bluuebunny/crossref_metadata_2025 huggingface dataset:
Premeiotic pairing of homologous chromosomes during
Drosophila
male meiosis
Authors: Rubin Thomas , Macaisne Nicolas , Vallés Ana Maria , Guilleman Clara , Gaugué Isabelle , Dal Toe Laurine , Huynh Jean-René
Published: November 2022

In the early stages of meiosis, maternal and paternal chromosomes pair with their homologous partner and recombine to ensure exchange of genetic information and proper segregation. These events can vary drastically between species and between males and females of the same species. In
Drosophila,
in contrast to females, males do not form synaptonemal complexes (SCs), do not recombine, and have no crossing over; yet, males are able to segregate their chromosomes properly. Here, we investigated the early steps of homolog pairing in
Drosophila
males. We found that homolog centromeres are not paired in germline stem cells (GSCs) and become paired in the mitotic region before meiotic entry, similarly to females. Surprisingly, male germline cells express SC proteins, which localize to centromeres and promote pairing. We further found that the SUN/KASH (LINC) complex and microtubules are required for homolog pairing as in females. Chromosome movements in males, however, are much slower than in females and we demonstrate that this slow dynamic is compensated in males by having longer cell cycles. In agreement, slowing down cell cycles was sufficient to rescue pairing-defective mutants in female meiosis. Our results demonstrate that although meiosis differs significantly between males and females, sex-specific cell cycle kinetics integrate similar molecular mechanisms to achieve proper centromere pairing.
Chemical imaging of cellular ultrastructure by null-deflection infrared spectroscopic measurements
Authors: Kenkel Seth , Gryka Mark , Chen Lin , Confer Matthew P. , Rao Anirudha , Robinson Scott , Prasanth Kannanganattu V. , Bhargava Rohit
Published: November 2022

Nearfield spectroscopic imaging techniques can be a powerful tool to map both cellular ultrastructure and molecular composition simultaneously but are currently limited in measurement capability. Resonance enhanced (RE) atomic force microscopy infrared (AFM-IR) spectroscopic imaging offers high-sensitivity measurements, for example, but probe-sample mechanical coupling, nonmolecular optical gradient forces, and noise overwhelm recorded chemical signals. Here, we analyze the key factors limiting AFM-IR measurements and propose an instrument design that enables high-sensitivity nanoscale IR imaging by combining null-deflection measurements with RE sensitivity. Our developed null-deflection scanning probe IR (NDIR) spectroscopic imaging provides ∼24× improvement in signal-to-noise ratio (SNR) compared with the state of the art, enables optimal signal recording by combining cantilever resonance with maximum laser power, and reduces background nonmolecular signals for improved analytical accuracy. We demonstrate the use of these properties for high-sensitivity, hyperspectral imaging of chemical domains in 100-nm-thick sections of cellular acini of a prototypical cancer model cell line, MCF-10A. NDIR chemical imaging enables facile recording of label-free, chemically accurate, high-SNR vibrational spectroscopic data from nanoscale domains, paving the path for routine studies of biomedical, forensic, and materials samples.
Temperature-sensitive contacts in disordered loops tune enzyme I activity
Authors: Burns Daniel , Singh Aayushi , Venditti Vincenzo , Potoyan Davit A.
Published: November 2022

Homologous enzymes with identical folds often exhibit different thermal and kinetic behaviors. Understanding how an enzyme sequence encodes catalytic activity at functionally optimal temperatures is a fundamental problem in biophysics. Recently it was shown that the residues that tune catalytic activities of thermophilic/mesophilic variants of the C-terminal domain of bacterial enzyme I (EIC) are largely localized within disordered loops, offering a model system with which to investigate this phenomenon. In this work, we use molecular dynamics simulations and mutagenesis experiments to reveal a mechanism of sequence-dependent activity tuning of EIC homologs. We find that a network of contacts in the catalytic loops is particularly sensitive to changes in temperature, with some contacts exhibiting distinct linear or nonlinear temperature-dependent trends. Moreover, these trends define structurally clustered dynamical modes and can distinguish regions that tend toward order or disorder at higher temperatures. Assaying several thermophilic EIC mutants, we show that complementary mesophilic mutations to the most temperature-sensitive positions exhibit the most enhanced activity, while mutations to relatively temperature insensitive positions exhibit the least enhanced activities. These results provide a mechanistic explanation of sequence-dependent temperature tuning and offer a computational method for rational enzyme modification.
Lactate supply overtakes glucose when neural computational and cognitive loads scale up
Authors: Dembitskaya Yulia , Piette Charlotte , Perez Sylvie , Berry Hugues , Magistretti Pierre J. , Venance Laurent
Published: November 2022

Neural computational power is determined by neuroenergetics, but how and which energy substrates are allocated to various forms of memory engram is unclear. To solve this question, we asked whether neuronal fueling by glucose or lactate scales differently upon increasing neural computation and cognitive loads. Here, using electrophysiology, two-photon imaging, cognitive tasks, and mathematical modeling, we show that both glucose and lactate are involved in engram formation, with lactate supporting long-term synaptic plasticity evoked by high-stimulation load activity patterns and high attentional load in cognitive tasks and glucose being sufficient for less demanding neural computation and learning tasks. Indeed, we show that lactate is mandatory for demanding neural computation, such as theta-burst stimulation, while glucose is sufficient for lighter forms of activity-dependent long-term potentiation (LTP), such as spike timing–dependent plasticity (STDP). We find that subtle variations of spike number or frequency in STDP are sufficient to shift the on-demand fueling from glucose to lactate. Finally, we demonstrate that lactate is necessary for a cognitive task requiring high attentional load, such as the object-in-place task, and for the corresponding in vivo hippocampal LTP expression but is not needed for a less demanding task, such as a simple novel object recognition. Overall, these results demonstrate that glucose and lactate metabolism are differentially engaged in neuronal fueling depending on the complexity of the activity-dependent plasticity and behavior.
Super-resolution re-scan second harmonic generation microscopy
Authors: Stanciu Stefan G. , Hristu Radu , Stanciu George A. , Tranca Denis E. , Eftimie Lucian , Dumitru Adrian , Costache Mariana , Stenmark Harald A. , Manders Harm , Cherian Amit , Tark-Dame Mariliis , Manders Erik M. M.
Published: November 2022

Second harmonic generation microscopy (SHG) is generally acknowledged as a powerful tool for the label-free three-dimensional visualization of tissues and advanced materials, with one of its most popular applications being collagen imaging. Despite the great need, progress in super-resolved SHG imaging lags behind the developments reported over the past years in fluorescence-based optical nanoscopy. In this work, we demonstrate super-resolved re-scan SHG, qualitatively and quantitatively showing on collagenous tissues the available resolution advantage over the diffraction limit. We introduce as well super-resolved re-scan two-photon excited fluorescence microscopy, an imaging modality not explored to date.
“You want me to be wrong”
Authors: Herman Thierry , Oswald Steve
Published: November 2022

This chapter discusses features of conspiratorial discourse related to the representation of social actors through the lens of rhetorical and argumentative analysis. Specifically, it identifies a previously undocumented variant of the straw man fallacy (a misrepresentation of an opponent’s position meant to refute it more easily), namely the ethotic straw man, which unscrupulous arguers can use to legitimate their own credibility and undermine their opponents’, thereby evading scientific discussion of relevant issues. A TV-interview with French virologist Didier Raoult, who championed hydroxychloroquine-based treatments in the early months of the COVID-19 pandemic, is taken as a case in point to explain why such quasi-populistic discourse, prominently centred on questions of ethos, fits conspiratorial narratives so well.
Fake conspiracy
Authors: Musolff Andreas
Published: November 2022

Conspiracy theories have an extraordinarily strong persuasive effect, as their huge increase during the public debate about the COVID-19 pandemic shows. How can they achieve such a communicative impact, given their flawed epistemic status? This chapter studies one COVID-19 related conspiracy theory, i.e. that the virus which caused the pandemic was “unleashed” by the Chinese government on the world, as propagated by the former US President Donald J. Trump and his political allies. Combining cognitive and pragmatic approaches, I analyse Trump’s metaphorical framing of the pandemic in terms of a war-like conflict with China as serving the goal of inducing the US public to suspend their “epistemic vigilance” (Sperber et al. 2010). The analysis shows that the application of epistemic vigilance hinges, inter alia, on the conspiracy theory’s figurative and narrative coherence. This analysis accounts both for the (qualified) success of Trump’s conspiracy theory and its weakness as regards the lack of corroborating ‘back-up’ arguments for his narrative. The result offers clues to ways of re-activating epistemic vigilance and thus, argumentative resistance, against conspiracy theories.
The New World Order on Twitter
Authors: Mora López Natalia
Published: November 2022

This chapter explores the evaluative language used in relation to the New World Order (NWO) conspiracy theory from the perspective of Appraisal Theory (Martin and White 2005) in English and Spanish. Given the scarcity of analyses that go beyond the distinction between positive and negative evaluation, this chapter discusses the authors’ approach to events and figures related to the New World Order (NWO) conspiracy theory. For that purpose, a corpus of 1,000 tweets about the NWO was annotated and analysed regarding Attitude realisations. The results show that authors use mainly a Judgement approach, which evaluates people socially and morally, in both languages. However, it is less frequent in Spanish, in favour of references to the value of the targeted entities (Appreciation). These evaluations were not found to be argued, but merely asserted.
Expressing stance towards COVID-19 conspiracy theories in Macedonian online forum discussions
Authors: Mitkovska Liljana , Saračević Fevzudina
Published: November 2022

This chapter examines how stancetaking strategies aid advocacy and refutation of prevalent COVID-19 related conspiracy theories on two Macedonian internet discussion fora. The socio-political background and the content of detected conspiracy theories debated in the forum threads are briefly discussed. The authors explore affective, epistemic and interpersonal positioning in posts by three groups of social actors: conspiracy theory proponents, conspiracy theory opponents and a group of undecided. Through quantitative and qualitative analysis of selected discussion sequences the chapter draws attention to dominant patterns of stancetaking in conspiracy theory argumentation.
Ideologies and the representation of identities in anti-vaccination conspiracy theories
Authors: Fiammenghi Carlotta
Published: November 2022

The present chapter analyses a corpus of newspaper articles published in national UK broadsheets and tabloids dealing with the controversy surrounding the safety of the measles, mumps, and rubella (MMR) vaccine. By adopting a corpus-assisted critical discourse studies approach, the chapter seeks to highlight how writers variably use language to legitimise or delegitimise their own, as well as their opponents’, claims and identities. The results show that there has been an increasing tendency in recent years among writers in the traditional, mainstream press to oppose anti-vaccination conspiracy theories by identifying and criticising “typical” anti-vaccinators conspiracy theorists, thus undermining their identities rather than their claims. However, these strategies risk to backfire if they push believers in anti-vaccination conspiracy theories towards online, fringe environments like internet fora and social media.
Collective identities in the online self-representation of conspiracy theorists
Authors: Zorzi Virginia
Published: November 2022

A possible explanation for the success of conspiracy theories among some people is that the amount, accuracy and reliability of information is often not what appeals most to an audience. Indeed, conspiracy theory endorsement may be favoured by the opportunity it offers people to identify with a set of values and self-images, as well as to feel part of a wider community of like-minded people. This makes identity an essential element for the dissemination of conspiracy theories. This chapter focuses on the linguistic construction of the identity of conspiracy theory supporters’ groups in six online articles promoting conspiracist content by applying Koller’s (2012) model for the analysis of collective identities. Results highlight a variety of strategies across and within conspiracy theories, as well as a convergence towards notions of individuality, humanity and intellectual and moral superiority which conspiracist groups attribute to themselves.
Anti-Sorosism
Authors: Richardson John , Wodak Ruth
Published: November 2022

This chapter presents a Discourse-Historical Analysis (DHA) of the antisemitic conspiracy theory at the heart of ‘anti-Sorosism’. Anti-Sorosism is a term used to label the global campaign against George Soros, a Jewish American philanthropist of Hungarian origin, launched by extreme-right activists (see Wodak 2020). We argue that anti-Sorosism is a modern synecdoche of the antisemitic ‘Jewish world conspiracy’. In addition to extreme-right individuals and organizations, several mainstream right-wing politicians have blamed George Soros for many complex global and local phenomena such as migration, the political decisions of the EU, the COVID pandemic, and so forth. Indeed, the Hungarian prime minister Viktor Orbán has instrumentalized Soros time and again as a Feindbild [enemy image] when campaigning against the rules and regulations of the European Union as well as when justifying and legitimizing his restrictive immigration policies.

In this chapter, we will first briefly trace the origins of this archetypical conspiracy theory throughout the 19th and 20th centuries up to the present. The chapter then turns to a case study examining posters produced by Hungary’s governing party Fidesz. Following a summary of the DHA and contextualization of the politics of Fidesz, and its leader Viktor Orbán, we then proceed to the multimodal discourse analysis of a series of posters produced and displayed in Hungary. We conclude by arguing that conspiracy theories help to simplify complex issues and to provide clearly separated Manichean divisions of the ‘innocent’ and of those ‘to blame’. In doing so, they help achieve a strategic political function for the Orbán government.
From strategic depiction of conspiracies to conspiracy theories
Authors: Madisson Mari-Liis , Ventsel Andreas
Published: November 2022

Our study focuses on the coverage of coronavirus-related conspiracies/conspiracy theories published in spring 2020 (n = 146) in Anglophone media outlets RT and Sputnik that are financed by the Russian government. In our analysis we rely on a semiotic approach to strategic (conspiracy) narratives. Our study demonstrates a significant shift in the representation of conspiracies: instead of the depiction of malicious acts of secret grouping, RT and Sputnik narrate about alarming effects of conspiracy theories. Coronavirus-related conspiracy theories are represented as a means that the US is using in blame games against China and Russia, as well as a propaganda-tool for scaring the Western audience.
“Gender ideology” and the discursive infrastructure of a transnational conspiracy theory
Authors: Zottola Angela , Borba Rodrigo
Published: November 2022

The formula “gender ideology” has recently gained political traction in several countries. This chapter investigates its conspiracist discursive infrastructure by probing two corpora of far-right media from Brazil and the US. Analysis indicates that “gender ideology” is framed within semantic realms of manipulation, puppeteering, falseness, and danger. It also suggests that anti-gender rhetoric acts as an all-encompassing narrative whereby a cohort of inchoate but ideologically interlinked conspiracy theories are lumped together in a seemingly coherent whole. Comparing datasets from two countries empirically illustrates how anti-gender rhetoric crosses transnational borders and adapts to local specifics along the way.
The combinative use of “imperative + final particle” in Tokyo language in the Meiji period
Authors: Chen Huiling , Du Jianying
Published: November 2022

Honorifics in Japanese as a rare linguistic system has received consistent attention in social and cultural linguistic studies. A typical linguistic structure of honorifics is “imperative + sentence-final particles (shuu-joshi)” (henceforth, “final particle”), which has been studied mainly as a compound expression in Tokyo language. Different from previous studies with separated attention towards imperative expressions and sentence-final particles in the Edo era as well as in modern Japan, this paper investigates the combinative use and diachronic changes of “imperative + final particle” during the Meiji period – a period of upheaval in the Tokyo dialect. The investigation takes multiple views including the positions and relations (social and psychological) between the interlocutors, and the context of the utterance. Results of the investigation lead to an insight into pragmatic norms and diachronic changes of the modern Tokyo dialect, specifically the tendencies, characteristics and the driving force.

This study finds the particular expressive effect accomplished by the combinational use of “imperative + final particle” in the modern Tokyo dialect. The speaker shapes the degree of respect or politeness with the selective use of imperatives, and signals the communicative attitude by adding sentence-final particles. This linguistic form manifests the demand for “acting upon”, unveils the social construct and cultural norms embedded in inter-personal communication. The analysis on the developmental trend of “imperative + final particle” suggests that the prototype of the Tokyo dialect brings to prominence the across-status expressions as a result of social, political and educational reforms.
Overlaps in collaboration adjustments
Authors: Takeda Lala U.
Published: November 2022

This study examines collaborative utterance overlaps in American English and Japanese interactions between the same participants in two genres, conversation and problem-solving tasks, from the perspective of metacommunication. Quantitative and qualitative analyses indicated that participants’ use of overlap varies in frequency and function by genre. In conversation tasks, speakers of both languages used overlaps to maintain coherence and keep the story on track. In problem-solving tasks, American English overlaps conveyed agreement with or acceptance of the proposed idea, whereas Japanese overlaps in this genre conveyed common understanding. Participants attended to situational adjustment, and the development of collaboration in interactions differed by context and genre depending on the purpose of the conversation and the amount of information shared by participants. These results suggest the importance of teaching students how to use overlaps in both American English and Japanese interactions to enhance their understanding and appreciation of the cultural nuances of collaboration.
Has madam read Wilson (2016)?
Authors: Piskorska Agnieszka
Published: November 2022

This paper offers an account of Polish addressative forms encoding deference and familiarity in terms of the relevance-theoretic notion of procedural meaning, which underlies a heterogeneous range of phenomena linked to different cognitive domains. The procedure encoded by pronouns used referentially can be seen as targeting the domain of inferential comprehension and contributing to the truth-conditional meaning of an utterance by identifying a referent of a pronoun. It is claimed here that addressative forms marking the politeness distinction encode another procedure, targeting the social cognition module and activating the hearer’s readiness to identify the form as (in)congruent with social norms. It is argued that the politeness element in addressative forms does not involve conceptual encoding. The potential of the T/V forms for giving rise to stylistic effects is also explored. It is suggested that the proposal can be extended to other languages with the T/V distinction.
MR1: An unconventional twist in the tail
Authors: Phalora Prabhjeet , Klenerman Paul
Published: November 2022

MR1 is a conserved molecule that binds microbial vitamin B metabolites and presents them to unconventional T cells. Lim and colleagues (2022. J. Cell Biol.https://doi.org/10.1083/jcb.202110125) uncover the role of AP2 in ensuring MR1 surface presentation, which relies on an atypical motif within the MR1 cytoplasmic tail.
NLRP1 activation by UVB: Shedding light on an enigmatic inflammasome
Authors: Sandstrom Andrew
Published: November 2022

In this issue of JEM, Jenster et al. (2022. J. Exp. Med. https://doi.org/10.1084/jem.20220837) investigate how UVB radiation promotes activation of the inflammatory immune sensor NLRP1, and in doing so uncover how NLRP1 recognizes a diverse range of ribotoxic stresses.
Generalized quasi-topological gravities: the whole shebang
Authors: Bueno Pablo , Cano Pablo A , Hennigar Robie A , Lu Mengqi , Moreno Javier
Published: November 2022

Generalized quasi-topological gravities (GQTGs) are higher-curvature extensions of Einstein gravity in D-dimensions. Their defining properties include possessing second-order linearized equations of motion around maximally symmetric backgrounds as well as non-hairy generalizations of Schwarzschild’s black hole characterized by a single function,

f
(
r
)
≡
−

g

t
t

=

g

r
r

−
1

, which satisfies a second-order differential equation. In (Bueno et al 2020 Class. Quantum Grav.
37 015002) GQTGs were shown to exist at all orders in curvature and for general D. In this paper we prove that, in fact, n − 1 inequivalent classes (as far as static and spherically symmetric solutions are concerned) of order-n GQTGs exist for

D
⩾
5

. Amongst these, we show that one—and only one—type of densities is of the quasi-topological kind, namely, such that the equation for f(r) is algebraic. Our arguments do not work for D = 4, in which case there seems to be a single unique GQT density at each order which is not of the quasi-topological kind. We compute the thermodynamic charges of the most general D-dimensional order-n GQTG, verify that they satisfy the first law and provide evidence that they can be entirely written in terms of the embedding function which determines the maximally symmetric vacua of the theory.
Real-time monitoring of plasma synthesis of functional materials by high power impulse magnetron sputtering and other PVD processes: towards a physics-constrained digital twin
Authors: Ehiasarian A P , Sugumaran A A , Hovsepian P Eh , Davies C , Hatto P
Published: November 2022

Plasma synthesis of thin films by physical vapour deposition (PVD) enables the creation of materials that drive significant innovations in modern life. High value manufacturing demand for tighter quality control and better resource utilisation can be met by a digital twin capable of modelling the deposition process in real time. Optical emission spectroscopy (OES) was combined with process parameters to monitor all stages of both high power impulse magnetron sputtering and conventional magnetron sputtering processes to provide a robust method of determining process repeatability and a reliable means of process control for quality assurance purposes. Strategies and physics-based models for the in-situ real-time monitoring of coating thickness, composition, crystallographic and morphological development for a CrAlYN/CrN nanoscale multilayer film were developed. Equivalents to the ion-to-neutral ratio and metal-to-nitrogen ratios at the substrates were derived from readily available parameters including the optical emission intensities of Cr I, N2 (C–B) and Ar I lines in combination with the plasma diffusivity coefficient obtained from the ratio of substrate and cathode current densities. These optically-derived equivalent parameters identified the deposition flux conditions which trigger the switch of dominant crystallographic texture from (111) to (220) observed in XRD pole figures and the development of coating morphology from faceted to dense for a range of magnetron magnetic field configurations. OES-based strategies were developed to monitor the progress of chamber evacuation, substrate cleaning and preventative chamber wall cleaning to support process optimisation and equipment utilisation. The work paves the way to implementation of machine learning protocols for monitoring and control of these and other processing activities, including coatings development and the use of alternative deposition techniques. The work provides essential elements for the creation of a digital twin of the PVD process to both monitor and predict process outcomes such as film thickness, texture and morphology in real time.
Machine learning for flow field measurements: a perspective
Authors: Discetti Stefano , Liu Yingzheng
Published: November 2022

Advancements in machine-learning (ML) techniques are driving a paradigm shift in image processing. Flow diagnostics with optical techniques is not an exception. Considering the existing and foreseeable disruptive developments in flow field measurement techniques, we elaborate this perspective, particularly focused to the field of particle image velocimetry. The driving forces for the advancements in ML methods for flow field measurements in recent years are reviewed in terms of image preprocessing, data treatment and conditioning. Finally, possible routes for further developments are highlighted.
Accurate real-time SLAM based on two-step registration and multimodal loop detection
Authors: Zhang Guangyi , Zhang Tao , Zhang Chen
Published: November 2022

To improve the accuracy and efficiency of 3D LiDAR mapping, this paper improves the traditional point cloud registration and loop-detection methods and proposes a new scheme for accurate and real-time simultaneous localization and mapping systems. Cluster constraints are introduced into the front-end point cloud registration, and a two-step point cloud registration algorithm combining normal distribution transform and iterative closest point is proposed to speed up the point cloud registration. The effectiveness of this registration algorithm is fully validated in three sets of point cloud registration experiments. A loop detection process based on a height global descriptor for multimodal fusion is designed at the back end. The point cloud is encoded by this descriptor and fused with camera image information to generate a 1D operator to improve the search efficiency of loop closure frames. The proposed method is extensively evaluated on the KITTI data set and tested in playground periphery, fountain and parking lot environments. The results show that the accuracy of the proposed method outperforms the state-of-the-art LOAM and LeGO-LOAM in all three different scenarios.
Formation and consumption of HO2 radicals in ns pulse O2–He plasmas over a liquid water surface
Authors: Telfah Hamzeh , Jans Elijah , Raskar Sai , Adamovich Igor V
Published: November 2022

Hydroperoxyl (HO2) radicals are an important precursor in the formation of hydrogen peroxide (H2O2), a key species in plasma-liquid interactions, such that their formation and consumption pathways need to be understood. In this work, the generation and decay of HO2 have been studied in a controlled environment, in ns pulse discharge O2–He plasmas in contact with a liquid water surface. For this, time-resolved, absolute number densities of HO2 in O2–He mixtures excited by a repetitive ns pulse discharge are measured in situ by cavity ring down spectroscopy (CRDS). The discharge cell with external electrodes to generate the plasma and a water reservoir are integrated into the CRDS cavity. The high-reflectivity cavity mirrors are purged with helium to protect them from water vapor condensation. The experimental results are obtained at near room temperature, both during the discharge pulse burst and in the afterglow. The HO2 number density is inferred from the CRDS data using a spectral model exhibiting good agreement with previous measurements of absolute HO2 absorption cross sections. HO2 is generated during the discharge burst and decays in the afterglow between the bursts. The HO2 number density is also measured vs. the O2 fraction in the mixture. Comparison with the kinetic modeling predictions demonstrates good agreement with the data and identifies the dominant HO2 generation and decay processes. HO2 in the plasma is formed predominantly by the recombination of H atoms, generated by the electron impact dissociation of water vapor, with O2 molecules. Reactions with O atoms and hydroxyl (OH) radicals are among the main HO2 decay processes in the afterglow. HO2 is also detected when O2 is not present in the mixture. In this case, it is generated primarily by the recombination of OH radicals, via the formation of H2O2. The results demonstrate that CRDS can also be used for HO2 and other plasma chemical reaction product measurements in atmospheric pressure plasma jets impinging on a liquid water surface in ambient air.
Emission of gravitational waves by superconducting cosmic strings
Authors: Rybak I.Yu. , Sousa L.
Published: November 2022

We study the gravitational radiation emission efficiency Γ of superconducting cosmic strings. We demonstrate, by using a solvable model of transonic strings, that the presence of a current leads to a suppression of the gravitational emission of cusps, kinks and different types of loops. We also show that, when a current is present, the spectrum of emission of loops with cusps is exponentially suppressed as the harmonic mode increases, thus being significantly different from the power law spectrum of currentless loops. Furthermore, we establish a phenomenological relationship between Γ and the value of the current on cosmic strings. We conjecture that this relation should be valid for an arbitrary type of current-carrying string. We use this result to study the potential impact of current on the stochastic gravitational wave background generated by cosmic strings with additional degrees of freedom and show that both the amplitude and shape of the spectrum may be significantly affected.
Digitally predicting protein localization and manipulating protein activity in fluorescence images using 4D reslicing GAN
Authors: Jiao Yang , Gu Lingkun , Jiang Yingtao , Weng Mo , Yang Mei
Published: November 2022

Motivation

While multi-channel fluorescence microscopy is a vital imaging method in biological studies, the number of channels that can be imaged simultaneously is limited by technical and hardware limitations such as emission spectra cross-talk. One solution is using deep neural networks to model the localization relationship between two proteins so that the localization of one protein can be digitally predicted. Furthermore, the input and predicted localization implicitly reflect the modeled relationship. Accordingly, observing the response of the prediction via manipulating input localization could provide an informative way to analyze the modeled relationships between the input and the predicted proteins.

Results

We propose a protein localization prediction (PLP) method using a cGAN named 4D Reslicing Generative Adversarial Network (4DR-GAN) to digitally generate additional channels. 4DR-GAN models the joint probability distribution of input and output proteins by simultaneously incorporating the protein localization signals in four dimensions including space and time. Because protein localization often correlates with protein activation state, based on accurate PLP, we further propose two novel tools: digital activation (DA) and digital inactivation (DI) to digitally activate and inactivate a protein, in order to observing the response of the predicted protein localization. Compared with genetic approaches, these tools allow precise spatial and temporal control. A comprehensive experiment on six pairs of proteins shows that 4DR-GAN achieves higher-quality PLP than Pix2Pix, and the DA and DI responses are consistent with the known protein functions. The proposed PLP method helps simultaneously visualize additional proteins, and the developed DA and DI tools provide guidance to study localization-based protein functions.

Availability and implementation

The open-source code is available at https://github.com/YangJiaoUSA/4DR-GAN.

Supplementary information

Supplementary data are available at Bioinformatics online.
Deep learning of protein sequence design of protein–protein interactions
Authors: Syrlybaeva Raulia , Strauch Eva-Maria
Published: November 2022

Motivation

As more data of experimentally determined protein structures are becoming available, data-driven models to describe protein sequence–structure relationships become more feasible. Within this space, the amino acid sequence design of protein–protein interactions is still a rather challenging subproblem with very low success rates—yet, it is central to most biological processes.

Results

We developed an attention-based deep learning model inspired by algorithms used for image-caption assignments to design peptides or protein fragment sequences. Our trained model can be applied for the redesign of natural protein interfaces or the designed protein interaction fragments. Here, we validate the potential by recapitulating naturally occurring protein–protein interactions including antibody–antigen complexes. The designed interfaces accurately capture essential native interactions and have comparable native-like binding affinities in silico. Furthermore, our model does not need a precise backbone location, making it an attractive tool for working with de novo design of protein–protein interactions.

Availability and implementation

The source code of the method is available at https://github.com/strauchlab/iNNterfaceDesign

Supplementary information

Supplementary data are available at Bioinformatics online.
Sibling Separation: Learning from Those with Former Foster Care Experiences
Authors: Wojciak Armeda Stevenson , Tomfohrde Olivia , Simpson Jessica E , Waid Jeffrey
Published: November 2022

Sibling relationships of youth in foster care are often complicated as many youth are separated from their sibling(s) at one point or another. Quantitative studies have identified ways in which sibling placement influences youth outcomes. Fewer qualitative studies have been conducted to understand youth perspectives about their sibling relationships. The purpose of this qualitative study was to examine sibling relationships and sibling separation amongst adults with prior foster care experience. Thematic analysis indicated two overarching themes: ‘Sibling Separation was Common’ and ‘Effects of Sibling Separation’. Each theme was comprised of multiple sub-themes that are discussed in detail and explored through an ambiguous loss lens. Recommendations and implications for supporting sibling relationships for youth in care are provided.
Agonistic/antagonistic properties of lactones in food flavors on the sensory ion channels TRPV1 and TRPA1
Authors: Ogawa Yukino , Zhou Lanxi , Kaneko Shu , Kusakabe Yuko
Published: November 2022

Flavor compounds provide aroma and sensations in the oral cavity. They are not present alone in the oral cavity, but rather in combination with several other food ingredients. This study aimed to clarify the relationship between the mixing of pungent flavor compounds and the response of pungent receptors, TRPV1 and TRPA1 channels. We focused on lactones that activate TRPV1 despite their presence in bland foods, such as dairy products and fruits, and analyzed their interaction with receptors using TRPV1- and TRPA1-expressing HEK293 cells. We found that γ-octalactone, γ-nonalactone, and δ-nonalactone activated TRPA1. When mixed with pungent components, some γ- and δ-lactones inhibited capsaicin-mediated TRPV1 responses, and δ-dodecalactone inhibited allyl isothiocyanate-mediated TRPA1 responses. Furthermore, the dose–response relationship of capsaicin and γ-nonalactone to TRPV1 suggests that γ-nonalactone acts as an agonist or antagonist of TRPV1, depending on its concentration. Conversely, γ-nonalactone and δ-dodecalactone were found to act only as agonists and antagonists, respectively, against TRPA1. These results suggest that lactones in foods may not only endow food with aroma, but also play a role in modulating food pungency by acting on TRPV1 and TRPA1. The dose–response relationships of a mixture of flavor compounds with TRPV1 and TRPA1 provide insights into the molecular physiological basis of pungency that may be the cornerstone for developing new spice mix recipes.
Rhythm monitoring, success definition, recurrence, and anticoagulation after atrial fibrillation ablation: results from an EHRA survey
Authors: Schwab Ana Carolina , Anic Ante , Farkowski Michal M , Guerra Jose , Iliodromitis Konstantinos E , Jubele Kristine , Providencia Rui , Chun Julian K R , Boveda Serge
Published: November 2022

Atrial fibrillation (AF) is a major challenge for the healthcare field. Pulmonary vein isolation is the most effective treatment for the maintenance of sinus rhythm. However, clinical endpoints for the procedure vary significantly among studies. There is no consensus on the definition of recurrence and no clear roadmap on how to deal with recurrences after a failed ablation. The purpose of this study was to perform a survey in order to show how clinicians currently approach this knowledge gap. An online survey, supported by the European Heart Rhythm Association (EHRA) Scientific Initiatives Committee, was conducted between 1 April 2022 and 8 May 2022. An anonymous questionnaire was disseminated via social media and EHRA newsletters, for clinicians to complete. This consisted of 18 multiple-choice questions regarding rhythm monitoring, definitions of a successful ablation, clinical practices after a failed AF ablation, and the continuance of anticoagulation. A total of 107 replies were collected across Europe. Most respondents (82%) perform routine monitoring for AF recurrences after ablation, with 51% of them preferring a long-term monitoring strategy. Cost was reported to have an impact on the choice of monitoring strategy. Self-screening was recommended by most (71%) of the respondents. The combination of absence of symptoms and recorded AF was the definition of success for most (83%) of the respondents. Cessation of anticoagulation after ablation was an option mostly for patients with paroxysmal AF and a low CHA2DS2-VASc score. The majority of physicians perform routine monitoring after AF ablation. For most physicians, the combination of the absence of symptoms and electrocardiographic endpoints defines a successful result after AF ablation.
The Association Between Exposure to Air Pollution and Dementia Incidence: The Modifying Effect of Smoking
Authors: Chen Guo-Chong , Nyarko Hukportie Daniel , Wan Zhongxiao , Li Fu-Rong , Wu Xian-Bo
Published: November 2022

Background

The influence of overall air pollution on dementia risk and the potential effect modification by other risk factors remain to be clarified.

Methods

We included 459 844 UK residents who were free of dementia and had data on the exposure to particulate matter (PM)2.5, PM2.5–10, PM10, NO2, and NOx during baseline recruitment. The combined exposure to various PMs and NOx was estimated by using an air pollution score. Hazard ratios (HRs) and 95% confidence intervals (CIs) for incident dementia were estimated by multivariable Cox models.

Results

During a median 11.7 years follow-up, 5 905 incident cases of all-cause dementia were identified. With the exception of PM2.5–10, all other air pollutants were separately associated with a higher risk of all-cause dementia (all p-trend < .001) with generally similar associations for dementia subtypes. An increasing air pollution score was associated with higher risks of all-cause as well as individual dementia outcomes, with adjusted HRs (95% CI) of 1.27 (1.18, 1.37) for all-cause dementia, 1.27 (1.14, 1.43) for Alzheimer’s disease, and 1.35 (1.16, 1.57) for vascular dementia when comparing the highest with the lowest quartile of the score (all p-trend < .001). These associations of air pollution score with dementia and its subtypes were observed among never and former smokers but not among current smokers (all p-interaction  < .030).

Conclusion

Air pollution was associated with a higher risk of dementia among nonsmokers but not current smokers. Additional studies are required to confirm our findings and to explore the potential mechanisms underlying the possible effect modification by smoking status.
Fasting and Post-Load Glucose and Non-Esterified Fatty Acids and Risk of Heart Failure and Its Subtypes in Older Adults
Authors: Oesterle Adam , Buzkova Petra , Pellegrini Cara N , Hirsch Calvin , Tracy Russell P , Siscovick David S , Djousse Luc , Mukamal Ken J , Kizer Jorge R
Published: November 2022

Background

Glucose and non-esterified fatty acids (NEFA) are myocardial fuels whose fasting and post-prandial levels are under different homeostatic regulation. The relationships of fasting and post-load glucose and NEFA with incident heart failure (HF) remain incompletely defined.

Methods

Serum glucose and NEFA were measured during fasting and 2 hours post-oral glucose tolerance test, performed in Cardiovascular Health Study participants not receiving hypoglycemic medication. Participants with prevalent HF or lacking relevant data were excluded. Outcomes were incident HF (primary), and HF with preserved (HFpEF) and reduced (HFrEF) ejection fraction (secondary).

Results

Among 2 238 participants (age 78 ± 4) with a median follow-up of 9.9 years, there were 737 HF events. After adjustment for demographic and lifestyle factors, both fasting (hazard ratio [HR] = 1.11 per SD [95% confidence interval {CI} = 1.01–1.23], p = .040) and post-load (HR = 1.14 per SD [1.05–1.24], p = 0.002) glucose were significantly associated with incident HF. No association was seen for fasting or post-load NEFA. Upon mutual adjustment, only post-load glucose (HR = 1.11 [1.003–1.22], p = .044), but not fasting glucose (HR = 1.06 [0.94–1.20], p = .340), remained associated with HF. Further adjustment for cardiovascular disease and other risk factors in the causal pathway did not affect the association for post-load glucose, but eliminated that for fasting glucose. Associations for fasting and post-load glucose appeared stronger with higher adiposity and were observed specifically for HFrEF but not HFpEF.

Conclusions

Fasting and post-load glucose, but not NEFA, were associated with incident HF. The association was especially robust for post-load glucose, suggesting that pathways involved in post-prandial dysglycemia could offer new targets for HF prevention late in life.
Adverse Childhood Experiences, Inflammation, and Depressive Symptoms in Late Life: A Population-Based Study
Authors: Li Chao , Xiang Shiting
Published: November 2022

Objectives

This study investigated the association and dose–response relationship between adverse childhood experiences (ACEs) and depressive symptoms in late life and explored the mediating roles of inflammatory markers in the ACEs–depressive symptom association among Chinese older adults.

Methods

This study was conducted using 2014 life history survey data and 2015 follow-up data from the China Health and Retirement Longitudinal Study. Data on ACEs and depression, inflammatory markers of high-sensitivity C-reactive protein (CRP), and white blood cell were collected. The association between ACEs and depressive symptoms was examined using logistic regression, and the mediation effects of inflammatory markers were evaluated.

Results

A total of 6,518 individuals over 60 years were included in the analysis. Compared to no ACE exposure, the adjusted odd ratios ranged from 1.377 (95% confidence interval [CI], 1.133–1.673) when participants had been exposed to 2 ACEs to 1.809 (95% CI, 1.451–2.256) when participants were exposed to 4 or more ACEs. A significant dose–response relationship between cumulative ACE scores and depression was observed. Six of the 12 ACE exposures were related to increased odds of depressive symptoms. CRP appeared to partially mediate the ACE–depressive symptom association, and the proportion of the effect of ACEs on depression was 1.17% (P = 0.008).

Discussion

A dose–response association exists between ACEs and the prevalence of depressive symptoms among older Chinese adults. CRP partially mediated the ACE–depressive symptom association in late life. Emphasizing interventions targeting individuals with ACE exposure may minimize the burden of late-life depression in China.
Characterization of novel antibodies that recognize sialylated keratan sulfate and lacto-N-fucopentaose I on human induced pluripotent cells: comparison with existing antibodies
Authors: Nakao Hiromi , Yamaguchi Tomoko , Kawabata Kenji , Higashi Katsuaki , Nonaka Motohiro , Tuiji Makoto , Nagai Yuko , Toyoda Hidenao , Yamaguchi Yoshiki , Kawasaki Nobuko , Kawasaki Toshisuke
Published: November 2022

This report describes the isolation and characterization of two new antibodies, R-6C (IgM) and R-13E (IgM), which were generated in C57BL/6 mice (Mus musculus) using the Tic (JCRB1331) human induced pluripotent cell (hiPSC) line as an antigen, and their comparisons with two existing antibodies, R-10G (IgG1) and R-17F (IgG1). Their epitopes were studied by western blotting after various glycosidase digestions, binding analyses using enzyme-linked immunosorbent assays (ELISAs) and microarrays with various synthetic oligosaccharides. The minimum epitope structures identified were: Siaα2–3Galβ1–3GlcNAc(6S)β1–3Galβ1–4GlcNAc(6S)β1 (R-6C), Fucα1–2Galβ1–3GlcNAcβ1–3Galβ1 (R-13E), Galβ1–4GlcNAc(6S)β1–3Galβ1–4GlcNAc(6S)β1 (R-10G), and Fucα1–2Galβ1–3GlcNAβ1–3Galβ1–4Glc (lacto-N-fucopentaose I) (R-17F). Most glycoprotein epitopes are expressed as O-glycans. The common feature of these epitopes is the presence of an N-acetyllactosamine type 1 structure (Galβ1–3GlcNAc) at their nonreducing termini, followed by a type 2 structure (Galβ1–4GlcNAc); this arrangement comprises a type 1-type 2 motif. This motif is also shared by TRA-1-60, a traditional onco-fetal antigen. In contrast, the R-10G epitope has a type 2-type 2 motif. Among these antibodies, R-17F and R-13E exhibit cytotoxic activity toward hiPSCs. R-17F and R-13E exhibit extremely high similarity in the amino acid sequences in their complementarity-determining regions (CDRs), which is consistent with their highly similar glycan recognition. These antibodies are excellent tools for investigating the biological functions of glycoconjugates in hiPSCs/hESCs; they could be useful for the selection, isolation and selective killing of such undifferentiated pluripotent stem cells.