Cu, Zn, Mo, W, Ta, and Zr; halides of Al, Mg, Na, K, Ca, Cd, Pb, Ag, and Tl; and sulfates of Na, K, Pb, Ca, and Ba; the only silicate was As‐bearing orthoclase. Droplets of H2SO4 formed the liquid phase of the condensation aerosol. Some of the aerosol components, such as magnetite spherules or phosphate‐carbonate‐fluorite association, likely had a nonvolcanic origin (country rocks and wood fly ash). The volcanic aerosols and their contained minerals, discharged at Tolbachik and elsewhere, result in a physical and chemical effect on the environment in the region of such volcanoes.
On Energetic Electron Dynamics During Geomagnetic Quiet Times in Earth's Inner Radiation Belt due to Atmospheric Collisional Loss and CRAND as a Source
Authors: Xiang Zheng , Li Xinlin , Temerin M. A. , Ni Binbin , Zhao Hong , Zhang Kun , Khoo Leng Ying
Published: February 2020

To investigate the role of atmospheric collisions and cosmic ray albedo neutron decay (CRAND) in the dynamics of energetic electrons in the Earth's inner radiation belt during geomagnetic quiet times, a drift‐collision‐source model that includes azimuthal drift, pitch angle diffusion from elastic collision, energy loss from inelastic collision, and a CRAND source is developed. In the model, the bounce‐averaged pitch angle diffusion coefficients and energy loss rates are calculated based on scattering of electrons with neutrals given by the NRLMSISE‐00 model and with ions and electrons given by International Reference Ionosphere (IRI) 2012 model. The electron source rate from CRAND follows the recently developed drift‐source model in Xiang et al. (2019). For 304‐keV quasi‐trapped electrons at L = 1.25, simulation results with CRAND show good agreement with Detection of Electro‐Magnetic Emissions Transmitted from Earthquake Regions satellite observations, confirming that CRAND is the main source for these quasi‐trapped electrons, in contrast to the previous understanding that these quasi‐trapped electrons were formed by wide‐angle scattering of the trapped populations. For trapped electrons, 153, 304, and 509 keV at L < 1.3, the simulation results with only azimuthal drift and atmospheric collisions show a much quicker decrease than observations, while simulation results including a CRAND source are generally comparable to the observations, suggesting that CRAND is an important source of trapped hundreds of kiloelectron‐volt electrons at L < 1.3 during quiet times and provides a baseline for the electron flux even during active times as well. Furthermore, these results suggest that actual radial diffusion rates in the inner belt are lower than previous estimates in which CRAND contributions were not considered.
Preeruptive P‐T Conditions and H2O Concentration of the Aso‐4 Silicic End‐Member Magma Based on High‐Pressure Experiments
Authors: Ushioda Masashi , Miyagi Isoji , Suzuki Toshihiro , Takahashi Eiichi , Hoshizumi Hideo
Published: February 2020

To constrain the preeruptive physical and chemical conditions (pressure, temperature, H2O content, and fO2) of the most recent and largest eruption (Aso‐4) of Aso volcano, Japan, we compared phase assemblages and chemical compositions of erupted material with those of experimentally determined run charges of the silicic end‐member magma of Aso‐4 (the KJ5665 pumice and MY5774 welded lens from the Aso‐4 pyroclastic flow deposit; SiO2 = 70.5 wt %). Experimental conditions were as follows: starting material = KJ5665 pumice, pressure = 100–700 MPa, temperature range = 810–950 °C, and injected H2O content = 2.9–6.7 wt %. The starting material comprised mainly rhyolitic glass with plagioclase, orthopyroxene, magnetite, and ilmenite phenocrysts. Hornblende phenocrysts are not found on cross sections of the KJ5665 pumice. Core compositions of these phenocrysts are unimodal. Using the magnetite‐ilmenite thermometer, the preeruptive magmatic temperature and fO2 of KJ5665 were estimated to be ~900 °C and Nickel‐Nickel oxide (NNO) +1.1 log units, respectively. Run products contain plagioclase (An20–48), orthopyroxene (Mg# = 53–72), magnetite, ilmenite, biotite, and K‐feldspar. Hornblende was not observed. Preeruptive conditions of the silicic end‐member magma of the Aso‐4 eruption are estimated to be ~900 °C, ≤ 300 MPa, and ≤ 3 wt % H2O.
Flexible and Modular Simultaneous Modeling of Flow and Reactive Transport in Rivers and Hyporheic Zones
Authors: Li Bing , Liu Xiaofeng , Kaufman Matthew H. , Turetcaia Anna , Chen Xingyuan , Cardenas M. Bayani
Published: February 2020

Investigations of coupled multiphysics processes in rivers and hyporheic zones have extensively used numerical models. Most existing models use a sequential, one‐way coupling between the surface and subsurface domains. Such one‐way coupling potentially introduces error. To overcome this, a fully coupled model, hyporheicFoam, was developed using the open‐source computational platform OpenFOAM. It captures the coupled flow and multicomponent reactive transport processes within both surface and subsurface domains and across their interface. The coupling between two domains is implemented by mapping conservative flux boundary conditions at the interface through an iterative algorithm. Reactive transport is enabled by specifying a reaction network. To start, we have implemented reaction kinetics following the double Monod‐type model with inhibition. The model capability is illustrated through modeling of both conservative and reactive hyporheic flow and transport through dune bedforms. With the novel coupled model, it is now possible to quantify reactions wherein the reactants and products are constantly exchanging between domains and have feedbacks. hyporheicFoam can simulate large, three‐dimensional cases owing to the computational flexibility and power offered by the code structure and parallel design of OpenFOAM.
Wnt signaling in cancer: therapeutic targeting of Wnt signaling beyond β-catenin and the destruction complex
Authors: Jung Youn-Sang , Park Jae-Il
Published: February 2020

Wnt/β-catenin signaling is implicated in many physiological processes, including development, tissue homeostasis, and tissue regeneration. In human cancers, Wnt/β-catenin signaling is highly activated, which has led to the development of various Wnt signaling inhibitors for cancer therapies. Nonetheless, the blockade of Wnt signaling causes side effects such as impairment of tissue homeostasis and regeneration. Recently, several studies have identified cancer-specific Wnt signaling regulators. In this review, we discuss the Wnt inhibitors currently being used in clinical trials and suggest how additional cancer-specific regulators could be utilized to treat Wnt signaling-associated cancer.
Carrier-assisted differential detection
Authors: Shieh William , Sun Chuanbowen , Ji Honglin
Published: February 2020

To overcome power fading induced by chromatic dispersion in optical fiber communications, optical field recovery is a promising solution for direct detection short-reach applications, such as fast-evolving data center interconnects (DCIs). To date, various direct detection schemes capable of optical field recovery have been proposed, including Kramers−Kronig (KK) and signal−signal beat interference (SSBI) iterative cancellation (IC) receivers. However, they are all restricted to the single sideband (SSB) modulation format, thus conspicuously losing half of the electrical spectral efficiency (SE) compared with double sideband (DSB) modulation. Additionally, SSB suffers from the noise folding issue, requiring a precise optical filter that complicates the receiver design. As such, it is highly desirable to investigate the field recovery of DSB signals via direct detection. In this paper, for the first time, we propose a novel receiver scheme called carrier-assisted differential detection (CADD) to realize optical field recovery of complex-valued DSB signals via direct detection. First, CADD doubles the electrical SE compared with the KK and SSBI IC receivers by adopting DSB modulation without sacrificing receiver sensitivities. Furthermore, by using direct detection without needing a precise receiver optical filter, CADD can employ cost-effective uncooled lasers as opposed to expensive temperature-controlled lasers in coherent systems. Our proposed receiver architecture opens a new class of direct detection schemes that are suitable for photonic integration analogous to homodyne receivers in coherent detection.
Electrogenic sulfide oxidation mediated by cable bacteria stimulates sulfate reduction in freshwater sediments
Authors: Sandfeld Tobias , Marzocchi Ugo , Petro Caitlin , Schramm Andreas , Risgaard-Petersen Nils
Published: February 2020

Cable bacteria are filamentous members of the Desulfobulbaceae family that oxidize sulfide with oxygen or nitrate by transferring electrons over centimeter distances in sediments. Recent studies show that freshwater sediments can support populations of cable bacteria at densities comparable to those found in marine environments. This is surprising since sulfide availability is presumably low in freshwater sediments due to sulfate limitation of sulfate reduction. Here we show that cable bacteria stimulate sulfate reduction in freshwater sediment through promotion of sulfate availability. Comparing experimental freshwater sediments with and without active cable bacteria, we observed a three- to tenfold increase in sulfate concentrations and a 4.5-fold increase in sulfate reduction rates when cable bacteria were present, while abundance and community composition of sulfate-reducing microorganisms (SRM) were unaffected. Correlation and ANCOVA analysis supported the hypothesis that the stimulation of sulfate reduction activity was due to relieve of the kinetic limitations of the SRM community through the elevated sulfate concentrations in sediments with cable bacteria activity. The elevated sulfate concentration was caused by cable bacteria-driven sulfide oxidation, by sulfate production from an indigenous sulfide pool, likely through cable bacteria-mediated dissolution and oxidation of iron sulfides, and by enhanced retention of sulfate, triggered by an electric field generated by the cable bacteria. Cable bacteria in freshwater sediments may thus be an integral component of a cryptic sulfur cycle and provide a mechanism for recycling of the scarce resource sulfate, stimulating sulfate reduction. It is possible that this stimulation has implication for methanogenesis and greenhouse gas emissions.
Effects of tetrahedral framework nucleic acid/wogonin complexes on osteoarthritis
Authors: Sirong Shi , Yang Chen , Taoran Tian , Songhang Li , Shiyu Lin , Yuxin Zhang , Xiaoru Shao , Tao Zhang , Yunfeng Lin , Xiaoxiao Cai
Published: February 2020

Osteoarthritis, a disorder characterized by articular cartilage deterioration, varying degrees of inflammation, and chondrocyte apoptosis, is the most common chronic joint disease. To slow or reverse its progression, inflammation should be inhibited, and chondrocyte proliferation should be promoted. Tetrahedral framework nucleic acids can be internalized by chondrocytes (even inflammatory chondrocytes) and can enhance their proliferation and migration. Wogonin, a naturally occurring flavonoid, suppresses oxidative stress and inhibits inflammation. In this study, tetrahedral framework nucleic acids were successfully self-assembled and used to load wogonin. We confirmed the effective formation of tetrahedral framework nucleic acid/wogonin complexes by dynamic light scattering, zeta potential analysis, transmission electron microscopy, and fluorescence spectrophotometry. Tetrahedral framework nucleic acids, wogonin, and especially tetrahedral framework nucleic acid/wogonin complexes effectively alleviated inflammation in vitro and in vivo and prevented cartilage destruction. In addition, these materials remarkably downregulated the expression of inflammatory mediators and matrix metalloproteinases, upregulated chondrogenic markers, and promoted tissue inhibitor of metalloproteinase 1 and B-cell lymphoma 2 expression. In vivo, after treatment with tetrahedral framework nucleic acid/wogonin complexes, the bone mineral density in regenerated tissues was much higher than that found in the untreated groups. Histologically, the complexes enhanced new tissue regeneration, significantly suppressed chondrocyte apoptosis, and promoted chondrogenic marker expression. They also inhibited cell apoptosis, increased chondrogenic marker expression, and suppressed the expression of inflammatory mediators in osteoarthritis. Therefore, we believe that tetrahedral framework nucleic acid/wogonin complexes can be used as an injectable form of therapy for osteoarthritis.
IgSF11 regulates osteoclast differentiation through association with the scaffold protein PSD-95
Authors: Kim Hyunsoo , Takegahara Noriko , Walsh Matthew C. , Middleton Sarah A. , Yu Jiyeon , Shirakawa Jumpei , Ueda Jun , Fujihara Yoshitaka , Ikawa Masahito , Ishii Masaru , Kim Junhyong , Choi Yongwon
Published: February 2020

Osteoclasts are multinucleated, giant cells derived from myeloid progenitors. While receptor activator of NF-κB ligand (RANKL) stimulation is the primary driver of osteoclast differentiation, additional signaling further contributes to osteoclast maturation. Here, we demonstrate that immunoglobulin superfamily member 11 (IgSF11), whose expression increases during osteoclast differentiation, regulates osteoclast differentiation through interaction with postsynaptic density protein 95 (PSD-95), a scaffold protein with multiple protein interaction domains. IgSF11 deficiency in vivo results in impaired osteoclast differentiation and bone resorption but no observed defect in bone formation. Consequently, IgSF11-deficient mice exhibit increased bone mass. Using in vitro osteoclast culture systems, we show that IgSF11 functions through homophilic interactions. Additionally, we demonstrate that impaired osteoclast differentiation in IgSF11-deficient cells is rescued by full-length IgSF11 and that the IgSF11-PSD-95 interaction requires the 75 C-terminal amino acids of IgSF11. Our findings reveal a critical role for IgSF11 during osteoclast differentiation and suggest a role for IgSF11 in a receptor- and signal transduction molecule-containing protein complex.
Errors in determination of net survival: cause-specific and relative survival settings
Authors: Bright Chloe J. , Brentnall Adam R. , Wooldrage Kate , Myles Jonathon , Sasieni Peter , Duffy Stephen W.
Published: February 2020

Background

Cause-specific and relative survival estimates differ. We aimed to examine these differences in common cancers where by possible identifying the most plausible sources of error in each estimate.

Methods

Ten-year cause-specific and relative survival were estimated for lung, breast, prostate, ovary, oesophagus and colorectal cancers. The cause-specific survival was corrected for misclassification of cause of death. The Pohar-Perme relative survival estimator was modified by (1) correcting for differences in deaths from ischaemic heart disease (IHD) between cancers and general population; or (2) correcting the population hazard for smoking (lung cancer only).

Results

For all cancers except breast and prostate, relative survival was lower than cause-specific. Correction for published error rates in cause of death gave implausible results. Correction for rates of IHD death gave slightly different relative survival estimates for lung, oesophagus and colorectal cancers. For lung cancer, when the population hazard was inflated for smoking, survival estimates were increased.

Conclusion

Results agreed with the consensus that relative survival is usually preferable. However, for some cancers, relative survival might be inaccurate (e.g. lung and prostate). Likely solutions include enhancing life tables to include other demographic variables than age and sex, and to stratify relative survival calculation by cause of death.
Combined lifestyle factors, incident cancer, and cancer mortality: a systematic review and meta-analysis of prospective cohort studies
Authors: Zhang Yan-Bo , Pan Xiong-Fei , Chen Junxiang , Cao Anlan , Zhang Yu-Ge , Xia Lu , Wang Jing , Li Huiqi , Liu Gang , Pan An
Published: February 2020

Background

Cancer poses a huge disease burden, which could be reduced by adopting healthy lifestyles mainly composed of healthy diet, body weight, physical activity, limited alcohol consumption, and avoidance of smoking. However, no systematic review has summarised the relations of combined lifestyle factors with cancer morbidity and mortality.

Methods

EMBASE and PubMed were searched up to April 2019. Cohort studies investigating the association of combined lifestyle factors with risks of incident cancer and cancer mortality were selected. Summary hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using random-effects models. Heterogeneity and publication bias tests were conducted.

Results

The HRs (95% CIs) comparing individuals with the healthiest versus the least healthy lifestyles were 0.71 (0.66–0.76; 16 studies with 1.9 million participants) for incident cancer and 0.48 (0.42–0.54; 30 studies with 1.8 million participants) for cancer mortality. Adopting the healthiest lifestyles was also associated with 17 to 58% lower risks of bladder, breast, colon, endometrial, oesophageal, kidney, liver, lung, rectal, and gastric cancer. The relations were largely consistent and significant among participants with different characteristics in the subgroup analyses.

Conclusions

Adopting healthy lifestyles is associated with substantial risk reduction in cancer morbidity and mortality, and thus should be given priority for cancer prevention.
Development of prediction models for lymph node metastasis in endometrioid endometrial carcinoma
Authors: Berg Hege F. , Ju Zhenlin , Myrvold Madeleine , Fasmer Kristine E. , Halle Mari K. , Hoivik Erling A. , Westin Shannon N. , Trovik Jone , Haldorsen Ingfrid S. , Mills Gordon B. , Krakstad Camilla , Werner Henrica M. J.
Published: February 2020

Background

In endometrioid endometrial cancer (EEC), current clinical algorithms do not accurately predict patients with lymph node metastasis (LNM), leading to both under- and over-treatment. We aimed to develop models that integrate protein data with clinical information to identify patients requiring more aggressive surgery, including lymphadenectomy.

Methods

Protein expression profiles were generated for 399 patients using reverse-phase protein array. Three generalised linear models were built on proteins and clinical information (model 1), also with magnetic resonance imaging included (model 2), and on proteins only (model 3), using a training set, and tested in independent sets. Gene expression data from the tumours were used for confirmatory testing.

Results

LNM was predicted with area under the curve 0.72–0.89 and cyclin D1; fibronectin and grade were identified as important markers. High levels of fibronectin and cyclin D1 were associated with poor survival (p = 0.018), and with markers of tumour aggressiveness. Upregulation of bothFN1andCCND1messenger RNA was related to cancer invasion and mesenchymal phenotype.

Conclusions

We demonstrate that data-driven prediction models, adding protein markers to clinical information, have potential to significantly improve preoperative identification of patients with LNM in EEC.
Metformin reduces HGF-induced resistance to alectinib via the inhibition of Gab1
Authors: Chen Hengyi , Lin Caiyu , Peng Tao , Hu Cheng , Lu Conghua , Li Li , Wang Yubo , Han Rui , Feng Mingxia , Sun FenFen , He Yong
Published: February 2020

Alectinib is a second-generation anaplastic lymphoma kinase (ALK) inhibitor that has sufficient clinical efficacy and satisfactory safety in ALK-positive non-small cell lung cancer (NSCLC) patients with or without brain metastasis. Alectinib has now become an important drug in the first-line treatment of advanced ALK-positive NSCLC; however, resistance is almost inevitable. The increased expression of hepatocyte growth factor (HGF) and its physiological receptor tyrosine kinase MET have been shown to be linked to acquired resistance to various tyrosine kinase inhibitors (TKIs), and this phenomenon has been observed in some ALK-positive NSCLC tumour tissues. In this study, we found that HGF levels in the culture supernatant of an ALK-positive cell line tended to increase with time and could be further increased by alectinib in a time-dependent manner. Exogenous or endogenous HGF did not cause resistance to the ALK/MET double-targeted small molecule inhibitor crizotinib, but it was an important cause of alectinib resistance. Furthermore, Gab1 was a key effector in the HGF/MET signal transduction pathway that mediated alectinib resistance. The antidiabetic drug metformin combined with alectinib overcame alectinib resistance triggered by HGF/MET through disrupting the complex between MET and Gab1, thereby inhibiting Gab1 phosphorylation and the activation of downstream signal transduction pathways. These results suggest that metformin combined with alectinib may be useful for overcoming alectinib resistance induced by the activation of the HGF/MET signalling pathway and improving the efficacy of alectinib.
PALB2 chromatin recruitment restores homologous recombination in BRCA1-deficient cells depleted of 53BP1
Authors: Belotserkovskaya Rimma , Raga Gil Elisenda , Lawrence Nicola , Butler Richard , Clifford Gillian , Wilson Marcus D. , Jackson Stephen P.
Published: February 2020

Loss of functional BRCA1 protein leads to defects in DNA double-strand break (DSB) repair by homologous recombination (HR) and renders cells hypersensitive to poly (ADP-ribose) polymerase (PARP) inhibitors used to treat BRCA1/2-deficient cancers. However, upon chronic treatment of BRCA1-mutant cells with PARP inhibitors, resistant clones can arise via several mechanisms, including loss of 53BP1 or its downstream co-factors. Defects in the 53BP1 axis partially restore the ability of a BRCA1-deficient cell to form RAD51 filaments at resected DSBs in a PALB2- and BRCA2-dependent manner, and thereby repair DSBs by HR. Here we show that depleting 53BP1 in BRCA1-null cells restores PALB2 accrual at resected DSBs. Moreover, we demonstrate that PALB2 DSB recruitment in BRCA1/53BP1-deficient cells is mediated by an interaction between PALB2’s chromatin associated motif (ChAM) and the nucleosome acidic patch region, which in 53BP1-expressing cells is bound by 53BP1’s ubiquitin-directed recruitment (UDR) domain.
Nicotianamine-chelated iron positively affects iron status, intestinal morphology and microbial populations in vivo (Gallus gallus)
Authors: Beasley Jesse T. , Johnson Alexander A. T. , Kolba Nikolai , Bonneau Julien P. , Glahn Raymond P. , Ozeri Lital , Koren Omry , Tako Elad
Published: February 2020

Wheat flour iron (Fe) fortification is mandatory in 75 countries worldwide yet many Fe fortificants, such as Fe-ethylenediaminetetraacetate (EDTA), result in unwanted sensory properties and/or gastrointestinal dysfunction and dysbiosis. Nicotianamine (NA) is a natural chelator of Fe, zinc (Zn) and other metals in higher plants and NA-chelated Fe is highly bioavailable in vitro. In graminaceous plants NA serves as the biosynthetic precursor to 2′ -deoxymugineic acid (DMA), a related Fe chelator and enhancer of Fe bioavailability, and increased NA/DMA biosynthesis has proved an effective Fe biofortification strategy in several cereal crops. Here we utilized the chicken (Gallus gallus) model to investigate impacts of NA-chelated Fe on Fe status and gastrointestinal health when delivered to chickens through intraamniotic administration (short-term exposure) or over a period of six weeks as part of a biofortified wheat diet containing increased NA, Fe, Zn and DMA (long-term exposure). Striking similarities in host Fe status, intestinal functionality and gut microbiome were observed between the short-term and long-term treatments, suggesting that the effects were largely if not entirely due to consumption of NA-chelated Fe. These results provide strong support for wheat with increased NA-chelated Fe as an effective biofortification strategy and uncover novel impacts of NA-chelated Fe on gastrointestinal health and functionality.
A new nonlinear viscoelastic model and mathematical solution of solids for improving prediction accuracy
Authors: Xu Qinwu , Engquist Björn , Solaimanian Mansour , Yan Kezhen
Published: February 2020

We developed an innovative material nonlinear viscoelastic model with physical mechanism and mathematical solution to improve existing ones. The relaxation modulus transits from the glassy stage to the rubbery stage through a time-dependent viscosity in a continuous spectrum considering the nonlinear strain hardening. Experimental results of differential solid materials including asphalt concrete, agarose gel, vaginal tissue, polymer, agar, bone, spider silk, and hydrogel demonstrate that the developed model is superior to generalized Maxwell model or Prony series for more accurate prediction outside of the range for data fitting while using much less model parameters. Numerical simulation results indicate that the new model has improved accuracy. It is stable numerically, and does not reduce computation speed. Therefore, the model may be used to simulate a broad range of viscoelastic solids for predicting experimental data and responses with improved accuracy.
Active nuclear import of the deacetylase Sirtuin-2 is controlled by its C-terminus and importins
Authors: Eldridge Matthew J. G. , Pereira Jorge M. , Impens Francis , Hamon Mélanie A.
Published: February 2020

The NAD-dependent deacetylase Sirtuin-2 (SIRT2) functions in diverse cellular processes including the cell cycle, metabolism, and has important roles in tumorigenesis and bacterial infection. SIRT2 predominantly resides in the cytoplasm but can also function in the nucleus. Consequently, SIRT2 localisation and its interacting partners may greatly impact its function and need to be defined more clearly. In this study we used mass spectrometry to determine the interactomes of SIRT2 in whole cells and in specific cellular fractions; cytoplasm, nucleus and chromatin. Using this approach, we identified novel interacting partners of SIRT2. These included a number of proteins that function in nuclear import. We show that multiple importins interact with and contribute to the basal nuclear shuttling of SIRT2 and that one of these, IPO7 is required for SIRT2 mediated H3K18 deacetylation in response to bacterial infection. Furthermore, we reveal that the unstructured C-terminus of SIRT2 negatively regulates importin-binding and nuclear transport. This study demonstrates that SIRT2 is actively transported into the nucleus via a process regulated by its C-terminus and provides a resource of SIRT2 interacting partners.
Human cytomegalovirus promoting endothelial cell proliferation by targeting regulator of G-protein signaling 5 hypermethylation and downregulation
Authors: Zhang Xiaoni , Tang Na , Xi Dongmei , Feng Qian , Liu Yongmin , Wang Lamei , Tang Yan , Zhong Hua , He Fang
Published: February 2020

Interactions between human cytomegalovirus (HCMV) infection and environmental factors can increase susceptibility to essential hypertension (EH). Although endothelial dysfunction is the initial factor of EH, the epigenetic mechanisms through which HCMV infection induces endothelial cell dysfunction are poorly understood. Here, we evaluated whether HCMV regulated endothelial cell function and assessed the underlying mechanisms. Microarray analysis in human umbilical vein endothelial cells (HUVECs) treated with HCMV AD169 strain in the presence of hyperglycemia and hyperlipidemia revealed differential expression of genes involved in hypertension. Further analyses validated that the regulator of G-protein signaling 5 (RGS5) gene was downregulated in infected HUVECs and showed that HCMV infection promoted HUVEC proliferation, whereas hyperglycemia and hyperlipidemia inhibited HUVEC proliferation. Additionally, treatment with decitabine (DAC) and RGS5 reversed the effects of HCMV infection on HUVEC proliferation, but not triggered by hyperglycemia and hyperlipidemia. In summary, upregulation of RGS5 may be a promising treatment for preventing HCMV-induced hypertension.
3D Patterning of cells in Magnetic Scaffolds for Tissue Engineering
Authors: Goranov V. , Shelyakova T. , De Santis R. , Haranava Y. , Makhaniok A. , Gloria A. , Tampieri A. , Russo A. , Kon E. , Marcacci M. , Ambrosio L. , Dediu V. A.
Published: February 2020

A three dimensional magnetic patterning of two cell types was realised in vitro inside an additive manufactured magnetic scaffold, as a conceptual precursor for the vascularised tissue. The realisation of separate arrangements of vascular and osteoprogenitor cells, labelled with biocompatible magnetic nanoparticles, was established on the opposite sides of the scaffold fibres under the effect of non-homogeneous magnetic gradients and loading magnetic configuration. The magnetisation of the scaffold amplified the guiding effects by an additional trapping of cells due to short range magnetic forces. The mathematical modelling confirmed the strong enhancement of the magnetic gradients and their particular geometrical distribution near the fibres, defining the preferential cell positioning on the micro-scale. The manipulation of cells inside suitably designed magnetic scaffolds represents a unique solution for the assembling of cellular constructs organised in biologically adequate arrangements.
Mineral Fabric as a Hidden Variable in Fracture Formation in Layered Media
Authors: Jiang Liyang , Yoon Hongkyu , Bobet Antonio , Pyrak-Nolte Laura J.
Published: February 2020

Two longstanding goals in subsurface science are to induce fractures with a desired geometry and to adaptively control the interstitial geometry of existing fractures in response to changing subsurface conditions. Here, we demonstrate that microscopic mineral fabric and structure interact with macroscopic strain fields to generate emergent meso-scale geometries of induced fractures. These geometries define preferential directions of flow. Using additively manufactured rock, we demonstrate that highly conductive flow paths can be formed in tensile fractures by creating corrugated surfaces. Generation, suppression and enhancement of corrugations depend on the relative orientation between mineral fabric and layering. These insights into the role of micro-scale structure on macro-scale flow provide a new method for designing subsurface strategies to maximize potential production or to inhibit flow.