bluuebunny/crossref_metadata_2025 huggingface dataset:
Macrophage Migration Inhibitory Factor as a Predictor for Long-term Improvements After Mindfulness-Based Group Therapy or Treatment as Usual for Depression, Anxiety or Stress and Adjustment Disorders
Authors: Sundquist Kristina , Palmér Karolina , Memon Ashfaque A. , Sundquist Jan , Wang Xiao
Published: March 2020

Objectives

Identification of biological markers that can guide treatment selection is considered to be a viable solution for personalized treatment for patients with psychiatric disorders. This study investigated whether macrophage migration inhibitory factor (MIF) levels at baseline were associated with mindfulness-based group therapy or cognitive behavioral therapy response in patients with mild to moderate symptoms of depression, anxiety, or stress- and adjustment disorders.

Methods

A total of 168 patients (aged 21–65 years) with psychiatric disorders were included from a randomized controlled trial. Plasma MIF levels in all the patients were analyzed using Luminex assay.

Results

Higher MIF levels at baseline were significantly associated with better long-term (1-year follow-up) improvement in psychiatric symptoms, as measured by changes in the Montgomery-Åsberg Depression Rating Scale (MADRS-S), compared with lower MIF levels, after adjustment for baseline MADRS-S score, age, sex, BMI, and pharmacotherapy (β = 5.89, p = 0.001). Patients with higher levels of MIF (8235–23,391 pg/ml) had an almost 6 points’ larger decrease in MADRS-S score after 1 year compared with those with lower MIF (727–8223 pg/ml) at baseline. Similar trends were seen after 8 weeks, albeit non-significant (β = 1.99, p = 0.18).

Conclusions

The findings indicate that higher plasma MIF levels at baseline may predict better long-term outcomes with psychotherapeutic interventions for mild to moderate symptoms of depression, anxiety, or stress and adjustment disorders. MIF levels may serve as a potential biomarker that can guide treatment selection for the personalized treatment for patients with psychiatric disorders.
Einfluss von Merkmalen ebener Figuren auf das Erkennen von Achsensymmetrie – Eine Analyse von Aufgabenlösungen
Authors: Götz Daniela , Gasteiger Hedwig , Kühnhenrich Maria
Published: March 2020

Symmetrie ist ein bedeutendes Thema in der Mathematik, zu dem Verständnis bereits in der Grundschule angebahnt werden kann. Über Lernprozesse beim Erwerb des Verständnisses der Achsensymmetrie und dabei auftretende (Fehl‑)Vorstellungen von Schülerinnen und Schülern ist bisher eher wenig bekannt. Systematische Fehleranalysen können eine erste Datenbasis liefern, aus der sich Rückschlüsse auf das Symmetrieverständnis ziehen lassen, und die eine gute Ausgangslage für didaktische Überlegungen sein kann. Diese Studie analysiert den Einfluss der Merkmale einer Figur (z. B. Ausrichtung der Achse, Art der Symmetrie) auf die Lösungshäufigkeit, achsensymmetrische von nicht-achsensymmetrischen Figuren zu unterscheiden und Symmetrieachsen richtig einzuzeichnen. Sie arbeitet typische Fehler von Schülerinnen und Schülern unter Berücksichtigung unterschiedlicher Aufgabenmerkmale heraus. Basis dafür ist ein Aufgabenpool von 18 Aufgaben zum Identifizieren und Einzeichnen von Symmetrieachsen, den Schülerinnen und Schüler der Jahrgangsstufe 3 (n = 212) bearbeiteten. Es zeigen sich sowohl der Einfluss spezieller Aufgabenmerkmale auf die Lösungshäufigkeiten der Kinder als auch typische Fehler, vor allem bei drehsymmetrischen Figuren. Die Ergebnisse dieser Studie geben erste Hinweise auf Fehlkonzepte von Schülerinnen und Schülern bezüglich Vorstellungen zur Achsensymmetrie und können sowohl in der weiteren Forschung als auch in der Unterrichtspraxis als Ausgangspunkt für detaillierte qualitative Analysen der Antworten von Schülerinnen und Schülern genutzt werden.
Well-controlled area seepage law and disturbance degree between production wells prediction of tight gas reservoir: a case study of Sulige gas field, Ordos Basin, NW China
Authors: Xiao Feng , Xu Wen , Wang Jinkai
Published: March 2020

Based on a sum of well test interpretation analysis, the flowage characteristics of the gas in reservoir were analyzed from physical parameters and double-logarithm curve characteristics of gas wells. The result showed that the permeability of gas well-fracturing area is greatly improved, which is the main area to provide productivity. The speed of pressure transmission was slow because of extremely low permeability of outside the fracturing area and fluid flow was dominated by a linear flow. And three common well test interpretation models were extracted. The characteristics of bi-zonal compound reservoir of gas wells were specified by combination with peripheral supply and pressure change characteristics of gas wells. Variations of reservoir pressure and flowing bottom-hole pressure with time were simulated and quantified under different physical parameters and daily production. And the rational proration scheme of gas production wells was established by integration with numerical simulation method. Numerical simulation results of 21 sets of well patterns showed that there were two recovery inflection points. And a new model was built to research well interference degree that was defined by a new and original mathematical expression about production. The result showed that the infill well pattern should be controlled at 500 m × (500–600) m.
EStradiol and PRogesterone in In vitro ferTilization (ESPRIT): a multicenter study evaluating third- versus second-generation estradiol and progesterone immunoassays
Authors: Polyzos N. P. , Anckaert E. , Drakopoulos P. , Tournaye H. , Schiettecatte J. , Donner H. , Bobba G. , Miles G. , Verhagen-Kamerbeek W. D. J. , Bosch E.
Published: March 2020

Purpose

To assess estradiol (E2) and progesterone levels during ovarian stimulation determined by third-generation (Gen III) and second-generation (Gen II) Elecsys® immunoassays.

Methods

E2 and progesterone concentrations were measured using Elecsys® Gen III and Gen II immunoassays, and progesterone concentrations on the day of ovulation triggering were determined by LC–MS/MS. This was a retrospective, non-interventional study conducted at European tertiary referral infertility clinics in women aged 18–45 years, with a body mass index 18–35 kg/m2, regular menses, and both ovaries.

Results

Serum samples were obtained from 230 women classified by oocyte retrieval as poor (33.0%; 0–3 oocytes), normal (40.9%; 4–15 oocytes), or high (26.1%; > 15 oocytes) responders. E2 and progesterone levels increased during ovarian stimulation, with greatest increases observed in high responders. Elecsys® Gen III and Gen II assay results were highly correlated for E2 (Pearson’s r = 0.99) and progesterone (r = 0.89); Gen III results were lower than Gen II for both E2 and progesterone. On the day of triggering, Gen III E2 and progesterone levels showed a difference of − 15.0% and − 27.9%, respectively. Progesterone levels (on day of triggering) measured by LC–MS/MS correlated better with Gen III (0.98) than Gen II (0.90). Mean relative differences for Gen III and Gen II assays versus LC–MS/MS were 14.6% and 62.8%, respectively.

Conclusion

E2 and progesterone levels determined with Elecsys® Gen II and III assays were highly correlated; results were lower for Gen III versus Gen II. Differences observed for progesterone on the day of triggering may be clinically relevant.
A modified particle swarm optimization based on decomposition with different ideal points for many-objective optimization problems
Authors: Qin Shufen , Sun Chaoli , Zhang Guochen , He Xiaojuan , Tan Ying
Published: March 2020

Many evolutionary algorithms have been proposed for multi-/many-objective optimization problems; however, the tradeoff of convergence and diversity is still the challenge for optimization algorithms. In this paper, we propose a modified particle swarm optimization based on decomposition framework with different ideal points on each reference vector, called MPSO/DD, for many-objective optimization problems. In the MPSO/DD algorithm, the decomposition strategy is used to ensure the diversity of the population, and the ideal point on each reference vector can draw the population converge faster to the optimal front. The position of each individual will be updated by learning the demonstrators in its neighborhood that have less distance to the ideal point along the reference vector. Eight state-of-the-art evolutionary multi-/many-objective optimization algorithms are adopted to compare the performance with MPSO/DD for solving many-objective optimization problems. The experimental results on seven DTLZ test problems with 3, 5, 8, 10, 15 and 20 objectives, respectively, show the efficiency of our proposed method on solving problems with high-dimensional objective space.
Correction to: The Fubini Product and Its Applications
Authors: Uuye Otgonbayar , Zacharias Joachim
Published: March 2020

The article The Fubini Product and Its Applications, written by Otgonbayar Uuye and Joachim Zacharias, was originally published electronically on the publisher’s internet portal on 11 February 2020 without open access. With the author(s).
Photoacoustic viscoelasticity imaging for the detection of acute hepatitis: a feasibility study
Authors: Wang Qian , Shi Yujiao
Published: March 2020

Biomechanical assessments are essential for the understanding of physiological states and the characterization of certain tissue pathologies such as liver cirrhosis. In this work, we showed by the photoacoustic viscoelasticity (PAVE) imaging that obvious mechanical change was also observed in the development of the acute hepatitis owing to the hepatocyte enlargement and intracellular fluid increment, indicating that the PAVE technique can be developed as a supplementary method for detecting acute hepatitis in future. The feasibility of the PAVE imaging is validated by a group of agar phantoms. Furthermore, acute hepatitis pathological animal models were established and imaged ex vivo and in situ by the PAVE technique to demonstrate its capability for the mechanical characterization of acute hepatitis, and the imaging results were consistent with pathological results. The feasibility study of detecting acute hepatitis by the PAVE technique proved that this method has potential to be developed as a clinical biomechanical imaging method to supplement current clinical strategy for liver disease detection.
Is sickle cell disease-related neurotoxicity a systemic endotheliopathy?
Authors: Palomo Marta , Diaz-Ricart Maribel , Carreras Enric
Published: March 2020

The aim of the present article is to review the role of endothelial damage and dysfunction in the vaso-occlusive episodes associated with sickle cell disease (SCD). This inherited hematological disorder leads to irreversible damage of multiple organs through a wide variety of mechanisms, such as sickling of red cells, oxidative state due to ischemic-reperfusion episodes, inflammation, hypercoagulation state, and platelet activation, among others. In SCD, the endothelium arises as the key entity where most of these processes, which eventually lead to increased morbidly and mortality, interact. This review begins with the already accepted idea that organ-specific vasculopathy precedes clinical manifestation, and briefly explains one of the main triggers of vaso-occlusive episodes, the complex interplay between blood cells and the dysfunctional endothelium. Endothelial protective strategies emerge as a potential tool for the prevention of organ-specific disease in SCD. Actually, this knowledge is currently used for the development of potential pharmacologic interventions to improve the lives of SCD patients.
Guidelines for Data Acquisition, Quality and Curation for Observational Research Designs (DAQCORD)
Authors: Ercole Ari , Brinck Vibeke , George Pradeep , Hicks Ramona , Huijben Jilske , Jarrett Michael , Vassar Mary , Wilson Lindsay ,   the DAQCORD collaborators
Published: March 2020

Background:

High-quality data are critical to the entire scientific enterprise, yet the complexity and effort involved in data curation are vastly under-appreciated. This is especially true for large observational, clinical studies because of the amount of multimodal data that is captured and the opportunity for addressing numerous research questions through analysis, either alone or in combination with other data sets. However, a lack of details concerning data curation methods can result in unresolved questions about the robustness of the data, its utility for addressing specific research questions or hypotheses and how to interpret the results. We aimed to develop a framework for the design, documentation and reporting of data curation methods in order to advance the scientific rigour, reproducibility and analysis of the data.

Methods:

Forty-six experts participated in a modified Delphi process to reach consensus on indicators of data curation that could be used in the design and reporting of studies.

Results:

We identified 46 indicators that are applicable to the design, training/testing, run time and post-collection phases of studies.

Conclusion:

The Data Acquisition, Quality and Curation for Observational Research Designs (DAQCORD) Guidelines are the first comprehensive set of data quality indicators for large observational studies. They were developed around the needs of neuroscience projects, but we believe they are relevant and generalisable, in whole or in part, to other fields of health research, and also to smaller observational studies and preclinical research. The DAQCORD Guidelines provide a framework for achieving high-quality data; a cornerstone of health research.
SOLUTION BRANCHES OF NONLINEAR EIGENVALUE PROBLEMS ON RESTRICTED DOMAINS
Authors: ARORA SHANE
Published: March 2020

We extend bifurcation results of nonlinear eigenvalue problems from real Banach spaces to any neighbourhood of a given point. For points of odd multiplicity on these restricted domains, we establish that the component of solutions through the bifurcation point either is unbounded, admits an accumulation point on the boundary, or contains an even number of odd-multiplicity points. In the simple-multiplicity case, we show that branches of solutions in the directions of corresponding eigenvectors satisfy similar conditions on such restricted domains.
SLAVERY AND ITS AFTERMATH IN THE MANDARA MOUNTAINS
Authors: CHÉTIMA MELCHISEDEK
Published: March 2020

Based on long-term oral historical research in the Mandara Mountains, this article traces the ways in which memories of slavery have been preserved in songs which are usually not part of the more formal oral historical narratives. It historicizes this process by focusing on the selective memories of different generations as well as on the influence of colonial and post-colonial politics, particularly post-1990 democratic politics in Cameroon. The major change over time is the shift from the shameful memory of slavery to be repressed – or treated only obliquely – to its public claim as a political resource after the democratic transition of the 1990s. In retelling the history of being sold as slaves, the residents of the Mandara Mountains reversed the negative meaning of slavery to use it to celebrate their resistance to Islam and to voice political claims. This new narrative congeals around beingkirdi, a new regional and trans-religious identity claimed by Christians and pagans in the mountains.
Exception and the Rule: Agamben, Stuff Happens, and Representation in the Post-Truth Age
Authors: Wilson Alex D.
Published: March 2020

The contemporary post-truth environment imposes limitations and ethical consid erations upon the political theatre-maker’s ability to highlight political leaders’ exceptional acts of deception. By unpacking and applying Giorgio Agamben’s writing on the State of Exception to post-truth political performances, Alex D. Wilson discusses in this article how political deception is an exceptional act of sovereign power and how the state of exception is an inherently performative phenomenon. The inherent challenges this state of affairs presents to the theatre are discussed with particular reference to David Hare’s Stuff Happens (2004), which, it is argued, falls into its own state of exception in terms of its approach to truth. Alex D. Wilson is a PhD candidate in Theatre Studies at the University of Otago, who recently completed an MA which explored ethical authorship of British theatrical work produced in response to the 2003 Invasion of Iraq. He is the artistic director of Arcade, a Dunedin-based performing arts company.
INSTRUMENTAL VARIABLE QUANTILE REGRESSION WITH MISCLASSIFICATION
Authors: Ura Takuya
Published: March 2020

This article investigates the instrumental variable quantile regression model (Chernozhukov and Hansen, 2005,Econometrica73, 245–261; 2013,Annual Review of Economics, 5, 57–81) with a binary endogenous treatment. It offers two identification results when the treatment status is not directly observed. The first result is that, remarkably, the reduced-form quantile regression of the outcome variable on the instrumental variable provides a lower bound on the structural quantile treatment effect under the stochastic monotonicity condition. This result is relevant, not only when the treatment variable is subject to misclassification, but also when any measurement of the treatment variable is not available. The second result is for the structural quantile function when the treatment status is measured with error; the sharp identified set is characterized by a set of moment conditions under widely used assumptions on the measurement error. Furthermore, an inference method is provided in the presence of other covariates.
Alternative observational designs to estimate the effectiveness of one dose of oral cholera vaccine in Lusaka, Zambia
Authors: Ferreras E. , Blake A. , Chewe O. , Mwaba J. , Zulu G. , Poncin M. , Rakesh A. , Page A. L. , Quilici M. L. , Azman A. S. , Cohuet S. , Ciglenecki I. , Malama K. , Chizema-Kawesha E. , Luquero F. J.
Published: March 2020

We conducted a matched case-control (MCC), test-negative case-control (TNCC) and case-cohort study in 2016 in Lusaka, Zambia, following a mass vaccination campaign. Confirmed cholera cases served as cases in all three study designs. In the TNCC, control-subjects were cases with negative cholera culture and polymerase chain reaction results. Matched controls by age and sex were selected among neighbours of the confirmed cases in the MCC study. For the case-cohort study, we recruited a cohort of randomly selected individuals living in areas considered at-risk of cholera. We recruited 211 suspected cases (66 confirmed cholera cases and 145 non-cholera diarrhoea cases), 1055 matched controls and a cohort of 921. Adjusted vaccine effectiveness of one dose of oral cholera vaccine (OCV) was 88.9% (95% confidence interval (CI) 42.7–97.8) in the MCC study, 80.2% (95% CI: 16.9–95.3) in the TNCC design and 89.4% (95% CI: 64.6–96.9) in the case-cohort study. Three study designs confirmed the short-term effectiveness of single dose OCV. Major healthcare-seeking behaviour bias did not appear to affect our estimates. Most of the protection among vaccinated individuals could be attributed to the direct effect of the vaccine.
Creating a Novel Disaster Medicine Virtual Reality Training Environment
Authors: Gout Laurent , Hart Alexander , Houze-Cerfon Charles-Henri , Sarin Ritu , Ciottone Gregory R. , Bounes Vincent
Published: March 2020

Introduction:

Disasters are high-acuity, low-frequency events which require medical providers to respond in often chaotic settings. Due to this infrequency, skills can atrophy, so providers must train and drill to maintain them. Historically, drilling for disaster response has been costly, and thus infrequent. Virtual Reality Environments (VREs) have been demonstrated to be acceptable to trainees, and useful for training Disaster Medicine skills. The improved cost of virtual reality training can allow for increased frequency of simulation and training.

Problem:

The problem addressed was to create a novel Disaster Medicine VRE for training and drilling.

Methods:

A VRE was created using SecondLife (Linden Lab; San Francisco, California USA) and adapted for use in Disaster Medicine training and drilling. It is easily accessible for the end-users (trainees), and is adaptable for multiple scenario types due to the presence of varying architecture and objects. Victim models were created which can be role played by educators, or can be virtual dummies, and can be adapted for wide ranging scenarios. Finally, a unique physiologic simulator was created which allows for dummies to mimic disease processes, wounds, and treatment outcomes.

Results:

The VRE was created and has been used extensively in an academic setting to train medical students, as well as to train and drill disaster responders.

Conclusions:

This manuscript presents a new VRE for the training and drilling of Disaster Medicine scenarios in an immersive, interactive experience for trainees.
A 20‐Year Climatology of Madden‐Julian Oscillation Convection: Large‐Scale Precipitation Tracking From TRMM‐GPM Rainfall
Authors: Kerns Brandon W. , Chen Shuyi S.
Published: March 2020

This study presents a 20‐year climatology of the Madden‐Julian Oscillation (MJO) convection based on Large‐scale Precipitation Tracking (LPT) using TRMM‐GPM Multisatellite Precipitation Analysis (TMPA) data from 1998–2018 over the global tropics‐midlatitudes (50°S–50°N). A total of 215 convective events are identified as MJO LPT systems over the 20 years, extending the results of Kerns and Chen (2016, https://doi.org/10.1002/2015JD024661). MJO LPT systems provide quantitative information regarding size, intensity, and location of the MJO convection in both the longitudinal and meridional directions. The MJO contributes up to 40–50% of the annual precipitation over the tropical Indo‐Pacific warm pool. MJO LPT systems have distinct seasonal and interannual variability. While MJO LPT systems are generally confined over the equatorial tropics during Boreal winter, some MJO LPT systems propagate northeast in the Bay of Bengal or from the South China Sea to the western North Pacific during Boreal summer. MJO LPT systems are more than doubled over the Indian Ocean (IO) and Maritime Continent (MC) during La Nina compared to El Nino. The 63% of MJO LPT systems initiate over the tropical IO, 26% over the MC and western Pacific, and 11% from the central Pacific to South America. About 40% of the MJO LPT systems that initialized over the IO were unable to propagate through the MC, namely, the barrier effect. The MC barrier effect is most pronounced during the spring and autumn transitions. This 20‐year MJO LPT climatology product will be provided as a supplement to this publication.
A Microbial Functional Group‐Based CH4 Model Integrated Into a Terrestrial Ecosystem Model: Model Structure, Site‐Level Evaluation, and Sensitivity Analysis
Authors: Song Chaoqing , Luan Junwei , Xu Xiaofeng , Ma Minna , Aurela Mika , Lohila Annalea , Mammarella Ivan , Alekseychik Pavel , Tuittila Eeva‐Stiina , Gong Wei , Chen Xiuzhi , Meng Xianhong , Yuan Wenping
Published: March 2020

Wetlands are one of the most important terrestrial ecosystems for land‐atmosphere CH4 exchange. A new process‐based, biophysical model to quantify CH4 emissions from natural wetlands was developed and integrated into a terrestrial ecosystem model (Integrated Biosphere Simulator). The new model represents a multisubstance system (CH4, O2, CO2, and H2) and describes CH4 production, oxidation, and three transport processes (diffusion, plant‐mediated transport, and ebullition). The new model uses several critical microbial mechanisms to represent the interaction of anaerobic fermenters and homoacetogens, hydrogenotrophic, and acetoclastic methanogens, and methanotrophs in CH4 production and oxidation. We applied the model to 24 different wetlands globally to compare the simulated CH4 emissions to observations and conducted a sensitivity analysis. The results indicated that (1) for most sites, the model was able to capture the magnitude and variation of observed CH4 emissions under varying environmental conditions; (2) the parameters that regulate dissolved organic carbon and acetate production, and acetoclastic methanogenesis had the significant impact on simulated CH4 emissions; (3) the representation of the process components of CH4 cycling showed that CH4 oxidation was about half or more of CH4 production, and plant‐mediated transport was the dominant pathway at most sites; and (4) the seasonality of simulated CH4 emissions can be controlled by soil temperature, water table position, or combinations thereof.
Carbon Flux Variability From a Relatively Simple Ecosystem Model With Assimilated Data Is Consistent With Terrestrial Biosphere Model Estimates
Authors: Quetin Gregory R. , Bloom A. Anthony , Bowman Kevin W. , Konings Alexandra G.
Published: March 2020

Modeling the net carbon balance is challenging due to the knowledge gaps in the variability and processes controlling gross carbon fluxes. Terrestrial carbon cycle modeling is susceptible to several sources of bias, including meteorological uncertainty, model structural uncertainty, and model parametric uncertainty. To determine the impact of these uncertainties, we compare three model‐derived representations of the global terrestrial carbon balance across 1997–2009: (1) observation‐constrained model‐data fusion (CARBon Data Model FraMEwork, CARDAMOM), (2) the reanalysis‐driven Trends in Net Land‐Atmosphere Carbon Exchange (TRENDY) land biosphere model ensemble, and (3) the Coupled Model Intercomparison Project 5 (CMIP5) Earth System Model ensemble. We consider the spread in carbon cycle simulations attributable primarily to parametric uncertainty (CARDAMOM), structural uncertainty (TRENDY), and combined structural and simulated meteorological uncertainty (CMIP5). We find that the spread across the CARDAMOM ensemble long‐term mean—produced by parameter uncertainty—is larger than the spread of TRENDY and CMIP5 for net biosphere exchange (NBE) but similar for gross primary productivity (GPP). The carbon flux dynamics of CARDAMOM compares to models in TRENDY as well as models in TRENDY compare to each other in many regions for NBE seasonal (nine of 12), NBE interannual (11 of 12), and GPP seasonal variability (7 of 12), although not for GPP interannual variability (2 of 12). The simple model structure of CARDAMOM and systematic assimilation of observations is sufficient to produce carbon dynamics within the range of more complex models. These results are encouraging for the use of model‐data fusion products with empirically estimated uncertainty for global carbon cycle studies.
Full Domestic Supply Chains of Blue Virtual Water Flows Estimated for Major U.S. Cities
Authors: Garcia Susana , Rushforth Richard , Ruddell Benjamin L. , Mejia Alfonso
Published: March 2020

Through the trade of products and services, cities indirectly depend on distant water sources to function, prosper, and grow. To fully account for indirect (virtual) water dependencies, virtual water flows need to be known along complex supply chains. To this purpose, we build a new environmental multiregional input–output model for U.S. regions. The model is used to quantify the domestic, blue virtual water flows and analyze the water footprints of 69 major U.S. cities. Our results show a large inequality in the urban water consumed for economic production: just 7 out of the 69 cities included in this study account for 35% of the U.S. national water footprint of production. This is due to the production of water‐intensive agricultural products in the metropolitan areas of western cities. The inequality reduces for the urban water footprint of consumption because, through the supply chains of industrialized food sectors, western virtual water is partially transferred to eastern cities as final demand. The water embodied in industrial products and services tends to be higher in western cities than in eastern cities; that is, the water embodied in food services could be several times higher in Los Angeles than in New York City. Trade hub cities attract large inflows of products which are mostly transformed for consumption elsewhere. Thus, the omission of product interdependencies within trade hub cities can increase by several times their water footprints of consumption. Overall, the proposed model is able to enhance subnational estimates of U.S. virtual water flows.
Thank You to Our 2019 Peer Reviewers
Authors: Filippelli Gabriel , Colwell Rita R. , Anenberg Susan , Balbus John , Ceccarelli Daniela , Hudson‐Edwards Karen A. , Jutla Antarpreet , Miao Chiyuan , Sandifer Paul A. , Vengosh Avner
Published: March 2020

Key Points

The editors thank the 2019 peer reviewers
Symbiolite formation: a powerful in vitro model to untangle the role of bacterial communities in the photosynthesis-induced formation of microbialites
Authors: Nitschke Matthew R , Fidalgo Cátia , Simões João , Brandão Cláudio , Alves Artur , Serôdio João , Frommlet Jörg C
Published: March 2020

Microbially induced calcification is an ancient, community-driven mineralisation process that produces different types of microbialites. Symbiolites are photosynthesis-induced microbialites, formed by calcifying co-cultures of dinoflagellates from the family Symbiodiniaceae and bacteria. Symbiolites encase the calcifying community as endolithic cells, pointing at an autoendolithic niche of symbiotic dinoflagellates, and provide a rare opportunity to study the role of bacteria in bacterial–algal calcification, as symbiodiniacean cultures display either distinct symbiolite-producing (SP) or non-symbiolite-producing (NP) phenotypes. Using Illumina sequencing, we found that the bacterial communities of SP and NP cultures differed significantly in the relative abundance of 23 genera, 14 families, and 2 phyla. SP cultures were rich in biofilm digesters from the phylum Planctomycetes and their predicted metagenomes were enriched in orthologs related to biofilm formation. In contrast, NP cultures were dominated by biofilm digesters from the Bacteroidetes, and were inferred as enriched in proteases and nucleases. Functional assays confirmed the potential of co-cultures and bacterial isolates to produce biofilms and point at acidic polysaccharides as key stimulators for mineral precipitation. Hence, bacteria appear to influence symbiolite formation primarily through their biofilm-producing and modifying activity and we anticipate that symbiolite formation, as a low-complexity in vitro model, will significantly advance our understanding of photosynthesis-induced microbial calcification processes.
Protection from β-cell apoptosis by inhibition of TGF-β/Smad3 signaling
Authors: Lee Ji-Hyeon , Mellado-Gil Jose Manuel , Bahn Young Jae , Pathy Sushrut M. , Zhang Ying E. , Rane Sushil G.
Published: March 2020

Prevailing insulin resistance and the resultant hyperglycemia elicits a compensatory response from pancreatic islet beta cells (β-cells) that involves increases in β-cell function and β-cell mass. However, the sustained metabolic stress eventually leads to β-cell failure characterized by severe β-cell dysfunction and progressive loss of β-cell mass. Whereas, β-cell dysfunction is relatively well understood at the mechanistic level, the avenues leading to loss of β-cell mass are less clear with reduced proliferation, dedifferentiation, and apoptosis all potential mechanisms. Butler and colleagues documented increased β-cell apoptosis in pancreas from lean and obese human Type 2 diabetes (T2D) subjects, with no changes in rates of β-cell replication or neogenesis, strongly suggesting a role for apoptosis in β-cell failure. Here, we describe a permissive role for TGF-β/Smad3 in β-cell apoptosis. Human islets undergoing β-cell apoptosis release increased levels of TGF-β1 ligand and phosphorylation levels of TGF-β’s chief transcription factor, Smad3, are increased in human T2D islets suggestive of an autocrine role for TGF-β/Smad3 signaling in β-cell apoptosis. Smad3 phosphorylation is similarly increased in diabetic mouse islets undergoing β-cell apoptosis. In mice, β-cell-specific activation of Smad3 promotes apoptosis and loss of β-cell mass in association with β-cell dysfunction, glucose intolerance, and diabetes. In contrast, inactive Smad3 protects from apoptosis and preserves β-cell mass while improving β-cell function and glucose tolerance. At the molecular level, Smad3 associates with Foxo1 to propagate TGF-β-dependent β-cell apoptosis. Indeed, genetic or pharmacologic inhibition of TGF-β/Smad3 signals or knocking down Foxo1 protects from β-cell apoptosis. These findings reveal the importance of TGF-β/Smad3 in promoting β-cell apoptosis and demonstrate the therapeutic potential of TGF-β/Smad3 antagonism to restore β-cell mass lost in diabetes.
MMP9 mediates acute hyperglycemia-induced human cardiac stem cell death by upregulating apoptosis and pyroptosis in vitro
Authors: Yadav Santosh K. , Kambis Tyler N. , Kar Sumit , Park Song Y. , Mishra Paras K.
Published: March 2020

Providing a conducive microenvironment is critical to increase survival of transplanted stem cells in regenerative therapy. Hyperglycemia promotes stem cell death impairing cardiac regeneration in the diabetic heart. Understanding the molecular mechanisms of high glucose-induced stem cell death is important for improving cardiac regeneration in diabetic patients. Matrix metalloproteinase-9 (MMP9), a collagenase, is upregulated in the diabetic heart, and ablation of MMP9 decreases infarct size in the non-diabetic myocardial infarction heart. In the present study, we aim to investigate whether MMP9 is a mediator of hyperglycemia-induced cell death in human cardiac stem cells (hCSCs) in vitro. We created MMP9−/− hCSCs to test the hypothesis that MMP9 mediates hyperglycemia-induced oxidative stress and cell death via apoptosis and pyroptosis in hCSCs, which is attenuated by the lack of MMP9. We found that hyperglycemia induced oxidative stress and increased cell death by promoting pyroptosis and apoptosis in hCSCs, which was prevented in MMP9−/− hCSCs. These findings revealed a novel intracellular role of MMP9 in mediating stem cell death and provide a platform to assess whether MMP9 inhibition could improve hCSCs survival in stem cell therapy at least in acute hyperglycemic microenvironment.
Strain-induced stripe phase in charge-ordered single layer NbSe2
Authors: Cossu Fabrizio , Palotás Krisztián , Sarkar Sagar , Di Marco Igor , Akbari Alireza
Published: March 2020

Charge density waves are ubiquitous phenomena in metallic transition metal dichalcogenides. In NbSe2, a triangular 3 × 3 structural modulation is coupled to a charge modulation. Recent experiments reported evidence for a triangular-stripe transition at the surface, due to strain or accidental doping and associated to a 4 × 4 modulation. We employ ab initio calculations to investigate the strain-induced structural instabilities in a pristine single layer and analyse the energy hierarchy of the structural and charge modulations. Our results support the observation of phase separation between triangular and stripe phases in 1H-NbSe2, relating the stripe phase to compressive isotropic strain, favouring the 4 × 4 modulation. The observed wavelength of the charge modulation is also reproduced with a good accuracy.
Carbon dots-fed Shewanella oneidensis MR-1 for bioelectricity enhancement
Authors: Yang Chenhui , Aslan Hüsnü , Zhang Peng , Zhu Shoujun , Xiao Yong , Chen Lixiang , Khan Nasar , Boesen Thomas , Wang Yuanlin , Liu Yang , Wang Lei , Sun Ye , Feng Yujie , Besenbacher Flemming , Zhao Feng , Yu Miao
Published: March 2020

Bioelectricity generation, by Shewanella oneidensis (S. oneidensis) MR-1, has become particularly alluring, thanks to its extraordinary prospects for energy production, pollution treatment, and biosynthesis. Attempts to improve its technological output by modification of S. oneidensis MR-1 remains complicated, expensive and inefficient. Herein, we report on the augmentation of S. oneidensis MR-1 with carbon dots (CDs). The CDs-fed cells show accelerated extracellular electron transfer and metabolic rate, with increased intracellular charge, higher adenosine triphosphate level, quicker substrate consumption and more abundant extracellular secretion. Meanwhile, the CDs promote cellular adhesion, electronegativity, and biofilm formation. In bioelectrical systems the CDs-fed cells increase the maximum current value, 7.34 fold, and power output, 6.46 fold. The enhancement efficacy is found to be strongly dependent on the surface charge of the CDs. This work demonstrates a simple, cost-effective and efficient route to improve bioelectricity generation of S. oneidensis MR-1, holding promise in all relevant technologies.
Extracellular nanovesicles for packaging of CRISPR-Cas9 protein and sgRNA to induce therapeutic exon skipping
Authors: Gee Peter , Lung Mandy S. Y. , Okuzaki Yuya , Sasakawa Noriko , Iguchi Takahiro , Makita Yukimasa , Hozumi Hiroyuki , Miura Yasutomo , Yang Lucy F. , Iwasaki Mio , Wang Xiou H. , Waller Matthew A. , Shirai Nanako , Abe Yasuko O. , Fujita Yoko , Watanabe Kei , Kagita Akihiro , Iwabuchi Kumiko A. , Yasuda Masahiko , Xu Huaigeng , Noda Takeshi , Komano Jun , Sakurai Hidetoshi , Inukai Naoto , Hotta Akitsu
Published: March 2020

Prolonged expression of the CRISPR-Cas9 nuclease and gRNA from viral vectors may cause off-target mutagenesis and immunogenicity. Thus, a transient delivery system is needed for therapeutic genome editing applications. Here, we develop an extracellular nanovesicle-based ribonucleoprotein delivery system named NanoMEDIC by utilizing two distinct homing mechanisms. Chemical induced dimerization recruits Cas9 protein into extracellular nanovesicles, and then a viral RNA packaging signal and two self-cleaving riboswitches tether and release sgRNA into nanovesicles. We demonstrate efficient genome editing in various hard-to-transfect cell types, including human induced pluripotent stem (iPS) cells, neurons, and myoblasts. NanoMEDIC also achieves over 90% exon skipping efficiencies in skeletal muscle cells derived from Duchenne muscular dystrophy (DMD) patient iPS cells. Finally, single intramuscular injection of NanoMEDIC induces permanent genomic exon skipping in a luciferase reporter mouse and in mdx mice, indicating its utility for in vivo genome editing therapy of DMD and beyond.
Paradoxical activation of the protein kinase-transcription factor ERK5 by ERK5 kinase inhibitors
Authors: Lochhead Pamela A. , Tucker Julie A. , Tatum Natalie J. , Wang Jinhua , Oxley David , Kidger Andrew M. , Johnson Victoria P. , Cassidy Megan A. , Gray Nathanael S. , Noble Martin E. M. , Cook Simon J.
Published: March 2020

The dual protein kinase-transcription factor, ERK5, is an emerging drug target in cancer and inflammation, and small-molecule ERK5 kinase inhibitors have been developed. However, selective ERK5 kinase inhibitors fail to recapitulate ERK5 genetic ablation phenotypes, suggesting kinase-independent functions for ERK5. Here we show that ERK5 kinase inhibitors cause paradoxical activation of ERK5 transcriptional activity mediated through its unique C-terminal transcriptional activation domain (TAD). Using the ERK5 kinase inhibitor, Compound 26 (ERK5-IN-1), as a paradigm, we have developed kinase-active, drug-resistant mutants of ERK5. With these mutants, we show that induction of ERK5 transcriptional activity requires direct binding of the inhibitor to the kinase domain. This in turn promotes conformational changes in the kinase domain that result in nuclear translocation of ERK5 and stimulation of gene transcription. This shows that both the ERK5 kinase and TAD must be considered when assessing the role of ERK5 and the effectiveness of anti-ERK5 therapeutics.
Plasmonic nanostar photocathodes for optically-controlled directional currents
Authors: Pettine Jacob , Choo Priscilla , Medeghini Fabio , Odom Teri W. , Nesbitt David J.
Published: March 2020

Plasmonic nanocathodes offer unique opportunities for optically driving, switching, and steering femtosecond photocurrents in nanoelectronic devices and pulsed electron sources. However, angular photocurrent distributions in nanoplasmonic systems remain poorly understood and are therefore difficult to anticipate and control. Here, we provide a direct momentum-space characterization of multiphoton photoemission from plasmonic gold nanostars and demonstrate all-optical control over these currents. Versatile angular control is achieved by selectively exciting different tips on single nanostars via laser frequency or linear polarization, thereby rotating the tip-aligned directional photoemission as observed with angle-resolved 2D velocity mapping and 3D reconstruction. Classical plasmonic field simulations combined with quantum photoemission theory elucidate the role of surface-mediated nonlinear excitation for plasmonic field enhancements highly concentrated at the sharp tips (Rtip = 3.4 nm). We thus establish a simple mechanism for femtosecond spatiotemporal current control in designer nanosystems.
Microglia clear neuron-released α-synuclein via selective autophagy and prevent neurodegeneration
Authors: Choi Insup , Zhang Yuanxi , Seegobin Steven P. , Pruvost Mathilde , Wang Qian , Purtell Kerry , Zhang Bin , Yue Zhenyu
Published: March 2020

Microglia maintain brain homeostasis by removing neuron-derived components such as myelin and cell debris. The evidence linking microglia to neurodegenerative diseases is growing; however, the precise mechanisms remain poorly understood. Herein, we report a neuroprotective role for microglia in the clearance of neuron-released α-synuclein. Neuronal α-synuclein activates microglia, which in turn engulf α-synuclein into autophagosomes for degradation via selective autophagy (termed synucleinphagy). Synucleinphagy requires the presence of microglial Toll-like receptor 4 (TLR4), which induces transcriptional upregulation ofp62/SQSTM1through the NF-κB signaling pathway. Induction of p62, an autophagy receptor, is necessary for the formation of α-synuclein/ubiquitin-positive puncta that are degraded by autophagy. Finally, disruption of microglial autophagy in mice expressing human α-synuclein promotes the accumulation of misfolded α-synuclein and causes midbrain dopaminergic neuron degeneration. Our study thus identifies a neuroprotective function of microglia in the clearance of α-synuclein via TLR4-NF-κB-p62 mediated synucleinphagy.
Amyloid-β42/40 ratio drives tau pathology in 3D human neural cell culture models of Alzheimer’s disease
Authors: Kwak Sang Su , Washicosky Kevin J. , Brand Emma , von Maydell Djuna , Aronson Jenna , Kim Susan , Capen Diane E. , Cetinbas Murat , Sadreyev Ruslan , Ning Shen , Bylykbashi Enjana , Xia Weiming , Wagner Steven L. , Choi Se Hoon , Tanzi Rudolph E. , Kim Doo Yeon
Published: March 2020

The relationship between amyloid-β (Aβ) species and tau pathology in Alzheimer’s disease (AD) is not fully understood. Here, we provide direct evidence that Aβ42/40 ratio, not total Aβ level, plays a critical role in inducing neurofibrillary tangles (NTFs) in human neurons. Using 3D-differentiated clonal human neural progenitor cells (hNPCs) expressing varying levels of amyloid β precursor protein (APP) and presenilin 1 (PS1) with AD mutations, we show that pathogenic tau accumulation and aggregation are tightly correlated with Aβ42/40 ratio. Roles of Aβ42/40 ratio on tau pathology are also confirmed with APP transmembrane domain (TMD) mutant hNPCs, which display differential Aβ42/40 ratios without mutant PS1. Moreover, naïve hNPCs co-cultured with APP TMD I45F (high Aβ42/40) cells, not with I47F cells (low Aβ42/40), develop robust tau pathology in a 3D non-cell autonomous cell culture system. These results emphasize the importance of reducing the Aβ42/40 ratio in AD therapy.
Dichloromethylation of enones by carbon nitride photocatalysis
Authors: Mazzanti Stefano , Kurpil Bogdan , Pieber Bartholomäus , Antonietti Markus , Savateev Aleksandr
Published: March 2020

Small organic radicals are ubiquitous intermediates in photocatalysis and are used in organic synthesis to install functional groups and to tune electronic properties and pharmacokinetic parameters of the final molecule. Development of new methods to generate small organic radicals with added functionality can further extend the utility of photocatalysis for synthetic needs. Herein, we present a method to generate dichloromethyl radicals from chloroform using a heterogeneous potassium poly(heptazine imide) (K-PHI) photocatalyst under visible light irradiation for C1-extension of the enone backbone. The method is applied on 15 enones, with γ,γ-dichloroketones yields of 18–89%. Due to negative zeta-potential (−40 mV) and small particle size (100 nm) K-PHI suspension is used in quasi-homogeneous flow-photoreactor increasing the productivity by 19 times compared to the batch approach. The resulting γ,γ-dichloroketones, are used as bifunctional building blocks to access value-added organic compounds such as substituted furans and pyrroles.
Dynamics of bacterial population growth in biofilms resemble spatial and structural aspects of urbanization
Authors: Paula Amauri J. , Hwang Geelsu , Koo Hyun
Published: March 2020

Biofilms develop from bacteria bound on surfaces that grow into structured communities (microcolonies). Although surface topography is known to affect bacterial colonization, how multiple individual settlers develop into microcolonies simultaneously remains underexplored. Here, we use multiscale population-growth and 3D-morphometric analyses to assess the spatiotemporal development of hundreds of bacterial colonizers towards submillimeter-scale microcolony communities. Using an oral bacterium (Streptococcus mutans), we find that microbial cells settle on the surface randomly under sucrose-rich conditions, regardless of surface topography. However, only a subset of colonizers display clustering behavior and growth following a power law. These active colonizers expand three-dimensionally by amalgamating neighboring bacteria into densely populated microcolonies. Clustering and microcolony assembly are dependent on exopolysaccharides, while population growth dynamics and spatial structure are affected by cooperative or antagonistic microbes. Our work suggests that biofilm assembly resembles certain spatial-structural features of urbanization, where population growth and expansion can be influenced by type of settlers, neighboring cells, and further community merging and scaffolding occurring at various scales.
Single molecule analysis reveals monomeric XPA bends DNA and undergoes episodic linear diffusion during damage search
Authors: Beckwitt Emily C. , Jang Sunbok , Carnaval Detweiler Isadora , Kuper Jochen , Sauer Florian , Simon Nina , Bretzler Johanna , Watkins Simon C. , Carell Thomas , Kisker Caroline , Van Houten Bennett
Published: March 2020

Nucleotide excision repair (NER) removes a wide range of DNA lesions, including UV-induced photoproducts and bulky base adducts. XPA is an essential protein in eukaryotic NER, although reports about its stoichiometry and role in damage recognition are controversial. Here, by PeakForce Tapping atomic force microscopy, we show that human XPA binds and bends DNA by ∼60° as a monomer. Furthermore, we observe XPA specificity for the helix-distorting base adduct N-(2’-deoxyguanosin-8-yl)-2-acetylaminofluorene over non-damaged dsDNA. Moreover, single molecule fluorescence microscopy reveals that DNA-bound XPA exhibits multiple modes of linear diffusion between paused phases. The presence of DNA damage increases the frequency of pausing. Truncated XPA, lacking the intrinsically disordered N- and C-termini, loses specificity for DNA lesions and shows less pausing on damaged DNA. Our data are consistent with a working model in which monomeric XPA bends DNA, displays episodic phases of linear diffusion along DNA, and pauses in response to DNA damage.