bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamic acetylation profile during mammalian neurulation
Authors: Massa Valentina , Avagliano Laura , Grazioli Paolo , De Castro Sandra C. P. , Parodi Chiara , Savery Dawn , Vergani Patrizia , Cuttin Serena , Doi Patrizia , Bulfamante Gaetano , Copp Andrew J. , Greene Nicholas D. E.
Published: November 2019

Background

Neural tube defects (NTDs) result from failure of neural tube closure during embryogenesis. These severe birth defects of the central nervous system include anencephaly and spina bifida, and affect 0.5–2 per 1,000 pregnancies worldwide in humans. It has been demonstrated that acetylation plays a pivotal role during neural tube closure, as animal models for defective histone acetyltransferase proteins display NTDs. Acetylation represents an important component of the complex network of posttranslational regulatory interactions, suggesting a possible fundamental role during primary neurulation events. This study aimed to assess protein acetylation contribution to early patterning of the central nervous system both in human and murine specimens.

Methods

We used both human and mouse (Cited2
−/−) samples to analyze the dynamic acetylation of proteins during embryo development through immunohistochemistry, western blot analysis and quantitative polymerase chain reaction.

Results

We report the dynamic profile of histone and protein acetylation status during neural tube closure. We also report a rescue effect in an animal model by chemical p53 inhibition.

Conclusions

Our data suggest that the p53‐acetylation equilibrium may play a role in primary neurulation in mammals.
The phage display of Bacillus subtilis Lipase A significantly enhances catalytic activity due to altered nanoscale distribution in colloidal solution
Authors: Nahar Sharifun , Sokullu Esen , Gauthier Marc A.
Published: November 2019

Screening libraries of mutant proteins by phage display is now relatively common. However, one unknown factor is how the bacteriophage scaffold itself influences the properties of the displayed protein. This communication evaluates the effect of solution parameters on the catalytic activity of phage displayed Bacillus subtilis Lipase A (BSLA), compared to the free enzyme in solution. While the pH‐ and temperature‐activity profiles of BSLA were not intrinsically affected by phage display, the nanoscale distribution of BSLA within the micellar assay buffer was. This lead to a pronounced increase of activity of phage–BSLA relative to the free enzyme, owing to the accumulation of phage–BSLA at the substrate‐rich micelles. Considering this result obtained for BSLA, caution is warranted and similar effects should be considered when selecting other enzymes/proteins by phage display, as the activity of the displayed protein may differ from that of the free protein.
Analytical solution for a hybrid Logistic‐Monod cell growth model in batch and continuous stirred tank reactor culture
Authors: Xu Peng
Published: November 2019

Monod and Logistic growth models have been widely used as basic equations to describe cell growth in bioprocess engineering. In the case of the Monod equation, the specific growth rate is governed by a limiting nutrient, with the mathematical form similar to the Michaelis–Menten equation. In the case of the Logistic equation, the specific growth rate is determined by the carrying capacity of the system, which could be growth‐inhibiting factors (i.e., toxic chemical accumulation) other than the nutrient level. Both equations have been found valuable to guide us build unstructured kinetic models to analyze the fermentation process and understand cell physiology. In this work, we present a hybrid Logistic‐Monod growth model, which accounts for multiple growth‐dependent factors including both the limiting nutrient and the carrying capacity of the system. Coupled with substrate consumption and yield coefficient, we present the analytical solutions for this hybrid Logistic‐Monod model in both batch and continuous stirred tank reactor (CSTR) culture. Under high biomass yield (Yx/s) conditions, the analytical solution for this hybrid model is approaching to the Logistic equation; under low biomass yield condition, the analytical solution for this hybrid model converges to the Monod equation. This hybrid Logistic‐Monod equation represents the cell growth transition from substrate‐limiting condition to growth‐inhibiting condition, which could be adopted to accurately describe the multi‐phases of cell growth and may facilitate kinetic model construction, bioprocess optimization, and scale‐up in industrial biotechnology.
Quantification of cobimetinib, cabozantinib, dabrafenib, niraparib, olaparib, vemurafenib, regorafenib and its metabolite regorafenib M2 in human plasma by UPLC–MS/MS
Authors: Krens Stefanie D. , van der Meulen Eric , Jansman Frank G.A. , Burger David M. , van Erp Nielka P.
Published: November 2019

A sensitive and selective ultra‐high performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method for the simultaneous determination of seven oral oncolytics (two PARP inhibitors, i.e. olaparib and niraparib, and five tyrosine kinase inhibitors, i.e. cobimetinib, cabozantinib, dabrafenib, vemurafenib and regorafenib, plus its active metabolite regorafenib M2) in EDTA plasma was developed and validated. Stable isotope‐labelled internal standards were used for each analyte. A simple protein precipitation method was performed with acetonitrile. The LC–MS/MS system consisted of an Acquity H‐Class UPLC system, coupled to a Xevo TQ‐S micro tandem mass spectrometer. The compounds were separated on a Waters CORTECS UPLC C18 column (2.1 × 50 mm, 1.6 μm particle size) and eluted with a gradient elution system. The ions were detected in the multiple reaction monitoring mode. The method was validated for cobimetinib, cabozantinib, dabrafenib, niraparib, olaparib, vemurafenib, regorafenib and regorafenib M2 over the ranges 6–1000, 100–5000, 10–4000, 200–2000, 200–20,000, 5000–100,000, 500–10,000 and 500–10,000 μg/L, respectively. Within‐day accuracy values for all analytes ranged from 86.8 to 115.0% with a precision of <10.4%. Between‐day accuracy values ranged between 89.7 and 111.9% with a between‐day precision of <7.4%. The developed method was successfully used for guiding therapy with therapeutic drug monitoring in cancer patients and clinical research programs in our laboratory.
Quantification of selected aroma compounds in e‐cigarette products and toxicity evaluation in HUVEC/Tert2 cells
Authors: Noël Jean‐Christophe , Rainer Daniela , Gstir Ronald , Rainer Matthias , Bonn Günther
Published: November 2019

During recent years, the number of consumers using so‐called e‐cigarettes, which are electrical devices to aerosolize a liquid consisting of propylene glycol, glycerol, optional nicotine and flavoring chemicals, has been increasing. Aromas vary from common flavors such as mint to more unusual flavors such as buttermilk or pepperoni pizza. Consumers today can buy e‐concentrates that consist of propylene glycol and aroma to blend their own desired flavor at home. Little is known about the composition and concentration of various aroma molecules in the different e‐liquids and e‐concentrates. In addition, the process of EU‐wide regulation is still ongoing. The aim of this research study was to identify and quantify possible undesirable aroma compounds in e‐liquids and e‐concentrates. Flavoring chemicals such as estragole, benzaldehyde and cinnamaldehyde were quantified. The measurements were carried out on a GC–MS system. The results show the presence of highly concentrated flavoring compounds and limonene oxide in lemon‐flavored e‐concentrates. In the final step, samples and single‐aroma standards were tested for their toxicity to HUVEC/Tert2 cells, where some single‐flavoring chemicals such as cinnamic aldehyde revealed significant toxic effects.
Visualizing the relationship among indicators for lone actor terrorist attacks: Multidimensional scaling and the TRAP‐18
Authors: Goodwill Alasdair , Meloy J. Reid
Published: November 2019

This validation study analyses data from a sample of North American terrorist attackers (n = 33) and non‐attackers (n = 23) through the lens of the Terrorist Radicalization Assessment Protocol (TRAP‐18; Meloy, 2017) utilizing a multivariate statistical approach – multidimensional scaling – to visualize potential clustering (co‐occurrence) of risk factors. Rarely done in terrorism research, the results plotted in two‐dimensional space show the clustering and co‐occurrence of most of the eight proximal warning behaviors among the attackers, but not among the non‐attackers, and less of a clustering and association of distal characteristics, but their presence in both attackers and non‐attackers. These findings provide further empirical support for the rational‐theoretical model of the TRAP‐18, a structured professional judgment instrument for threat assessment of lone actor terrorists. It advances the quantitative analysis of operationally relevant and behaviorally observable indicators for use by law enforcement and counterterrorism professionals and their consultants. Findings are discussed in relation to other research on pre‐offense behaviors of lone actor terrorists, and recommendations are made for both operational use and further research.
Silencing circular RNA VANGL1 inhibits progression of bladder cancer by regulating miR‐1184/IGFBP2 axis
Authors: Yang Dengke , Qian Haining , Fang Zhen , Xu An , Zhao Shutian , Liu Bingyan , Li Dong
Published: November 2019

Circular RNA VANGL1 (circVANGL1) is generated from two exons of the Van Gogh‐like 1 (VANGL1) gene and serves as a tumor promoter by sponging certain microRNAs (miRNAs). However, the role of circVANGL1 in bladder cancer (BC) is still unclear. So, in order to investigate the role of circVANGL1 in BC, quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR) was employed to evaluate the circVANGL1 expression in tumor tissues from BC patients and in BC cell lines. Small interfering RNA against circVANGL1 was constructed and stably transfected into human bladder epithelium immortalized cells (SV‐HUC). Cell invasion and migration were detected in Transwell chambers, cell proliferation was determined by CCK8 assays, and tumorigenesis in nude mice was examined to assess the effect of circVANGL1 in BC. Subcellular localization of circVANGL1 was confirmed by fluorescence in situ hybridization. The interactive relationships among circVANGL1, miRNA, and relative proteins were confirmed by luciferase reporter assays. The results showed that circVANGL1 was upregulated in both BC tissues and cell lines. Silencing the expression of circVANGL1 suppressed cell invasion, migration, and proliferation during in vitro experiments. Mechanistically, we demonstrated that circVANGL1 upregulated the expression of miR‐1184 target gene insulin‐like growth factor‐binding protein 2 (IGFBP2) by sponging miR‐1184, which promoted the aggressive biological behaviors of BC. Taken together, our results indicate that circVANGL1 acts as a tumor promoter through the novel circVANGL1/miR‐1184/IGFBP2 axis. Hopefully, our study will provide new ideas for the clinical treatment of BC.
Circ_0001658 promotes the proliferation and metastasis of osteosarcoma cells via regulating miR‐382‐5p/YB‐1 axis
Authors: Wang Lisong , Wang Pengbin , Su Xiujun , Zhao Bo
Published: November 2019

Circular RNA (circRNA) can modulate the gene expression via sponging microRNA (miRNA) in multiple malignancies. Nevertheless, the detailed function of circ_0001658 in osteosarcoma (OS) and its regulatory mechanism remain elusive. Real‐time PCR was carried out to detect the expressions of circ_0001658, miR‐382‐5p, and Y box‐binding protein 1 (YB‐1) mRNA in OS tissues. Besides, western blot was done to monitor YB‐1 expression in OS cells. Chi‐squared test was used to analyse the correlation between circ_0001658 and clinicopathologic characteristics of OS patients. CCK8 assay, colony formation assay, flow cytometry, and transwell assay were performed to determine the function of circ_0001658. Moreover, dual‐luciferase reporter gene assay was done to verify the targeting relationship between circ_0001658 and miR‐382‐5p. Compared with adjacent tissues, circ_0001658 displayed a significantly higher expression in OS tissues. Circ_0001658 could facilitate the proliferation, migration, and invasion of OS cells and impede apoptosis by sponging miR‐382‐5p. Further, circ_0001658 was proved to directly and negatively regulate the expression of miR‐382‐5 while positively modulate the expression of YB‐1. Circ_0001658 promotes the proliferation and metastasis of OS cells via modulating miR‐382‐5p/YB‐1 axis.

Significance of the study

In recent years, the expression and function of circular RNA in cancer have been the focus of tumour research. The study on circular RNA helps elucidate the molecular pathology of tumorigenesis and cancer progression. This study demonstrated that circ_0001658 promotes the proliferation and metastasis of OS cells via modulating miR‐382‐5p/YB‐1 axis. To our best knowledge, this work is the first to study the expression and function of circ_0001658 in cancer.
Effects of flavonoids on tongue squamous cell carcinoma
Authors: Gutiérrez‐Venegas Gloria , Sánchez‐Carballido Manuel Alejandro , Delmas Suárez Claire , Gómez‐Mora Juan Arturo , Bonneau Noémie
Published: November 2019

Squamous cell carcinoma (SCC) of the tongue is associated with tobacco use, alcohol abuse, and human papillomavirus (HPV) infections. While clinical outcomes have recently improved for HPV‐positive patients in general, 50% of patients suffering from tongue cancer die within 5 years of being diagnosed. Flavonoids are secondary plant metabolites with a wide range of biological activities including antioxidant, anti‐inflammatory, and anticancer activities. Flavonoids have generated high interest as therapeutic agents owing to their low toxicity and their effects on a large variety of cancer cell types. In this literature review, we evaluate the actions of flavonoids on SCC of the tongue demonstrated in both in vivo and in vitro models.
Mathematical modelling in high school chemistry: Titration curves
Authors: Kraska Thomas
Published: November 2019

In der Schule, aber auch darüber hinaus werden die Fächer aus Sicht der Lernenden häufig isoliert gesehen. Demgegenüber sind in einem Fach auch immer Beiträge anderer Fächer erforderlich. Im Fach Chemie sind dies unter anderem Kenntnisse in angewandter Mathematik. Um möglichst früh den Bezug der Chemie zur Mathematik zu verdeutlichen, können bereits in der Schule Prinzipien der mathematischen Modellierung eingeführt werden. Hier wird anhand eines konkreten Beispiels gezeigt, wie man die mathematische Modellierung bzw. Simulation eines Standardexperiments in der Schulchemie, die Titration einprotoniger starker sowie schwacher Säuren mit einer starken Base, durchführen kann. Die Herleitung basiert ausschließlich auf mathematischen Fähigkeiten, die in der Sekundarstufe I vermittelt werden, und ist so für die gymnasiale Oberstufe geeignet. Das Thema fügt sich in die Lehrpläne als eine Vertiefung ein. Durch diese Art der Implementierung der Mathematik im Chemieunterricht kann auch einer möglichen Entfremdung des Schulfachs Chemie von dem Studienfach Chemie entgegengewirkt werden. Die hier durchgeführten Herleitungen sind mit Blick auf die Nachvollziehbarkeit bewusst ausführlich und sollten für die Anwendung im Chemieunterricht angepasst werden. Die Art der Herleitungen bietet außerdem Möglichkeiten, übergeordnete Modellierungsmethoden der Naturwissenschaften zu vermitteln.
Dynamic motions of molecular motors in the actin cytoskeleton
Authors: Jung Wonyeong , Tabatabai A. Pasha , Thomas Jacob J. , Tabei S. M. Ali , Murrell Michael P. , Kim Taeyoon
Published: November 2019

During intracellular transport, cellular cargos, such as organelles, vesicles, and proteins, are transported within cells. Intracellular transport plays an important role in diverse cellular functions. Molecular motors walking on the cytoskeleton facilitate active intracellular transport, which is more efficient than diffusion‐based passive transport. Active transport driven by kinesin and dynein walking on microtubules has been studied well during recent decades. However, mechanisms of active transport occurring in disorganized actin networks via myosin motors remain elusive. To provide physiologically relevant insights, we probed motions of myosin motors in actin networks under various conditions using our well‐established computational model that rigorously accounts for the mechanical and dynamical behaviors of the actin cytoskeleton. We demonstrated that myosin motions can be confined due to three different reasons in the absence of F‐actin turnover. We verified mechanisms of motor stalling using in vitro reconstituted actomyosin networks. We also found that with F‐actin turnover, motors consistently move for a long time without significant confinement. Our study sheds light on the importance of F‐actin turnover for effective active transport in the actin cytoskeleton.
Development of an error‐detection examination for conservative dentistry education
Authors: Yoneda Masahiro , Yamada Kazuhiko , Izumi Toshio , Matsuzaki Etsuko , Maruta Michito , Hatakeyama Junko , Morita Hiromitsu , Tsuzuki Takashi , Anan Hisashi , Hirofuji Takao
Published: November 2019

Objective

For dental students, textbooks and lectures provide basic knowledge, and simulated and actual clinical training provide learning in technical and communication skills. At our college, conservative dentistry is taught in the third and fourth years of a 6‐year undergraduate degree. Clinical training is undertaken subsequently in the fifth year and includes cavity preparation and composite resin filling tasks. However, despite the clinical importance of a full understanding surrounding these procedures, sixth‐year students occasionally provide incorrect answers regarding these procedures in assessments. Although they demonstrated a basic understanding of the procedures, they may have forgotten the acquired knowledge during their clinical training. Therefore, we developed an error‐detection examination to evaluate and improve fifth‐year students' knowledge.

Methods

Written detailed treatment procedures for standardized, typical, cases were presented to students. Some critical steps were intentionally written incorrectly, and students had to identify and correct these. After correcting the steps, students gave a presentation to their peers on their corrections. This was followed by a summary of the correct answers and a short lecture by the teacher. Students then completed a questionnaire investigating their experience of the examination.

Results

Students misunderstood some key treatment steps, such as pretreatment of composite resin filling, amalgam removal, and ceramic inlay fitting. The questionnaire revealed that this method of testing applied knowledge was new to students and helped them to identify knowledge gaps. The test also increased their motivation to study conservative dentistry. Students were open to taking similar tests in different areas.

Conclusion

Although conservative dentistry is a basic field of dental treatment, mistakes in treatment can lead to early treatment failure or reduce the lifetime of a restored tooth. Therefore, students need to have a deep understanding of procedures. Error‐detection examinations may help students identify knowledge gaps and provide useful feedback to teachers to identify areas that they should stress in earlier years.
One‐Pot Synthesis of Renewable Phthalic Anhydride from 5‐Hydroxymethfurfural by using MoO3/Cu(NO3)2 as Catalyst
Authors: Jia Wenlong , Sun Yong , Zuo Miao , Feng Yunchao , Tang Xing , Zeng Xianhai , Lin Lu
Published: November 2019

Herein, a synthetic pathway to renewable phthalic anhydride (PA) from 5‐hydroxymethfurfural (HMF) in one pot is reported. The commonly available catalysts MoO3 and Cu(NO3)2 play a crucial role in integrating the multiple steps of the reaction, namely decarbonylation of HMF to active furyl intermediate (AFI), oxidation of HMF to maleic anhydride (MA), Diels–Alder cycloaddition of AFI and MA, and subsequent dehydration, in one pot. Under mild reaction conditions, a 63.2 % yield of PA is obtained from HMF. Compared with the currently reported route to renewable PA based on the Diels–Alder cycloaddition of biomass‐derived MA and furan, this convenient one‐pot synthesis represents a great improvement in efficiency.
Multi‐site reproducibility of a human immunophenotyping assay in whole blood and peripheral blood mononuclear cells preparations using CyTOF technology coupled with Maxpar Pathsetter, an automated data analysis system
Authors: Bagwell Charles Bruce , Hunsberger Benjamin , Hill Beth , Herbert Donald , Bray Christopher , Selvanantham Thirumahal , Li Stephen , Villasboas Jose C. , Pavelko Kevin , Strausbauch Michael , Rahman Adeeb , Kelly Gregory , Asgharzadeh Shahab , Gomez‐Cabrero Azucena , Behbehani Gregory , Chang Hsiaochi , Lyberger Justin , Montgomery Ruth , Zhao Yujiao , Inokuma Margaret , Goldberger Ofir , Stelzer Greg
Published: November 2019

High‐dimensional mass cytometry data potentially enable a comprehensive characterization of immune cells. In order to positively affect clinical trials and translational clinical research, this advanced technology needs to demonstrate a high reproducibility of results across multiple sites for both peripheral blood mononuclear cells (PBMC) and whole blood preparations. A dry 30‐marker broad immunophenotyping panel and customized automated analysis software were recently engineered and are commercially available as the Fluidigm® Maxpar® Direct™ Immune Profiling Assay™. In this study, seven sites received whole blood and six sites received PBMC samples from single donors over a 2‐week interval. Each site labeled replicate samples and acquired data on Helios™ instruments using an assay‐specific acquisition template. All acquired sample files were then automatically analyzed by Maxpar Pathsetter™ software. A cleanup step eliminated debris, dead cells, aggregates, and normalization beads. The second step automatically enumerated 37 immune cell populations and performed label intensity assessments on all 30 markers. The inter‐site reproducibility of the 37 quantified cell populations had consistent population frequencies, with an average %CV of 14.4% for whole blood and 17.7% for PBMC. The dry reagent coupled with automated data analysis is not only convenient but also provides a high degree of reproducibility within and among multiple test sites resulting in a comprehensive yet practical solution for deep immune phenotyping.
Case series of a hybrid closed‐loop system used in pregnancies in clinical practice
Authors: Polsky Sarit , Akturk Halis K.
Published: November 2019

Background

Hybrid closed‐loop (HCL) therapy is rarely studied in pregnancy. We present three cases of women with type 1 diabetes who used the Medtronic 670G HCL system for most or all of gestation.

Methods

The Medtronic 670G system has a manual mode (no automated insulin delivery) and an auto mode (AM, HCL therapy). Women in this case series used AM off‐label in gestation.

Results

Case 1 started HCL therapy in the second trimester, her sensor glucose time spent <3.9 and >10 mmol/L improved thereafter. Case 1 had average sensor glucose (ASG) levels of 6.4 ± 2.4 mmol/L in the first trimester, 7.0 ± 2.7 mmol/L in the second trimester before HCL use, 7.1 ± 2.1 mmol/L in the second trimester after HCL use, and 6.8 ± 1.9 mmol/L in the third trimester. Case 1 continued AM during operative delivery and post‐partum. Cases 2 and 3 used HCL therapy throughout gestation but with inconsistent time in AM. When they increased time in AM their glycaemic indices improved. Case 2 had ASG of 9.5 ± 3.4, 8.6 ± 2.9, and 7.9 ± 2.5 mmol/L in the first through third trimesters, respectively. Case 3 had ASG of 11.1 ± 4.8 and 3.9 to 10 mmol/L in the first and second trimesters, respectively. Case 2 continued HCL therapy post‐partum, Case 3 did not.

Conclusions

CareLink® Clinical Software only reports the non‐pregnant time in range. Nonetheless, this represents the first report of HCL therapy in pregnancy with a system approved by the Food and Drug Administration in non‐pregnant populations.
Detection of black market follistatin 344
Authors: Reichel Christian , Gmeiner Günter , Thevis Mario
Published: November 2019

Follistatin, a myostatin‐inhibiting protein, is prohibited according to chapter S4 of the “WADA 2019 List of Prohibited Substances and Methods”. While currently no approved pharmaceutical formulations of follistatin are available, follistatin can be bought on the black market. Most of the products are labeled “follistatin 344” (FS344), a few “follistatin 315”. A study on FS344 black market products was performed and an electrophoretic detection method for serum and urine developed. While only nine of the 17 tested products actually contained follistatin, in some of the others growth promoting peptides were found (e.g. MGF, GHRP‐2). Surprisingly, all nine products contained His‐tagged FS344 and a high degree of its oligomers. The detection method is based on immunomagnetic purification followed by SDS‐PAGE and Western blotting with a monoclonal anti‐His antibody. Alternatively, a monoclonal anti‐follistatin antibody can be used. For immunoprecipitation (IP), a polyclonal anti‐follistatin antibody is applied. An evaluation of suitable antibodies for IP and immunoblotting is also presented. Furthermore, practically all currently available follistatin standards were investigated. The detection limit of the method for black market FS344 in urine is ca 0.1 ng/mL for 10 mL. For a sample volume of 100 μL, an LOD of 5 ng/mL could be achieved for serum. Due to the presence of His‐tags an unambiguous differentiation from endogenous follistatin is possible.
Unfolding the effects of different forestry treatments on microclimate in oak forests: results of a 4‐yr experiment
Authors: Kovács Bence , Tinya Flóra , Németh Csaba , Ódor Péter
Published: November 2019

A stable below‐canopy microclimate of forests is essential for their biodiversity and ecosystem functionality. Forest management necessarily modifies the buffering capacity of woodlands. However, the specific effects of different forestry treatments on site conditions, the temporal recovery after the harvests, and the reason for the contrasts between treatments are still poorly understood. The effects of four different forestry treatments (clear‐cutting, retention tree group, preparation cutting, and gap‐cutting) on microclimatic variables were studied within a field experiment in a managed oak‐dominated stand in Hungary, before (2014) and after (2015–2017) the interventions by complete block design with six replicates. From the first post‐treatment year, clear‐cuts differed the most from the uncut control due to the increased irradiance and heat load. Means and variability of air and soil temperature increased, air became dryer along with higher soil moisture levels. Retention tree groups could effectively ameliorate the extreme temperatures but not the mean values. Preparation cutting induced slight changes from the original buffered and humid forest microclimate. Despite the substantially more incoming light, gap‐cutting could retain the cool and humid air conditions and showed the highest increase in soil moisture after the interventions. For most microclimate variables, we could not observe any obvious trend within 3 yr. However, soil temperature variability decreased with time in clear‐cuts, while soil moisture difference continuously increased in gap‐ and clear‐cuts. Based on multivariate analyses, the treatments separated significantly based mainly on the temperature maxima and variability. We found that (1) the effect sizes among treatment levels were consistent throughout the years, (2) the climatic recovery time for variables appears to be far more than 3 yr, and (3) the applied silvicultural methods diverged mainly among the temperature maxima. Based on our study, the spatially heterogeneous and fine‐scaled treatments of continuous cover forestry (gap‐cutting, selection systems) are recommended. By applying these practices, the essential structural elements creating buffered microclimate could be more successfully maintained. Thus, forestry interventions could induce less pronounced alterations in environmental conditions for forest‐dwelling organism groups.
What is known and unknown about the effects of plastic pollution: A meta‐analysis and systematic review
Authors: Bucci K. , Tulio M. , Rochman C. M.
Published: November 2019

As a consequence of the global ubiquity of plastic pollution, scientists, decision‐makers, and the public often ask whether macroplastics (>5 mm) and microplastics (<5 mm) have a realized ecological threat. In 2016, we conducted a systematic review of the literature and made a call for further research testing hypotheses about ecological effects. In the subsequent years, the amount of relevant research has risen tremendously. Here, we reassess the literature to determine the current weight of evidence about the effects of plastic pollution across all levels of biological organization. Our data spans marine, freshwater, and terrestrial environments. We extracted data from 139 lab and field studies testing 577 independent effects across a variety of taxa and with various types, sizes, and shapes of plastic. Overall, 59% of the tested effects were detected. Of these, 58% were due to microplastics and 42% were due to macroplastics. Of the effects that were not detected, 94% were from microplastics and 6% were from macroplastics. We found evidence that whether or not an effect is detected, as well as the severity and direction of the effect, is driven by dose, particle shape, polymer type, and particle size. Based on our analyses, there is no doubt that macroplastics are causing ecological effects, however, the effects of microplastics are much more complex. We also assessed the environmental relevancy of experimental studies by comparing the doses used in each exposure to the concentrations and sizes of microplastics found in the environment. We determined that only 17% of the concentrations used in experimental studies have been found in nature, and that 80% of particle sizes used in experiments fall below the size range of the majority of environmental sampling. Based on our systematic review and meta‐analysis, we make a call for future work that recognizes the complexity of microplastics and designs tests to better understand how different types, sizes, shapes, doses, and exposure durations affect wildlife. We also call for more ecologically and environmentally relevant studies, particularly in freshwater and terrestrial environments.
Fragmentation and thresholds in hydrological flow‐based ecosystem services
Authors: Thomas Amy , Masante Dario , Jackson Bethanna , Cosby Bernard , Emmett Bridget , Jones Laurence
Published: November 2019

Loss and fragmentation of natural land cover due to expansion of agricultural areas is a global issue. These changes alter the configuration and composition of the landscape, particularly affecting those ecosystem services (benefits people receive from ecosystems) that depend on interactions between landscape components. Hydrological mitigation describes the bundle of ecosystem services provided by landscape features such as woodland that interrupt the flow of runoff to rivers. These services include sediment retention, nutrient retention and mitigation of overland water flow. The position of woodland in the landscape and the landscape topography are both important for hydrological mitigation. Therefore, it is crucial to consider landscape configuration and flow pathways in a spatially explicit manner when examining the impacts of fragmentation. Here we test the effects of landscape configuration using a large number (>7,000) of virtual landscape configurations. We created virtual landscapes of woodland patches within grassland, superimposed onto real topography and stream networks. Woodland patches were generated with user‐defined combinations of patch number and total woodland area, placed randomly in the landscape. The Ecosystem Service model used hydrological routing to map the “mitigated area” upslope of each woodland patch. We found that more fragmented woodland mitigated a greater proportion of the catchment. Larger woodland area also increased mitigation, however, this increase was nonlinear, with a threshold at 50% coverage, above which there was a decline in service provision. This nonlinearity suggests that the benefit of any additional woodland depends on two factors: the level of fragmentation and the existing area of woodland. Edge density (total edge of patches divided by area of catchment) was the best single metric in predicting mitigated area. Distance from woodland to stream was not a significant predictor of mitigation, suggesting that agri‐environment schemes planting riparian woodland should consider additional controls such as the amount of fragmentation in the landscape. These findings highlight the potential benefits of fragmentation to hydrological mitigation services. However, benefits for hydrological services must be balanced against any negative effects of fragmentation or habitat loss on biodiversity and other services.
Inorganic N addition replaces N supplied to switchgrass (Panicum virgatum) by arbuscular mycorrhizal fungi
Authors: Jach‐Smith Laura C. , Jackson Randall D.
Published: November 2019

Arbuscular mycorrhizal fungi (AMF) provide many benefits in agroecosystems including improved soil tilth, carbon sequestration, and water and nutrient transfer to plants.AMFare known to affect plant nitrogen (N) dynamics and transfer N to plants, but there have been few studies addressing whether the amount of N transferred to plants byAMFis agronomically relevant. We used δ15N natural abundance methods and δ15N mass balance equations to estimate the amount of plant N derived fromAMFtransfer in perennial grasses managed for bioenergy production under different N addition treatments (0, 56, and 196 kg N/ha). Differentiation of δ15N among plant, soil N, andAMFpools was higher than anticipated leading to calculations of 34–55% of plant N transferred byAMFin the treatments receiving no N addition to 6–22% of plant N transferred to plants in high‐N addition treatments.AMFextra‐radical hyphae biomass was significantly reduced in the high‐N (196 kg N/ha) addition treatments, which was negatively correlated to enriched plant δ15N. Our results suggest that N addition decreasesAMFN transfer to plants. When N was limiting to plant growth,AMFsupplied agronomically significant amounts of plant N, and a higher proportion of overall plant N. Because differentiation between N pools was greater than expected, stable isotope measurements can be used to estimate N transfer toAMFplant hosts.
Drought exacerbates negative consequences of high‐intensity cattle grazing in a semiarid grassland
Authors: Souther Sara , Loeser Matthew , Crews Timothy E. , Sisk Thomas
Published: November 2019

Grasslands managed for grazing are the largest land‐use category globally, with a significant proportion of these grasslands occurring in semiarid and arid regions. In such dryland systems, the effect of grazing on native plant diversity has been equivocal, some studies suggesting that grazing reduces native plant diversity, others that grazing increases or has little impact on diversity. One impediment toward generalizing grazing effects on diversity in this region is that high levels of interannual variation in precipitation may obfuscate vegetative response patterns. By analyzing a long‐term data set collected over a 20‐yr period in a semiarid grassland, we explicitly evaluated the role of climate in regulating the effect of cattle grazing on plant communities, finding that climate interacted with grazing intensity to shape grassland communities. Community composition of plots that were intensively grazed varied considerably in response to climatic variation and native species richness was low relative to ungrazed and moderately grazed plots. Following a severe drought in 2002, exotic species richness rapidly increased in the high‐intensity grazing plots. While this pattern was mirrored in the other treatments, exotic species richness increased to a greater extent and was slower to return to pre‐drought levels in the high‐intensity grazing plots. Overall, moderate grazing, even compared to grazing cessation, stabilized grassland communities through time, increased resilience to drought, and maintained the highest levels of native plant diversity and lowest levels of exotic diversity. These findings suggest that grazing, at moderate levels, may support grassland resilience to climate change in semiarid regions. However, grazing that exceeds tolerances, particularly in combination with extreme climatic events, like drought, can alter plant composition over relatively long timescales and possibly increase invasibility by nonnative species.
Behavioral inhibition moderates the association between overvaluation of shape and weight and noncompensatory purging in eating disorders
Authors: Liebman Rachel E. , Coniglio Kathryn A. , Becker Kendra R. , Tabri Nassim , Keshishian Ani C. , Wons Olivia , Keel Pamela K. , Eddy Kamryn T. , Thomas Jennifer J.
Published: November 2019

Objective

The cognitive‐behavioral therapy (CBT) model of eating disorders suggests that compensatory purging behaviors (e.g., self‐induced vomiting, inappropriate laxative use) are primarily driven by binge eating. However, many individuals endorse purging in the absence of binge eating (i.e., noncompensatory purging [NCP]). Research is needed to understand why some individuals purge in the absence of objective or subjective binge‐eating episodes.

Method

Given the importance of overvaluation of shape/weight in the CBT model, and the existing evidence linking temperamental characteristics like behavioral inhibition (i.e., the tendency to withdraw in response to threat cues) with purging in general, we tested whether behavioral inhibition moderated the relationship between overvaluation of shape/weight and NCP in a sample of individuals in a residential eating disorder treatment center (N = 143).

Results

Overvaluation was more strongly related to NCP in individuals with high (relative to low) levels of behavioral inhibition. Among individuals low in behavioral inhibition, overvaluation predicted engagement in NCP to a much weaker extent.

Discussion

For those high (relative to low) in behavioral inhibition, both emotional avoidance and overvaluation may be important targets in the treatment of NCP, particularly in the absence of binge eating.
On the hunt for the alternate host of Hemileia vastatrix
Authors: Koutouleas Athina , Jørgen Lyngs Jørgensen Hans , Jensen Birgit , Lillesø Jens‐Peter Barnekow , Junge Alexander , Ræbild Anders
Published: November 2019

Coffee leaf rust (CLR), caused by the fungal pathogen Hemileia vastatrix, has plagued coffee production worldwide for over 150 years. Hemileia vastatrix produces urediniospores, teliospores, and the sexual basidiospores. Infection of coffee by basidiospores of H. vastatrix has never been reported and thus far, no alternate host, capable of supporting an aecial stage in the disease cycle, has been found. Due to this, some argue that an alternate host of H. vastatrix does not exist. Yet, to date, the plant pathology community has been puzzled by the ability of H. vastatrix to overcome resistance in coffee cultivars despite the apparent lack of sexual reproduction and an aecidial stage. The purpose of this study was to introduce a new method to search for the alternate host(s) of H. vastatrix. To do this, we present the novel hypothetical alternate host ranking (HAHR) method and an automated text mining (ATM) procedure, utilizing comprehensive biogeographical botanical data from the designated sites of interests (Ethiopia, Kenya and Sri Lanka) and plant pathology insights. With the HAHR/ATM methods, we produced prioritized lists of potential alternate hosts plant of coffee leaf rust. This is a first attempt to seek out an alternate plant host of a pathogenic fungus in this manner. The HAHR method showed the highest‐ranking probable alternate host as Psychotria mahonii, Rubus apetalus, and Rhamnus prinoides. The cross‐referenced results by the two methods suggest that plant genera of interest are Croton, Euphorbia, and Rubus. The HAHR and ATM methods may also be applied to other plant–rust interactions that include an unknown alternate host or any other biological system, which rely on data mining of published data.
Glacial cycles drive rapid divergence of cryptic field vole species
Authors: Fletcher Nicholas K. , Acevedo Pelayo , Herman Jeremy S. , Paupério Joana , Alves Paulo C. , Searle Jeremy B.
Published: November 2019

Understanding the factors that contribute to the generation of reproductively isolated forms is a fundamental goal of evolutionary biology. Cryptic species are an especially interesting challenge to study in this context since they lack obvious morphological differentiation that provides clues to adaptive divergence that may drive reproductive isolation. Geographical isolation in refugial areas during glacial cycling is known to be important for generating genetically divergent populations, but its role in the origination of new species is still not fully understood and likely to be situation dependent. We combine analysis of 35,434 single‐nucleotide polymorphisms (SNPs) with environmental niche modeling (ENM) to investigate genomic and ecological divergence in three cryptic species formerly classified as the field vole (Microtus agrestis). The SNPs demonstrate high genomic divergence (pairwiseFSTvalues of 0.45–0.72) and little evidence of gene flow among the three field vole cryptic species, and we argue that genetic drift may have been a particularly important mechanism for divergence in the group. The ENM reveals three areas as potential glacial refugia for the cryptic species and differing climatic niches, although with spatial overlap between species pairs. This evidence underscores the role that glacial cycling has in promoting genetic differentiation and reproductive isolation by subdivision into disjunct distributions at glacial maxima in areas relatively close to ice sheets. Future investigation of the intrinsic barriers to gene flow between the field vole cryptic species is required to fully assess the mechanisms that contribute to reproductive isolation. In addition, the Portuguese field vole (M. rozianus) shows a high inbreeding coefficient and a restricted climatic niche, and warrants investigation into its conservation status.
The distribution and spread of naturally occurring Medea selfish genetic elements in the United States
Authors: Cash Sarah A. , Lorenzen Marce D. , Gould Fred
Published: November 2019

Selfish genetic elements (SGEs) are DNA sequences that are transmitted to viable offspring in greater than Mendelian frequencies. Medea SGEs occur naturally in some populations of red flour beetle (Tribolium castaneum) and are expected to increase in frequency within populations and spread among populations. The large‐scale U.S. distributions of Medea‐4 (M4) had been mapped based on samples from 1993 to 1995. We sampled beetles in 2011–2014 and show that the distribution of M4 in the United States is dynamic and has shifted southward. By using a genetic marker of Medea‐1 (M1), we found five unique geographic clusters with high and low M1 frequencies in a pattern not predicted by microsatellite‐based analysis of population structure. Our results indicate the absence of rigid barriers to Medea spread in the United States, so assessment of what factors have limited its current distribution requires further investigation. There is great interest in using synthetic SGEs, including synthetic Medea, to alter or suppress pest populations, but there is concern about unpredicted spread of these SGEs and potential for populations to become resistant to them. The finding of patchy distributions of Medea elements suggests that released synthetic SGEs cannot always be expected to spread uniformly, especially in target species with limited dispersal.
The EMPagliflozin compaRative effectIveness and SafEty (EMPRISE) study programme: Design and exposure accrual for an evaluation of empagliflozin in routine clinical care
Authors: Patorno Elisabetta , Najafzadeh Mehdi , Pawar Ajinkya , Franklin Jessica M. , Déruaz‐Luyet Anouk , Brodovicz Kimberly G. , Santiago Ortiz Adrian J. , Bessette Lily G. , Kulldorff Martin , Schneeweiss Sebastian
Published: November 2019

Background

The EMPA‐REG OUTCOME trial showed that empagliflozin reduced the risk of cardiovascular death and hospitalization for heart failure (HHF) in diabetic patients with cardiovascular disease. EMPRISE is a study programme on the effectiveness, safety and healthcare utilization of empagliflozin in routine care, leveraging real‐world data from two commercial and one federal US data sources from 2014 to 2019.

Objectives

To describe rationale and design of EMPRISE, assess ability to minimize confounding and evaluate the time to reach sufficient statistical power for a key study outcome, HHF, using baseline information from the first year of EMPRISE.

Methods

In 3 claims data sets, we identified a 1:1 propensity score (PS)‐matched cohort of diabetic patients ≥18 years initiating empagliflozin or a dipeptidyl peptidase‐4 inhibitor (DPP4i), resulting in 6643 total pairs. The PS model included >140 baseline covariates. We measured covariate balance via standardized differences (SD) and postmatching c‐statistic. We computed the incidence rate (IR) of HHF, predicted exposure accrual over time and calculated expected power.

Results

After PS matching, patient characteristics were balanced with SD <0.1 and c‐statistic between 0.54 and 0.59. The population IR of HHF was 4.4 per 1000 person‐years using a specific HHF definition and 14.8 using a broader HHF definition. In our projection, 80%‐powered analyses would require a minimum of 169 HHF events, expected to accumulate by year 3 (specific definition) or year 2 (broader definition).

Conclusion

Baseline information from EMPRISE provided evidence of solid confounding control and adequate exposure accrual with expected powered analyses for the primary outcomes.
Suppressing the excessive aggregation of nonfullerene acceptor in blade‐coated active layer by using n‐type polymer additive to achieve large‐area printed organic solar cells with efficiency over 15%
Authors: Dong Sheng , Zhang Kai , Jia Tao , Zhong Wenkai , Wang Xiaohui , Huang Fei , Cao Yong
Published: November 2019

In this study, we demonstrate that high‐efficiency blade‐coated organic solar cells (OSCs) can be obtained by using polymer additive N2200 to suppress the excessive aggregation of nonfullerene acceptor. When using the blade‐coating method, OSCs based on the blends of PM6:IT‐4F and PM6:Y6 show moderate efficiencies of 9.9% and 13.2%, respectively. However, when a small amount of N2200 is added into the binary active layers, the resulting blade‐coated OSCs show much higher efficiencies of 13.0% and 16.0%. Careful investigation reveals that the polymer additive suppresses the excessive aggregation of nonfullerene acceptors in the blade‐coated active layer. This enhances the device performance by ensuring a more favorable morphology with appropriate domain size, improving charge extraction, and suppressing charge recombination. Based on this understanding, large‐area OSC devices (1.0 cm2) are successfully obtained by blade coating, which display encouraging efficiencies of 12.3% and 15.1%.

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