bluuebunny/crossref_metadata_2025 huggingface dataset:
A tunable self-bias effect in rubbery magnetoelectric materials
Authors: Tan Kai , Jia Rong , Deng Qian
Published: October 2024

Magnetoelectric (ME) composites have recently received extensive attention due to their much higher ME coefficients and relatively high operating temperatures compared to single-phase ME materials. However, the ME coefficients of ME composites depend on the external magnetic field, and high ME coefficients usually require the presence of a biased external DC magnetic field. In this work, we propose a hybrid magnetoactive elastomer, which is a rubber matrix embedded with both soft iron particles and hard NdFeB particles. It is found that such a hybrid MAE shows a nonzero piezomagnetic coefficient even as the applied magnetic field approaches zero. Based on this phenomenon, we further propose a soft ME material with a self-bias effect and experimentally demonstrate that the self-bias effect can be tailored by changing the residual magnetization of the hybrid MAE and the charge density of the electret layer. This work successfully demonstrates a new mechanism of the self-bias effect for magnetoelectric materials and introduces a new member to the family of ME materials.
Impact and freezing characteristics of deionized water droplets on cold curved surfaces
Authors: Liu Xuanchen , Liu Liansheng , Hu Ziyi , Li Rongji , Wang Ziyue
Published: October 2024

Processes involving droplet impact and subsequent freezing occur widely in practical engineering applications. In the present study, a visualization experimental setup is utilized to investigate the effects of the impact of single millimeter-scale droplets on curved surfaces at room and low temperatures. The influences of the Weber number We, wall temperature, and wall wettability on the dynamics of droplet impact and the characteristics of ice formation are examined. The morphological evolution of droplet impact and the variations of the dimensionless spreading coefficient are analyzed. The results indicate that at high We (We = 277), droplets reach their maximum spread on cold walls in a shorter time than on room-temperature walls, and their peak spreading coefficient is smaller. Upon impact with a cold wall, droplets exhibit a spread–splatter behavior. Low temperatures suppress the oscillatory behavior of droplets on a curved wall. In the case of a hydrophilic wall surface, as the impact We increases from 42 to 277, the impact mode gradually transitions from spread–retract–freeze to spread–splatter–freeze. The maximum spreading coefficient first increases and then decreases with increasing impact We. At high We (We = 277), the wall wettability has a minimal effect on the dynamics of droplet impact and freezing, with a spread–splatter–freeze mode being exhibited for both hydrophobic and hydrophilic walls, and the final freezing morphology is similar.
Models of care for voluntary assisted dying: a qualitative study of Queensland’s approach in its first year of operation
Authors: White Ben P. , Ward Amanda , Feeney Rachel , Ley Greaves Laura , Willmott Lindy
Published: October 2024

Objective Voluntary assisted dying (VAD) began in Queensland in January 2023 but little is known about its practical operation. This research examined models of care for providing VAD in Queensland. Methods Semi-structured interviews were conducted with 24 participants involved with VAD delivery across Queensland’s 16 Health and Hospital Services (HHSs). Participants included HHS VAD Coordinators, nurse practitioners and nurses who acted as administering practitioners, and Queensland VAD Support and Pharmacy Service (QVAD SPS) staff. Results Five themes about Queensland VAD models of care were developed: VAD is accessed almost exclusively through the public sector via HHSs, influenced by a Health Service Directive; local models of care vary; nurses play significant roles facilitating access to and providing VAD; QVAD SPS has been instrumental supporting HHSs and ensuring statewide access as back-up VAD provider; and VAD services need more resourcing. Conclusions The Queensland approach to providing VAD has been largely successful in ensuring patient access across the state. However, it differs from previous Australian VAD models with access predominantly through the public sector, greater roles played by nurse practitioners/nurses, and VAD being provided by QVAD SPS. Under-resourcing and consistency in provision of VAD services remain challenges.
Assessing the population structure and genetic diversity of wheat germplasm with the iPBS-retrotransposons marker system
Authors: Baran Nurettin
Published: October 2024

Context Wheat (Triticum aestivum L.) is an important crop that provides food to millions of people all over the world. Currently, wheat production is limited due to various biotic and abiotic stresses resulting from uneven patterns of climate change. Therefore, it is very important to develop climate-resilient wheat cultivars. Crop genetic diversity allows the scientific community to identify genetic variations that can be utilised in the development of improved cultivars. Aims This study planned to characterise the wheat germplasm with the iPBS-retrotransposons marker system. Methods A total of 30 iPBS-retrotransposons markers were screened and among these, the 12 most polymorphic markers were selected for further analysis. Key results Molecular characterisation yielded a total of 170 bands, of which 143 were polymorphic. A substantial level of genetic diversity was observed (mean effective number of alleles: 1.37, Shannon’s information index: 0.23, gene diversity: 0.35). Maximum genetic distance was observed in G9 and G60 genotypes. Analysis of molecular variance revealed that most genetic variation (95%) occurred within the populations. The model-based structure algorithm divided the studied germplasm into three populations based on their collection regions. Similarly, the neighbour-joining analysis also divided 70 tested wheat genotypes into three populations, whereas principal coordinate analysis divided the evaluated germplasm into four populations. Conclusions This study confirms the iPBS-retrotransposons as an ideal marker for the genetic diversity assessment studies for any crop, especially for wheat. Implications The results presented here will be helpful for the scientific community in the marker-assisted breeding of wheat.
Ad-hoc specialized corpora in translation teaching
Authors: Aragrande Gaia
Published: October 2024

This paper shows how building a specialised corpus of heritage tourism texts (Heritage Tourism Corpus — HT Corpus) represents
the ideal trade-union between the need of developing lingua-cultural competence in a specialized language and training
the ability of translating tourist texts from Italian to English especially when it comes to domain-specific terminology and
cultural-specific items.

The HT Corpus comprises texts from anglophone heritage tourism websites (approx. 1 mln words). It was built by professors at
the University of Bologna as part of an MA course on English for Special Purposes and translation. This paper thus contains a progress
report relaying preliminary findings from the classroom. Within this MA course, the use of the HT Corpus has a twofold aim: (1) letting
students familiarise and investigate the ESP of tourism by perusing the HT Corpus mainly with frequency lists, collocations and keywords;
(2) aiding them in the translation of Italian heritage tourism source texts (STs) into English target texts (TTs).
The challenges of translation and interpretation in international projects
Authors: García Antonio Bueno
Published: October 2024

This work presents a practical perspective on the challenges of translation and interpretation in the context of an
international project. It uses the European Twinning project titled “Support to the Ministry of Higher Education and Scientific Research
for the strengthening of pedagogical competencies of teacher-researchers and the governance capacities of managers” (PAPERS) as a case
study. The unique situations that emerged during this project, from linguistic, cultural, social, political, economic, and even health
perspectives — arising from the impact of the 2019 coronavirus pandemic in its midway development — make it an intriguing subject for
observation within the domains of Translation, Interpretation, Education, and related areas concerning learning methods and the use of new
technologies.
Chapter 11. “Getting personal with you”
Authors: Droz-dit-Busset Olivia , Spilioti Tereza
Published: October 2024

Since the Middle Ages, confession has been one of the ‘most highly valued techniques for producing truth’ (Foucault 1978). While confessional monologues have been researched in reality TV discourse (Lorenzo-Dus 2009; Tolson 2006), the communicative potential of confessional talk for Social Media Influencers has been largely underexplored. This chapter aims to fill this gap by exploring confession as a distinct genre in the communicative repertoire of lifestyle and beauty YouTubers. In this regard, we first map this genre in terms of its key themes, formal features and media production choices. Drawing on Giaxoglou’s (2021) notion of affective positioning, we also examine how the influencers and their audiences are affectively positioned in the discourse of confessional videos through the deployment of verbal, non-verbal, as well as other material (camera) and graphic (emojis) resources. We conclude this chapter by demonstrating how this type of positioning intersects with the production of an authentic selfhood on YouTube.
Where Did It Come From? Where Will It Go?
Authors: Williamson Timothy
Published: October 2024

This chapter is an overview of both the origins of the knowledge-first approach in Knowledge and its Limits and some of the most promising directions in which it is now developing. The first half discusses knowledge-first epistemology in the tradition of Oxford realism, the author’s earlier work on indiscriminability, the relation between knowledge and action, externalism about content and externalism about attitudes, and assertability, and the origin of the phrase ‘knowledge first’. The second half discusses a revised treatment of the relation between knowledge and action, a knowledge-first approach to the psychology of mind reading, formal models of knowledge, and the nature of epistemic norms.
Śrīharṣa on the Indefinability of Knowledge Events
Authors: Das Nilanjan
Published: October 2024

In Sanskrit philosophy, epistemologists were preoccupied with the notion of pramā. A pramā, roughly, is a mental event of learning or knowledge acquisition—an experience or thought in undergoing which an agent learns or comes to know something. Call any such mental event a knowledge event. The twelfth-century Sanskrit philosopher Śrīharṣa argued that knowledge events are indefinable. Any satisfactory (and therefore non-circular) definition of knowledge events will have to include an anti-luck condition that doesn’t appeal back to the notion of learning or knowledge acquisition itself. But there is no such anti-luck condition. Śrīharṣa went on to claim that, given some other assumptions, the indefinability of knowledge events should give us reason to doubt that our ordinary attributions of knowledge events are reliably tracking any sui generis mental kind. This chapter reconstructs Śrīharṣa’s position and explains how it extends to contemporary knowledge-first approaches to epistemology.
How the Brain Makes Knowledge First
Authors: Gordon Robert M
Published: October 2024

To interpret the actions of others, it has been proposed that the brain harnesses its capacity for action planning to test hypothetical ways of generating another agent’s actions. This inverse use of action planning runs concurrently with planning one’s own actions and in the default case is constrained by the same inputs (agent-neutral coding) for self and other. The upshot is that factual input is passed along to the other agent as known facts. Thereby the brain makes knowledge the default epistemic attribution to others and can focus its resources on detecting exceptions. A postscript updates the author’s early work on factive emotions, which anticipated aspects of a knowledge-first epistemology.
Knowledge-First Philosophy of Science
Authors: Bird Alexander
Published: October 2024

This chapter examines the implications of knowledge‐first epistemology for philosophy of science, starting with the idea that belief aims at knowledge. Correspondingly, it claims that scientific belief and science itself aim at scientific knowledge. This implies an account of scientific progress as the accumulation of scientific knowledge. More importantly, it argues that we can also infer an account of scientific evidence: science aims at producing knowledge by making inferences from evidence; science can achieve this if and only if evidence is knowledge. This knowledge‐first equation, E=K, runs counter to empiricist conceptions of evidence and observation as tied to perception. The chapter notes that it provides an answer to problems raised by the Duhem–Quine thesis. It also enables a picture of science that allows that as hypotheses come to be known, the evidential basis of science can become ever more ‘theory‐laden’ in a benign way, allowing for further scientific progress.
Deep learning in template-free de novo biosynthetic pathway design of natural products
Authors: Xie Xueying , Gui Lin , Qiao Baixue , Wang Guohua , Huang Shan , Zhao Yuming , Sun Shanwen
Published: October 2024

Natural products (NPs) are indispensable in drug development, particularly in combating infections, cancer, and neurodegenerative diseases. However, their limited availability poses significant challenges. Template-free de novo biosynthetic pathway design provides a strategic solution for NP production, with deep learning standing out as a powerful tool in this domain. This review delves into state-of-the-art deep learning algorithms in NP biosynthesis pathway design. It provides an in-depth discussion of databases like Kyoto Encyclopedia of Genes and Genomes (KEGG), Reactome, and UniProt, which are essential for model training, along with chemical databases such as Reaxys, SciFinder, and PubChem for transfer learning to expand models’ understanding of the broader chemical space. It evaluates the potential and challenges of sequence-to-sequence and graph-to-graph translation models for accurate single-step prediction. Additionally, it discusses search algorithms for multistep prediction and deep learning algorithms for predicting enzyme function. The review also highlights the pivotal role of deep learning in improving catalytic efficiency through enzyme engineering, which is essential for enhancing NP production. Moreover, it examines the application of large language models in pathway design, enzyme discovery, and enzyme engineering. Finally, it addresses the challenges and prospects associated with template-free approaches, offering insights into potential advancements in NP biosynthesis pathway design.
DynProfiler: a Python package for comprehensive analysis and interpretation of signaling dynamics leveraged by deep learning techniques
Authors: Tsutsui Masato , Okada Mariko
Published: October 2024

Signaling dynamics encode important features and regulatory mechanisms of biological systems, and recent studies have reported the use of simulated signaling dynamics with mechanistic modeling as biomarkers for human diseases. Given the success of deep learning techniques, it is expected that they can extract informative patterns from simulation results more effectively than traditional approaches involving manual feature selection, which can be used for subsequent analyses, such as patient stratification and survival prediction. Here, we propose DynProfiler, which utilizes the entire signaling dynamics, including intermediate variables, as input and leverages deep learning techniques to extract informative features without requiring any labels. Furthermore, DynProfiler incorporates a modern explainable AI solution to provide quantitative time-dependent importance scores for each dynamics. Using simulated dynamics of patients with breast cancer as an example, we demonstrate DynProfiler’s ability to extract high-quality features that can predict mortality risk and identify important dynamics, highlighting upregulated phosphorylated GSK3β as a biomarker for poor prognosis. Overall, this tool can be useful for clinical application, as well as for elucidating biological system dynamics.

Availability and implementation

The DynProfiler Python library is available in GitHub at https://github.com/okadalabipr/DynProfiler.
BioPred: an R package for biomarkers analysis in precision medicine
Authors: Liu Zihuan , Sun Yan , Huang Xin
Published: October 2024

The R package BioPred offers a suite of tools for subgroup and biomarker analysis in precision medicine. Leveraging Extreme Gradient Boosting (XGBoost) along with propensity score weighting and A-learning methods, BioPred facilitates the optimization of individualized treatment rules to streamline subgroup identification. BioPred also enables the identification of predictive biomarkers and obtaining their importance rankings. Moreover, the package provides graphical plots tailored for biomarker analysis. This tool enables clinical researchers seeking to enhance their understanding of biomarkers and patient population in drug development.

Availability and implementation

The package is available at CRAN and https://github.com/deeplearner0731/BioPred.
CyCadas: accelerating interactive annotation and analysis of clustered cytometry data
Authors: Hunewald Oliver , Demczuk Agnieszka , Longworth Joseph , Ollert Markus
Published: October 2024

Motivation

Single cell profiling by cytometry has emerged as a key technology in biology, immunology and clinical-translational medicine. The correct annotation, which refers to the identification of clusters as specific cell populations based on their marker expression, of clustered high-dimensional cytometry data, is a critical step of the analysis. Its accuracy determines the correct interpretation of the biological data. Despite the progress in various clustering algorithms, the annotation of clustered data still remains a manual, time consuming and error-prone task. We developed a user-friendly cluster annotation and differential abundance detection tool that can be applied on data generated with Self Organizing Map clustering algorithms, thus simplifying the annotation process of datasets that consist of hundreds or thousands of clusters.

Results

We present Cytometry Cluster Annotation and Differential Abundance Suite (CyCadas), a semi-automated software tool that facilitates cluster annotation in cytometry data by offering both visual and computational guidance. CyCadas addresses the critical need for efficient and accurate annotation of high-resolution clustered cytometry data, significantly reducing the time needed to perform the analysis compared to both manual gating approaches and manual annotation of clustered data. The tool features a user-friendly interface, visual tools enabling data exploration and automated threshold estimation to separate negative and positive marker expression. It facilitates the definition and annotation of cell phenotypes among multiple clusters in a tree-based data structure. Finally, it calculates the abundance of various cell populations across the conditions with statistical interpretation. It is an ideal resource for researchers aiming to streamline their cytometry workflow.

Availability and implementation

CyCadas is available as open source at: https://github.com/DII-LIH-Luxembourg/cycadas.
Individualized cortical gyrification in neonates with congenital heart disease
Authors: Cromb Daniel , Wilson Siân , Bonthrone Alexandra F , Chew Andrew , Kelly Christopher , Kumar Manu , Cawley Paul , Dimitrova Ralica , Arichi Tomoki , Tournier J Donald , Pushparajah Kuberan , Simpson John , Rutherford Mary , Hajnal Joseph V , Edwards A David , Nosarti Chiara , O’Muircheartaigh Jonathan , Counsell Serena J
Published: October 2024

Congenital heart disease is associated with impaired early brain development and adverse neurodevelopmental outcomes. This study investigated how individualized measures of preoperative cortical gyrification index differ in 142 infants with congenital heart disease, using a normative modelling approach with reference data from 320 typically developing infants. Gyrification index Z-scores for the whole brain and six major cortical areas were generated using two different normative models: one accounting for post-menstrual age at scan, post-natal age at scan and sex, and another additionally accounting for supratentorial brain volume. These Z-scores were compared between congenital heart disease and control groups to test the hypothesis that cortical folding in infants with congenital heart disease deviates from the normal developmental trajectory. The relationships between whole-brain gyrification index Z-scores from the two normative models and both cerebral oxygen delivery and neurodevelopmental outcomes were also investigated. Global and regional brain gyrification was significantly reduced in neonates with congenital heart disease, but not when supratentorial brain volume was accounted for. This finding suggests that whilst cortical folding is reduced in congenital heart disease, it is primarily driven by a reduction in brain size. There was a significant positive correlation between cerebral oxygen delivery and whole-brain gyrification index Z-scores in congenital heart disease, but not when supratentorial brain volume was accounted for. Cerebral oxygen delivery is therefore likely to play a more important role in the biological processes underlying volumetric brain growth than cortical folding. No significant associations between whole-brain gyrification index Z-scores and motor/cognitive outcomes or autism traits were identified in the 70 infants with congenital heart disease who underwent neurodevelopmental assessment at 22-months. Our results suggest that chronic in utero and early post-natal hypoxia in congenital heart disease is associated with reductions in cortical folding that are proportional to reductions in supratentorial brain volume.
Fibroblast-specific TGF-β signaling mediates cardiac dysfunction, fibrosis, and hypertrophy in obese diabetic mice
Authors: Tuleta Izabela , Hanna Anis , Humeres Claudio , Aguilan Jennifer T , Sidoli Simone , Zhu Fenglan , Frangogiannis Nikolaos G
Published: October 2024

Aims

Transforming growth factor (TGF)-β is up-regulated in the diabetic myocardium and may mediate fibroblast activation. We aimed at examining the role of TGF-β-induced fibroblast activation in the pathogenesis of diabetic cardiomyopathy.

Methods and results

We generated lean and obese db/db mice with fibroblast-specific loss of TbR2, the Type 2 receptor-mediating signaling through all three TGF-β isoforms, and mice with fibroblast-specific Smad3 disruption. Systolic and diastolic function, myocardial fibrosis, and hypertrophy were assessed. Transcriptomic studies and in vitro experiments were used to dissect mechanisms of fibroblast activation. Fibroblast-specific TbR2 loss attenuated systolic and diastolic dysfunction in db/db mice. The protective effects of fibroblast TbR2 loss in db/db mice were associated with attenuated fibrosis and reduced cardiomyocyte hypertrophy, suggesting that in addition to their role in fibrous tissue deposition, TGF-β-stimulated fibroblasts may also exert paracrine actions on cardiomyocytes. Fibroblast-specific Smad3 loss phenocopied the protective effects of fibroblast TbR2 loss in db/db mice. Db/db fibroblasts had increased expression of genes associated with oxidative response (such as Fmo2, encoding flavin-containing monooxygenase 2), matricellular genes (such as Thbs4 and Fbln2), and Lox (encoding lysyl oxidase). Ingenuity pathway analysis (IPA) predicted that neurohumoral mediators, cytokines, and growth factors (such as AGT, TGFB1, and TNF) may serve as important upstream regulators of the transcriptomic profile of diabetic mouse fibroblasts. IPA of scRNA-seq data identified TGFB1, p53, MYC, PDGF-BB, EGFR, and WNT3A/CTNNB1 as important upstream regulators underlying fibroblast activation in db/db hearts. Comparison of the transcriptome of fibroblasts from db/db mice with fibroblast-specific Smad3 loss and db/db Smad3 fl/fl controls identified Thbs4 [encoding thrombospondin-4 (TSP-4), a marker of activated fibroblasts] as a candidate diabetes-induced fibrogenic mediator. However, in vitro experiments showed no significant activating effects of matricellular or intracellular TSP-4 on cardiac fibroblasts.

Conclusion

Fibroblast-specific TGF-β/Smad3 signaling mediates ventricular fibrosis, hypertrophy, and dysfunction in Type 2 diabetes.
Familial risk of myocardial infarction with non-obstructive and obstructive coronary arteries: a nation-wide cohort study
Authors: Hakansson Felicia H K , Svensson Per , Pettersson Hans J , Ehrenborg Ewa , Spaak Jonas , Nordenskjold Anna M , Eggers Kai M , Tornvall Per
Published: October 2024

Aims

The familial risk among patients with myocardial infarction with non-obstructive coronary arteries (MINOCA) is unknown. Previous studies of family history in myocardial infarction (MI) have not made a distinction between MINOCA and MI due to coronary artery disease (MI-CAD), based on angiographic findings. We therefore sought to investigate familial risk of MI without and with obstructive coronary arteries.

Methods and results

Register-based cohort study with a total of 15 462 MINOCA cases, 204 424 MI-CAD cases, 38 220 control subjects without MI, and with non-obstructive coronary arteries. First-degree relatives were identified in 1995–2020. Cox proportional hazard regression models were used to compare familial risk in MINOCA and MI-CAD with control subjects. During a mean follow-up of 8.1 ± 4.2 years, MINOCA occurred in 1.0% of first-degree relatives with MINOCA whereas MI-CAD occurred in 9.7% of first-degree relatives of MINOCA. The age- and sex-adjusted hazard ratio (HR) for a MINOCA relative experiencing MINOCA and MI-CAD, compared to control subjects, was 0.99 [95% confidence interval (CI) 0.80–1.23] and 1.10 (95% CI 1.03–1.18), respectively. During a mean follow-up of 8.5 ± 4.8 years, MI-CAD occurred in 12.2% of first-degree relatives with MI-CAD with age- and sex-adjusted HR 1.43 (95% CI 1.37–1.49).

Conclusion

No increased familial risk of MINOCA was observed for MINOCA patients whereas there was an increased familial risk for MI-CAD when compared to control subjects. These results may indicate that genetic factors and shared environmental factors within a family leading to CAD are important also for MINOCA, thus MI-CAD and MINOCA could share underlying mechanisms.
Microbiome Geographic Population Structure (mGPS) Detects Fine-Scale Geography
Authors: Zhang Yali , McCarthy Leo , Ruff Emil , Elhaik Eran
Published: October 2024

Over the past decade, sequencing data generated by large microbiome projects showed that taxa exhibit patchy geographical distribution, raising questions about the geospatial dynamics that shape natural microbiomes and the spread of antimicrobial resistance genes. Answering these questions requires distinguishing between local and nonlocal microorganisms and identifying the source sites for the latter. Predicting the source sites and migration routes of microbiota has been envisioned for decades but was hampered by the lack of data, tools, and understanding of the processes governing biodiversity. State-of-the-art biogeographical tools suffer from low resolution and cannot predict biogeographical patterns at a scale relevant to ecological, medical, or epidemiological applications. Analyzing urban, soil, and marine microorganisms, we found that some taxa exhibit regional-specific composition and abundance, suggesting they can be used as biogeographical biomarkers. We developed the microbiome geographic population structure, a machine learning–based tool that utilizes microbial relative sequence abundances to yield a fine-scale source site for microorganisms. Microbiome geographic population structure predicted the source city for 92% of the samples and the within-city source for 82% of the samples, though they were often only a few hundred meters apart. Microbiome geographic population structure also predicted soil and marine sampling sites for 86% and 74% of the samples, respectively. We demonstrated that microbiome geographic population structure differentiated local from nonlocal microorganisms and used it to trace the global spread of antimicrobial resistance genes. Microbiome geographic population structure's ability to localize samples to their water body, country, city, and transit stations opens new possibilities in tracing microbiomes and has applications in forensics, medicine, and epidemiology.
Sharp decline in male fertility in F2 hybrids of the female-heterogametic silk moth Bombyx
Authors: Matsukawa Kana , Kato Yasuko , Yoshida Aya , Onishi Hisaka , Nakano Sachiko , Itoh Masanobu , Takano-Shimizu-Kouno Toshiyuki
Published: October 2024

Sexual selection drives rapid evolution of morphological, physiological, and behavioral traits, especially in males, and it may also drive the rapid evolution of hybrid male sterility. Indeed, the faster male theory of speciation was once viewed as a major cause of Haldane's rule in male-heterogametic XY taxa, but is increasingly being replaced by the genetic conflict hypothesis partly because it cannot explain the faster evolution of hybrid female sterility in female-heterogametic ZW taxa. The theory nonetheless predicts that there should be more genes for hybrid male sterility than for hybrid female sterility even in such taxa, but this remains untested. Thus, finding evidence for the faster male theory of reproductive isolation beyond the F1 generation in ZW systems still represents a challenge to studying the impact of sexual selection. In this study, we examined F2 hybrids between the domesticated silkworm Bombyx mori and the wild silk moth Bombyx mandarina, which have ZW sex determination. We found that although only females showed reduced fertility in the F1 generation, the F2 hybrid males had a significant reduction in fertility compared with the parental and F1 males. Importantly, 27% of the F2 males and 15% of the F2 females were completely sterile, suggesting the presence of recessive incompatibilities causing male sterility in female-heterogametic taxa.
The distribution of beneficial mutational effects between two sister yeast species poorly explains natural outcomes of vineyard adaptation
Authors: Longan Emery R , Fay Justin C
Published: October 2024

Domesticated strains of Saccharomyces cerevisiae have adapted to resist copper and sulfite, 2 chemical stressors commonly used in winemaking. S. paradoxus has not adapted to these chemicals despite being consistently present in sympatry with S. cerevisiae in vineyards. This contrast could be driven by a number of factors including niche differences or differential access to resistance mutations between species. In this study, we used a comparative mutagenesis approach to test whether S. paradoxus is mutationally constrained with respect to acquiring greater copper and sulfite resistance. For both species, we assayed the rate, effect size, and pleiotropic costs of resistance mutations and sequenced a subset of 150 mutants. We found that the distributions of mutational effects displayed by the 2 species were similar and poorly explained the natural pattern. We also found that chromosome VIII aneuploidy and loss of function mutations in PMA1 confer copper resistance in both species, whereas loss of function mutations in REG1 was only a viable route to copper resistance in S. cerevisiae. We also observed a de novo duplication of the CUP1 gene in S. paradoxus but not in S. cerevisiae. For sulfite, loss of function mutations in RTS1 and KSP1 confer resistance in both species, but mutations in RTS1 have larger effects in S. paradoxus. Our results show that even when available mutations are largely similar, species can differ in the adaptive paths available to them. They also demonstrate that assays of the distribution of mutational effects may lack predictive insight concerning adaptive outcomes.
Species assignment from seal diet samples using shape analyses in a machine learning framework
Authors: Mion Monica , Berg Florian , Saltalamacchia Francesco , Bartolino Valerio , Lövgren Johan , Bergenius Nord Mikaela , Gilljam David , Blass Martina , Lundström Karl
Published: October 2024

The identification and quantification of prey ingested is a limiting factor in trophic ecology studies and is fundamental for assessing the impact of a predator on prey populations. Vendace (Coregonus albula) and whitefish (C. lavaretus) are two congeneric species, which are commonly preyed on by Baltic ringed seals (Pusa hispida). The otoliths of these two species are, however, very similar and distinguishing between them in the seal diet using visual inspection has so far been challenging. Here, otolith shape outline analyses were used in combination with machine learning techniques to discriminate between eroded vendace and whitefish otoliths from ringed seal diet samples. An experiment of in vitro digestion of the otoliths was performed to train a machine learning model. Our model is able to self-assign known digested otoliths back to their species of origin with >90% accuracy. Furthermore, 89% (N = 690) of the otoliths collected from digestive tract samples could be successfully assigned to species level, i.e. vendace or whitefish. This method is readily applicable for improved understanding of ringed seal feeding habits and predator–prey interactions, as well as large-scale applications to generate seal-predation matrix inputs for stock assessments of vendace and whitefish. Further development of the machine learning techniques to discriminate between prey species in seal and other piscivorous diets is strongly encouraged.
Ontological Security and Climate Policy in Jair Bolsonaro’s Brazil: Understanding the Emotional Underpinnings of Environmental Destruction
Authors: Maitino Martin , Vieira Marco
Published: October 2024

In this paper, we examine Brazil's climate/environmental discourse and policy during Jair Bolsonaro's administration (2019–2022), focusing on the relationship between the state leader and the powerful agricultural sector. We address the following question: What factors drove and sustained Bolsonaro's strong connection with Brazilian agribusiness, leading to the normalization of policies and discourses that undermined Brazil's environmental commitments and stance in global climate negotiations? We argue that, by mobilizing and embracing collective experiences and symbols of Brazilian agribusiness and confronting those who were seen as threats to these, Jair Bolsonaro's administration promoted a fantasized and emotionally charged conception of Brazil's national identity that merged the nation to the symbolic orientation of a sub-national group. The inter-subjective constitution of ontological security, through emotional attachments, was the outcome of a temporary symbiosis between these two state/societal actors which embraced and realized a shared fantasy, leading to the normalization of a set of climate policies, discourses, and practices. Drawing on Lacan, we propose that the enjoyment (jouissance), deriving from the inter-relationship between the pursuit of a desired fantasy of nationhood and the fixation on those who were perceived as obstacles to it, was the driving force behind the ontological security aspirations and the accompanying political projects of both state actors and the agricultural sector that persisted even after Bolsonaro's departure from the presidency.
On the Indexes in Some Continental Editions of Milton’s Pro Populo Anglicano Defensio and Salmasius’s Defensio Regia, with an Addendum on the Publisher Adrienne Brillet
Authors: Vozar T M
Published: October 2024

This article examines the indexes in some Continental editions of John Milton’s Pro populo Anglicano defensio and Claudius Salmasius’s Defensio Regia. Previously little noticed, the indexes are treated here both as a marketing device for publishers and as a guide for the perusal of the polemics. The authorship of the index to the Pro populo Anglicano defensio is considered in relation to the bibliography of that work as well as Milton’s attitudes toward indexing. The Miltonic index is shown to possess a rhetorical construction in its own right and to provide a means for readers to easily access the main points of the controversy. The later Salmasian index is approached similarly. An addendum highlights the career of the Parisian publisher Adrienne Brillet, who printed both indexes in a unique joint edition of the polemics, with special attention to her dealings with Salmasius.
MIR164B ensures robust Arabidopsis leaf development by compensating for compromised POLYCOMB REPRESSIVE COMPLEX2 function
Authors: Maugarny Aude , Vialette Aurélie , Adroher Bernard , Sarthou Anne-Sophie , Mathy-Franchet Nathalie , Azzopardi Marianne , Nicolas Antoine , Roudier François , Laufs Patrick
Published: October 2024

Robustness is pervasive throughout biological systems, enabling them to maintain persistent outputs despite perturbations in their components. Here, we reveal a mechanism contributing to leaf morphology robustness in the face of genetic perturbations. In Arabidopsis (Arabidopsis thaliana), leaf shape is established during early development through the quantitative action of the CUP-SHAPED COTYLEDON2 (CUC2) protein, whose encoding gene is negatively regulated by the co-expressed MICRORNA164A (MIR164A) gene. Compromised epigenetic regulation due to defective Polycomb Repressive Complex 2 (PRC2) function results in the transcriptional derepression of CUC2 but has no impact on CUC2 protein dynamics or early morphogenesis. We solve this apparent paradox by showing that compromised PRC2 function simultaneously derepresses the expression of another member of the MIR164 gene family, MIR164B. This mechanism dampens CUC2 protein levels, thereby compensating for compromised PRC2 function and canalizing early leaf morphogenesis. Furthermore, we show that this compensation mechanism is active under different environmental conditions. Our findings shed light on how the interplay between different steps of gene expression regulation can contribute to developmental robustness.
Integrated approaches in nutraceutical delivery systems: optimizing ADME dynamics for enhanced therapeutic potency and clinical impact
Authors: Paul-Chima Ugwu Okechukwu , Ugwu Chinyere Nneoma , Alum Esther Ugo
Published: October 2024

Objectives

Nutraceuticals is a general term for a variety of bioactive compounds such as polyphenols and omega-3 fatty acids which have shown promising ability in the field of health. Efficacy of these drugs somewhat relies on their absorption, distribution, metabolism, and excretion (ADME) processes in the body.

Methods

This review provides a comprehensive understanding of ADME principles blended with the pharmacological insights into design customized nutraceutical interventions dependent on individual well-being. This review discusses absorption dynamics starting from ingestion and excretion and further examines how they relate to a therapeutic outcome. In addition, special focus is paid to breakthrough methods like artificial intelligence and multidisciplinary cooperations among other ways of improving nutraceutical science. Both nanotechnology and encapsulation techniques, together with other novel approaches, aim at improving the bioavailability of foods. This is important for the continuing advancements in food engineering.

Key findings

Any combination of such strategies will ensure effectiveness of nutraceuticals in personalized medicine, which in turn enables better lifestyle choices for the population.

Conclusions

It is crucial to add ADME-understanding to pharmacology-based insights into make nutraceutical adjustments according to the situation. Innovations in the forms of AI and multidisciplinary cooperation remain crucial in the progress of nutraceutical science. Methods like nanotechnology and encapsulation are powerful tools of improving bioavailability and tailor-made medicine, which in turn, will be responsible for healthier lives.
Repetitive Transcranial Magnetic Stimulation (rTMS) Treatment Reduces Variability in Brain Function in Schizophrenia: Data From a Double-Blind, Randomized, Sham-Controlled Trial
Authors: Schifani Christin , Hawco Colin , Daskalakis Zafiris J , Rajji Tarek K , Mulsant Benoit H , Tan Vinh , Dickie Erin W , Moxon-Emre Iska , Blumberger Daniel M , Voineskos Aristotle N
Published: October 2024

Background/Hypothesis

There is increasing awareness of interindividual variability in brain function, with potentially major implications for repetitive transcranial magnetic stimulation (rTMS) efficacy. We perform a secondary analysis using data from a double-blind randomized controlled 4-week trial of 20 Hz active versus sham rTMS to dorsolateral prefrontal cortex (DLPFC) during a working memory task in participants with schizophrenia. We hypothesized that rTMS would change local functional activity and variability in the active group compared with sham.

Study Design

83 participants were randomized in the original trial, and offered neuroimaging pre- and post-treatment. Of those who successfully completed both scans (n = 57), rigorous quality control left n = 42 (active/sham: n = 19/23), who were included in this analysis. Working memory-evoked activity during an N-Back (3-Back vs 1-Back) task was contrasted. Changes in local brain activity were examined from an 8 mm ROI around the rTMS coordinates. Individual variability was examined as the mean correlational distance (MCD) in brain activity pattern from each participant to others within the same group.

Results

We observed an increase in task-evoked left DLPFC activity in the active group compared with sham (F1,36 = 5.83, False Discovery Rate (FDR))-corrected P = .04). Although whole-brain activation patterns were similar in both groups, active rTMS reduced the MCD in activation pattern compared with sham (F1,36 = 32.57, P < .0001). Reduction in MCD was associated with improvements in attention performance (F1,16 = 14.82, P = .0014, uncorrected).

Conclusions

Active rTMS to DLPFC reduces individual variability of brain function in people with schizophrenia. Given that individual variability is typically higher in schizophrenia patients compared with controls, such reduction may “normalize” brain function during higher-order cognitive processing.
Multi-defense pathways against electrophiles through adduct formation by low molecular weight substances with sulfur atoms
Authors: Kumagai Yoshito , Abiko Yumi , Akiyama Masahiro , Unoki Takamitsu , Shinkai Yasuhiro
Published: October 2024

There is a variety of electrophiles in the environment. In addition, there are precursor chemicals that undergo metabolic activation by enzymes and conversion to electrophiles in the body. Although electrophiles covalently bind to protein nucleophiles, they also form adducts associated with adaptive or toxic responses. Low molecular weight compounds containing sulfur are capable of blocking such adduct formation by capturing the electrophiles. In this review, we present our findings on the capture and inactivation of electrophiles by: (i) intracellular glutathione, (ii) reactive sulfur species, and (iii) extracellular cysteine (formed during the production of sulfur adducts). These actions not only substantially suppress electrophilic activity but also regulate protein adduct formation.
Patulin Inhibition of Specific Apple Microbiome Members Uncovers Hanseniaspora uvarum as a Potential Biocontrol Agent
Authors: Eagan Justin L. , Digman Evan R. , den Boon Martijn , Regalado Roberto , Rawa Mira S. A. , Hull Christina M. , Keller Nancy P.
Published: October 2024

Penicillium expansum is a major postharvest pathogen of apples, causing loss in fruits through tissue damage, as well as in apple products due to contamination with the mycotoxin patulin. During infections, patulin is a cultivar-dependent virulence factor that facilitates apple lesion development. Patulin also has characterized antimicrobial activity and is important for inhibiting other competitive phytopathogens, but the role of this inhibitory activity has not been investigated in the context of the apple microbiome. In our current study, we isolated 68 apple microbiota and characterized their susceptibility to P. expansum extracts. We found gram-negative bacteria and basidiomycete yeast to demonstrate largely patulin-specific growth inhibition compared with gram-positive and ascomycete isolates. From co-cultures, we identified a Hanseniaspora and Gluconobacter pairing that reduced P. expansum biomass and found that H. uvarum alone is sufficient to reduce apple disease progression in vivo. We investigated possible mechanisms of H. uvarum biocontrol activity and found modest inhibition on apple puree plates, as well as a trend toward lower patulin levels at the wound site. Active biocontrol activity required live yeast, which was also effective in controlling Botrytis cinerea apple infections. Lastly, we explored the breadth of H. uvarum biocontrol activity with over 30 H. uvarum isolates and found consistent inhibition of P. expansum apple disease.
Pyriofenone Interacts with the Major Facilitator Superfamily Transporter of Phytopathogenic Fungi to Potentially Control Tea Leaf Spot Caused by Lasiodiplodia theobromae
Authors: Zhang Xiaolin , Liu Fenghua , Li Dongxue , Guo Di , Ma Yue , Zhou Jing-Jiang , Wang Delu , Chen Zhuo
Published: October 2024

Tea leaf spot caused by Lasiodiplodia theobromae is a newly discovered fungal disease in southwest China. Due to a lack of knowledge of its epidemiology and control strategies, the disease has a marked impact on tea yield and quality. Pyriofenone is a new fungicide belonging to the aryl phenyl ketone fungicide group, which has shown marked efficacy in controlling various fungal diseases. However, its mechanism of action is not yet understood. This study found that pyriofenone exhibits strong in vitro inhibitory activity against various phytopathogenic fungi. Specifically, it showed strong inhibitory activity against L. theobromae, with a half-maximal effective concentration (EC50) value of 0.428 μg/ml determined by measuring the mycelial growth rate. Morphological observations, using optical, scanning electron, and transmission electron microscopy, revealed that pyriofenone induces morphological abnormalities in L. theobromae hyphae. At lower doses, the hyphae became swollen, the distance between septa decreased, and the hyphal growth rate slowed. At higher doses and longer exposures, the hyphae collapsed. Transcriptomic and bioinformatic analyses indicated that pyriofenone can affect the expression of genes related to membrane transporters. Homology modeling suggested that pyriofenone may bind to a candidate target protein of the major facilitator superfamily transporter, with a free binding energy of −7.1 kcal/mol. This study suggests that pyriofenone may potentially regulate the transport of metabolites in L. theobromae, thus affecting hyphal metabolism and interfering with hyphal growth. Pyriofenone exhibits in vitro inhibitory activity against various tea foliar pathogens and holds promise for future applications to the control of tea foliar diseases.