bluuebunny/crossref_metadata_2025 huggingface dataset:
Three Attitudes Towards Nature
Authors: Martin Christian
Published: September 2021

In his introductions to the encyclopaedicPhilosophy of Natureand to theLectures on the Philosophy of Nature, Hegel distinguishes between three ‘attitudes’ (Verhaltensweisen,Einstellungen) towards nature—the theoretical, the practical and the philosophical attitude. According to him there is a certain ‘contradiction’ or tension between our theoretical attitude towards nature, which makes it an object of scientific inquiry, and the practical attitude that we assume as living rational beings who intervene in nature and shape it according to our purposes. This article focuses on how exactly to pinpoint that tension and on how it is resolved in what Hegel calls the ‘philosophical’ or ‘comprehending’ attitude towards nature.
Close Encounters of an Unprecedented Kind: Police and German Enemy Aliens in Britain during the First World War
Authors: Shpayer-Makov Haia
Published: September 2021

The First World War introduced new tasks into British policing. One significant addition was the close and systematic surveillance of aliens residing in Britain, a role never before undertaken by the British police and one that would previously have been considered un-English. During the war, various official bodies participated in the regulation of the lives of foreigners, but the police played a crucial part. Foreigners hailing from enemy countries, particularly Germans, bore the brunt of police attention, which can be described as nothing short of discriminatory and oppressive. This article examines the new responsibilities of the British police for controlling German nationals and the public response to the new policing. It also assesses the police's wartime performance and the implications of their conduct for the lives of these Germans, all of which has hitherto been little explored. The police were widely considered, both by large segments of the British public and in many other countries, as the best police force in the world, morally superior to other constabularies, especially in their relatively tolerant attitudes toward the public. Their conduct in a time of national crisis, and particularly the degree of tolerance they exercised in their relations with a hated, indeed outcast minority, offers an illuminating case study.
Neurodevelopmental disorders and subsequent risk of violent victimization: exploring sex differences and mechanisms
Authors: Ghirardi Laura , Kuja-Halkola Ralf , Pettersson Erik , Sariaslan Amir , Arseneault Louise , Fazel Seena , D'Onofrio Brian M. , Lichtenstein Paul , Larsson Henrik
Published: September 2021

Background

Neurodevelopmental disorders (NDs) are associated with experiences of victimization, but mechanisms remain unclear. We explored sex differences and the role of familial factors and externalizing problems in the association between several NDs and violent victimization in adolescence and young adulthood.

Methods

Individuals born in Sweden 1985–1997, residing in Sweden at their 15th birthday, were followed until date of violent victimization causing a hospital visit or death, death due to other causes, emigration, or December 31, 2013, whichever came first. The exposures were diagnoses of attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), intellectual disability (ID) and other NDs. We used three different Cox regression models: a crude model, a model adjusted for familial confounding using sibling-comparisons, and a model additionally adjusted for externalizing problems.

Results

Among 1 344 944 individuals followed, on average, for 5 years, 74 487 were diagnosed with NDs and 37 765 had a hospital visit or died due to violence. ADHD was associated with an increased risk of violent victimization in males [hazard ratio (HR) 2.56; 95% confidence interval (CI) 2.43–2.70) and females (HR 5.39; 95% CI 4.97–5.85). ASD and ID were associated with an increased risk of violent victimization in females only. After adjusting for familial factors and externalizing problems, only ADHD was associated with violent victimization among males (HR 1.27; 95% CI 1.06–1.51) and females (HR 1.69; 95% CI 1.21–2.36).

Conclusions

Females with NDs and males with ADHD are at greater risk of being victim of severe violence during adolescence and young adulthood. Relevant mechanisms include shared familial liability and externalizing problems. ADHD may be independently associated with violent victimization.
A gradual separation from the world: a qualitative exploration of existential loneliness in old age
Authors: Carr Sam , Fang Chao
Published: September 2021

This study sought to explore qualitatively experiences of existential loneliness (EL) in 80 older people living in retirement communities across the United Kingdom and Australia. Qualitative semi-structured interviews permitted in-depth exploration of issues such as biographical narrative, close relationships, loss, feelings of loneliness and retirement living. It was our intention to conduct a large-scale, deep-listening exercise that would provide further clues about EL in older people and the circumstances that give rise to such feelings. Data provided rich insight into older people's inner lives. Core themes identified loss of close attachments, lack of physical touch and intimacy, deterioration of health and body, and lack of an emotional language through which to express EL as central to older people's experiences. Furthermore, there was a suggestion that the move to retirement living was for many people inextricably connected to their experience of EL. Our data further support and extend the notion that EL can be thought of as a gradual sense of separation from the world and that ageing intensifies a myriad of social, emotional and physical circumstances that prompt its emergence. This sense of existential isolation need not be thought of as exclusive to those experiencing extreme frailty or who face death imminently – our data pointed to a clear and gradual emergence of EL throughout later life.
SCULPTURAL TRADITIONALISM AND INNOVATION IN THE CLASSIC MAYA KINGDOM OF SAK TZ'I', MEXICO
Authors: Matsumoto Mallory E. , Scherer Andrew K. , Golden Charles , Houston Stephen
Published: September 2021

In this article we analyze the content and form of 58 stone monuments at the archaeological site of Lacanjá Tzeltal, Chiapas, Mexico, which recent research confirms was a capital of the Classic Maya polity Sak Tz'i' (“White Dog”). Sak Tz'i' kings carried the titleajaw(“lord”) rather than the epithetk'uhul ajaw(“holy lord”) claimed by regional powers, implying that Sak Tz'i' was a lesser kingdom in terms of political authority. Lacanjá Tzeltal's corpus of sculptured stone, however, is explicitly divergent and indicates the community's marked cultural autonomy from other western Maya kingdoms. The sculptures demonstrate similarities with their neighbors in terms of form and iconographic and hieroglyphic content, underscoring Lacanjá Tzeltal artisans’ participation in the region's broader culture of monumental production. Nevertheless, sculptural experimentations demonstrate not only that lesser courts like Lacanjá Tzeltal were centers of innovation, but that the lords of Sak Tz'i' may have fostered such cultural distinction to underscore their independent political character. This study has broader implications for understanding interactions between major and secondary polities, artistic innovation, and the development of community identity in the Classic Maya world.
La liaison dans un corpus de hits francophones (1956–2017)
Authors: Coutanson Gasparde , Badin Flora
Published: September 2021

Dans cette contribution, nous analysons un corpus de chansons ayant accédé à la première place de classements musicaux réalisés pour la France entre 1956 et 2017. Cette base de données nous permet de nous questionner sur le type d’oralité que produit l’industrie du disque francophone. Si les chansons présentent des caractéristiques conceptionnelles relevant de la distance (Koch et Oesterreicher, 2001), quelques traits linguistiques relevés sont pourtant illustratifs d’une proximité conceptionnelle. Nous nous intéressons plus particulièrement aux liaisons dans les chansons, à leur possible réalisation dans ces productions préparées en comparaison avec des corpus spontanés ou de locuteurs professionnels, aux liaisons variables (que nous considérons comme une marque de distance) et à l’évolution diachronique de leur réalisation. Pour mener à bien cette analyse, nous avons utilisé un outil facilitant l’étude sur corpus des liaisons, que nous présenterons. C’est surtout la réalisation de certaines liaisons variables, comme aprèssuis, étaisoujamais, plus spécifiquement réalisées dans notre corpus, qui concourt au caractère distant de ces productions langagières. Au fil du temps, la réalisation des liaisons variables a diminué dans les chansons, par exemple aprèsestou préposition, les rapprochant de productions relevant de la proximité.
Hypercorrection in English: an intervarietal corpus-based study
Authors: COLLINS PETER
Published: September 2021

This article aims to provide a fresh approach to the study of hypercorrection, the misguided application of a real or imagined rule – typically in response to prescriptive pressure – in which the speaker's attempt to be ‘correct’ leads to an ‘incorrect’ result. Instead of more familiar sources of information on hypercorrection such as attitude elicitation studies and prescriptive commentary, insights are sought from quantitative and qualitative data extracted from the 2-billion-word Global Web-based English corpus (GloWbE; Davies 2013). Five categories are investigated: case-marked pronouns, -lyand non-lyadverbs, agreement with number-transparent nouns, (extended uses of) irrealiswere, and ‘hyperforeign’ noun suffixation. The nature and extent of hypercorrection in these categories, across the twenty English varieties represented in GloWbE, are investigated and discussed. Findings include a tendency for hypercorrection to be more common in American than in British English, and more prevalent in the ‘Inner Circle’ (IC) than in the ‘Outer Circle’ (OC) varieties (particularly with established constructions which have been the target of institutionalised prescriptive commentary over a long period of time).
Analysis of rating scales: A pervasive problem in bilingualism research and a solution with Bayesian ordinal models
Authors: Veríssimo João
Published: September 2021

Research in bilingualism often involves quantifying constructs of interest by the use of rating scales: for example, to measure language proficiency, dominance, or sentence acceptability. However, ratings are a type of ordinal data, which violates the assumptions of the statistical methods that are commonly used to analyse them. As a result, the validity of ratings is compromised and the ensuing statistical inferences can be seriously distorted. In this article, we describe the problem in detail and demonstrate its pervasiveness in bilingualism research. We then provide examples of how bilingualism researchers can employ an appropriate solution using Bayesian ordinal models. These models respect the inherent discreteness of ratings, easily accommodate non-normality, and allow modelling unequal psychological distances between response categories. As a result, they can provide more valid, accurate, and informative inferences about graded constructs such as language proficiency. Data and code are publicly available in an OSF repository athttps://osf.io/grs8x.
Probabilistic Reconstruction of Austenite Microstructure from Electron Backscatter Diffraction Observations of Martensite
Authors: Brust Alexander , Payton Eric , Hobbs Toren , Sinha Vikas , Yardley Victoria , Niezgoda Stephen
Published: September 2021

The fine microstructure resulting from the martensitic transformation drives many of the desired mechanical properties for quench-and-temper steels. The scale of martensite features correlates with austenite grain size, such that finer austenite grains produce finer martensitic structures. Measuring prior austenite grain (PAG) size from observations of the hierarchical martensitic structure using etch-based techniques remains challenging, especially for fine-grained specimens with low C and P content. This has driven an interest in our field in reconstructing prior austenite microstructure from electron backscatter diffraction (EBSD) data collected on tempered martensite. However, reliably reconstructing the data is not straightforward because (1) up to 24 variants can theoretically be observed from a single PAG; (2) the shear-induced plasticity that arises from martensite formation produces significant scatter in the pole figure; (3) there is inherent noise in Hough-indexed EBSD data; (4) annealing twins exist within many PAGs, producing martensite variants of similar orientations when compared with the parent grains; and (5) variation in austenite orientation can occur across a single PAG. To the author's knowledge, the majority of reconstruction algorithms published to date utilize either point-to-point or flood-fill approaches, which can produce artifacts due to the relatively high probability of adjacent EBSD observations falling within any reasonable tolerance angle with 24 variants in a parent and four annealing twin orientations. Therefore, we propose a probabilistic austenite reconstruction technique based on a clustering algorithm known as graph cutting. We demonstrate its application to steels and a binary ferrous alloy, then validate the results against chemical etching and retained austenite orientations. The graph cutting technique utilizes the misorientation distribution of martensitic variants and the potential austenite orientations for each observation, as estimated via Bayesian inference of the experimental orientation relationship and its scatter. It is found that this technique produces accurate reconstructions with identification of annealing twins in the PAGs, even in the presence of a large fraction of poorly indexed data points.
Modeling the Dynamics of Dense Pyroclastic Flows on Venus: Insights Into Pyroclastic Eruptions
Authors: Ganesh Indujaa , McGuire Luke A. , Carter Lynn M.
Published: September 2021

On Venus, relatively young deposits near volcanic and coronal summits with unique radar characteristics have been proposed to be emplaced by pyroclastic density currents (PDCs). The proposed units are laterally extensive, long‐runout deposits showing moderate to high radar backscatter and circular polarization ratio in 12.6 cm wavelength synthetic aperture radar data. Previous studies have hypothesized that a recent resumption of volcanic activity in the form of PDC‐forming eruptions could have emplaced these deposits. We model the dynamics of dense PDCs using a 2D, depth‐averaged framework focusing on regions where stereo‐derived topography coverage is available; this includes the flanks of Irnini Mons, Anala Mons, Didilia Corona, and Pavlova Corona. Two different mechanisms of initiation which includes impulsive collapse of an eruption column and sustained pyroclastic fountaining are considered. The results emphasize the importance of pyroclastic flow fluidization via high pore pressure in emplacing long‐runout deposits along gently sloping (<2°) volcanic flanks. We also show that collapse of columns >1.2–1.4 km tall as well as pyroclastic fountains lasting >400 s with fountain heights of 50 m are capable of generating pyroclastic flows that could emplace some of the smaller deposits studied. For the large deposits at Irnini Mons, more energetic flows resulting from taller column heights would be necessary; the dynamics of such flows under Venus's conditions are not well understood. Distinguishing between the two initiation styles, that is, column collapse and sustained fountaining is not feasible with currently available datasets and would require higher resolution imagery and topography data.
Leakage pressures for gasketless superhydrophobic fluid interconnects for modular lab-on-a-chip systems
Authors: Brown Christopher R. , Zhao Xiaoxiao , Park Taehyun , Chen Pin-Chuan , You Byoung Hee , Park Daniel S. , Soper Steven A. , Baird Alison , Murphy Michael C.
Published: September 2021

Chip-to-chip and world-to-chip fluidic interconnections are paramount to enable the passage of liquids between component chips and to/from microfluidic systems. Unfortunately, most interconnect designs add additional physical constraints to chips with each additional interconnect leading to over-constrained microfluidic systems. The competing constraints provided by multiple interconnects induce strain in the chips, creating indeterminate dead volumes and misalignment between chips that comprise the microfluidic system. A novel, gasketless superhydrophobic fluidic interconnect (GSFI) that uses capillary forces to form a liquid bridge suspended between concentric through-holes and acting as a fluid passage was investigated. The GSFI decouples the alignment between component chips from the interconnect function and the attachment of the meniscus of the liquid bridge to the edges of the holes produces negligible dead volume. This passive seal was created by patterning parallel superhydrophobic surfaces (water contact angle ≥ 150°) around concentric microfluidic ports separated by a gap. The relative position of the two polymer chips was determined by passive kinematic constraints, three spherical ball bearings seated in v-grooves. A leakage pressure model derived from the Young–Laplace equation was used to estimate the leakage pressure at failure for the liquid bridge. Injection-molded, Cyclic Olefin Copolymer (COC) chip assemblies with assembly gaps from 3 to 240 µm were used to experimentally validate the model. The maximum leakage pressure measured for the GSFI was 21.4 kPa (3.1 psig), which corresponded to a measured mean assembly gap of 3 µm, and decreased to 0.5 kPa (0.073 psig) at a mean assembly gap of 240 µm. The effect of radial misalignment on the efficacy of the gasketless seals was tested and no significant effect was observed. This may be a function of how the liquid bridges are formed during the priming of the chip, but additional research is required to test that hypothesis.
Microdevice for directional axodendritic connectivity between micro 3D neuronal cultures
Authors: Ming Yixuan , Abedin Md Joynal , Tatic-Lucic Svetlana , Berdichevsky Yevgeny
Published: September 2021

Neuronal cultures are widely used in neuroscience research. However, the randomness of circuits in conventional cultures prevents accurate in vitro modeling of cortical development and of the pathogenesis of neurological and psychiatric disorders. A basic feature of cortical circuits that is not captured in standard cultures of dissociated cortical cells is directional connectivity. In this work, a polydimethylsiloxane (PDMS)-based device that achieves directional connectivity between micro 3D cultures is demonstrated. The device consists of through-holes for micro three-dimensional (μ3D) clusters of cortical cells connected by microtrenches for axon and dendrite guidance. The design of the trenches relies in part on the concept of axonal edge guidance, as well as on the novel concept of specific dendrite targeting. This replicates dominant excitatory connectivity in the cortex, enables the guidance of the axon after it forms a synapse in passing (an “en passant” synapse), and ensures that directional selectivity is preserved over the lifetime of the culture. The directionality of connections was verified morphologically and functionally. Connections were dependent on glutamatergic synapses. The design of this device has the potential to serve as a building block for the reconstruction of more complex cortical circuits in vitro.
DMD-based hyperspectral microscopy with flexible multiline parallel scanning
Authors: Dong Xue , Tong Geng , Song Xuankun , Xiao Xingchen , Yu Yiting
Published: September 2021

As one of the most common hyperspectral microscopy (HSM) techniques, line-scanning HSM is currently utilized in many fields. However, its scanning efficiency is still considered to be inadequate since many biological and chemical processes occur too rapidly to be captured. Accordingly, in this work, a digital micromirror device (DMD) based on microelectromechanical systems (MEMS) is utilized to demonstrate a flexible multiline scanning HSM system. To the best of our knowledge, this is the first line-scanning HSM system in which the number of scanning lines N can be tuned by simply changing the DMD’s parallel scanning units according to diverse applications. This brilliant strategy of effortless adjustability relies only on on-chip scanning methods and totally exploits the benefits of parallelization, aiming to achieve nearly an N-time improvement in the detection efficiency and an N-time decrease in the scanning time and data volume compared with the single-line method under the same operating conditions. To validate this, we selected a few samples of different spectral wavebands to perform reflection imaging, transmission imaging, and fluorescence imaging with varying numbers of scanning lines. The results show the great potential of our DMD-based HSM system for the rapid development of cellular biology, material analysis, and so on. In addition, its on-chip scanning process eliminates the inherent microscopic architecture, making the whole system compact, lightweight, portable, and not subject to site constraints.
Melatonin enhances radiofrequency-induced NK antitumor immunity, causing cancer metabolism reprogramming and inhibition of multiple pulmonary tumor development
Authors: Li Ming , Hao Bingjie , Zhang Menghuan , Reiter Russel J. , Lin Shumeng , Zheng Tiansheng , Chen Xiangyun , Ren Yanbei , Yue Liduo , Abay Baigenzhin , Chen Guojie , Xu Xiao , Shi Yufeng , Fan Lihong
Published: September 2021

Surgery is the common treatment for early lung cancer with multiple pulmonary nodules, but it is often accompanied by the problem of significant malignancy of other nodules in non-therapeutic areas. In this study, we found that a combined treatment of local radiofrequency ablation (RFA) and melatonin (MLT) greatly improved clinical outcomes for early lung cancer patients with multiple pulmonary nodules by minimizing lung function injury and reducing the probability of malignant transformation or enlargement of nodules in non-ablated areas. Mechanically, as demonstrated in an associated mouse lung tumor model, RFA not only effectively remove treated tumors but also stimulate antitumor immunity, which could inhibit tumor growth in non-ablated areas. MLT enhanced RFA-stimulated NK activity and exerted synergistic antitumor effects with RFA. Transcriptomics and proteomics analyses of residual tumor tissues revealed enhanced oxidative phosphorylation and reduced acidification as well as hypoxia in the tumor microenvironment, which suggests reprogrammed tumor metabolism after combined treatment with RFA and MLT. Analysis of residual tumor further revealed the depressed activity of MAPK, NF-kappa B, Wnt, and Hedgehog pathways and upregulated P53 pathway in tumors, which was in line with the inhibited tumor growth. Combined RFA and MLT treatment also reversed the Warburg effect and decreased tumor malignancy. These findings thus demonstrated that combined treatment of RFA and MLT effectively inhibited the malignancy of non-ablated nodules and provided an innovative non-invasive strategy for treating early lung tumors with multiple pulmonary nodules. Trial registration: www.chictr.org.cn, identifier ChiCTR2100042695, http://www.chictr.org.cn/showproj.aspx?proj=120931.
Associations between childhood maltreatment and DNA methylation of the oxytocin receptor gene in immune cells of mother–newborn dyads
Authors: Ramo-Fernández Laura , Gumpp Anja M. , Boeck Christina , Krause Sabrina , Bach Alexandra M. , Waller Christiane , Kolassa Iris-Tatjana , Karabatsiakis Alexander
Published: September 2021

The neuropeptide oxytocin (OXT) and its receptor (OXTR) modulate interpersonal relationships, particularly mother–child interactions. DNA methylation (DNAm) changes of theOXTRgene were observed in individuals who experienced Childhood Maltreatment (CM). A modulatory role of single nucleotide polymorphisms (SNP) withinOXTRin association with CM on the regulation of OXTR was also postulated. Whether these CM-induced epigenetic alterations are biologically inherited by the offspring remains unknown. We thus investigated possible intergenerational effects of maternal CM exposure on DNAm andOXTRgene expression, additionally accounting for the possible influence of three SNP: rs53576 and rs2254298 (OXTRgene), and rs2740210 (OXTgene). We used theChildhood Trauma Questionnaireto classify mothers into individuals with (CM+) or without CM (CM−). Maternal peripheral immune cells were isolated from venous blood (N = 117) and fetal immune cells from the umbilical cord (N = 113) after parturition. DNA methylation was assessed using MassARRAY. Taqman assays were performed for genotyping and gene expression analyses. Among mothers, CM was not associated withOXTRmean methylation or gene expression. However, four CpG sites showed different methylation levels in CM− compared to CM+. In mothers, theOXTRrs53576 andOXTrs2740210 allelic variations interacted with CM load on theOXTRmean methylation. Maternal and newborns’ mean methylation ofOXTRwere positively associated within CM− dyads, but not in CM+ dyads. We show gene×environment interactions on the epigenetic regulation of the oxytocinergic signaling and show the intergenerational comparability of theOXTRDNAm might be altered in infants of CM+ mothers.
Osteoblastic glucocorticoid signaling exacerbates high-fat-diet- induced bone loss and obesity
Authors: Kim Sarah , Henneicke Holger , Cavanagh Lauryn L. , Macfarlane Eugenie , Thai Lee Joanne , Foong Daphne , Gasparini Sylvia J. , Fong-Yee Colette , Swarbrick Michael M. , Seibel Markus J. , Zhou Hong
Published: September 2021

Chronic high-fat diet (HFD) consumption not only promotes obesity and insulin resistance, but also causes bone loss through mechanisms that are not well understood. Here, we fed wild-type CD-1 mice either chow or a HFD (43% of energy from fat) for 18 weeks; HFD-fed mice exhibited decreased trabecular volume (−28%) and cortical thickness (−14%) compared to chow-fed mice. In HFD-fed mice, bone loss was due to reduced bone formation and mineral apposition, without obvious effects on bone resorption. HFD feeding also increased skeletal expression of sclerostin and caused deterioration of the osteocyte lacunocanalicular network (LCN). In mice fed HFD, skeletal glucocorticoid signaling was activated relative to chow-fed mice, independent of serum corticosterone concentrations. We therefore examined whether skeletal glucocorticoid signaling was necessary for HFD-induced bone loss, using transgenic mice lacking glucocorticoid signaling in osteoblasts and osteocytes (HSD2OB/OCY-tg mice). In HSD2OB/OCY-tg mice, bone formation and mineral apposition rates were not suppressed by HFD, and bone loss was significantly attenuated. Interestingly, in HSD2OB/OCY-tg mice fed HFD, both Wnt signaling (less sclerostin induction, increased β-catenin expression) and glucose uptake were significantly increased, relative to diet- and genotype-matched controls. The osteocyte LCN remained intact in HFD-fed HSD2OB/OCY-tg mice. When fed a HFD, HSD2OB/OCY-tg mice also increased their energy expenditure and were protected against obesity, insulin resistance, and dyslipidemia. Therefore, glucocorticoid signaling in osteoblasts and osteocytes contributes to the suppression of bone formation in HFD-fed mice. Skeletal glucocorticoid signaling is also an important determinant of glucose uptake in bone, which influences the whole-body metabolic response to HFD.
Cyclic AMP-binding protein Epac1 acts as a metabolic sensor to promote cardiomyocyte lipotoxicity
Authors: Laudette Marion , Sainte-Marie Yannis , Cousin Grégoire , Bergonnier Dorian , Belhabib Ismahane , Brun Stéphanie , Formoso Karina , Laib Loubna , Tortosa Florence , Bergoglio Camille , Marcheix Bertrand , Borén Jan , Lairez Olivier , Fauconnier Jérémy , Lucas Alexandre , Mialet-Perez Jeanne , Moro Cédric , Lezoualc’h Frank
Published: September 2021

Cyclic adenosine monophosphate (cAMP) is a master regulator of mitochondrial metabolism but its precise mechanism of action yet remains unclear. Here, we found that a dietary saturated fatty acid (FA), palmitate increased intracellular cAMP synthesis through the palmitoylation of soluble adenylyl cyclase in cardiomyocytes. cAMP further induced exchange protein directly activated by cyclic AMP 1 (Epac1) activation, which was upregulated in the myocardium of obese patients. Epac1 enhanced the activity of a key enzyme regulating mitochondrial FA uptake, carnitine palmitoyltransferase 1. Consistently, pharmacological or genetic Epac1 inhibition prevented lipid overload, increased FA oxidation (FAO), and protected against mitochondrial dysfunction in cardiomyocytes. In addition, analysis of Epac1 phosphoproteome led us to identify two key mitochondrial enzymes of the the β-oxidation cycle as targets of Epac1, the long-chain FA acyl-CoA dehydrogenase (ACADL) and the 3-ketoacyl-CoA thiolase (3-KAT). Epac1 formed molecular complexes with the Ca2+/calmodulin-dependent protein kinase II (CaMKII), which phosphorylated ACADL and 3-KAT at specific amino acid residues to decrease lipid oxidation. The Epac1-CaMKII axis also interacted with the α subunit of ATP synthase, thereby further impairing mitochondrial energetics. Altogether, these findings indicate that Epac1 disrupts the balance between mitochondrial FA uptake and oxidation leading to lipid accumulation and mitochondrial dysfunction, and ultimately cardiomyocyte death.
Metabolite profiling and transcriptome analyses reveal novel regulatory mechanisms of melatonin biosynthesis in hickory
Authors: Chen Wenchao , Zhang Jiaqi , Zheng Shan , Wang Zhanqi , Xu Chuanmei , Zhang Qixiang , Wu Jiasheng , Lou Heqiang
Published: September 2021

Studies have shown that melatonin regulates the expression of various elements in the biosynthesis and catabolism of plant hormones. In contrast, the effects of these different plant hormones on the biosynthesis and metabolism of melatonin and their underlying molecular mechanisms are still unclear. In this study, the melatonin biosynthesis pathway was proposed from constructed metabolomic and transcriptomic libraries from hickory (Carya cathayensis Sarg.) nuts. The candidate pathway genes were further identified by phylogenetic analysis, amino-acid sequence alignment, and subcellular localization. Notably, most of the transcription factor-related genes coexpressed with melatonin pathway genes were hormone-responsive genes. Furthermore, dual-luciferase and yeast one‐hybrid assays revealed that CcEIN3 (response to ethylene) and CcAZF2 (response to abscisic acid) could activate melatonin biosynthesis pathway genes, a tryptophan decarboxylase coding gene (CcTDC1) and an N-acetylserotonin methyltransferase coding gene (CcASMT1), by directly binding to their promoters, respectively. Our results provide a molecular basis for the characterization of novel melatonin biosynthesis regulatory mechanisms and demonstrate for the first time that abscisic acid and ethylene can regulate melatonin biosynthesis.
Downregulated expression of S2-RNase attenuates self-incompatibility in “Guiyou No. 1” pummelo
Authors: Hu Jianbing , Xu Qiang , Liu Chenchen , Liu Binghao , Deng Chongling , Chen Chuanwu , Wei Zhuangmin , Ahmad Muhammad Husnain , Peng Kang , Wen Hao , Chen Xiangling , Chen Peng , Larkin Robert M , Ye Junli , Deng Xiuxin , Chai Lijun
Published: September 2021

Self-incompatibility (SI) substantially restricts the yield and quality of citrus. Therefore, breeding and analyzing self-compatible germplasm is of great theoretical and practical significance for citrus. Here, we focus on the mechanism of a self-compatibility mutation in ‘Guiyou No. 1’ pummelo (Citrus maxima), which is a spontaneous mutant of ‘Shatian’ pummelo (Citrus maxima, self-incompatibility). The rate of fruit set and the growth of pollen tubes in the pistil confirmed that a spontaneous mutation in the pistil is responsible for the self-compatibility of ‘Guiyou No. 1’. Segregation ratios of the S genotype in F1 progeny, expression analysis, and western blotting validated that the reduced levels of S2-RNase mRNA contribute to the loss of SI in ‘Guiyou No. 1’. Furthermore, we report a phased assembly of the ‘Guiyou No. 1’ pummelo genome and obtained two complete and well-annotated S haplotypes. Coupled with an analysis of SV variations, methylation levels, and gene expression, we identified a candidate gene (CgHB40), that may influence the regulation of the S2-RNase promoter. Our data provide evidence that a mutation that affects the pistil led to the loss of SI in ‘Guiyou No. 1’ by influencing a poorly understood mechanism that affects transcriptional regulation. This work significantly advances our understanding of the genetic basis of the SI system in citrus and provides information on the regulation of S-RNase genes.
The use of shared haplotype length information for pedigree reconstruction in asexually propagated outbreeding crops, demonstrated for apple and sweet cherry
Authors: Howard Nicholas P. , Peace Cameron , Silverstein Kevin A. T. , Poets Ana , Luby James J. , Vanderzande Stijn , Durel Charles-Eric , Muranty Hélène , Denancé Caroline , van de Weg Eric
Published: September 2021

Pedigree information is of fundamental importance in breeding programs and related genetics efforts. However, many individuals have unknown pedigrees. While methods to identify and confirm direct parent–offspring relationships are routine, those for other types of close relationships have yet to be effectively and widely implemented with plants, due to complications such as asexual propagation and extensive inbreeding. The objective of this study was to develop and demonstrate methods that support complex pedigree reconstruction via the total length of identical by state haplotypes (referred to in this study as “summed potential lengths of shared haplotypes”, SPLoSH). A custom Python script, HapShared, was developed to generate SPLoSH data in apple and sweet cherry. HapShared was used to establish empirical distributions of SPLoSH data for known relationships in these crops. These distributions were then used to estimate previously unknown relationships. Case studies in each crop demonstrated various pedigree reconstruction scenarios using SPLoSH data. For cherry, a full-sib relationship was deduced for ‘Emperor Francis, and ‘Schmidt’, a half-sib relationship for ‘Van’ and ‘Windsor’, and the paternal grandparents of ‘Stella’ were confirmed. For apple, 29 cultivars were found to share an unknown parent, the pedigree of the unknown parent of ‘Cox’s Pomona’ was reconstructed, and ‘Fameuse’ was deduced to be a likely grandparent of ‘McIntosh’. Key genetic resources that enabled this empirical study were large genome-wide SNP array datasets, integrated genetic maps, and previously identified pedigree relationships. Crops with similar resources are also expected to benefit from using HapShared for empowering pedigree reconstruction.
The Arabidopsis pattern recognition receptor EFR enhances fire blight resistance in apple
Authors: Piazza Stefano , Campa Manuela , Pompili Valerio , Costa Lorenza Dalla , Salvagnin Umberto , Nekrasov Vladimir , Zipfel Cyril , Malnoy Mickael
Published: September 2021

Fire blight disease, caused by the bacterium Erwinia amylovora (E. amylovora), is responsible for substantial losses in cultivated apples worldwide. An important mechanism of plant immunity is based on the recognition of conserved microbial molecules, named pathogen-associated or microbe-associated molecular patterns (PAMPs or MAMPs), through pattern recognition receptors (PRRs), leading to pattern-triggered immunity (PTI). The interspecies transfer of PRRs represents a promising strategy to engineer broad-spectrum and durable disease resistance in crops. EFR, the Arabidopsis thaliana PRR for the PAMP elf18 derived from the elongation factor thermal unstable (EF-Tu) proved to be effective in improving bacterial resistance when expressed into Solanaceae and other plant species. In this study, we tested whether EFR can affect the interaction of apple with E. amylovora by its ectopic expression in the susceptible apple rootstock M.26. Stable EFR expression led to the activation of PAMP-triggered immune response in apple leaves upon treatment with supernatant of E. amylovora, as measured by the production of reactive oxygen species and the induction of known defense genes. The amount of tissue necrosis associated with E. amylovora infection was significantly reduced in the EFR transgenic rootstock compared to the wild-type. Our results show that the expression of EFR in apple rootstock may be a valuable biotechnology strategy to improve the resistance of apple to fire blight.
EpiScanpy: integrated single-cell epigenomic analysis
Authors: Danese Anna , Richter Maria L. , Chaichoompu Kridsadakorn , Fischer David S. , Theis Fabian J. , Colomé-Tatché Maria
Published: September 2021

EpiScanpy is a toolkit for the analysis of single-cell epigenomic data, namely single-cell DNA methylation and single-cell ATAC-seq data. To address the modality specific challenges from epigenomics data, epiScanpy quantifies the epigenome using multiple feature space constructions and builds a nearest neighbour graph using epigenomic distance between cells. EpiScanpy makes the many existing scRNA-seq workflows from scanpy available to large-scale single-cell data from other -omics modalities, including methods for common clustering, dimension reduction, cell type identification and trajectory learning techniques, as well as an atlas integration tool for scATAC-seq datasets. The toolkit also features numerous useful downstream functions, such as differential methylation and differential openness calling, mapping epigenomic features of interest to their nearest gene, or constructing gene activity matrices using chromatin openness. We successfully benchmark epiScanpy against other scATAC-seq analysis tools and show its outperformance at discriminating cell types.
Exceptional dynamical quantum phase transitions in periodically driven systems
Authors: Hamazaki Ryusuke
Published: September 2021

Extending notions of phase transitions to nonequilibrium realm is a fundamental problem for statistical mechanics. While it was discovered that critical transitions occur even for transient states before relaxation as the singularity of a dynamical version of free energy, their nature is yet to be elusive. Here, we show that spontaneous symmetry breaking can occur at a short-time regime and causes universal dynamical quantum phase transitions in periodically driven unitary dynamics. Unlike conventional phase transitions, the relevant symmetry is antiunitary: its breaking is accompanied by a many-body exceptional point of a nonunitary operator obtained by space-time duality. Using a stroboscopic Ising model, we demonstrate the existence of distinct phases and unconventional singularity of dynamical free energy, whose signature can be accessed through quasilocal operators. Our results open up research for hitherto unknown phases in short-time regimes, where time serves as another pivotal parameter, with their hidden connection to nonunitary physics.
Major restructuring of marine plankton assemblages under global warming
Authors: Benedetti Fabio , Vogt Meike , Elizondo Urs Hofmann , Righetti Damiano , Zimmermann Niklaus E. , Gruber Nicolas
Published: September 2021

Marine phytoplankton and zooplankton form the basis of the ocean’s food-web, yet the impacts of climate change on their biodiversity are poorly understood. Here, we use an ensemble of species distribution models for a total of 336 phytoplankton and 524 zooplankton species to determine their present and future habitat suitability patterns. For the end of this century, under a high emission scenario, we find an overall increase in plankton species richness driven by ocean warming, and a poleward shift of the species’ distributions at a median speed of 35 km/decade. Phytoplankton species richness is projected to increase by more than 16% over most regions except for the Arctic Ocean. In contrast, zooplankton richness is projected to slightly decline in the tropics, but to increase strongly in temperate to subpolar latitudes. In these latitudes, nearly 40% of the phytoplankton and zooplankton assemblages are replaced by poleward shifting species. This implies that climate change threatens the contribution of plankton communities to plankton-mediated ecosystem services such as biological carbon sequestration.
Microglia-neuron interaction at nodes of Ranvier depends on neuronal activity through potassium release and contributes to remyelination
Authors: Ronzano R. , Roux T. , Thetiot M. , Aigrot M. S. , Richard L. , Lejeune F. X. , Mazuir E. , Vallat J. M. , Lubetzki C. , Desmazières A.
Published: September 2021

Microglia, the resident immune cells of the central nervous system, are key players in healthy brain homeostasis and plasticity. In neurological diseases, such as Multiple Sclerosis, activated microglia either promote tissue damage or favor neuroprotection and myelin regeneration. The mechanisms for microglia-neuron communication remain largely unkown. Here, we identify nodes of Ranvier as a direct site of interaction between microglia and axons, in both mouse and human tissues. Using dynamic imaging, we highlight the preferential interaction of microglial processes with nodes of Ranvier along myelinated fibers. We show that microglia-node interaction is modulated by neuronal activity and associated potassium release, with THIK-1 ensuring their microglial read-out. Altered axonal K+flux following demyelination impairs the switch towards a pro-regenerative microglia phenotype and decreases remyelination rate. Taken together, these findings identify the node of Ranvier as a major site for microglia-neuron interaction, that may participate in microglia-neuron communication mediating pro-remyelinating effect of microglia after myelin injury.
Processive dynamics of the usher assembly platform during uropathogenic Escherichia coli P pilus biogenesis
Authors: Du Minge , Yuan Zuanning , Werneburg Glenn T. , Henderson Nadine S. , Chauhan Hemil , Kovach Amanda , Zhao Gongpu , Johl Jessica , Li Huilin , Thanassi David G.
Published: September 2021

Uropathogenic Escherichia coli assemble surface structures termed pili or fimbriae to initiate infection of the urinary tract. P pili facilitate bacterial colonization of the kidney and pyelonephritis. P pili are assembled through the conserved chaperone-usher pathway. Much of the structural and functional understanding of the chaperone-usher pathway has been gained through investigations of type 1 pili, which promote binding to the bladder and cystitis. In contrast, the structural basis for P pilus biogenesis at the usher has remained elusive. This is in part due to the flexible and variable-length P pilus tip fiber, creating structural heterogeneity, and difficulties isolating stable P pilus assembly intermediates. Here, we circumvent these hindrances and determine cryo-electron microscopy structures of the activated PapC usher in the process of secreting two- and three-subunit P pilus assembly intermediates, revealing processive steps in P pilus biogenesis and capturing new conformational dynamics of the usher assembly machine.
Stable, active CO2 reduction to formate via redox-modulated stabilization of active sites
Authors: Li Le , Ozden Adnan , Guo Shuyi , Garcı́a de Arquer F. Pelayo , Wang Chuanhao , Zhang Mingzhe , Zhang Jin , Jiang Haoyang , Wang Wei , Dong Hao , Sinton David , Sargent Edward H. , Zhong Miao
Published: September 2021

Electrochemical reduction of CO2 (CO2R) to formic acid upgrades waste CO2; however, up to now, chemical and structural changes to the electrocatalyst have often led to the deterioration of performance over time. Here, we find that alloying p-block elements with differing electronegativities modulates the redox potential of active sites and stabilizes them throughout extended CO2R operation. Active Sn-Bi/SnO2 surfaces formed in situ on homogeneously alloyed Bi0.1Sn crystals stabilize the CO2R-to-formate pathway over 2400 h (100 days) of continuous operation at a current density of 100 mA cm−2. This performance is accompanied by a Faradaic efficiency of 95% and an overpotential of ~ −0.65 V. Operating experimental studies as well as computational investigations show that the stabilized active sites offer near-optimal binding energy to the key formate intermediate *OCHO. Using a cation-exchange membrane electrode assembly device, we demonstrate the stable production of concentrated HCOO– solution (3.4 molar, 15 wt%) over 100 h.
Silicon-photomultiplier-based PET/CT reduces the minimum detectable activity of iodine-124
Authors: Kersting David , Jentzen Walter , Fragoso Costa Pedro , Sraieb Miriam , Sandach Patrick , Umutlu Lale , Conti Maurizio , Zarrad Fadi , Rischpler Christoph , Fendler Wolfgang Peter , Herrmann Ken , Weber Manuel
Published: September 2021

The radioiodine isotope pair 124I/131I is used in a theranostic approach for patient-specific treatment of differentiated thyroid cancer. Lesion detectability is notably higher for 124I PET (positron emission tomography) than for 131I gamma camera imaging but can be limited for small and low uptake lesions. The recently introduced silicon-photomultiplier-based (SiPM-based) PET/CT (computed tomography) systems outperform previous-generation systems in detector sensitivity, coincidence time resolution, and spatial resolution. Hence, SiPM-based PET/CT shows an improved detectability, particularly for small lesions. In this study, we compare the size-dependant minimum detectable 124I activity (MDA) between the SiPM-based Biograph Vision and the previous-generation Biograph mCT PET/CT systems and we attempt to predict the response to 131I radioiodine therapy of lesions additionally identified on the SiPM-based system. A tumour phantom mimicking challenging conditions (derived from published patient data) was used; i.e., 6 small spheres (diameter of 3.7–9.7 mm), 9 low activity concentrations (0.25–25 kBq/mL), and a very low signal-to-background ratio (20:1). List-mode emission data (single-bed position) were divided into frames of 4, 8, 16, and 30 min. Images were reconstructed with ordinary Poisson ordered-subsets expectation maximization (OSEM), additional time-of-flight (OSEM-TOF) or TOF and point spread function modelling (OSEM-TOF+PSF). The signal-to-noise ratio and the MDA were determined. Absorbed dose estimations were performed to assess possible treatment response to high-activity 131I radioiodine therapy. The signal-to-noise ratio and the MDA were improved from the mCT to the Vision, from OSEM to OSEM-TOF and from OSEM-TOF to OSEM-TOF+PSF reconstructed images, and from shorter to longer emission times. The overall mean MDA ratio of the Vision to the mCT was 0.52 ± 0.18. The absorbed dose estimations indicate that lesions ≥ 6.5 mm with expected response to radioiodine therapy would be detectable on both systems at 4-min emission time. Additional smaller lesions of therapeutic relevance could be detected when using a SiPM-based PET system at clinically reasonable emission times. This study demonstrates that additional lesions with predicted response to 131I radioiodine therapy can be detected. Further clinical evaluation is warranted to evaluate if negative 124I PET scans on a SiPM-based system can be sufficient to preclude patients from blind radioiodine therapy.