bluuebunny/crossref_metadata_2025 huggingface dataset:
Mindfulness and Nonattachment-To-Self in Athletes: Can Letting Go Build Well-being and Self-actualization?
Authors: Lewis Kelsey J. , Walton Courtney C. , Slemp Gavin R. , Osborne Margaret S.
Published: October 2022

Objectives

Many athletes seek to embody a mindful state when competing. However, amidst competitive pressures and demands to perform at their best, athletes report similar or even higher levels of psychological distress than community norms. Despite the widespread use of mindfulness as a sport performance strategy, few studies have examined the mechanisms behind mindfulness, and the role egoic fixation plays, in athlete well-being. The current study aimed to explore the role of mindfulness and nonattachment-to-self (NTS) in athlete well-being and self-actualization.

Methods

An online survey was administered to 223 athletes (53.8% men), predominantly from Australia and New Zealand. Two-thirds of the sample were elite athletes. We used structural equation modeling to test a hypothesized model whereby NTS mediates the relationship between mindfulness and both well-being and self-actualization. We also tested an alternative model that positioned mindfulness as the mediator between NTS as the predictor, and well-being and self-actualisation as outcomes.

Results

Both models exhibited similar fit to the data, although the alternative model displayed slightly better fit than the hypothesized model. Partial mediation was found for the hypothesized and alternative models, highlighting both as plausible pathways. Interestingly, NTS was found to exhibit a stronger effect on well-being and self-actualization than mindfulness, suggesting it may play a central role in athlete well-being.

Conclusion

The findings highlight the need for researchers to consider mindfulness and NTS in tandem, acknowledging the role that egoic fixation plays in athlete mental health—especially when designing mindful-based interventions for athletes.
Development and Application of FOCUS App for Assessment of Approaches to Learning in 3–8-Year-Old Children in Kenya: A Design-Based Research Approach
Authors: Amukune Stephen , Barrett Karen Caplovitz , Szabó Norbert , Józsa Krisztián
Published: October 2022

Performance-based tools to assess school readiness domains such as Approaches to Learning are lacking in Low and Middle-Income Countries such as Kenya. This study aims to develop the Kenyan version of the FOCUS app (Finding Out Children's Unique Strengths), a game-like computer tablet assessment of two Approaches to Learning domains: mastery motivation and executive functions. We used a design-based research approach to develop and validate the FOCUS app, initially designed for the US and Hungarian Cultures, to suit the Kenyan context. We later followed children longitudinally from preschool to grade 1, to assess the applicability of the FOCUS app to the two grade levels. Results showed that the FOCUS app is valid and reliable. There was no significant difference in mastery motivation between the two waves. The FOCUS App can complement other school readiness tools to assess Approaches to Learning as one of the strategies to enhance school and life success.
Entrustable Professional Activities and Learning: The Postgraduate Trainee Perspective
Authors: Stephan Alice , Cheung Gary , van der Vleuten Cees
Published: October 2022

Objective

Entrustable professional activities (EPAs) are used as clinical activities in postgraduate psychiatry training in Australasia. This study aimed to explore psychiatry trainees’ perceptions of the impact of EPAs on their motivation and learning.

Methods

A constructivist grounded theory approach was used to conceptualize the impact of EPAs on trainees’ motivation and learning. A purposive sample of trainees was recruited from across New Zealand. Semi-structured individual interviews were used for data collection and continued until theoretical saturation was reached.

Results

The impact of EPAs on learning was mediated by the trainee’s appraisals of subjective control, value, and the costs of engaging with EPAs. When appraisals were positive, EPAs encouraged a focus on particular learning needs and structured learning with the supervisor. However, when appraisals were negative, EPAs encouraged a superficial approach to learning. Trainee appraisals and their subsequent impact on motivation and learning were most affected by EPA granularity, alignment of EPAs with clinical practice, and the supervisor’s conscientiousness in their approach to EPAs.

Conclusions

To stimulate learning, EPAs must be valued by both trainees and supervisors as constituting a coherent work-based curriculum that encompasses the key fellowship competencies. If EPAs are to be effective as clinical tasks for learning, ongoing faculty development must be the leading priority.
Why We Need to Invest in Large-Scale, Long-Term Monitoring Programs in Landscape Ecology and Conservation Biology
Authors: Lindenmayer David B. , Lavery Tyrone , Scheele Ben C.
Published: October 2022

Purpose of Review

Large-scale and/or long-term monitoring has many important roles in landscape ecology and conservation biology. We explore some of these roles in this review. We also briefly discuss some of the key design issues that need to be considered when developing long-term, large-scale monitoring to ensure it is effective.

Recent Findings

Much has been written on the importance of ecological monitoring, but the record on monitoring in landscape ecology and conservation remains generally poor. For populations of many species and for many environmental management interventions, monitoring is rarely done, or done well. This review outlines some of the reasons it is critical to invest in well-designed, implemented, and maintained monitoring. New ways of using monitoring data, such as in environmental accounting and mandated environmental reporting, might provide avenues for garnering greater support for monitoring programs in the future.

We discuss seven of the most important roles of monitoring in landscape ecology and conservation biology. These are (1) documenting responses to environmental change, (2) answering key ecological questions, (3) testing existing ecological theory and developing new theory, (4) quantifying the effectiveness of management interventions, (5) informing environmental prediction systems, (6) engaging citizen scientists and the general public, and (7) contributing data and other insights to environmental initiatives. We illustrate these key roles with examples, drawn from existing large-scale, long-term work in a range of environments in Australia. We argue that some of these functions can only be realized if a monitoring program is well designed, implemented, and maintained.
Formal groupoids
Authors: McQuillan Michael
Published: October 2022

We provide foundations for a characteristic free study of foliated varieties in terms of infinitesimal actions of formal groupoids. The ultimate goal is the bi-rational geometry of the same, and to this end we prove a cone theorem for foliations in curves, together with structure theorems for extremal rays, and, of course, a minimal model theorem for surfaces. All possible wild ramification effects of Deligne–Mumford champ are built in, along with the occasional use of Artin champ to address the $$\mathbb Q$$
Q
-Gorenstein condition.
When Research Topic Trend Prediction Meets Fact-Based Annotations
Authors: Wang Jiachen , Xu Jiajie , Chen Wei , Zhao Lei
Published: October 2022

The unprecedented growth of publications in many research domains brings the great convenience for tracing and analyzing the evolution and development of research topics. Despite the significant contributions made by existing studies, they usually extract topics from the titles of papers, instead of obtaining topics from the authoritative sessions provided by venues (e.g., AAAI, NeurIPS, and SIGMOD). To make up for the shortcoming of existing work, we develop a novel framework namely RTTP(Research Topic Trend Prediction). Specifically, the framework contains the following two components: (1) a topic alignment strategy called TAS is designed to obtain the detailed contents of research topics in each year, (2) an enhanced prediction network called EPN is designed to capture the research trend of known years for prediction. In addition, we construct two real-world datasets of specific research domains in computer science, i.e., database and data mining, computer architecture and parallel programming. The experimental results demonstrate that the problem is well solved and our solution outperforms the state-of-the-art methods.
Entrepreneurship programs and their underlying pedagogy in secondary education in the Netherlands
Authors: Göksen-Olgun Sultan , Groot Wim , Wakkee Ingrid
Published: October 2022

Despite the increase in entrepreneurship initiatives and interventions, there is a poor understanding of entrepreneurship programs' principles and learning objectives in secondary education. This study provides insight into the current range of entrepreneurship programs and their underlying pedagogy in secondary education in the Netherlands. To structure the analysis, we used the 11 design principles of Baggen et al. (Entrep Educ Pedagog 5(3):347–374, 2022). Data were collected from three different sources: the Vecon Business Schools (VBS) application forms, interviews with VBS schools, and additional documents. The findings show that most schools are unfamiliar with the definitions of entrepreneurship education. Many of the principles of broad entrepreneurship education focus on personal growth and the development of an entrepreneurial mindset. These are not always recognizable in secondary schools' current offerings of entrepreneurship education. Furthermore, the pedagogies on which entrepreneurship programs are based are mostly traditional, despite literature showing that (socially) constructivist entrepreneurship programs lend themselves better to developing an entrepreneurial mindset.
Exploration of non-trivial relations for the non-steady state nucleation rate: usefulness of the elliptic theta functions for its experimental estimations
Authors: Shigetomi Shota , Nishiwaki Mizuki
Published: October 2022

It is known that the non-steady state nucleation rate can be expressed as the product of the steady state nucleation rate and an elliptic theta function. However, there has been no research where rich mathematical properties of the elliptic theta functions were utilized to analyze the non-steady state nucleation processes. In this paper, we achieved two objectives by using the properties. The first one is to derive non-trivial relations for the non-steady state nucleation rate by using the rich mathematical properties of the elliptic theta functions, which could not be discovered in the conventional classical nucleation theory because of its complexities. The second one is to find solutions to two problems by solving a difference equation for the non-steady state nucleation rate: (i) it requires a large amount of effort and cost to estimate the time evolution of the non-steady state nucleation rate under some special conditions, and (ii) it is impossible to measure the non-steady state nucleation rate under some special cases. It is shown that our result help reduce the estimation cost of the non-steady state nucleation rate and makes mechanical estimation of the non-steady state nucleation rate possible from the past to the future.

Article highlights

Non-trivial relations for the non-steady state nucleation rate are found from the mathematical properties of the elliptic theta functions.

It is shown that our result help reduce the estimation cost of the non-steady state nucleation rate.

It is shown that our result makes mechanical estimation of the non-steady state nucleation rate possible from the past to the future.
Evaluation of steric entanglement in coiled-coil and domain-swapped protein interfaces using 3D printed models
Authors: Blaber Michael
Published: October 2022

Oligomeric protein interfaces involve non-covalent attractive forces plus potential steric entanglement. 70 years ago, Crick proposed a “Knobs in Holes” model for coiled-coil protein interfaces. Subsequently, modifications to this model have been proposed, describing either a “leucine zipper”, “jigsaw puzzle”, or a “peptide Velcro” interface. These principally describe forms of steric entanglement that may enhance oligomer stability. However, such entanglement has not been rigorously evaluated since it is not possible to experimentally eliminate intrinsic non-covalent attractive forces. 3D printing provides a novel means to evaluate steric entanglement of protein interfaces in the absence of attractive forces. Surprisingly, quantitation of the energy required to dissociate various coiled-coil protein interfaces of 3D printed protein models suggests minimal steric entanglement. Conversely, evaluation of domain-swapped interfaces of symmetric protein oligomers, differing by circular permutation, identifies extensive potential steric entanglement. Combined with available experimental data, the results suggest that steric entanglement of a protein interface can contribute to kinetic trapping of both folding and unfolding pathways. Steric entanglement of protein interfaces is therefore postulated to be an undesirable property for naturally evolved and designed protein oligomers.
Implicit Cognitions, Use Expectancies and Gratification in Social-Networks-Use Disorder and Tobacco Use Disorder
Authors: Schmidt Lasse David , Wegmann Elisa , Bischof Anja , Klein Lena , Zhou Chang , Rozgonjuk Dmitri , Kannen Christopher , Borgwardt Stefan , Brand Matthias , Montag Christian , Rumpf Hans-Jürgen
Published: October 2022

Abstract: Aims: The problematic use of social networks is discussed as a further specific type of Internet-use disorders. Our project aims to clarify whether social-networks-use disorder (SNUD) is marked by characteristics of addictive behaviors by tracking behavior and investigating the relevance of 1) implicit cognitions, 2) the experiences of gratification and compensation and 3) use expectancies in SNUD compared to tobacco-use disorder. Methodology: Four groups will be examined: individuals with 1) SNUD without tobacco use, 2) risky use patterns with regard to social networks without tobacco use, 3) tobacco use disorder and 4) healthy controls. All participants first complete a laboratory examination including the Implicit Association Test (IAT) and the Approach-Avoidance task (AAT). We will use smartphone-based data tracking for 14 days following laboratory testing to record smoking and social-networks-use patterns. During this period, we further measure use expectancies and the experience of gratification and compensation by means of a smartphone-based experience sampling method (ESM). Conclusions: This is the first study to examine relevant characteristics of addictive behaviors in individuals with SNUD compared to individuals with tobacco use, using a combination of experimental psychological methods and smartphone-based measurements. We expect that this investigative approach will contribute to a deeper understanding of the processes involved in SNUD.
Schwindel – wie weiter?
Authors: Rickenbacher-Frey Sarah , Zimmerli Lukas , Ernst Susanne
Published: October 2022

Zusammenfassung. Schwindel ist ein sehr häufiges Symptom mit umfangreicher Differenzialdiagnose, die sowohl gutartige als auch ernsthafte Erkrankungen umfasst. Akutmediziner müssen die Mehrzahl der Patientinnen und Patienten mit selbstlimitierenden gutartigen Beschwerden von jenen mit ernsthaften Erkrankungen unterscheiden können. Unser strukturiertes Vorgehen soll als Leitfaden für die Akutmedizin dienen.
Pharmacotherapeutic undertreatment of ADHD in elite-level cycling and anti-doping regulations
Authors: Liebrenz Michael , Smith Alexander , Buadze Anna
Published: October 2022

Abstract. Introduction: Attention Deficit/Hyperactivity Disorder (ADHD) in elite-level cycling is an overlooked area of clinical enquiry. Whilst former riders have raised awareness about ADHD, there is scant evidence about pharmacotherapeutic treatment levels of this disorder. This is a pertinent concern amidst contemporaneous anti-doping contexts, as common medicines for ADHD are prohibited during active competition by the World Anti-Doping Agency and thus require a Therapeutic Use Exemption (TUE). Methods: We conducted a preliminary investigation into pharmacotherapeutic treatment rates of ADHD in elite-level riders. We gathered secondary, publicly-available data about cyclists in the Registered Testing Pool (RTP) from the professional body, the Union Cycliste International (UCI), in 2020 and 2021. We then compared this with the total TUEs for prohibited medications granted on behalf of the UCI during this timeframe. Results: 1,265 elite-level riders were included in the RTP sample in 2020, as compared to 10 TUEs. 1,234 elite-level riders were included in the 2021 RTP sample, as compared to 10 TUEs. Discussion: Based on these data, we estimate that ADHD may be undertreated in this cohort of elite-level cyclists per general trends. We highlight the adverse mental health effects of medicinal undertreatment for ADHD and its implications for the sport. We also hypothesise potential reasons for this, including stigmatisation, negative conceptions of doping allegations, and possible medicolegal consequences. Conclusion: ADHD in elite-level cycling has received little coverage, especially in relation to treatment rates. Detailed research examining this issue and awareness campaigns are required to protect the mental health of elite-level riders.
Amazon Basin Tree Rings Hold a Record of the Region’s Rainfall
Authors: Fritts Rachel
Published: October 2022

New research provides a 200-year reconstruction of interannual rainfall in the Amazon basin using oxygen isotopes preserved in tree rings in Ecuador and Bolivia.
Global Modeling of the Inner Magnetosphere Under the Influence of a Magnetic Cloud Associated With an Interplanetary Coronal Mass Ejection: Energy Conversion and Ultra‐Low Frequency Wave Activity
Authors: Jauer P. R. , Wang C. , Echer E. , Souza V. M. , Da Silva L. A. , Marchezi J. P. , Alves L. R. , Alves M. V. , Douglas S. , Loesch C. , Liu Z. , Hui L. , Vieira L. E. A. , Gonzalez W. D. , Denardini C. M. , Medeiros C. , Costa J. E. R.
Published: October 2022

The interaction and response of the magnetic cloud‐type structure with Earth's magnetosphere were modeled by the SWMF/BATS‐R‐US code. The conversion of magnetic (Em), kinetic (Ek), and internal (Ei) energies was analyzed as well as the wave power integrated in the ultra‐low frequency (ULF) range of the poloidal (Eϕ) and toroidal (Er) electric field components in the equatorial region of the magnetosphere, in seven 2‐hr long intervals, namely, I1 through I7. The intensity of energy conversion and wave activity for I1 and I7 intervals was negligible. The energy conversion started in the I2 interval and extended to the I3, I4, and I5 intervals. The power of the Eϕ and Er components in the dayside and nightside regions is clearly observed. The I4 corresponds to interplanetary magnetic field (IMF) Bz mostly southward and the I5 has similar amplitudes of the Bz and By components, corresponding to the period of the high geomagnetic activity. The conversion rate for the I4 and I5 was similar, however, the integrated power spectral density (IPSD) of the Eϕ and Er components is more intense in I5. During the I6 interval, with predominant IMF By, the energy conversion rate is intensified mostly for inner radial distances R < 6 RE, and the Ek component becomes close to zero for outer regions. The energy conversion regions are located spatially close to or overlapping with regions where the IPSD in the ULF range is intensified. The energy conversion in the inner magnetosphere occurred preferentially between Em and Ei, with the Ek energy component always present but with lower intensities.
Quantifying the Relationship Between Atmospheric River Origin Conditions and Landfall Temperature
Authors: Gonzales Katerina R. , Swain Daniel L. , Roop Heidi A. , Diffenbaugh Noah S.
Published: October 2022

The temperature of landfalling atmospheric rivers (ARs) has direct implications for regional water resources. Compared to cool ARs, warm ARs can result in more surface runoff and flooding, less water availability via low snow accumulations and enhanced snowmelt, and greater challenges for storm forecasting and reservoir operations. Based on case studies, ARs with subtropical origin locations and warm origin conditions are assumed to be associated with warmer landfall temperatures—though, to date, this has not yet been demonstrated systematically. We analyze North Pacific ARs that made landfall along the West Coast of North America from 1980 to 2017. We find that ARs originating over the subtropical Pacific Ocean near Hawaii (“Pineapple Express”‐type ARs) are indeed 1.5°C warmer and 2 kg/m2 moister in winter than ARs originating elsewhere. We extend this analysis for the full study population of ARs by quantifying AR origin conditions, including the spatial distribution of origin temperature, moisture content, and integrated vapor transport (IVT). We use fixed effects multivariate regression to quantify the relative influence of the origin conditions on landfall temperature. Our regression models show that AR origins with lower latitudes, longer AR lifetimes, and stronger IVT are associated with warmer landfall temperatures and that ARs that start warm generally stay warm. We also find that the phase of the El Niño/Southern Oscillation does not exhibit a consistent relationship with AR landfall temperature. Overall, our results partially affirm—yet also complicate—common assumptions about the role of different origin conditions in landfalling AR temperature.
A Physics‐Informed Bayesian Storyline Approach to Assess Sediment Transport in the Mekong
Authors: Xu Bo , He Xiaogang
Published: October 2022

The Mekong Delta, home to 20 million people, is experiencing significant land loss due to rising sea levels, accelerating land subsidence, and declining sediment supply. Robust estimates of the sediment flux delivered to Mekong Delta (SFMD) and the relative contribution of sediment load (RCSL) from individual subbasins are key to designing future adaptation strategies, such as strategic dam planning, sand mining, and delta groundwater management. However, existing estimates of SFMDand RCSL are largely deterministic without uncertainty quantification or using a uniform sampling to represent uncertainty. They also remain questionable due to data inconsistency and methodological biases caused by overlooked physical processes. Here, we develop a hybrid physics‐based data‐driven modeling framework to constrain the probability distribution of SFMDand RCSL and explore how they change under plausible climate change and land‐use change scenarios, leveraging recent advances in Bayesian inference (i.e., reasoning by refutation). We find that pure yield‐based approaches, which typically ignore sediment retention, can lead to higher estimates of RCSL from upstream regions compared with the physics‐based approach. Our best estimate of historical (1962–2005) SFMDcombining multiple lines of evidence shows a median of 106 Mt/yr with a 5%–95% range of 66–160 Mt/yr. Over the analyzed range of land‐use and climate change scenarios, future changes in SFMDseem to be more sensitive to the latter, especially changes in wet‐season precipitation. Our estimate of RCSL from the Upper Mekong River Basin is likely (>66% probability) in the range of 0.25–0.39 with a mean of 0.34 in all plausible scenarios.
Molecular targeted therapy for anticancer treatment
Authors: Min Hye-Young , Lee Ho-Young
Published: October 2022

Since the initial clinical approval in the late 1990s and remarkable anticancer effects for certain types of cancer, molecular targeted therapy utilizing small molecule agents or therapeutic monoclonal antibodies acting as signal transduction inhibitors has served as a fundamental backbone in precision medicine for cancer treatment. These approaches are now used clinically as first-line therapy for various types of human cancers. Compared to conventional chemotherapy, targeted therapeutic agents have efficient anticancer effects with fewer side effects. However, the emergence of drug resistance is a major drawback of molecular targeted therapy, and several strategies have been attempted to improve therapeutic efficacy by overcoming such resistance. Herein, we summarize current knowledge regarding several targeted therapeutic agents, including classification, a brief biology of target kinases, mechanisms of action, examples of clinically used targeted therapy, and perspectives for future development.
Circular RNA CREBBP modulates cartilage degradation by activating the Smad1/5 pathway through the TGFβ2/ALK1 axis
Authors: Xu Yiyang , Mao Guping , Long Dianbo , Deng Zengfa , Xin Ruobin , Zhang Ziji , Xue Ting , Liao Weiming , Xu Jie , Kang Yan
Published: October 2022

Osteoarthritis, characterized by articular cartilage degradation, is the leading cause of chronic disability in older adults. Studies have indicated that circular RNAs are crucial regulators of chondrocyte development and are involved in the progression of osteoarthritis. In this study, we investigated the function and mechanism of a circular RNA and its potential for osteoarthritis therapy. The expression levels of circCREBBP, screened by circular RNA sequencing during chondrogenic differentiation in adipose tissue-derived stem cells, and TGFβ2 were significantly increased in the cartilage of patients with osteoarthritis and IL-1β-induced chondrocytes. circCREBBP knockdown increased anabolism in the extracellular matrix and inhibited chondrocyte degeneration, whereas circCREBBP overexpression led to the opposite effects. Luciferase reporter assays, rescue experiments, RNA immunoprecipitation, and RNA pulldown assays confirmed that circCREBBP upregulated TGFβ2 expression by sponging miR-1208, resulting in significantly enhanced phosphorylation of Smad1/5 in chondrocytes. Moreover, intra-articular injection of adeno-associated virus-sh-circCrebbp alleviated osteoarthritis in a mouse model of destabilization of the medial meniscus. Our findings reveal a critical role for circCREBBP in the progression of osteoarthritis and provide a potential target for osteoarthritis therapy.
Roles of RIPK3 in necroptosis, cell signaling, and disease
Authors: Morgan Michael J. , Kim You-Sun
Published: October 2022

Receptor-interacting protein kinase-3 (RIPK3, or RIP3) is an essential protein in the “programmed” and “regulated” cell death pathway called necroptosis. Necroptosis is activated by the death receptor ligands and pattern recognition receptors of the innate immune system, and the findings of many reports have suggested that necroptosis is highly significant in health and human disease. This significance is largely because necroptosis is distinguished from other modes of cell death, especially apoptosis, in that it is highly proinflammatory given that cell membrane integrity is lost, triggering the activation of the immune system and inflammation. Here, we discuss the roles of RIPK3 in cell signaling, along with its role in necroptosis and various pathways that trigger RIPK3 activation and cell death. Lastly, we consider pathological situations in which RIPK3/necroptosis may play a role.
Evaluation of Nav1.8 as a therapeutic target for Pitt Hopkins Syndrome
Authors: Martinowich Keri , Das Debamitra , Sripathy Srinidhi Rao , Mai Yishan , Kenney Rakaia F. , Maher Brady J.
Published: October 2022

Pitt Hopkins Syndrome (PTHS) is a rare syndromic form of autism spectrum disorder (ASD) caused by autosomal dominant mutations in the Transcription Factor 4 (TCF4) gene. TCF4 is a basic helix-loop-helix transcription factor that is critical for neurodevelopment and brain function through its binding to cis-regulatory elements of target genes. One potential therapeutic strategy for PTHS is to identify dysregulated target genes and normalize their dysfunction. Here, we propose that SCN10A is an important target gene of TCF4 that is an applicable therapeutic approach for PTHS. Scn10a encodes the voltage-gated sodium channel Nav1.8 and is consistently shown to be upregulated in PTHS mouse models. In this perspective, we review prior literature and present novel data that suggests inhibiting Nav1.8 in PTHS mouse models is effective at normalizing neuron function, brain circuit activity and behavioral abnormalities and posit this therapeutic approach as a treatment for PTHS.
Asgard ESCRT-III and VPS4 reveal conserved chromatin binding properties of the ESCRT machinery
Authors: Nachmias Dikla , Melnikov Nataly , Zorea Alvah , Sharon Maya , Yemini Reut , De-picchoto Yasmin , Tsirkas Ioannis , Aharoni Amir , Frohn Bela , Schwille Petra , Zarivach Raz , Mizrahi Itzhak , Elia Natalie
Published: October 2022

The archaeal Asgard superphylum currently stands as the most promising prokaryotic candidate, from which eukaryotic cells emerged. This unique superphylum encodes for eukaryotic signature proteins (ESP) that could shed light on the origin of eukaryotes, but the properties and function of these proteins is largely unresolved. Here, we set to understand the function of an Asgard archaeal protein family, namely the ESCRT machinery, that is conserved across all domains of life and executes basic cellular eukaryotic functions, including membrane constriction during cell division. We find that ESCRT proteins encoded in Loki archaea, express in mammalian and yeast cells, and that the Loki ESCRT-III protein, CHMP4-7, resides in the eukaryotic nucleus in both organisms. Moreover, Loki ESCRT-III proteins associated with chromatin, recruited their AAA-ATPase VPS4 counterpart to organize in discrete foci in the mammalian nucleus, and directly bind DNA. The human ESCRT-III protein, CHMP1B, exhibited similar nuclear properties and recruited both human and Asgard VPS4s to nuclear foci, indicating interspecies interactions. Mutation analysis revealed a role for the N terminal region of ESCRT-III in mediating these phenotypes in both human and Asgard ESCRTs. These findings suggest that ESCRT proteins hold chromatin binding properties that were highly preserved through the billion years of evolution separating Asgard archaea and humans. The conserved chromatin binding properties of the ESCRT membrane remodeling machinery, reported here, may have important implications for the origin of eukaryogenesis.
Nephrons, podocytes and chronic kidney disease: Strategic antihypertensive therapy for renoprotection
Authors: Haruhara Kotaro , Kanzaki Go , Tsuboi Nobuo
Published: October 2022

Chronic kidney disease (CKD) is one of the strongest risk factors for hypertension, and hypertension can exacerbate the progression of CKD. Thus, the management of CKD and antihypertensive therapy are inextricably linked. Research over the past decades has shown that the human kidney is more diverse than initially thought. Subjects with low nephron endowment are at increased risk of developing CKD and hypertension, which is consistent with the theory of the developmental origins of health and disease. Combined with other lifetime risks of CKD, hypertension may lead to a vicious cycle consisting of podocyte injury, glomerulosclerosis and further loss of nephrons. Of note, recent studies have shown that the number of nephrons correlates well with the number of podocytes, suggesting that these two components are intrinsically linked and may influence each other. Both nephrons and podocytes have no or very limited regenerative capacity and are destined to decrease throughout life. Therefore, one of the best strategies to slow the progression of CKD is to maintain the “numbers” of these essential components necessary to preserve renal function. To this end, both the achievement of an optimal blood pressure and a maximum reduction in urinary protein excretion are essential. Lifestyle modifications and antihypertensive drug therapy must be carefully individualized to address the potential diversity of the kidneys.
A single transcription factor facilitates an insect host combating Bacillus thuringiensis infection while maintaining fitness
Authors: Guo Zhaojiang , Guo Le , Qin Jianying , Ye Fan , Sun Dan , Wu Qingjun , Wang Shaoli , Crickmore Neil , Zhou Xuguo , Bravo Alejandra , Soberón Mario , Zhang Youjun
Published: October 2022

Maintaining fitness during pathogen infection is vital for host survival as an excessive response can be as detrimental as the infection itself. Fitness costs are frequently associated with insect hosts countering the toxic effect of the entomopathogenic bacterium Bacillus thuringiensis (Bt), which delay the evolution of resistance to this pathogen. The insect pest Plutella xylostella has evolved a mechanism to resist Bt toxins without incurring significant fitness costs. Here, we reveal that non-phosphorylated and phosphorylated forms of a MAPK-modulated transcription factor fushi tarazu factor 1 (FTZ-F1) can respectively orchestrate down-regulation of Bt Cry1Ac toxin receptors and up-regulation of non-receptor paralogs via two distinct binding sites, thereby presenting Bt toxin resistance without growth penalty. Our findings reveal how host organisms can co-opt a master molecular switch to overcome pathogen invasion with low cost, and contribute to understanding the underlying mechanism of growth-defense tradeoffs during host-pathogen interactions in P. xylostella.
Targeting EGFR-dependent tumors by disrupting an ARF6-mediated sorting system
Authors: Guo Huiling , Wang Juan , Ren Su , Zheng Lang-Fan , Zhuang Yi-Xuan , Li Dong-Lin , Sun Hui-Hui , Liu Li-Ying , Xie Changchuan , Wu Ya-Ying , Wang Hong-Rui , Deng Xianming , Li Peng , Zhao Tong-Jin
Published: October 2022

Aberrant activation of EGFR due to overexpression or mutation is associated with poor prognosis in many types of tumors. Here we show that blocking the sorting system that directs EGFR to plasma membrane is a potent strategy to treat EGFR-dependent tumors. We find that EGFR palmitoylation by DHHC13 is critical for its plasma membrane localization and identify ARF6 as a key factor in this process. N-myristoylated ARF6 recognizes palmitoylated EGFR via lipid-lipid interaction, recruits the exocyst complex to promote EGFR budding from Golgi, and facilitates EGFR transporting to plasma membrane in a GTP-bound form. To evaluate the therapeutic potential of this sorting system, we design a cell-permeable peptide, N-myristoylated GKVL-TAT, and find it effectively disrupts plasma membrane localization of EGFR and significantly inhibits progression of EGFR-dependent tumors. Our findings shed lights on the underlying mechanism of how palmitoylation directs protein sorting and provide an potential strategy to manage EGFR-dependent tumors.
Experimental reconstructions of 3D atomic structures from electron microscopy images using a Bayesian genetic algorithm
Authors: De Backer Annick , Van Aert Sandra , Faes Christel , Arslan Irmak Ece , Nellist Peter D. , Jones Lewys
Published: October 2022

We introduce a Bayesian genetic algorithm for reconstructing atomic models of monotype crystalline nanoparticles from a single projection using Z-contrast imaging. The number of atoms in a projected atomic column obtained from annular dark field scanning transmission electron microscopy images serves as an input for the initial three-dimensional model. The algorithm minimizes the energy of the structure while utilizing a priori information about the finite precision of the atom-counting results and neighbor-mass relations. The results show promising prospects for obtaining reliable reconstructions of beam-sensitive nanoparticles during dynamical processes from images acquired with sufficiently low incident electron doses.
Immunogenicity of SARS-CoV-2 spike antigens derived from Beta & Delta variants of concern
Authors: Akache Bassel , Renner Tyler M. , Stuible Matthew , Rohani Nazanin , Cepero-Donates Yuneivy , Deschatelets Lise , Dudani Renu , Harrison Blair A. , Gervais Christian , Hill Jennifer J. , Hemraz Usha D. , Lam Edmond , Régnier Sophie , Lenferink Anne E. G. , Durocher Yves , McCluskie Michael J.
Published: October 2022

Using our strongly immunogenic SmT1 SARS-CoV-2 spike antigen platform, we developed antigens based on the Beta & Delta variants of concern (VOC). These antigens elicited higher neutralizing antibody activity to the corresponding variant than comparable vaccine formulations based on the original reference strain, while a multivalent vaccine generated cross-neutralizing activity in all three variants. This suggests that while current vaccines may be effective at reducing severe disease to existing VOC, variant-specific antigens, whether in a mono- or multivalent vaccine, may be required to induce optimal immune responses and reduce infection against arising variants.
Immunogenicity of MultiTEP platform technology-based Tau vaccine in non-human primates
Authors: Hovakimyan Armine , Zagorski Karen , Chailyan Gor , Antonyan Tatevik , Melikyan Levon , Petrushina Irina , Batt Dash G. , King Olga , Ghazaryan Manush , Donthi Aashrit , Foose Caitlynn , Petrovsky Nikolai , Cribbs David H. , Agadjanyan Michael G. , Ghochikyan Anahit
Published: October 2022

Pathological forms of Tau protein are directly associated with neurodegeneration and correlate with Alzheimer’s Disease (AD) symptoms, progression, and severity. Previously, using various mouse models of Tauopathies and AD, we have demonstrated the immunogenicity and efficacy of the MultiTEP-based adjuvanted vaccine targeting the phosphatase activating domain (PAD) of Tau, AV-1980R/A. Here, we analyzed its immunogenicity in non-human primates (NHP), the closest phylogenic relatives to humans with a similar immune system, to initiate the transition of this vaccine into clinical trials. We have demonstrated that AV-1980R/A is highly immunogenic in these NHPs, activating a broad but unique to each monkey repertoire of MultiTEP-specific T helper (Th) cells that, in turn, activate B cells specific to PAD. The resulting anti-PAD IgG antibodies recognize pathological Tau tangles and Tau-positive neuritis in AD case brain sections with no staining in control non-AD cases. These published data and efficacy results support the AV-1980R/A vaccine progression to first-in-human clinical trials.
Personalizing exoskeleton assistance while walking in the real world
Authors: Slade Patrick , Kochenderfer Mykel J. , Delp Scott L. , Collins Steven H.
Published: October 2022

Personalized exoskeleton assistance provides users with the largest improvements in walking speed1 and energy economy2–4 but requires lengthy tests under unnatural laboratory conditions. Here we show that exoskeleton optimization can be performed rapidly and under real-world conditions. We designed a portable ankle exoskeleton based on insights from tests with a versatile laboratory testbed. We developed a data-driven method for optimizing exoskeleton assistance outdoors using wearable sensors and found that it was equally effective as laboratory methods, but identified optimal parameters four times faster. We performed real-world optimization using data collected during many short bouts of walking at varying speeds. Assistance optimized during one hour of naturalistic walking in a public setting increased self-selected speed by 9 ± 4% and reduced the energy used to travel a given distance by 17 ± 5% compared with normal shoes. This assistance reduced metabolic energy consumption by 23 ± 8% when participants walked on a treadmill at a standard speed of 1.5 m s−1. Human movements encode information that can be used to personalize assistive devices and enhance performance.
Maturation and circuit integration of transplanted human cortical organoids
Authors: Revah Omer , Gore Felicity , Kelley Kevin W. , Andersen Jimena , Sakai Noriaki , Chen Xiaoyu , Li Min-Yin , Birey Fikri , Yang Xiao , Saw Nay L. , Baker Samuel W. , Amin Neal D. , Kulkarni Shravanti , Mudipalli Rachana , Cui Bianxiao , Nishino Seiji , Grant Gerald A. , Knowles Juliet K. , Shamloo Mehrdad , Huguenard John R. , Deisseroth Karl , Pașca Sergiu P.
Published: October 2022

Self-organizing neural organoids represent a promising in vitro platform with which to model human development and disease1–5. However, organoids lack the connectivity that exists in vivo, which limits maturation and makes integration with other circuits that control behaviour impossible. Here we show that human stem cell-derived cortical organoids transplanted into the somatosensory cortex of newborn athymic rats develop mature cell types that integrate into sensory and motivation-related circuits. MRI reveals post-transplantation organoid growth across multiple stem cell lines and animals, whereas single-nucleus profiling shows progression of corticogenesis and the emergence of activity-dependent transcriptional programs. Indeed, transplanted cortical neurons display more complex morphological, synaptic and intrinsic membrane properties than their in vitro counterparts, which enables the discovery of defects in neurons derived from individuals with Timothy syndrome. Anatomical and functional tracings show that transplanted organoids receive thalamocortical and corticocortical inputs, and in vivo recordings of neural activity demonstrate that these inputs can produce sensory responses in human cells. Finally, cortical organoids extend axons throughout the rat brain and their optogenetic activation can drive reward-seeking behaviour. Thus, transplanted human cortical neurons mature and engage host circuits that control behaviour. We anticipate that this approach will be useful for detecting circuit-level phenotypes in patient-derived cells that cannot otherwise be uncovered.
Coral community data Heron Island Great Barrier Reef 1962–2016
Authors: Tanner Jason E. , Connell Joseph H.
Published: October 2022

Here we describe benthic composition data derived from benthic photoquadrats collected over 41 surveys between 1962 and 2016 at four sites on Heron reef, at the southern end of Australia’s Great Barrier Reef, to assess change in coral composition over time. Surveys have often been annual, in a few years sub-annual, and the longest gap is six years. A subset of the data from two sites with the most complete records has been fully processed to allow the size of all individual colonies, and changes in species composition and cover, to be tracked over time. The taxonomy in these quadrats has been carefully checked for internal consistency, and is generally at the species level. A second subset has been processed, but has not been through full quality control, while a third subset exists as images only. This is the longest, 56 years, regular photographic record of coral cover in existence, and provides a valuable temporal contrast dating back in time to more recent studies of greater geographic extent and/or resolution.
Factors determining the dorsal coloration pattern of aposematic salamanders
Authors: Barzaghi Benedetta , Melotto Andrea , Cogliati Paola , Manenti Raoul , Ficetola Gentile Francesco
Published: October 2022

Aposematic bright colors have a key role for animal defense and can be expressed through metabolic production or by acquiring pigments from diet. Aposematic coloration can be related to both local adaptations and availability of trophic resources. The European fire salamander (Salamandra salamandra) shows significant color variability and occurs across a broad range of habitats. Here we combined field observations with common rearing experiments to disentangle the role of environmental conditions and local adaptations in determining aposematic coloration of salamander populations. We assessed color variation and measured habitat features and food availability in adults from 25 populations. Furthermore, we reared newborn larvae from 10 populations under different food availability and analyzed color of metamorphs. To assess color pattern, we measured the percentage of yellow covering the body, and the Hue, Saturation and Value of yellow coloration. Adult showed strong variation of color pattern; variation was strongly related to the individual's size, to habitat productivity and to food availability. Under common garden conditions, differences between populations were not anymore evident, and coloration was only affected by resource availability during larval development. Our results suggest that environmental conditions and food availability are more important than local adaptations in determining differences in aposematic color pattern.
The future of Viscum album L. in Europe will be shaped by temperature and host availability
Authors: Walas Łukasz , Kędziora Wojciech , Ksepko Marek , Rabska Mariola , Tomaszewski Dominik , Thomas Peter A. , Wójcik Roman , Iszkuło Grzegorz
Published: October 2022

Viscum album L. is a plant of great importance due to its influence on the host trees and, by extension, entire ecosystems. The species is also significant to humans—on the one hand, because of its use in medicine, and on the other, because of the growing threat it poses to the stability of conifer stands. Therefore, it is important to recognize the future range of three mistletoe subspecies (Viscum album subsp. album, V. album subsp. austriacum, and V. album subsp. abietis). Modelling of the potential range of these subspecies was performed using MAXENT software. Locations were collected from literature and databases. A total number of 3335 stands were used. Bioclimatic data for the current conditions and three future scenarios (SSP 1.26, SSP 3.70, SSP 5.85) were downloaded from the CHELSA database. The results confirmed that the temperature is the key variable on the potential range of the analysed subspecies. V. album subsp. abietis is withdrawing from its range according to all scenarios. In the case of V. album subsp. austriacum, a slight range shift is visible. Only the V. album subsp. album will expand non-directionally. The reason is most likely a very large number of host species and greater genetic variability compared to the subspecies found on conifers.
Nonlinear seepage erosion model of water inrush considering particle size distribution of karst collapse column and its engineering applications
Authors: Yang Bin , Shi Wenhao , Yang Xin
Published: October 2022

Water inrush through karst collapse column is one of the great disasters which threaten coal mine safety production. The particle size distribution of karst collapse column is one of its most basic physical properties, which has a strong correlation with particle migration, and is an important basis for evaluating the water inrush risk of collapse column. The nonlinear flow tests of broken rock under different gradation conditions were carried out by a custom-built apparatus, and the relationship equation between nonlinear flow parameters (permeability and non-Darcy factor) and Talbol power exponent n were constructed. A nonlinear flow model with variable mass of water inrush from karst collapse column was established. The spatio-temporal evolution law of pressure, velocity, porosity and concentration under particle loss and the influence of particle gradation on the water inrush risk of karst collapse column at Fan gezhuang mine were discussed. During the water inrush, the flow state of fluids in karst collapse column gradually transitions from a weak inertial flow to a strong one, eventually becoming a turbulent flow. The flow model based on single flow state cannot reflect the essence of flow regime transition in water inrush. The larger n is, the stronger the water permeability of the karst collapse column, the faster the particles migrate and are lost, the faster the flow channel with high porosity develops, the shorter the time for the water inflow to reach its peak value, and the greater the risk of water inrush.