bluuebunny/crossref_metadata_2025 huggingface dataset:
Hindering or Helping? User Preferences for Features of Recorded Mindfulness Training
Authors: Stanko-Kaczmarek Maja , Jankowski Tomasz , Koczyk Anna , Krzyzaniak Wadim , Meder Kalina , Dulian Kajetan
Published: December 2023

Objectives

Despite its numerous benefits, practicing mindfulness involves certain challenges. This study investigates the impact of various characteristics of recorded mindfulness practice instructions on recipients’ evaluations, focusing on elements that may evoke negative reactions and hinder mindfulness practice.

Method

A total of 138 participants evaluated 24 recordings of mindfulness practice excerpts. The recordings differed in terms of the speaker’s gender, the form and pace of the message, the presence of whispering, and the number of artifacts. Respondents rated each recording using a scale and provided open-ended responses about their subjective perception of the recordings. The study employed hierarchical multilevel modeling to analyze the collected data.

Results

The results indicated that recipient gender did not influence preferences for male or female-voiced recordings. However, properties such as form, pace, whispering, and artifacts did affect evaluations. Least favored instruction elements included plural pronouns, slow pacing, primarily whispered speech, and a high number of artifacts. Some differences in evaluations were observed between female and male recording conditions. Additionally, qualitative data revealed participants’ subjective reactions to recordings with varying characteristics, and the study identified the most favorable characteristics of the recordings.

Conclusions

The study results identified which qualities of recorded mindfulness instructions are least preferred and may present obstacles to initiating or continuing the practice. Therefore, this study may help create more optimal instructions and improve the design of apps and platforms offering mindfulness practice recordings, enhancing the quality and accessibility of practice for a broader audience.

Preregistration

This study is not preregistered.
The Need for a Prevention Program for Child Sexual Abuse in Brazil: A Report of Shortfall Care to Pedophilia and its Critical Consequences
Authors: Furian Gabriel , Beier Klaus Michael , Schwarz Karine , da Silva Dhiordan Cardoso , Grundmann Dorit , Lobato Maria Inês Rodrigues
Published: December 2023

From a case report of a person with pedophilic disorder, this paper focuses on the issue of pedophilia, child sexual abuse, and the need for specific prevention and treatment strategies in Brazil. It seems inevitable to increase awareness for this topic within the mental health care system to protect children and reduce the risk for sexual offense in individuals at-risk. This is a case report of an individual, known by medical-psychiatric and forensic facilities for a past history of patricide, who revealed his pedophilic fantasies and behavior belatedly. To assess a pedophilic disorder and screen for other paraphilic contents, a screening questionnaire and clinical interview were used during the patient hospitalization in 2020 for a proper evaluation of sexual history and past offending behaviors. A review of the literature on pedophilia prevention programs was also carried out. WW is a middle-aged man admitted to a psychiatric unit for a severe episode of major depressive disorder and at risk of suicide. During recovery, he reported pedophilic fantasies and behaviors in his life. Sexual fantasies involving children and actual sexual offenses have remained unknown to mental health professionals and unreported to legal authorities. WW’s case alarmingly emphasizes the need for the training of health care professionals and for preventive strategies in Brazil for those who are at risk of engaging in offending sexual behaviors in a combined and intensive effort to protect children from sexual offense.
Human Enhancement Without Organizational Knowledge and by Organizational Order
Authors: Döbler Niklas Alexander , Carbon Claus-Christian , Schaub Harald
Published: December 2023

Organizations strive to ensure and maintain the reliability, safety, security, usability, and competitiveness of their processes, goods, and services. Improvement of employees’ skills and abilities contributes to these ends and is a relevant issue for the field of human factors. However, going a step further than designing ergonomics, implementing protocols, and conducting training is the attempt to enhance employee skills directly through various technological means. So-called Human Enhancement aims at direct technological interference with the employees’ skills and is a notoriously controversial yet deeply historical phenomenon. Drawing from empirical and theoretical literature on Human Enhancement, we seek to provide an initial analysis of this phenomenon in an organizational context. One motivational aspect of contemporary Human Enhancement is the need to meet internal, often self-related, or external, usually social or organizational, demands. Given the different effects and means of Human Enhancement, some forms are illicit, sanctioned, and/or condemned as morally wrong, while others are obligatory and well-established. Enhancement efforts can be based on individual initiative and, hence, without organizational knowledge. The opposite of the spectrum are enhancements applied by organizational order. We also emphasize how an organizational culture may incentivize engagement with illicit means of Human Enhancement. Potentially linked to safety and security-related aspects, its enhancement effects in relation to these two poles can inform stakeholders in their regulatory decisions.
Freedom of Religion or Belief in the European Convention on Human Rights
Authors: Roberts Caroline K.
Published: December 2023

The right to freedom of thought, conscience and religion in Article 9 of the European Convention on Human Rights (ECHR) has become increasingly significant and contested. Through an examination of ECHR Article 9, its drafting history, and the related jurisprudence of the European Court of Human Rights (ECtHR), Caroline K. Roberts challenges the classic approach to this right in the literature. Roberts argues that claims that there is, or should be, a clear binary and hierarchical distinction between the absolutely protected internal realm and the qualified external realm in this right are not founded textually or jurisprudentially. Rather, the primary materials suggest that the internal and external aspects are deeply interrelated, and this is reflected in the ECtHR's nuanced and holistic approach to ECHR Article 9 protection. This comprehensive, rigorous and up-to-date reappraisal of ECHR Article 9 and the related ECtHR jurisprudence will be essential reading for academics and practitioners.
Homeland Food Traditions in the Tiwanaku Colonies: Quinoa and Amaranthaceae Cultivation in the Middle Horizon (AD 600–1100) Locumba Valley, Peru
Authors: Garvin Suero Arianna , Goldstein Paul S. , d'Alpoim Guedes Jade , Sitek Matthew J.
Published: December 2023

The Tiwanaku civilization (around AD 500–1100) originated in the Bolivian altiplano of the south-central Andes and established agrarian colonies (AD 600–1100) in the Peruvian coastal valleys. Current dietary investigations at Tiwanaku colonial sites focus on maize, a coastal valley cultivar with ritual and political significance. Here, we examine Tiwanaku provincial foodways and ask to what degree the Tiwanaku settlers maintained their culinary and agrarian traditions as they migrated into the lower-altitude coastal valleys to farm the land. We analyze archaeobotanical remains from the Tiwanaku site of Cerro San Antonio (600 m asl) in the Locumba Valley and compare them to data from the Tiwanaku site in the altiplano and the Rio Muerto site in the Moquegua Valley during the period of state expansion. Our findings show high proportions of wild, weedy, and domesticated Amaranthaceae cultivars, suggesting that Tiwanaku colonists grew traditional high-valley (2,000–3,000 m asl) and altiplano (3,000–4,000 m asl) foods on the lowland frontier because of their established cultural dietary preferences and Amaranthaceae's ability to adapt to various agroclimatic and edaphic conditions.
WHAT DOES EGALITARIANISM REQUIRE?
Authors: Schmidtz David
Published: December 2023

Rawlsian theory notoriously claims that basic principles of justice apply to the design of a society’s basic structure. G. A. Cohen found it disturbingly convenient to treat fundamental principles as merely political rather than personal—that is, as applying exclusively to questions of institutional design and saying nothing about how to live. Instead, to Cohen, a sincere champion of egalitarian principles would, as they say, “walk the talk.”
WORKER PARTICIPATION AND THE EGALITARIAN CONCEPTION OF FAIR MARKET EXCHANGE
Authors: Christiano Thomas
Published: December 2023

I argue for an egalitarian conception of market exchange that places the idea of equal power at the center of a procedural evaluation of markets. I explain the fundamental concept of equal power in markets and show that the egalitarian conception gives us a remedial basis for society shaping markets so that they allow a significant place for worker participation in firms. I use the phrase “worker participation” to mean that workers participate in the authoritative direction of the firm. This can include collective bargaining and worker management to introduce the kind of flexibility that is desirable in regulating market economies. Worker participation is a remedy to the presence of rigidities in markets that strongly favor authoritarian firms and that follow from and maintain unequal power in markets. The argument differs from the traditional argument that draws a parallel between state and firm, and so does not entail a general requirement of worker participation. It allows for some degree of participation of owners of capital also in the governance of firms.
THREE SOURCES OF ECONOMIC INEQUALITY
Authors: Heath Joseph
Published: December 2023

There are three distinct forces that conspire to produce a great deal of economic misery. We can refer to them, for convenience, as misfortune, unfairness, and improvidence. Political philosophers have often shown an interest in one or another of these, but seldom all three. Furthermore, those who do acknowledge all three have often felt driven to collapse them into one root cause of inequality. My goal in this essay will be to argue that the three are independent of one another, but more importantly, that they each require distinct remedies. This is important for egalitarians because it defeats any attempt to develop a “one-size-fits-all” policy aimed at creating a more equal society. This analysis helps us to understand several of the tensions that arise in our attempts to combat inequality that are often obscured by an overemphasis on the power of redistributive taxation as well as generalized inattention to the way that successful welfare states achieve meaningful progress in promoting greater equality.
MUST EGALITARIANS RELY ON THE STATE TO ATTAIN DISTRIBUTIVE JUSTICE?
Authors: Pourvand Kaveh
Published: December 2023

It is widely accepted among political philosophers that distributive justice should be promoted by the state. This essay challenges this presumption by making two key claims. First, the state is not the only possible mechanism for attaining distributive justice. We could rely alternatively on the voluntary efforts and interactions of individuals and associations in civil society. The question of what mechanism we should rely on is a comparative and empirical one. What matters is which mechanism better promotes distributive justice. We cannot settle the question a priori in favor of the state. Second, several considerations suggest a presumption in favor of relying on civil society.
Transient second-degree high-grade atrioventricular block caused by myocarditis
Authors: Özelce Bilal , Pamuk Utku , Koca Serhat , Gürsu Hazım Alper , Çetin İbrahim İlker
Published: December 2023

Myocarditis is an inflammatory disease of the heart muscle that most commonly occurs after infectious diseases in childhood. The clinical picture of acute myocarditis ranges from asymptomatic infection to fulminant heart failure and sudden death (1). Most of the patients may present with nonspecific symptoms such as respiratory distress, chest pain, nausea, and vomiting (2). While rhythm abnormalities such as ventricular and supraventricular rhythm disorders can be observed in these patients, various degrees of atrioventricular blocks may rarely develop (3). In this article, we aimed to present a patient who developed second-degree, high-grade atrioventricular block after myocarditis and recovered completely after treatment.
Mapping the behaviour change potential of meal kits to positively influence parental food literacy
Authors: Fraser Kylie , Johnson Brittany J , Love Penelope , Spence Alison , Laws Rachel , Campbell Karen J
Published: December 2023

Objective:

This study aimed to examine the theoretical potential of meal kit subscription services in Australia to promote parental food literacy using the retrospective application of behaviour change frameworks.

Design:

A one-week subscription was purchased for all Australian-based meal kit subscription services (n 9) to access content and features available to subscribers. Behaviour change techniques (BCTs) identified in the subscription and meal planning features, meal kit delivery (i.e. ingredients and recipes) and website were coded using the behaviour change technique taxonomy (BCTTv1) and associated behaviour change frameworks. Identified BCTs were mapped to the theoretical domains framework to identify potential mechanisms of action for influencing parental food literacy development.

Setting:

Australia.

Results:

Thirty-five BCTs were identified across the nine meal kit services reviewed, ranging from nineteen to twenty-nine BCTs per company. Sixteen BCTs were common to all meal kits services, from the hierarchical clusters of ‘goals and planning’, ‘shaping knowledge’, ‘social support’, ‘natural consequences’, ‘comparison of behaviour’, ‘repetitions and substitution’, ‘associations’, ‘reward and threat’, ‘antecedents’ and ‘regulation’. Across the meal kit services, the most frequently identified mechanisms of action were motivation (n 27) and capability (n 19).

Conclusion:

These findings support the applicability of behaviour change frameworks to commercial meal kit subscription services and provide a theory-informed process for identifying BCTs that may be relevant for promoting parental food literacy within this context. Further research is required to explore how families engage with meal kit subscription services to determine the exposure and delivery of identified BCT content and to evaluate the potential influence on food literacy development.
Distress, demoralization, and fulfillment among palliative care providers during the COVID-19 pandemic
Authors: Tang Michael , Ann-Yi Sujin , Zhukovsky Donna S. , Fellman Bryan , Bruera Eduardo
Published: December 2023

Objectives

Prolonged distress is a risk factor for burnout among health-care providers (HCP) and may contribute to demoralization. We examined sources of distress during the COVID-19 pandemic and associations with demoralization.

Methods

This prospective cross-sectional survey of HCP was conducted among palliative care providers of an academic medical center. Participants completed a survey evaluating sources of distress and the Demoralization Scale-II (DS-II) to measure the intensity of demoralization.

Results

Of 106 eligible participants, 74 (70%) completed the survey. DS-II median (range) score was 2 (0–19). There were no statistically significant associations with demographic characteristics. Participants reported high rates of distress for multiple reasons and high rates of sense of fulfillment (90%) and satisfaction (89%) with their profession.

Significance of results

Our study identified high levels of distress but low demoralization rates. Further study to evaluate fulfillment and satisfaction as protective factors against demoralization and burnout is indicated.
New Perspectives on State Formation
Authors: Dincecco Mark
Published: December 2023

Governments in developed nations today collect high tax revenues and spend vast amounts on security, regulation, infrastructure, and social programs. Yet developed nations were in no way born with effective state institutions. What explains the emergence of the modern state? And, why did capable states first form historically in Western Europe? Proper answers to these questions are key to our understanding of modern forms of governance, including parliamentary democracy.
Do mountains kill states? Exploring the diversity of Southeast Asian highland communities
Authors: Leadbetter Michael Paul , Sastrawan Wayan Jarrah
Published: December 2023

Mountains and highlands are not what scholars have conventionally imagined them to be: environments that limit and constrain their inhabitants in deterministic ways. Rather, mountains and highlands provide unique opportunities for people to engage in creative transformation of their societies. Highland communities are connected to a wider world, and they radically remake and experiment with their landscapes, settlements, and societies. Mountains serve as birthplaces and testing grounds for statecraft, urbanism, irrigation, and monumental landscape engineering. Here we explore the diversity of highland communities by analysing the latest archaeological and historical discoveries from three regions across Southeast Asia: the Kulen mountains (Cambodia), the volcanoes of central Java (Indonesia), and the Ifugao highlands (the Philippines). We find that, far from being a negative image of the ‘civilized’ lowlands, mountains were creative, diverse, dynamic, and well-connected places. This compels us to change the way we conceive of today’s highland communities and their relationships to modern nation-states.
Gender- and sexuality-minoritised adolescents in DBT: a reflexive thematic analysis of minority-specific treatment targets and experience
Authors: Camp J. , Morris A. , Wilde H. , Smith P. , Rimes K. A.
Published: December 2023

Gender- and sexuality-minoritised (GSM) adolescents are at increased risk of self-harm and suicidal behaviours compared with their cisgender and heterosexual peers. This increased risk is thought to be explained in part by exposure to stigma and societal oppression. Dialectical behaviour therapy (DBT) is an evidence-based intervention for self-harm and suicidal behaviour that may have advantages for supporting GSM young people in distress. No study has yet sought to understand what GSM-associated difficulties may be important to consider in DBT for adolescents, or the experiences of GSM young people in a standard DBT programme. Therefore, this study aimed to understand the experiences of GSM young people in DBT and what difficulties and dilemmas associated with their gender and sexuality diversity were thought by them to be important to target in DBT. Qualitative interviews were conducted with 14 GSM young people in a comprehensive DBT programme and were analysed using reflexive thematic analysis. The analysis was supported by two further GSM young people who had finished DBT. The findings were split into three over-arching themes (Identity, Impact of Others, and Space for Sexual and Gender Identity in DBT), each with themes within. The identity-based theme included ‘identity confusion and acceptance’; the relationship-based themes included ‘cis-Heterosexism’ and ‘community connectedness’; and the space within DBT themes included ‘negotiating focus and targeting in DBT’ and ‘creating safety in DBT’. Findings are discussed in relation to implications and recommendations for therapists working with GSM young people within and outside of DBT.

Key learning aims

(1)

To learn about what gender- and sexuality-minoritised (GSM) young people consider to be important GSM-associated contributors to distress and thus potential treatment targets in DBT.

(2)

To learn about what GSM young people felt were barriers to negotiating GSM-associated difficulties as a focus in DBT and how safety was created in the therapeutic relationship.

(3)

To consider potential implications and recommendations for improvements to practice when supporting GSM young people in therapy.
Mapping Mars: Deep Learning Could Help Identify Jezero Crater Landing Site
Authors: Derouin Sarah
Published: December 2023

Researchers used new techniques to more precisely estimate ground elevations on Mars, producing a refined resolution map for rover landings.
Mapping Mantle Flows and Slab Anisotropy in the Cascadia Subduction Zone
Authors: Liang Xuran , Zhao Dapeng , Hua Yuanyuan , Xu Yi‐Gang
Published: December 2023

The Cascadia margin is an unusual subduction zone characterized by the downdip movement of young and thin oceanic plates, where mantle flow and intraslab deformation are still unclear. Here we present new anisotropic tomography of the Cascadia subduction zone, in which the hexagonal symmetry axis of anisotropy is tilting rather than horizontal or vertical as assumed in previous studies of seismic anisotropy. Subduction‐induced entrained and toroidal flows under the Cascadia margin are discriminated well by the spatial relationship between tilting‐axis anisotropy and slab geometry. The obliquely entrained flow is trapped in a narrow zone (<100 km wide) above and below the subducting slab and reaches ∼200 km depth, which is surrounded by large‐scale sub‐horizontal toroidal flow. The intraslab anisotropy is trench‐normal above 80 km depth but changes to trench‐parallel at 100–400 km depths, which may reflect fossil anisotropy overprinted by deep deformation beneath the arc, or joint effect of serpentinization and hydrous faulting.
Surface Temperature Pattern Scenarios Suggest Higher Warming Rates Than Current Projections
Authors: Alessi Marc J. , Rugenstein Maria A. A.
Published: December 2023

Atmosphere‐ocean general circulation models (AOGCMs) struggle to reproduce recently observed sea surface temperature (SST) trend patterns. Here, we quantify the relevance of this SST pattern uncertainty to global‐mean temperature projections through convolving Green's functions with SST pattern scenarios that differ from the ones AOGCMs produce by themselves. We find that future SST pattern uncertainty has a significant impact on projections, such as increasing total model uncertainty by 40% in a high‐emissions scenario by 2085. A reversal of the current cooling trend in the East Pacific over the next few decades could lead to a period of global‐mean warming with a 60% higher rate than currently projected. SST pattern uncertainty works through a destabilization of the shortwave cloud feedback to affect temperature projections. It is critical for climate change impact, adaptation, and mitigation assessments to incorporate this previously unaccounted for uncertainty until we trust the evolution of SST patterns in AOGCMs.
Anisotropy and Deformation Processes in Southern California From Rotational Observations
Authors: Tang Le , Igel Heiner , Montagner Jean‐Paul
Published: December 2023

Seismic anisotropy in the upper mantle reveals geodynamic processes and the tectonic evolution of the Earth. The two most powerful methods, surface wave tomography, and shear‐wave splitting observations, cannot investigate the deep local anisotropy with good vertical and lateral resolution, resulting in poor constraints on plate deformation processes of the complex plate boundary beneath the Southern California region. Here, we show that the amplitude ratio of translational displacement and rotation makes it possible to retrieve the local anisotropy in the upper mantle. Azimuthal anisotropy in the asthenosphere is well determined and resolved in lateral and vertical directions. The fast axis retrieved from amplitude observations indicates the local rapid changes in plate deformation and complex pattern of mantle flow, which is compatible with the distributions of horizontal mantle flow illuminated by geodetic measurements, providing new insights on geodynamic processes of the Southern California region.
Legacy Phosphorus and Ecosystem Memory Control Future Water Quality in a Eutrophic Lake
Authors: Hanson P. C. , Ladwig R. , Buelo C. , Albright E. A. , Delany A. D. , Carey C. C.
Published: December 2023

Lake water clarity, phytoplankton biomass, and hypolimnetic oxygen concentration are metrics of water quality that are highly degraded in eutrophic systems. Eutrophication is linked to legacy nutrients stored in catchment soils and in lake sediments. Long lags in water quality improvement under scenarios of nutrient load reduction to lakes indicate an apparent ecosystem memory tied to the interactions between water biogeochemistry and lake sediment nutrients. To investigate how nutrient legacies and ecosystem memory control lake water quality dynamics, we coupled nutrient cycling and lake metabolism in a model to recreate long‐term water quality of a eutrophic lake (Lake Mendota, Wisconsin, USA). We modeled long‐term recovery of water quality under scenarios of nutrient load reduction and found that the rates and patterns of water quality improvement depended on changes in phosphorus (P) and organic carbon storage in the water column and sediments. Through scenarios of water quality improvement, we showed that water quality variables have distinct phases of change determined by the turnover rates of storage pools—an initial and rapid water quality improvement due to water column flushing, followed by a much longer and slower improvement as sediment P pools were slowly reduced. Water clarity, phytoplankton biomass, and hypolimnetic dissolved oxygen differed in their time responses. Water clarity and algal biomass improved within years of nutrient reductions, but hypolimnetic oxygen took decades to improve. Even with reduced catchment loading, recovery of Lake Mendota to a mesotrophic state may require decades due to nutrient legacies and long ecosystem memory.
A Process‐Based Model to Track Water Pollutant Generation at High Resolution and Its Pathway to Discharge
Authors: Zhuang Yujie , Liu Xin , Yuan Zengwei , Sheng Hu , Gao Jianqi
Published: December 2023

The estimation of water pollutant loads is of crucial importance as it decides data inputs for both subsequent water quality models and watershed pollutant mitigation strategy. However, the generation of water pollutant loads at high resolution and the life‐cycle pathway of them from sources, through pipelines and wastewater treatment plants, finally to recipient water bodies remain unclear. This study aims to establish a process‐based Water Pollutant Loads Tracking model and applies it to a rapidly urbanizing watershed in Taihu Lake Basin, China at the resolution of 5 m × 5 m in 2017, whose terrain is flat, slowly lowing from west to east. Results show that, of 261.55 tons of the total phosphorus (TP) generation, 71.28% is collected, and 64.32% is treated, with only 26.46% discharged to the water bodies and 1.25% to the target ones. The spatial hotspots of TP generation are mainly concentrated in residential and industrial areas. Direct discharges from point sources and nonpoint runoffs, especially in rainy seasons, are recognized as the main challenges for local water pollution control. The main innovation of this study is to quantify the generation of water pollutant loads at high resolution and to trace the subsequent pathway to collection and discharge, and then to identify the potential substantial gap between generation and discharge, demonstrating the efficacy and broader applicability of this model.
Tumor-suppressive functions of protein lysine methyltransferases
Authors: Aziz Nur , Hong Yo Han , Kim Han Gyung , Kim Ji Hye , Cho Jae Youl
Published: December 2023

Protein lysine methyltransferases (PKMTs) play crucial roles in histone and nonhistone modifications, and their dysregulation has been linked to the development and progression of cancer. While the majority of studies have focused on the oncogenic functions of PKMTs, extensive evidence has indicated that these enzymes also play roles in tumor suppression by regulating the stability of p53 and β-catenin, promoting α-tubulin-mediated genomic stability, and regulating the transcription of oncogenes and tumor suppressors. Despite their contradictory roles in tumorigenesis, many PKMTs have been identified as potential therapeutic targets for cancer treatment. However, PKMT inhibitors may have unintended negative effects depending on the specific cancer type and target enzyme. Therefore, this review aims to comprehensively summarize the tumor-suppressive effects of PKMTs and to provide new insights into the development of anticancer drugs targeting PKMTs.
MiR-1246b, a novel miRNA molecule of extracellular vesicles in bronchoalveolar lavage fluid, promotes nodule growth through FGF14 in patients with lung cancer
Authors: Huang Jing , Ding Ming , Lu Yuan , Xu Lu , Zhang Yu , Han Shuhua , Zhu Xiaoli , Li Yiping , Chen Pingsheng
Published: December 2023

With the widespread development of chest computed tomography (CT), the detection rate of pulmonary nodules has increased; therefore, the classification of benign vs. malignant nodules has become a common problem in the clinic. MicroRNA, a potential tool, is expected to become a good choice for diagnosing and studying the occurrence and development of diseases through the vector of bronchoalveolar lavage fluid extracellular vesicles (BALF-EVs). In this study, radial endobronchial ultrasound (R-EBUS) was used to locate pulmonary nodules in patients. BALF was obtained, EVs were isolated, and small RNA sequencing was performed to screen differentially expressed miRNAs between benign and malignant pulmonary nodules. The binding targets and underlying mechanisms of the differentially expressed miRNAs were verified by in vitro and in vivo experiments. R-EBUS localization and sampling was used to obtain BALF, and EVs were successfully isolated and characterized. Differentially expressed miRNAs in BALF-EVs of patients with benign vs. malignant pulmonary nodules were screened by high-throughput small RNA sequencing. A new miRNA, miR-1246b, was identified. We found that FGF14 was the binding target of miR-1246b by luciferase assay. Subsequent mechanistic studies showed that miR-1246b inhibited the expression of FGF14 in lung cancer cells, further leading to ERK phosphorylation and epithelial-to-mesenchymal transition (EMT), which ultimately contributed to lung cancer cell proliferation, migration and invasion. In summary, our study demonstrates that the detection of miRNAs in BALF-EVs, a means of liquid biopsy, could assist in distinguishing malignant nodules from benign nodules. miR-1246b, which was extracted from BALF-EVs, targets FGF14 to promote lung cancer cell proliferation, migration and invasion.
Mitochondrial E3 ligase MARCH5 is a safeguard against DNA-PKcs-mediated immune signaling in mitochondria-damaged cells
Authors: Heo June , Park Yeon-Ji , Kim Yonghyeon , Lee Ho-Soo , Kim Jeongah , Kwon Soon-Hwan , Kang Myeong-Gyun , Rhee Hyun-Woo , Sun Woong , Lee Jae-Ho , Cho Hyeseong
Published: December 2023

Mitochondrial dysfunction is important in various chronic degenerative disorders, and aberrant immune responses elicited by cytoplasmic mitochondrial DNA (mtDNA) may be related. Here, we developed mtDNA-targeted MTERF1-FokI and TFAM-FokI endonuclease systems to induce mitochondrial DNA double-strand breaks (mtDSBs). In these cells, the mtDNA copy number was significantly reduced upon mtDSB induction. Interestingly, in cGAS knockout cells, synthesis of interferon β1 and interferon-stimulated gene was increased upon mtDSB induction. We found that mtDSBs activated DNA-PKcs and HSPA8 in a VDAC1-dependent manner. Importantly, the mitochondrial E3 ligase MARCH5 bound active DNA-PKcs in cells with mtDSBs and reduced the type І interferon response through the degradation of DNA-PKcs. Likewise, mitochondrial damage caused by LPS treatment in RAW264.7 macrophage cells increased phospho-HSPA8 levels and the synthesis of mIFNB1 mRNA in a DNA-PKcs-dependent manner. Accordingly, in March5 knockout macrophages, phospho-HSPA8 levels and the synthesis of mIFNB1 mRNA were prolonged after LPS stimulation. Together, cytoplasmic mtDNA elicits a cellular immune response through DNA-PKcs, and mitochondrial MARCH5 may be a safeguard to prevent persistent inflammatory reactions.
Class IIa HDACs inhibit cell death pathways and protect muscle integrity in response to lipotoxicity
Authors: Martin Sheree D. , Connor Timothy , Sanigorski Andrew , McEwen Kevin A. , Henstridge Darren C. , Nijagal Brunda , De Souza David , Tull Dedreia L. , Meikle Peter J. , Kowalski Greg M. , Bruce Clinton R. , Gregorevic Paul , Febbraio Mark A. , Collier Fiona M. , Walder Ken R. , McGee Sean L.
Published: December 2023

Lipotoxicity, the accumulation of lipids in non-adipose tissues, alters the metabolic transcriptome and mitochondrial metabolism in skeletal muscle. The mechanisms involved remain poorly understood. Here we show that lipotoxicity increased histone deacetylase 4 (HDAC4) and histone deacetylase 5 (HDAC5), which reduced the expression of metabolic genes and oxidative metabolism in skeletal muscle, resulting in increased non-oxidative glucose metabolism. This metabolic reprogramming was also associated with impaired apoptosis and ferroptosis responses, and preserved muscle cell viability in response to lipotoxicity. Mechanistically, increased HDAC4 and 5 decreased acetylation of p53 at K120, a modification required for transcriptional activation of apoptosis. Redox drivers of ferroptosis derived from oxidative metabolism were also reduced. The relevance of this pathway was demonstrated by overexpression of loss-of-function HDAC4 and HDAC5 mutants in skeletal muscle of obese db/db mice, which enhanced oxidative metabolic capacity, increased apoptosis and ferroptosis and reduced muscle mass. This study identifies HDAC4 and HDAC5 as repressors of skeletal muscle oxidative metabolism, which is linked to inhibition of cell death pathways and preservation of muscle integrity in response to lipotoxicity.
Structural insights into the role of GTPBP10 in the RNA maturation of the mitoribosome
Authors: Nguyen Thu Giang , Ritter Christina , Kummer Eva
Published: December 2023

Mitochondria contain their own genetic information and a dedicated translation system to express it. The mitochondrial ribosome is assembled from mitochondrial-encoded RNA and nuclear-encoded ribosomal proteins. Assembly is coordinated in the mitochondrial matrix by biogenesis factors that transiently associate with the maturing particle. Here, we present a structural snapshot of a large mitoribosomal subunit assembly intermediate containing 7 biogenesis factors including the GTPases GTPBP7 and GTPBP10. Our structure illustrates how GTPBP10 aids the folding of the ribosomal RNA during the biogenesis process, how this process is related to bacterial ribosome biogenesis, and why mitochondria require two biogenesis factors in contrast to only one in bacteria.
Role of PDGFRA+ cells and a CD55+ PDGFRALo fraction in the gastric mesenchymal niche
Authors: Manieri Elisa , Tie Guodong , Malagola Ermanno , Seruggia Davide , Madha Shariq , Maglieri Adrianna , Huang Kun , Fujiwara Yuko , Zhang Kevin , Orkin Stuart H. , Wang Timothy C. , He Ruiyang , McCarthy Neil , Shivdasani Ramesh A.
Published: December 2023

PDGFRA-expressing mesenchyme supports intestinal stem cells. Stomach epithelia have related niche dependencies, but their enabling mesenchymal cell populations are unknown, in part because previous studies pooled the gastric antrum and corpus. Our high-resolution imaging, transcriptional profiling, and organoid assays identify regional subpopulations and supportive capacities of purified mouse corpus and antral PDGFRA+ cells. Sub-epithelial PDGFRAHi myofibroblasts are principal sources of BMP ligands and two molecularly distinct pools distribute asymmetrically along antral glands but together fail to support epithelial growth in vitro. In contrast, PDGFRALo CD55+ cells strategically positioned beneath gastric glands promote epithelial expansion in the absence of other cells or factors. This population encompasses a small fraction expressing the BMP antagonist Grem1. Although Grem1+ cell ablation in vivo impairs intestinal stem cells, gastric stem cells are spared, implying that CD55+ cell activity in epithelial self-renewal derives from other subpopulations. Our findings shed light on spatial, molecular, and functional organization of gastric mesenchyme and the spectrum of signaling sources for epithelial support.
Direct probing of single-molecule chemiluminescent reaction dynamics under catalytic conditions in solution
Authors: Zhang Ziqing , Dong Jinrun , Yang Yibo , Zhou Yuan , Chen Yuang , Xu Yang , Feng Jiandong
Published: December 2023

Chemical reaction kinetics can be evaluated by probing dynamic changes of chemical substrates or physical phenomena accompanied during the reaction process. Chemiluminescence, a light emitting exoenergetic process, involves random reaction positions and kinetics in solution that are typically characterized by ensemble measurements with nonnegligible average effects. Chemiluminescent reaction dynamics at the single-molecule level remains elusive. Here we report direct imaging of single-molecule chemiluminescent reactions in solution and probing of their reaction dynamics under catalytic conditions. Double-substrate Michaelis–Menten type of catalytic kinetics is found to govern the single-molecule reaction dynamics in solution, and a heterogeneity is found among different catalyst particles and different catalytic sites on a single particle. We further show that single-molecule chemiluminescence imaging can be used to evaluate the thermodynamics of the catalytic system, resolving activation energy at the single-particle level. Our work provides fundamental insights into chemiluminescent reactions and offers an efficient approach for evaluating catalysts.
Origamic metal-organic framework toward mechanical metamaterial
Authors: Jin Eunji , Lee In Seong , Yang D. ChangMo , Moon Dohyun , Nam Joohan , Cho Hyeonsoo , Kang Eunyoung , Lee Junghye , Noh Hyuk-Jun , Min Seung Kyu , Choe Wonyoung
Published: December 2023

Origami, known as paper folding has become a fascinating research topic recently. Origami-inspired materials often establish mechanical properties that are difficult to achieve in conventional materials. However, the materials based on origami tessellation at the molecular level have been significantly underexplored. Herein, we report a two-dimensional (2D) porphyrinic metal-organic framework (MOF), self-assembled from Zn nodes and flexible porphyrin linkers, displaying folding motions based on origami tessellation. A combined experimental and theoretical investigation demonstrated the origami mechanism of the 2D porphyrinic MOF, whereby the flexible linker acts as a pivoting point. The discovery of the 2D tessellation hidden in the 2D MOF unveils origami mechanics at the molecular level.
Nonredox trivalent nickel catalyzing nucleophilic electrooxidation of organics
Authors: Yan Yuandong , Wang Ruyi , Zheng Qian , Zhong Jiaying , Hao Weichang , Yan Shicheng , Zou Zhigang
Published: December 2023

A thorough comprehension of the mechanism behind organic electrooxidation is crucial for the development of efficient energy conversion technology. Here, we find that trivalent nickel is capable of oxidizing organics through a nucleophilic attack and electron transfer via a nonredox process. This nonredox trivalent nickel exhibits exceptional kinetic efficiency in oxidizing organics that possess the highest occupied molecular orbital energy levels ranging from −7.4 to −6 eV (vs. Vacuum level) and the dual local softness values of nucleophilic atoms in nucleophilic functional groups, such as hydroxyls (methanol, ethanol, benzyl alcohol), carbonyls (formamide, urea, formaldehyde, glucose, and N-acetyl glucosamine), and aminos (benzylamine), ranging from −0.65 to −0.15. The rapid electrooxidation kinetics can be attributed to the isoenergetic channels created by the nucleophilic attack and the nonredox electron transfer via the unoccupied eg orbitals of trivalent nickel (t2g6eg1). Our findings are valuable in identifying kinetically fast organic electrooxidation on nonredox catalysts for efficient energy conversions.
Quorum-sensing synthase mutations re-calibrate autoinducer concentrations in clinical isolates of Pseudomonas aeruginosa to enhance pathogenesis
Authors: Simanek Kayla A. , Schumacher Megan L. , Mallery Caleb P. , Shen Stella , Li Lingyun , Paczkowski Jon E.
Published: December 2023

Quorum sensing is a mechanism of bacterial communication that controls virulence gene expression. Pseudomonas aeruginosa regulates virulence via two synthase/transcription factor receptor pairs: LasI/R and RhlI/R. LasR is considered the master transcriptional regulator of quorum sensing, as it upregulates rhlI/R. However, clinical isolates often have inactivating mutations in lasR, while maintaining Rhl-dependent signaling. We sought to understand how quorum sensing progresses in isolates with lasR mutations, specifically via activation of RhlR. We find that clinical isolates with lasR inactivating mutations often harbor concurrent mutations in rhlI. Using ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry, we discover that strains lacking lasR overproduce the RhlI-synthesized autoinducer and that RhlI variants re-calibrate autoinducer concentrations to wild-type levels, restoring virulent phenotypes. These findings provide a mechanism for the plasticity of quorum sensing progression in an acute infection niche.
Higher-order singularities in phase-tracked electromechanical oscillators
Authors: Zhou Xin , Ren Xingjing , Xiao Dingbang , Zhang Jianqi , Huang Ran , Li Zhipeng , Sun Xiaopeng , Wu Xuezhong , Qiu Cheng-Wei , Nori Franco , Jing Hui
Published: December 2023

Singularities ubiquitously exist in different fields and play a pivotal role in probing the fundamental laws of physics and developing highly sensitive sensors. Nevertheless, achieving higher-order (≥3) singularities, which exhibit superior performance, typically necessitates meticulous tuning of multiple (≥3) coupled degrees of freedom or additional introduction of nonlinear potential energies. Here we propose theoretically and confirm using mechanics experiments, the existence of an unexplored cusp singularity in the phase-tracked (PhT) steady states of a pair of coherently coupled mechanical modes without the need for multiple (≥3) coupled modes or nonlinear potential energies. By manipulating the PhT singularities in an electrostatically tunable micromechanical system, we demonstrate an enhanced cubic-root response to frequency perturbations. This study introduces a new phase-tracking method for studying interacting systems and sheds new light on building and engineering advanced singular devices with simple and well-controllable elements, with potential applications in precision metrology, portable nonreciprocal devices, and on-chip mechanical computing.
Insights into the ISG15 transfer cascade by the UBE1L activating enzyme
Authors: Wallace Iona , Baek Kheewoong , Prabu J. Rajan , Vollrath Ronnald , von Gronau Susanne , Schulman Brenda A. , Swatek Kirby N.
Published: December 2023

The attachment of the ubiquitin-like protein ISG15 to substrates by specific E1-E2-E3 enzymes is a well-established signalling mechanism of the innate immune response. Here, we present a 3.45 Å cryo-EM structure of a chemically trapped UBE1L-UBE2L6 complex bound to activated ISG15. This structure reveals the details of the first steps of ISG15 recognition and UBE2L6 recruitment by UBE1L (also known as UBA7). Taking advantage of viral effector proteins from severe acute respiratory coronavirus 2 (SARS-CoV-2) and influenza B virus (IBV), we validate the structure and confirm the importance of the ISG15 C-terminal ubiquitin-like domain in the adenylation reaction. Moreover, biochemical characterization of the UBE1L-ISG15 and UBE1L-UBE2L6 interactions enables the design of ISG15 and UBE2L6 mutants with altered selectively for the ISG15 and ubiquitin conjugation pathways. Together, our study helps to define the molecular basis of these interactions and the specificity determinants that ensure the fidelity of ISG15 signalling during the antiviral response.
Dynamic and static control of the off-target interactions of antisense oligonucleotides using toehold chemistry
Authors: Terada Chisato , Oh Kaho , Tsubaki Ryutaro , Chan Bun , Aibara Nozomi , Ohyama Kaname , Shibata Masa-Aki , Wada Takehiko , Harada-Shiba Mariko , Yamayoshi Asako , Yamamoto Tsuyoshi
Published: December 2023

Off-target interactions between antisense oligonucleotides (ASOs) with state-of-the-art modifications and biological components still pose clinical safety liabilities. To mitigate a broad spectrum of off-target interactions and enhance the safety profile of ASO drugs, we here devise a nanoarchitecture named BRace On a THERapeutic aSo (BROTHERS or BRO), which is composed of a standard gapmer ASO paired with a partially complementary peptide nucleic acid (PNA) strand. We show that these non-canonical ASO/PNA hybrids have reduced non-specific protein-binding capacity. The optimization of the structural and thermodynamic characteristics of this duplex system enables the operation of an in vivo toehold-mediated strand displacement (TMSD) reaction, effectively reducing hybridization with RNA off-targets. The optimized BROs dramatically mitigate hepatotoxicity while maintaining the on-target knockdown activity of their parent ASOs in vivo. This technique not only introduces a BRO class of drugs that could have a transformative impact on the extrahepatic delivery of ASOs, but can also help uncover the toxicity mechanism of ASOs.
All-fiber frequency agile triple-frequency comb light source
Authors: Bancel Eve-Line , Genier Etienne , Santagata Rosa , Conforti Matteo , Kudlinski Alexandre , Bouwmans Géraud , Vanvcincq Olivier , Labat Damien , Cassez Andy , Mussot Arnaud
Published: December 2023

Tricomb spectroscopy unveils a new dimension to standard linear and nonlinear spectroscopic analysis, offering the possibility to reveal the almost real-time evolution of complex systems with unprecedented accuracy. Current triple comb configurations are based on the use of mode-locked lasers, which impose constraints on the comb parameters, and require complex electronic synchronization, thus limiting potential applications. In this paper, we present the experimental demonstration of a new type of all-fiber, self-phase-locked, frequency-agile tri-comb light source. It is based on the nonlinear spectral broadening of three electro-optic modulator-based frequency combs in a three-core fiber. The exploitation of spatial multiplexing of light in optical fibers offers new possibilities to generate broadband-frequency combs that are highly coherent with each other. After characterizing the stability of the source and performing several dual-comb test measurements, we revealed the high mutual coherence between the three combs through the demonstration of a 2-D pump-probe four-wave mixing spectroscopy experiment.