bluuebunny/crossref_metadata_2025 huggingface dataset:
Environmental engagement, religion and spirituality in the context of secularization
Authors: Briguglio Marie , Garcia-Muñoz Teresa , Neuman Shoshana
Published: September 2020

Over the past half century, a literature has developed across a range of disciplines exploring the relationship between religion and environmental engagement, including pro-environmental attitudes and behaviours. Empirical results are diverse and the relationship seems to vary in size and direction, depending on definitions and the method of investigation adopted. An increasingly important phenomenon which has received far less attention is that of spirituality, within/out the context of a religion. This paper contributes to the literature by examining the question in a predominantly Roman Catholic European Union country where church attendance is in decline. It employs a nationally representative dataset (n = 1029) which includes diverse measures of religiosity and spirituality, as well as measures of interest in environmental issues, in wildlife and natural history, and engagement in countryside activities and gardening, together with relevant socio-economic control variables. Our findings confirm that the usual socio-economic determinants are associated with this type of environmental engagement. We find that church attendance adds no further explanatory power to environmental engagement. On the other hand, participation in socio-cultural religious activities and self-assessed spirituality are positively and significantly associated of various dimensions of environmental engagement.
Conditional maximum entropy and superstatistics
Authors: Davis Sergio
Published: September 2020

Superstatistics describes nonequilibrium steady states as superpositions of canonical ensembles with a probability distribution of temperatures. Rather than assume a certain distribution of temperature, recently [2020 J. Phys. A: Math. Theor.
53 045004] we have discussed general conditions under which a system in contact with a finite environment can be described by superstatistics together with a physically interpretable, microscopic definition of temperature. In this work, we present a new interpretation of this result in terms of the standard maximum entropy principle using conditional expectation constraints, and provide an example model where this framework can be tested.
Interfacial coupling effects on the thermal conductivity of few-layer graphene
Authors: Kan Yajing , Hong Feng , Wei Zhiyong , Bi Kedong
Published: September 2020

The thermal conductivities of both suspended and supported few-layer graphene (FLG) were investigated via molecular dynamics simulations. The results indicate that the thermal conductivity of a suspended FLG sample decreases by 3.9% from 511.2 W m−1 K−1 upon an increase in the number of layers from 1 to 20 layers, whereas it increases by 5.5% to 486.8 W m−1 K−1 in the case of supported FLG specimens on a smooth crystalline silicon surface. Both trends converge when the number of layers is higher than five. The effects of the substrate roughness on the supported FLG samples were also investigated. The results show that their thermal conductivity on a rough silicon surface is lower than that on a smooth silicon surface. In order to demonstrate the importance of interfacial coupling on the phonon transport properties, the coupling strength parameter was enhanced by a factor of 3 or 10 to see the influence on the thermal conductivity. The simulations show that the thermal conductivity decreases with an increasing coupling strength. Lastly, the phonon dispersion of a two-layer graphene specimen was calculated by varying the interlayer coupling strength. The calculations show that the coupling strength is mainly influenced by the out-of-plane phonon dispersion relation. The frequency of flexural acoustic (ZA’) phonons around the center of the first Brillouin zone increases significantly from 2.14 to 6.78 THz when the interlayer coupling strength is enhanced by a factor of 10. This may decrease the phonon group velocity and provide more scattering channels, and thus reduce the thermal conductivity.
Using models to improve optimizers for variational quantum algorithms
Authors: Sung Kevin J , Yao Jiahao , Harrigan Matthew P , Rubin Nicholas C , Jiang Zhang , Lin Lin , Babbush Ryan , McClean Jarrod R
Published: September 2020

Variational quantum algorithms are a leading candidate for early applications on noisy intermediate-scale quantum computers. These algorithms depend on a classical optimization outer-loop that minimizes some function of a parameterized quantum circuit. In practice, finite sampling error and gate errors make this a stochastic optimization with unique challenges that must be addressed at the level of the optimizer. The sharp trade-off between precision and sampling time in conjunction with experimental constraints necessitates the development of new optimization strategies to minimize overall wall clock time in this setting. In this work, we introduce two optimization methods and numerically compare their performance with common methods in use today. The methods are surrogate model-based algorithms designed to improve reuse of collected data. They do so by utilizing a least-squares quadratic fit of sampled function values within a moving trusted region to estimate the gradient or a policy gradient. To make fair comparisons between optimization methods, we develop experimentally relevant cost models designed to balance efficiency in testing and accuracy with respect to cloud quantum computing systems. The results here underscore the need to both use relevant cost models and optimize hyperparameters of existing optimization methods for competitive performance. The methods introduced here have several practical advantages in realistic experimental settings, and we have used one of them successfully in a separately published experiment on Google’s Sycamore device.
Coarse-grain cluster analysis of tensors with application to climate biome identification
Authors: DeSantis Derek , Wolfram Phillip J , Bennett Katrina , Alexandrov Boian
Published: September 2020

A tensor provides a concise way to codify the interdependence of complex data. Treating a tensor as a d-way array, each entry records the interaction between the different indices. Clustering provides a way to parse the complexity of the data into more readily understandable information. Clustering methods are heavily dependent on the algorithm of choice, as well as the chosen hyperparameters of the algorithm. However, their sensitivity to data scales is largely unknown.

In this work, we apply the discrete wavelet transform to analyze the effects of coarse-graining on clustering tensor data. We are particularly interested in understanding how scale affects clustering of the Earth’s climate system. The discrete wavelet transform allows classification of the Earth’s climate across a multitude of spatial-temporal scales. The discrete wavelet transform is used to produce an ensemble of classification estimates, as opposed to a single classification. Each element of the ensemble is a clustering at a different spatial-temporal scale. Information theoretic approaches are used to identify important scale lengths in clustering the L15 Climate Datset. We also discover a sub-collection of the ensemble that spans the majority of the variance observed, allowing for efficient consensus clustering techniques that can be used to identify climate biomes.
Adversarial reverse mapping of equilibrated condensed-phase molecular structures
Authors: Stieffenhofer Marc , Wand Michael , Bereau Tristan
Published: September 2020

A tight and consistent link between resolutions is crucial to further expand the impact of multiscale modeling for complex materials. We herein tackle the generation of condensed molecular structures as a refinement—backmapping—of a coarse-grained (CG) structure. Traditional schemes start from a rough coarse-to-fine mapping and perform further energy minimization and molecular dynamics simulations to equilibrate the system. In this study we introduce DeepBackmap: A deep neural network based approach to directly predict equilibrated molecular structures for condensed-phase systems. We use generative adversarial networks to learn the Boltzmann distribution from training data and realize reverse mapping by using the CG structure as a conditional input. We apply our method to a challenging condensed-phase polymeric system. We observe that the model trained in a melt has remarkable transferability to the crystalline phase. The combination of data-driven and physics-based aspects of our architecture help reach temperature transferability with only limited training data.
Improving proton dose calculation accuracy by using deep learning
Authors: Wu Chao , Nguyen Dan , Xing Yixun , Montero Ana Barragan , Schuemann Jan , Shang Haijiao , Pu Yuehu , Jiang Steve
Published: September 2020

Pencil beam (PB) dose calculation is fast but inaccurate due to the approximations when dealing with inhomogeneities. Monte Carlo (MC) dose calculation is the most accurate method but it is time consuming. The aim of this study was to develop a deep learning model that can boost the accuracy of PB dose calculation to the level of MC dose by converting PB dose to MC dose for different tumor sites. The proposed model uses the PB dose and computed tomography image as inputs to generate the MC dose. We used 290 patients (90 head and neck, 93 liver, 75 prostate and 32 lung) to train, validate, and test the model. For each tumor site, we performed four numerical experiments to explore various combinations of training datasets. Training the model on data from all tumor sites together and using the dose distribution of each individual beam as input yielded the best performance for all four tumor sites. The average gamma passing rate (1 mm/1%) between the converted and the MC dose was 92.8%, 92.7%, 89.7% and 99.6% for head and neck, liver, lung, and prostate test patients, respectively. The average dose conversion time for a single field was less than 4 s. The trained model can be adapted to new datasets through transfer learning. Our deep learning-based approach can quickly boost the accuracy of PB dose to that of MC dose. The developed model can be added to the clinical workflow of proton treatment planning to improve dose calculation accuracy.
A nonlocal transport equation modeling complex roots of polynomials under differentiation
Authors: O’Rourke Sean , Steinerberger Stefan
Published: September 2020

Letpn:C→Cp_n:\mathbb {C} \rightarrow \mathbb {C}be a random complex polynomial whose roots are sampled i.i.d. from a radial distribution2πru(r)dr2\pi r u(r) drin the complex plane. A natural question is how the distribution of roots evolves under repeated (sayn/2−n/2-times) differentiation of the polynomial. We conjecture a mean-field expansion for the evolution ofψ(s)=u(s)s\psi (s) = u(s) s:<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="StartFraction partial-differential psi Over partial-differential t EndFraction equals StartFraction partial-differential Over partial-differential x EndFraction left-parenthesis left-parenthesis StartFraction 1 Over x EndFraction integral Subscript 0 Superscript x Baseline psi left-parenthesis s right-parenthesis d s right-parenthesis Superscript negative 1 Baseline psi left-parenthesis x right-parenthesis right-parenthesis period">∂ψ∂t=∂∂x((1x∫0xψ(s)ds)−1ψ(x)).\begin{equation*} \frac {\partial \psi }{\partial t} = \frac {\partial }{\partial x} \left ( \left ( \frac {1}{x} \int _{0}^{x} \psi (s) ds \right )^{-1} \psi (x) \right ). \end{equation*}The evolution ofψ(s)≡1\psi (s) \equiv 1corresponds to the evolution of random Taylor polynomials<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="p Subscript n Baseline left-parenthesis z right-parenthesis equals sigma-summation Underscript k equals 0 Overscript n Endscripts gamma Subscript k Baseline StartFraction z Superscript k Baseline Over k factorial EndFraction where gamma Subscript k Baseline tilde script upper N Subscript double-struck upper C Baseline left-parenthesis 0 comma 1 right-parenthesis period">pn(z)=∑k=0nγkzkk!whereγk∼NC(0,1).\begin{equation*} p_n(z) = \sum _{k=0}^{n}{ \gamma _k \frac {z^k}{k!}} \quad \text {where} \quad \gamma _k \sim \mathcal {N}_{\mathbb {C}}(0,1). \end{equation*}We discuss some numerical examples suggesting that this particular solution may be stable. We prove that the solution is linearly stable. The linear stability analysis reduces to the classical Hardy integral inequality. Many open problems are discussed.
Src kinases relax adherens junctions between the neighbors of apoptotic cells to permit apical extrusion
Authors: Teo Jessica L. , Tomatis Vanesa M. , Coburn Luke , Lagendijk Anne K. , Schouwenaar Irin-Maya , Budnar Srikanth , Hall Thomas E. , Verma Suzie , McLachlan Robert W. , Hogan Benjamin M. , Parton Robert G. , Yap Alpha S. , Gomez Guillermo A.
Published: September 2020

Apoptotic cell extrusion is predicted to accumulate local tissue stresses that represent a mechanical cost for the epithelium, but how such costs may be alleviated is poorly understood. Here we identify a Src family kinase-mechanosensitive early immediate response of neighbor cells that relieves mechanical stress and allows extrusion to occur.
Effects of Huangjiu, Baijiu and Red Wine Combined With High-Fat Diet on Glucose and Lipid Metabolism: Aggravate or Alleviate?
Authors: Zhao Liang , Ouyang Hanying , Zhang Nanhai , Wang Chengtao , Ji Baoping , Zhou Feng
Published: September 2020

Aim

To compare effects on certain health indices in rodents of different doses of alcoholic beverages, huangjiu (Chinese yellow wine), red wine and baijiu (Chinese liquor) combined with high-fat diet (HFD) and the pure HFD.

Methods

A total of 80 rats were randomly divided into eight groups and treated with (a) basal diet (3.5 kcal/g); (b) HFD (19.5% w/w lard, 4.5 kcal/g) and (c) HFD with low or high doses of separate alcoholic beverages (2.5 and 5 g/kg ethanol, respectively) for 28 weeks.

Results

Chronic drinking when combined with HFD was associated with reduced body weight, fat accumulation and serum TNF-α level, serum TG, TC and LDL-C levels, and improved glucose tolerance (OGTT) and insulin sensitivity (ITT), hepatic enzymes; elevated levels or activities of the antioxidant enzymes like superoxide dismutase, catalase and glutathione reductase, reduced the content of lipid peroxidation productions such as malondialdehyde, in comparison with the pure HFD intake. In addition, compared with HFD, drinking plus HFD improved microbiota dysbiosis, down-regulated the ratio of Firmicutes/Bacteroidetes and promoted the growth of some probiotics including Prevotellaceae_UCG-001 and norank_f__Bacteroidales_S24-7_group.

Conclusion

Overall, the three beverages showed different impacts on indicators but red wine showed the most ‘beneficial’ effects. Of course, higher ethanol dosages can be expected to cause overall negative health effects, and harms of high fat intake can be prevented by healthier diet.
panRGP: a pangenome-based method to predict genomic islands and explore their diversity
Authors: Bazin Adelme , Gautreau Guillaume , Médigue Claudine , Vallenet David , Calteau Alexandra
Published: September 2020

Motivation

Horizontal gene transfer (HGT) is a major source of variability in prokaryotic genomes. Regions of genome plasticity (RGPs) are clusters of genes located in highly variable genomic regions. Most of them arise from HGT and correspond to genomic islands (GIs). The study of those regions at the species level has become increasingly difficult with the data deluge of genomes. To date, no methods are available to identify GIs using hundreds of genomes to explore their diversity.

Results

We present here the panRGP method that predicts RGPs using pangenome graphs made of all available genomes for a given species. It allows the study of thousands of genomes in order to access the diversity of RGPs and to predict spots of insertions. It gave the best predictions when benchmarked along other GI detection tools against a reference dataset. In addition, we illustrated its use on metagenome assembled genomes by redefining the borders of the leuX tRNA hotspot, a well-studied spot of insertion in Escherichia coli. panRPG is a scalable and reliable tool to predict GIs and spots making it an ideal approach for large comparative studies.

Availability and implementation

The methods presented in the current work are available through the following software: https://github.com/labgem/PPanGGOLiN. Detailed results and scripts to compute the benchmark metrics are available at https://github.com/axbazin/panrgp_supdata.
Padhoc: a computational pipeline for pathway reconstruction on the fly
Authors: Casaní-Galdón Salvador , Pereira Cecile , Conesa Ana
Published: September 2020

Motivation

Molecular pathway databases represent cellular processes in a structured and standardized way. These databases support the community-wide utilization of pathway information in biological research and the computational analysis of high-throughput biochemical data. Although pathway databases are critical in genomics research, the fast progress of biomedical sciences prevents databases from staying up-to-date. Moreover, the compartmentalization of cellular reactions into defined pathways reflects arbitrary choices that might not always be aligned with the needs of the researcher. Today, no tool exists that allow the easy creation of user-defined pathway representations.

Results

Here we present Padhoc, a pipeline for pathway ad hoc reconstruction. Based on a set of user-provided keywords, Padhoc combines natural language processing, database knowledge extraction, orthology search and powerful graph algorithms to create navigable pathways tailored to the user’s needs. We validate Padhoc with a set of well-established Escherichia coli pathways and demonstrate usability to create not-yet-available pathways in model (human) and non-model (sweet orange) organisms.

Availability and implementation

Padhoc is freely available at https://github.com/ConesaLab/padhoc.

Supplementary information

Supplementary data are available at Bioinformatics online.
Text mining for modeling of protein complexes enhanced by machine learning
Authors: Badal Varsha D , Kundrotas Petras J , Vakser Ilya A
Published: September 2020

Motivation

Procedures for structural modeling of protein–protein complexes (protein docking) produce a number of models which need to be further analyzed and scored. Scoring can be based on independently determined constraints on the structure of the complex, such as knowledge of amino acids essential for the protein interaction. Previously, we showed that text mining of residues in freely available PubMed abstracts of papers on studies of protein–protein interactions may generate such constraints. However, absence of post-processing of the spotted residues reduced usability of the constraints, as a significant number of the residues were not relevant for the binding of the specific proteins.

Results

We explored filtering of the irrelevant residues by two machine learning approaches, Deep Recursive Neural Network (DRNN) and Support Vector Machine (SVM) models with different training/testing schemes. The results showed that the DRNN model is superior to the SVM model when training is performed on the PMC-OA full-text articles and applied to classification (interface or non-interface) of the residues spotted in the PubMed abstracts. When both training and testing is performed on full-text articles or on abstracts, the performance of these models is similar. Thus, in such cases, there is no need to utilize computationally demanding DRNN approach, which is computationally expensive especially at the training stage. The reason is that SVM success is often determined by the similarity in data/text patterns in the training and the testing sets, whereas the sentence structures in the abstracts are, in general, different from those in the full text articles.

Availabilityand implementation

The code and the datasets generated in this study are available at https://gitlab.ku.edu/vakser-lab-public/text-mining/-/tree/2020-09-04.

Supplementary information

Supplementary data are available at Bioinformatics online.
ORP9 knockdown delays the maturation of junction-related endocytic structures in the testis and leads to impaired sperm release†
Authors: Adams Arlo , Vogl Wayne
Published: September 2020

The release of late spermatids from the seminiferous epithelium requires the internalization of intercellular junctions by Sertoli cell specific structures called “tubulobulbar complexes” (TBCs). These large, endocytic devices likely evolved from classic clathrin-mediated-endocytosis (CME) machinery, but have several important morphological differences to CME vesicles. Most notable among these differences is that extensive endoplasmic reticulum (ER) membrane contact sites (MCSs) occur with TBCs and not with clathrin-coated pits. One of the well-established functions of ER MCSs is lipid exchange. Previously, we have established that the ORP9 lipid exchange protein is localized to the TBC-ER MCS; however, the function of ORP9 and lipid exchange at the sites is not known. Here we use an in vivo knockdown approach to probe function. The testes of Sprague–Dawley rats were injected with ORP9 targeted siRNA or non-targeted reagents, and the tissues examined by bright field, super-resolution stimulated emission depletion, and electron microscopy. The knockdown of ORP9 was achieved and maintained with daily injections of siRNA for 2-3 day intervals. Compared to controls, sections from ORP9 siRNA-injected testes had longer TBC tubes and fewer fused TBC bulbs. Late spermatids were also abnormally retained in the epithelium of knockdown tissue. These results suggest that ORP9 is necessary for normal TBC bulb vesiculation and fusion, most likely by changing the plasma membrane lipid profile of the TBC. These data also further support the conclusion that TBCs are part of the normal mechanism of sperm release.
Fence Ecology: Frameworks for Understanding the Ecological Effects of Fences
Authors: McInturff Alex , Xu Wenjing , Wilkinson Christine E , Dejid Nandintsetseg , Brashares Justin S
Published: September 2020

Investigations of the links between human infrastructure and ecological change have provided eye-opening insights into humanity's environmental impacts and contributed to global environmental policies. Fences are globally ubiquitous, yet they are often omitted from discussions of anthropogenic impacts. In the present article, we address this gap through a systematic literature review on the ecological effects of fences. Our overview provides five major takeaways: 1) an operational definition of fencing to structure future research, 2) an estimate of fence densities in the western United States to emphasize the challenges of accounting for fences in human-footprint mapping, 3) a framework exhibiting the ecological winners and losers that fences produce, 4) a typology of fence effects across ecological scales to guide research, and 5) a summary of research trends and biases that suggest that fence effects have been underestimated. Through highlighting past research and offering frameworks for the future, we aim with this work to formalize the nascent field of fence ecology.
Perception and Conflict in Conservation: The Rashomon Effect
Authors: Levin Phillip S , Gray Steven A , Möllmann Christian , Stier Adrian C
Published: September 2020

Conflict is a common feature in conservation and resource management. Environmental conflicts are frequently attributed to differences in values; however, variability in the perception of facts, rooted in social and cultural differences also underlies conflicts. Such differences in perception have been termed the Rashomon effect after the Kurosawa film. In the present article, we explore a conservation Rashomon effect—a phenomenon that results from a combination of differences in perspective, plausible alternative perspectives of a conservation issue, and the absence of evidence to elevate one perspective above others. As a remedy to the Rashomon effect, policy-makers have turned to scientists as honest brokers who share a common environmental reality. We evaluate this supposition and suggest that scientists, themselves, display Rashomon effects. We suggest that Rashomon effects can be reduced by acknowledging the plurality of reality, embracing epistemic pluralism, and prioritizing an inclusive process of resource management.
A Comparison of Quantitative R1 and Cortical Thickness in Identifying Age, Lifespan Dynamics, and Disease States of the Human Cortex
Authors: Erramuzpe A , Schurr R , Yeatman J D , Gotlib I H , Sacchet M D , Travis K E , Feldman H M , Mezer A A
Published: September 2020

Brain development and aging are complex processes that unfold in multiple brain regions simultaneously. Recently, models of brain age prediction have aroused great interest, as these models can potentially help to understand neurological diseases and elucidate basic neurobiological mechanisms. We test whether quantitative magnetic resonance imaging can contribute to such age prediction models. Using R1, the longitudinal rate of relaxation, we explore lifespan dynamics in cortical gray matter. We compare R1 with cortical thickness, a well-established biomarker of brain development and aging. Using 160 healthy individuals (6–81 years old), we found that R1 and cortical thickness predicted age similarly, but the regions contributing to the prediction differed. Next, we characterized R1 development and aging dynamics. Compared with anterior regions, in posterior regions we found an earlier R1 peak but a steeper postpeak decline. We replicate these findings: firstly, we tested a subset (N = 10) of the original dataset for whom we had additional scans at a lower resolution; and second, we verified the results on an independent dataset (N = 34). Finally, we compared the age prediction models on a subset of 10 patients with multiple sclerosis. The patients are predicted older than their chronological age using R1 but not with cortical thickness.
All-cause Mortality Due to Bacteremia during a 60-Day Non-Physician Healthcare Worker Strike
Authors: Jansåker Filip , Holm Mona Katrine Alberthe , Gradel Kim Oren , Knudsen Jenny Dahl , Boel Jonas Bredtoft ,   Danish Collaborative Bacteraemia Network (DACOBAN), Østergaard J D , Knudsen U S , Jensen M , Arpi M , Pinholt S Thønnings , Schønheyder H C , Søgaard M , Koch K , Smit J , Gradel K O
Published: September 2020

This study explored all-cause mortality of bacteremia diagnosed during a 60-day non-physician healthcare worker strike in 2008. A significant change, with 5.0% (95% confidence interval [CI] 1.2–8.7%, P < .01) absolute risk increase, was seen in 90-day mortality during the strike (n = 598) compared with the rest of the study period 2000–2015 (n = 75 647).
Carvedilol induces biased β1 adrenergic receptor-nitric oxide synthase 3-cyclic guanylyl monophosphate signalling to promote cardiac contractility
Authors: Wang Qingtong , Wang Ying , West Toni M , Liu Yongming , Reddy Gopireddy R , Barbagallo Federica , Xu Bing , Shi Qian , Deng Bingqing , Wei Wei , Xiang Yang K
Published: September 2020

Aims

β-blockers are widely used in therapy for heart failure and hypertension. β-blockers are also known to evoke additional diversified pharmacological and physiological effects in patients. We aim to characterize the underlying molecular signalling and effects on cardiac inotropy induced by β-blockers in animal hearts.

Methods and results

Wild-type mice fed high-fat diet (HFD) were treated with carvedilol, metoprolol, or vehicle and echocardiogram analysis was performed. Heart tissues were used for biochemical and histological analyses. Cardiomyocytes were isolated from normal and HFD mice and rats for analysis of adrenergic signalling, calcium handling, contraction, and western blot. Biosensors were used to measure β-blocker-induced cyclic guanosine monophosphate (cGMP) signal and protein kinase A activity in myocytes. Acute stimulation of myocytes with carvedilol promotes β1 adrenergic receptor (β1AR)- and protein kinase G (PKG)-dependent inotropic cardiac contractility with minimal increases in calcium amplitude. Carvedilol acts as a biased ligand to promote β1AR coupling to a Gi-PI3K-Akt-nitric oxide synthase 3 (NOS3) cascade and induces robust β1AR-cGMP-PKG signal. Deletion of NOS3 selectively blocks carvedilol, but not isoproterenol-induced β1AR-dependent cGMP signal and inotropic contractility. Moreover, therapy with carvedilol restores inotropic contractility and sensitizes cardiac adrenergic reserves in diabetic mice with minimal impact in calcium signal, as well as reduced cell apoptosis and hypertrophy in diabetic hearts.

Conclusion

These observations present a novel β1AR-NOS3 signalling pathway to promote cardiac inotropy in the heart, indicating that this signalling paradigm may be targeted in therapy of heart diseases with reduced ejection fraction.
Oestrogen inhibits salt-dependent hypertension by suppressing GABAergic excitation in magnocellular AVP neurons
Authors: Jin Xiangyan , Kim Woong Bin , Kim Mi-Na , Jung Won Woo , Kang Hyung Kyung , Hong Eun-Hwa , Kim Yoon Sik , Shim Wan Joo , Han Hee Chul , Colwell Christopher S , Kim Young-Beom , Kim Yang In
Published: September 2020

Aims

Abundant evidence indicates that oestrogen (E2) plays a protective role against hypertension. Yet, the mechanism underlying the antihypertensive effect of E2 is poorly understood. In this study, we sought to determine the mechanism through which E2 inhibits salt-dependent hypertension.

Methods and results

To this end, we performed a series of in vivo and in vitro experiments employing a rat model of hypertension that is produced by deoxycorticosterone acetate (DOCA)-salt treatment after uninephrectomy. We found that E2 prevented DOCA-salt treatment from inducing hypertension, raising plasma arginine-vasopressin (AVP) level, enhancing the depressor effect of the V1a receptor antagonist (Phenylac1,D-Tyr(Et)2,Lys6,Arg8,des-Gly9)-vasopressin, and converting GABAergic inhibition to excitation in hypothalamic magnocellular AVP neurons. Moreover, we obtained results indicating that the E2 modulation of the activity and/or expression of NKCC1 (Cl− importer) and KCC2 (Cl− extruder) underpins the effect of E2 on the transition of GABAergic transmission in AVP neurons. Lastly, we discovered that, in DOCA-salt-treated hypertensive ovariectomized rats, CLP290 (prodrug of the KCC2 activator CLP257, intraperitoneal injections) lowered blood pressure, and plasma AVP level and hyperpolarized GABA equilibrium potential to prevent GABAergic excitation from emerging in the AVP neurons of these animals.

Conclusion

Based on these results, we conclude that E2 inhibits salt-dependent hypertension by suppressing GABAergic excitation to decrease the hormonal output of AVP neurons.
The JAK Inhibitor Tofacitinib Rescues Intestinal Barrier Defects Caused by Disrupted Epithelial-macrophage Interactions
Authors: Spalinger Marianne R , Sayoc-Becerra Anica , Ordookhanian Christ , Canale Vinicius , Santos Alina N , King Stephanie J , Krishnan Moorthy , Nair Meera G , Scharl Michael , McCole Declan F
Published: September 2020

Background and Aims

Loss-of-function variants in protein tyrosine phosphatase non-receptor type-2 [PTPN2] promote susceptibility to inflammatory bowel diseases [IBD]. PTPN2 regulates Janus-kinase [JAK] and signal transducer and activator of transcription [STAT] signalling, while protecting the intestinal epithelium from inflammation-induced barrier disruption. The pan-JAK inhibitor tofacitinib is approved to treat ulcerative colitis, but its effects on intestinal epithelial cell-macrophage interactions and on barrier properties are unknown. We aimed to determine if tofacitinib can rescue disrupted epithelial-macrophage interaction and barrier function upon loss of PTPN2.

Methods

Human Caco-2BBe intestinal epithelial cells [IECs] and THP-1 macrophages expressing control or PTPN2-specific shRNA were co-cultured with tofacitinib or vehicle. Transepithelial electrical resistance and 4 kDa fluorescein-dextran flux were measured to assess barrier function. Ptpn2fl/fl and Ptpn2-LysMCre mice, which lack Ptpn2 in myeloid cells, were treated orally with tofacitinib citrate twice daily to assess the in vivo effect on the intestinal epithelial barrier. Colitis was induced via administration of 1.5% dextran sulphate sodium [DSS] in drinking water.

Results

Tofacitinib corrected compromised barrier function upon PTPN2 loss in macrophages and/or IECs via normalisation of: [i] tight junction protein expression; [ii] excessive STAT3 signalling; and [iii] IL-6 and IL-22 secretion. In Ptpn2-LysMCre mice, tofacitinib reduced colonic pro-inflammatory macrophages, corrected underlying permeability defects, and prevented the increased susceptibility to DSS colitis.

Conclusions

PTPN2 loss in IECs or macrophages compromises IEC-macrophage interactions and reduces epithelial barrier integrity. Both of these events were corrected by tofacitinib in vitro and in vivo. Tofacitinib may have greater therapeutic efficacy in IBD patients harbouring PTPN2 loss-of-function mutations.
Changes in the Summer Wild Bee Community Following a Bark Beetle Outbreak in a Douglas-fir Forest
Authors: Foote Gabriel G , Foote Nathaniel E , Runyon Justin B , Ross Darrell W , Fettig Christopher J
Published: September 2020

The status of wild bees has received increased interest following recent estimates of large-scale declines in their abundances across the United States. However, basic information is limited regarding the factors affecting wild bee communities in temperate coniferous forest ecosystems. To assess the early responses of bees to bark beetle disturbance, we sampled the bee community of a Douglas-fir, Pseudotsuga menziesii (Mirb.), forest in western Idaho, United States during a Douglas-fir beetle, Dendroctonus pseudotsugae Hopkins (Coleoptera: Curculionidae), outbreak beginning in summer 2016. We resampled the area in summer 2018 following reductions in forest canopy cover resulting from mortality of dominant and codominant Douglas-fir. Overall, results from rarefaction analyses indicated significant increases in bee diversity (Shannon’s H) in 2018 compared to 2016. Results from ANOVA also showed significant increases in bee abundance and diversity in 2018 compared to 2016. Poisson regression analyses revealed percent tree mortality from Douglas-fir beetle was positively correlated with increases in total bee abundance and species richness, where community response variables displayed a cubic trend with percent tree mortality. Percent reduction in canopy cover from 2016 to 2018 was also correlated with bee species richness and diversity. These findings suggest that wild bee communities may benefit from changes in forest structure following bark beetle outbreaks.
Percutaneous coronary intervention for delayed coronary obstruction due to endothelialization of self-expandable transcatheter heart valve: a case report
Authors: Takiguchi Hiroshi , Yamaji Kyohei , Shirai Shinichi , Ando Kenji
Published: September 2020

Background

Coronary obstruction is one of the serious complications associated with transcatheter aortic valve implantation (TAVI). Delayed coronary obstruction (DCO) is a rare manifestation of coronary obstruction.

Case summary

A 91-year-old woman was diagnosed with severe aortic stenosis. She underwent TAVI with a self-expandable valve, without any complications. After 8 months, she was readmitted to our hospital for effort angina. Transthoracic echocardiogram and myocardial scintigraphy suggested left coronary artery ischaemia. Computed tomography revealed that the transcatheter heart valve (THV) frame was covered with a low-density mass that occluded the left coronary sinus (LCS). Transoesophageal echocardiogram showed a Doppler signal flowing from the non-coronary sinus to the LCS through the roundabout route between the aortic wall and the THV. Percutaneous coronary intervention was performed for the roundabout route. Although intravascular ultrasound after the implantation of one drug-eluting stent showed the underexpansion of the stent, another stent deployment improved the expansion. After the procedure, her symptom improved.

Discussion

Reportedly, the mechanism of DCO occurring months or years after TAVI is thought to be thrombus formation or THV endothelialization. In our case, the low-density mass was considered to be endothelium which developed along the THV frame. Low sinotubular junction height and higher THV position could be the underlying mechanisms of DCO. Percutaneous coronary intervention is a possible treatment option for DCO caused by THV endothelialization.
Surgical management of a giant right coronary artery aneurysm with coronary arteriovenous fistula: case report
Authors: Guerrero Becerra Albert Franz , Palacio Andres Mauricio , Camacho Jaime , Sandoval Nestor
Published: September 2020

Background

Coronary artery aneurysms (CAAs) are uncommon, and giant aneurysms (>2 cm) are even more unusual. Coronary atherosclerosis and Kawasaki disease are the leading causes for this pathology. The treatment for this condition is controversial because the evidence is based on case report series.

Case summary

We describe the case of a 77-year-old female patient who presented with heart failure symptoms. She was diagnosed with a giant saccular aneurysm arising from the right coronary artery (RCA) ostium and a fistula between the RC and the left anterior descending artery (LAD) to the coronary sinus. And an atrial septal defect (ASD) and severe tricuspid regurgitation were also found. The patient underwent surgery through a medium sternotomy, the aneurysm was opened and resected under cardiopulmonary bypass. The RCA was ligated at the distal end of the aneurysm, and a saphenous vein graft bypass was performed. A coronary arteriovenous fistula from the distal portion of RC and LAD artery to a severely enlarged coronary sinus was found and corrected with an autologous pericardial patch. Closure of the ASD was performed with a pericardial patch and a tricuspid ring annuloplasty was done. Post-operative course was uneventful.

Discussion

There are few cases of giant coronary aneurysms associated with fistulas reported in the literature. Despite the endovascular percutaneous techniques available to treat these patients, we believe that surgical treatment was the best option for this particular case. We consider that surgical treatment is a very good option for giant CAAs associated with AV fistulas that are not susceptible for current endovascular available devices. The literature lacks evidence regarding the best approach for these cases, and we think that invasive treatment should be tailored according to the heart’s anatomy and patient risk.
Fashioning an enduring musical identity in image, sound and stone
Authors: Hatter Jane
Published: September 2020

Death and commemoration were central to the devotions that filled the side chapels and adorned the votive altars of 15th-century churches with exquisite sounds, forms and colours. Musicians participated in this outpouring of innovative memorials as both contributors to the ceremonies, providing the sacred harmonies that permeated these spaces on behalf of the deceased, and also as donors who funded their own visual and aural commemorations. How can this dual role help us understand the importance of musical identity for 15th-century professional singers and composers? Du Fay’s complex of commemorations—his will, personalized compositions and wall-mounted memorial—provides the most comprehensive specimen of this fascinating overlap between commemorator and commemorated, but there also remain many fragments from other musicians. Using Du Fay’s example, we can find connections between the visual and musical artefacts created or funded by other musicians, and infer that being remembered after death was an important impetus for the recognition of a distinct musical identity and the development of the professional composer.
Trade, price and quality upgrading effects of agri-food standards
Authors: Fiankor Dela-Dem Doe , Curzi Daniele , Olper Alessandro
Published: September 2020

This paper assesses how cross-country differences in public mandatory food standards affect trade, prices and product quality upgrading in the agri-food sector. We estimate different gravity-type models that exploit the bilateral difference in maximum residue limits (MRLs) over the period from 2005 to 2014 for 145 products across 59 countries. Our findings show that cross-country differences in MRLs restrict trade. However, conditional on trading, they increase product prices—even when we adjust prices for quality—with null effects on estimated product quality. These effects are pronounced for South–North trade but not for exports to the South.
Shorter telomere length, higher telomerase activity in association with tankyrase gene polymorphism contribute to high-altitude pulmonary edema
Authors: Miglani Manjula , Rain Manjari , Pasha Qadar , Raj V Samuel , Thinlas Tashi , Mohammad Ghulam , Gupta Archana , Pandey Ramendra Pati , Vibhuti Arpana
Published: September 2020

High-altitude pulmonary edema (HAPE) is a noncardiogenic form of pulmonary edema, which is induced upon exposure to hypobaric hypoxia at high altitude (HA). Hypobaric hypoxia generates reactive oxygen species that may damage telomeres and disturb normal physiological processes. Telomere complex comprises of multiple proteins, of which, tankyrase (TNKS) is actively involved in DNA damage repairs. We hence investigated the association of TNKS and telomeres with HAPE to delineate their potential role at HA. The study was performed in three groups, High-altitude pulmonary edema patients (HAPE-p, n = 200), HAPE-resistant sojourners (HAPE-r, n = 200) and highland permanent healthy residents (HLs, n = 200). Variants of TNKS were genotyped using polymerase chain reaction–restriction fragment length polymorphism. Plasma TNKS level was estimated using enzyme-linked immunosorbent assay, expression of TNKS and relative telomere length were assessed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and telomerase activity was assessed by the telomere repeat amplification protocol assay. TNKS poly-ADP ribosylates the telomere-repeat factor (TRF), which is a negative regulator of telomere length. Consequently, TRF expression was also measured by RT-qPCR. The TNKS heterozygotes rs7015700GA were prevalent in HLs compared to the HAPE-p and HAPE-r. The plasma TNKS was significantly decreased in HAPE-p than HAPE-r (P = 0.006). TNKS was upregulated 9.27 folds in HAPE-p (P = 1.01E-06) and downregulated in HLs by 3.3 folds (P = 0.02). The telomere length was shorter in HAPE-p compared to HAPE-r (P = 0.03) and HLs (P = 4.25E-4). The telomerase activity was significantly higher in HAPE-p compared to both HAPE-r (P = 0.01) and HLs (P = 0.001). HAPE-p had the lowest TNKS levels (0.186 ± 0.031 ng/μl) and the highest telomerase activity (0.0268 amoles/μl). The findings of the study indicate the association of TNKS and telomeres with HA adaptation/maladaptation.
Large Diversity in Nitrogen- and Sulfur-Containing Compatible Solute Profiles in Polar and Temperate Diatoms
Authors: Dawson H M , Heal K R , Torstensson A , Carlson L T , Ingalls A E , Young J N
Published: September 2020

Synopsis

Intense bottom-ice algal blooms, often dominated by diatoms, are an important source of food for grazers, organic matter for export during sea ice melt, and dissolved organic carbon. Sea-ice diatoms have a number of adaptations, including accumulation of compatible solutes, that allows them to inhabit this highly variable environment characterized by extremes in temperature, salinity, and light. In addition to protecting them from extreme conditions, these compounds present a labile, nutrient-rich source of organic matter, and include precursors to climate active compounds (e.g., dimethyl sulfide [DMS]), which are likely regulated with environmental change. Here, intracellular concentrations of 45 metabolites were quantified in three sea-ice diatom species and were compared to two temperate diatom species, with a focus on compatible solutes and free amino acid pools. There was a large diversity of metabolite concentrations between diatoms with no clear pattern identifiable for sea-ice species. Concentrations of some compatible solutes (isethionic acid, homarine) approached 1 M in the sea-ice diatoms, Fragilariopsis cylindrus and Navicula cf. perminuta, but not in the larger sea-ice diatom, Nitzschia lecointei or in the temperate diatom species. The differential use of compatible solutes in sea-ice diatoms suggests different adaptive strategies and highlights which small organic compounds may be important in polar biogeochemical cycles.
A Polylogarithmic Bound in the Nonlinear Roth Theorem
Authors: Peluse Sarah , Prendiville Sean
Published: September 2020

We show that sets of integers lacking the configuration $x$, $x+y$, $x+y^2$ have at most polylogarithmic density.
The 40 health systems, COVID-19 (40HS, C-19) study
Authors: Braithwaite Jeffrey , Tran Yvonne , Ellis Louise A , Westbrook Johanna
Published: September 2020

Background

The health, social and economic consequences of the severe acute respiratory syndrome coronavirus (SARS-CoV-2, henceforth COVID-19) pandemic have loomed large as every national government made decisions about how to respond. The 40 Health Systems, COVID-19 (40HS, C-19) study aimed to investigate relationships between governments’ capacity to respond (CTR), their response stringency, scope of COVID-19 testing and COVID-19 outcomes.

Methods

Data over March and April 2020 were extracted for 40 national health systems on prepandemic government CTR (Global Competitiveness Index), stringency measures (Oxford COVID-19 Government Response Tracker Stringency Index), approach to COVID-19 testing and COVID-19 cases and deaths (Our-World-in-Data). Multidimensional scaling (MDS) and cluster analysis were applied to examine latent dimensions and visualize country similarities and dissimilarities. Outcomes were tested using multivariate and one-way analyses of variances and Kruskal–Wallis H tests.

Results

The MDS model found three dimensions explaining 91% of the variance and cluster analysis identified five national groupings. There was no association between national governments’ prepandemic CTR and the adoption of early stringent public health measures or approach to COVID-19 testing. Two national clusters applied early stringency measures and reported significantly lower cumulative deaths. The best performing national cluster (comprising Australia, South Korea, Iceland and Taiwan) adopted relatively early stringency measures but broader testing earlier than others, which was associated with a change in disease trajectory and the lowest COVID-19 death rates. Two clusters (one with high CTR and one low) both adopted late stringency measures and narrow testing and performed least well in COVID-19 outcomes.

Conclusion

Early stringency measures and intrinsic national capacities to deal with a pandemic are insufficient. Extended stringency measures, important in the short term, are not economically sustainable. Broad-based testing is key to managing COVID-19.