bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sympathetic Stimulation Can Compensate for Hypocalcaemia-Induced Bradycardia in Human and Rabbit Sinoatrial Node Cells
Authors: Linder Moritz , Stary Tomas , Bitay Gergő , Nagy Norbert , Loewe Axel 
Published: August 2024

AbstractRegular activation of the heart originates from cyclic spontaneous depolarisations of sinoatrial node cells (SANC). Variations in electrolyte levels, commonly observed in haemodialysis (HD) patients, and the autonomic nervous system (ANS) profoundly affect the SANC function. Thus, we investigated the effects of hypocalcaemia and sympathetic stimulation on SANC beating rate (BR).The β-adrenergic (β-AR) signalling cascade, as described by Behar et al., was incorporated into the SANC models of Severi et al. (rabbit) and Fabbri et al. (human). Simulations were conducted across various extracellular calcium ([Ca2+]o) (0.6 to 1.8 mM) and isoprenaline concentrations [ISO] (0 to 1000 nM) for a sufficient time to allow transient oscillations to equilibrate and reach a limit cycle. The β-AR cell response of the extended models was validated against new Langendorff-perfused rabbit heart experiments and literature data.The extended models revealed that decreased [Ca2+]onecessitated an exponential-like increase in [ISO] to restore the basal BR. Specifically, at 1.2 mM [Ca2+]o, the Severi and Fabbri model required 15.5 and 7.3 nM [ISO], respectively, to restore the initial BR. Further reduction of [Ca2+]oto 0.6 mM required 60.0 and 41.7 nM [ISO] to compensate for hypocalcaemia. A sudden loss of sympathetic tone at low [Ca2+]oresulted in extreme bradycardia or even loss of automaticity within seconds.These findings suggest that hypocalcaemic bradycardia can be compensated for by an elevated sympathetic tone. The integration of the β-AR pathways led to a logarithmic BR increase and offers insights into potential pathomechanisms underlying sudden cardiac death (SCD) in HD patients.Key Points- We extended the sinoatrial node cell (SANC) models of Severi et al. (rabbit) and Fabbri et al. (human) with the β-adrenergic (β-AR) signalling cascade Behar et al. described.- Simulations were conducted across various extracellular calcium ([Ca2+]o) (0.6 to 1.8 mM) and isoprenaline concentrations [ISO] (0 to 1000 nM) to mimic conditions in haemodialysis patients.- An exponential-like increase in [ISO] compensated for hypocalcaemia-induced bradycardia in both models, while inter-species differences lead to more sensitivity of the extended Fabbri model towards hypocalcaemia and increased sympathetic tone.- The extended models may help to further understand the pathomechanisms of several cardiovascular diseases affecting pacemaking, such as the high occurrence of sudden cardiac death (SCD) in chronic kidney disease (CKD) patients.
How do self-fertilising and facultative sexual populations differ in mutation accumulation?
Authors: Kopčak Dominik , Hartfield Matthew 
Published: August 2024

AbstractSelf-fertilisation and asexual reproduction are both hypothesised to lead to long-term extinction due to inefficient selection acting against deleterious mutations. Self-fertilisation can counter these effects through creating homozygous genotypes and purging deleterious mutations. Although complete asexuality lacks meiotic gene exchange, mitotic gene conversion is a mechanism for creating homozygous regions that could limit deleterious mutation accumulation in a similar manner to self-fertilisation. Here, we compare mutation accumulation in self-fertilising and facultative sexual populations subject to mitotic gene conversion, to determine if the latter can purge deleterious mutations in an analogous manner to self-fertilisation. We first show analytically that this purging is most effective with high levels of asexuality and gene conversion, and when deleterious mutations are recessive. We further show using simulations that, when mitotic gene conversion becomes sufficiently high in obligate asexuals, there is a sudden reduction in the mutation count and a jump in homozygosity, reflecting mutation purging. However, this mechanism is not necessarily as efficient at purging compared to high levels of self-fertilisation, and elevated rates of mitotic gene conversion seem to be needed compared to empirical estimates. Hence, while mitotic gene conversion can remove recessive deleterious mutations, self-fertilisation seems to be a more effective mechanism for doing so.Teaser TextAsexuality has been argued to be an evolutionary ‘dead end’, due to a lack of gene exchange causing inefficient selection acting against deleterious mutations. It has been proposed that asexuals can counter these negative effects through mitotic gene conversion, which exposes mutations to selection within individual lineages. Here, we theoretically investigate how effective this mechanism is. We compare results to those obtained when individuals reproduce by self-fertilisation, which has similar effects on exposing deleterious variants. While mitotic gene conversion can be effective in removing recessive deleterious mutations, high rates are required and it is not always as effective as selfing.
Two-Photon NAD(P)H-FLIM reveals unperturbed energy metabolism ofAscaris suumlarvae, in contrast to host macrophages upon artemisinin derivatives exposure
Authors: Musimbi Zaneta D. , Kundik Arkadi , Krücken Jürgen , Hauser Anja E. , Rausch Sebastian , Seeberger Peter H. , Niesner Raluca , Leben Ruth , Hartmann Susanne 
Published: August 2024

AbstractSoil-transmitted helminths (STH) are widespread, withAscaris lumbricoidesinfecting millions globally. Malaria and STH co-infections are common in co-endemic regions. Artemisinin derivatives (ARTs)—artesunate, artemether, and dihydroartemisinin—are standard malaria treatments and are also known to influence the energy metabolism of parasites, tumors, and immune cells. Herein, we explore the potential of ARTs to influence ascariasis either by directly affecting larvae or indirectly by modifying macrophage responses.Ascaris suumthird-stage larvae and porcine IL-4 polarised (M2-like) macrophages were exposed to ARTsin vitro, and their metabolism was evaluated using two-photon NAD(P)H-FLIM. Both larvae and M2-like macrophages exhibited a steady-state bioenergetic profile of high oxidative phosphorylation and low anaerobic glycolysis. InA. suumlarvae, two metabolically distinct regions were identified, with particularly high DUOX activity in the pharynx compared to the midgut. The metabolic profile of both larval regions were, however, unperturbed by ARTs exposure. In contrast, exposure of M2-like macrophages to ARTs induced a metabolic shift towards high anaerobic glycolysis and reduced metabolic activity, suggesting a possible indirect effect of ARTs on the helminth infection. Overall, two-photon NAD(P)H-FLIM proved to be a powerful tool for studying specific metabolic pathways inAscarislarvae and host macrophages, offering valuable insights into the metabolic mechanisms of drug action on both parasite and host.
Simulation study of factors affecting the accuracy of transcriptome models under complex environments
Authors: Eiju Dan , Hashida Yoichi , Maeda Taro , Nagano Atsushi J. 
Published: August 2024

AbstractCharacterization of molecular responses in real and complex field environments is essential for understanding the environmental response of plants. Field transcriptomics, i.e. modelling large amounts of transcriptomic and meteorological data, is the most comprehensive method of studying gene expression dynamics in complex environments. However, it is not clear what factors influence the accuracy of field transcriptome models. In this study, a novel simulation system was developed. Using the system, we performed a large-scale simulation to reveal the factors affecting the accuracy of the models. We found that the factors that had the greatest impact on the accuracy are, in order of importance, the expression pattern of the gene, the number of samples in the training data, the diurnal coverage of the training data, and the temperature coverage of the training data. Validation using actually measured transcriptome data showed similar results to the simulations. Our simulation system and the analysis results will be helpful for developing efficient sampling strategies for training data and for generating simulated data for benchmarking new modelling methods. It will also be valuable to dissect the relative importance of various factors behind transcriptome dynamics in the real environment.Key messageNovel simulation system revealed how prediction accuracy of field transcriptome was affected by number and diversity of training data
Social complexity during early development has long-term effects on neuroplasticity in the social decision-making network
Authors: Loggia Océane La , Antunes Diogo F. , Aubin-Horth Nadia , Taborsky Barbara 
Published: August 2024

AbstractIn social species, early social experience shapes the development of appropriate social behaviours during conspecific interactions referred to as social competence. However, the underlying neuronal mechanisms responsible for the acquisition of social competence are largely unknown. One key candidate to influence social competence is neuroplasticity, which functions to restructure neural networks in response to novel experiences or alterations of the environment. One important mediator of this restructuring is the neurotrophin BDNF, which is well conserved among vertebrates. We studied the highly social fishNeolamprologus pulcher, in which the impact of early social experience on social competence has been previously shown. We investigated experimentally how variation of the early social environment impacts markers of neuroplasticity by analysing the relative expression of thebdnfgene and its receptorsp75NTRandTrkBacross nodes of the Social Decision-Making Network. In fish raised in larger groups,bdnfandTrkBwere upregulated in the anterior tuberal nucleus, compared to fish raised in smaller groups, whileTrkBwas downregulated andbdnfwas upregulated in the lateral part of the dorsal telencephalon. In the preoptic area (POA), all three genes were upregulated in fish raised in large groups, suggesting that early social experiences might lead to changes of the neuronal connectivity in the POA. Our results highlight the importance of the early social experience in programming the constitutive expression of neuroplasticity markers, suggesting that the effects of early social experience on social competence might be due to changes in neuroplasticity.
Computational screening of potential AT1R inhibitors fromNigella sativafor diabetic-hypertensive therapy
Authors: Tuli Tonima Rahman , Mia Mijan , Ulla SK Nazmul , Gazi Md. Shamim , Hasan Md. Nazmul , Biswas Partha , Tareq Md. Mohaimenul Islam 
Published: August 2024

AbstractHypertension, frequently coexists with Type 2 diabetes mellitus, causes due to Angiotensin II. Inhibiting Angiotensin II by targeting AT1R can potentially improve hypertension-related complications in patients with T2DM. In this study, we perform an in-silico screening based on molecular docking and molecular dynamic of 305 compounds of Nigella sativa against Angiotensin-II Type1 Receptor (AT1R). Molecular docking studies were conducted to investigate the binding affinities of the selected ligands with the target receptor and compared against the Losartan (control drug). Top 5 ligands were selected based on binding affinity. Subsequently, we conducted an ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) profiling to assess their pharmacokinetic and safety profiles. Our findings revealed two promising ligands Beta-amyrin (CID-73145) and Taraxerol (CID-92097), which exhibited strong binding affinities and favorable pharmacological profiles with no signs of acute toxicity. The molecular dynamic simulations (MD) including RMSD, RMSF, and MMGBSA binding free energy results showed that selected two ligands bind to AT1R more proficiently with good stability over 100 ns. The computational study serves as a foundational basis for subsequent laboratory and clinical research aimed at identifying selective, potent, and less toxic diabetic-hypertensive therapy targeting AT1R.
Immunological memory in a teleost fish: common carp IgM+B cells differentiate into memory and plasma cells
Authors: Chan Justin Tze Ho , Picard-Sánchez Amparo , Dedić Neira , Majstorović Jovana , Rebl Alexander , Holzer Astrid Sibylle , Korytář Tomáš 
Published: August 2024

AbstractFrom ancient cold-blooded fishes to mammals, all vertebrates are protected by adaptive immunity, and retain immunological memory. Although immunologists can demonstrate these phenomena in all fish, the responding cells remain elusive for lack of defining markers and tools to study them. Fundamentally, we posited that it is longevity that defines a memory cell like how antibody production defines a plasma cell. We infected the common carp withSphaerospora molnari, a cnidarian parasite which causes seasonal outbreaks to which no vaccine is available. B cells proliferated and expressed gene signatures of differentiation. Despite a half-year gap between EdU labeling and sampling, B cells retained the thymidine analogue, suggesting that these are at least six-month-old resting memory cells stemming from proliferating precursors. Additionally, we identified a lymphoid organ-resident population expressing exceptional levels of IgM as plasma cells. Thus, teleost fish produce the lymphocytes key to vaccination success and long-term disease protection, and immunological memory is universal and universally demonstrable.
ABC-seq expands small RNAs content with randomized adapter pools operation
Authors: Yu Huahang , Ye Mengying , Guo Yingying , Sun Yating , Cao Ke , zhang Dexin , Chen Feng , Zhao Yongxi 
Published: August 2024

AbstractCellular gene expression is widely regulated by a large number of small RNAs (smRNAs). The ability to in-depth analysis of smRNAs content is vital for comprehensive understanding their architecture and function. However, experimental approaches capable of realizing both high-content and low-byproduct sequencing analysis are lacking. Here, we develop ABC-seq (randomizedAdapter pool dimerBlocking andCleavage in smRNA sequencing). This method designs randomized adapter pools to recognize more smRNA species. Moreover, it operates two product structure-differentiated enzymatic reactions to maximally eliminate the byproducts of adapter dimers. Using ABC-seq, we detected a broader range of smRNAs including miRNAs, scRNAs, and snoRNAs in rat hypertrophic cardiomyocytes. Upon further analysis of miRNAs, we detected 66 more miRNAs compared to the control method, providing new insights into smRNA-directed gene regulation mechanisms. Furthermore, we revealed cancer drug response -associated smRNAs and uncovered their pivotal role in immune response modulation in non-small cell lung cancer. ABC-seq represents an evolutionary strategy for reshaping the smRNA landscape boundaries and paves the way for a deeper understanding of complex gene regulation networks.
Epigenetic control of commensal induced Th2 Responses and Intestinal immunopathology
Authors: Sangani Kishan A. , Parker Morgan E. , Anderson Hope D. , Chen Li , Pandey Surya P. , Pierre Joseph F. , Meisel Marlies , Riesenfeld Samantha J. , Hinterleitner Reinhard , Jabri Bana 
Published: August 2024

SummaryUnderstanding the initiation of T-helper (Th)-2 immunity is crucial for addressing allergic diseases that have been linked to the commensal microbiota. However, Th2 responses are notably absent from known host-microbiota intestinal immune circuits. Notably, the commensal protistTritrichomonasinduces a transient innate ILC2 circuit rather than a chronic Th2 circuit. Canonical Th2 responses rely on the induction of IL-4 production by innate cells. This study shows that the absence ofTet2, a DNA demethylase, reprograms naïve T cells to autonomously produce IL-4 upon T cell receptor stimulation, bypassing the need for IL-4 from innate cells for Th2 differentiation. Loss of this checkpoint induces chronic Th2 responses toTritrichomonas, associated with IL-25-dependent barrier dysfunction and increased susceptibility to allergic pathology in response to dietary antigens.Sentence SummaryRegulation of cell autonomous IL-4 in T cells is critical to prevent dysregulated Th2 immunity to commensals and predisposition to allergy.
Characterization of muscle growth and sarcomere branching in the striated musculature ofC. elegans
Authors: Fazyl A , Anbu A , Kollbaum S , Conklin E , Schroeder N , Vidal-Gadea AG 
Published: August 2024

ABSTRACTStriated muscles are essential for locomotion and survival. Their function and structure are highly conserved across taxa. Muscles are highly plastic. Muscle growth can occur through several distinct processes including developmental, allometric, and hypertrophic growth. Additionally, pathological conditions like Duchenne Muscular Dystrophy (DMD) can lead to abnormal muscle growth. While human muscle studies have revealed complex structural adaptations such as sarcomere branching, these processes remain less explored in model organisms likeCaenorhabditis elegans.In this study, we present an anatomical characterization of muscle growth inC. elegansunder various conditions that parallel those in mammalian systems. We examined developmental, allometric, and hypertrophic growth, as well as muscle atrophy in a DMD model,dys-1(eg33). We find thatC. elegansmuscles undergo growth patterns similar to those observed in mammals, with region-specific increases in myocyte size, sarcomere number, and band widths under different conditions. Moreover, we report for the first time the presence of sarcomere branching and splitting inC. elegansmuscles, phenomena previously described only in vertebrates and Drosophila.We further report that sarcomere branching is modulated by environmental conditions and pathological states, with increased branching in worms raised swimming and reduced branching in dystrophic muscles. These findings provide new insights into the mechanisms of muscle adaptation and highlight the potential ofC. elegansas a model for studying muscle pathologies like DMD, particularly during periods of rapid growth.
Novel of statistical quality control development and econometric applications
Authors: Areepong Yupaporn , Sukparungsee Saowanit 
Published: August 2024

PurposeThe purpose of this paper is to investigate and review the impact of the use of statistical quality control (SQC) development and analytical and numerical methods on average run length for econometric applications.Design/methodology/approachThis study used several academic databases to survey and analyze the literature on SQC tools, their characteristics and applications. The surveys covered both parametric and nonparametric SQC.FindingsThis survey paper reviews the literature both control charts and methodology to evaluate an average run length (ARL) which the SQC charts can be applied to any data. Because of the nonparametric control chart is an alternative effective to standard control charts. The mixed nonparametric control chart can overcome the assumption of normality and independence. In addition, there are several analytical and numerical methods for determining the ARL, those of methods; Markov Chain, Martingales, Numerical Integral Equation and Explicit formulas which use less time consuming but accuracy. New ideas of mixed parametric and nonparametric control charts are effective alternatives for econometric applications.Originality/valueIn terms of mixed nonparametric control charts, this can be applied to all data which no limitation in using of the proposed control chart. In particular, the data consist of volatility and fluctuation usually occurred in econometric solutions. Furthermore, to find the ARL as a performance measure, an explicit formula for the ARL of time series data can be derived using the integral equation and its accuracy can be verified using the numerical integral equation.
Understanding academic women’s silence in Poland: exploring with social cognitive theory
Authors: Lotfi Dehkharghani Leila , Menzies Jane , North-Samardzic Andrea , Casey Sarah Jane 
Published: August 2024

Purpose
This study aims to explore academic women’s silence from the perspective of social cognitive theory (Bandura, 1986), by examining the triadic influences of the individual, environment and behaviour, which impacts their silence. The study examines how women use personal, proxy and collective agency (Bandura, 2018) to reduce silence.

Design/methodology/approach
Interviewing 22 academics (20 women, 2 men) at a leading Polish university, this study used the Gioia et al. (2013) method to analyse the interviews, creating first- and second-order codes and final aggregated concepts.

Findings
This study finds, from an environmental perspective, that societal-level gendering, which is underpinned by critical social factors and institutional logics that are part of Poland’s culture promoting gender stereotypes and family values influences women’s silence. There is clear evidence for the regression of women’s rights, which compounds women’s silence. These societal-level factors influence a hierarchical, bureaucratic organizational structure, alongside gender segregation. From an individual perspective, reasons for silence include socialization, fear, women’s lack of power, inequality and self-silencing to mitigate harassment or discrimination. Collective agency was a strongly mentioned theme to help reduce silence, which includes implementing training and development initiatives, creating a safe platform to voice concerns, structural transformation and cultural change.

Originality/value
This study contributes to literature regarding women’s silence by exploring reasons for silence through the lens of Bandura’s social cognitive theory and agentic perspective, which demonstrates how silence could be reduced through collective action, in the understudied context of Poland, which highlights how country context intersects with organizational context and individual experience, influencing women’s silence.
Collective response capacity: Developing crisis leadership in organisations
Authors: Nesse Synnøve , Schei Vidar , Mitroff Ian 
Published: August 2024

AbstractHow can crisis leadership be developed before an organisational crisis occurs? This article addresses this important question by reviewing three individual‐level leadership perspectives (leader personality traits, leadership styles, and functional leadership) and three organisational level perspectives (leadership as contextual, leadership as collective, and leadership as dynamic), on how to develop crisis leadership with regard to recruitment, selection, and training. While crisis leadership is often perceived as something individual “leaders are born with” or as a variant of general leadership abilities, such an understanding leaves much to chance in terms of who will be effective leaders in a crisis, as well as the development of leadership capacity in organisations before a crisis actually occurs. This passive approach not only contradicts research on what constitutes effective crisis leadership but also is perceived to be unethical in terms of the potential consequences ineffective leadership can have in a crisis. This article provides an integrative overview of current and hitherto dispersed crisis leadership development research, showing how recruitment, selection and training to achieve collective crisis leadership capacity encompasses switching between organisational and individual level perspectives. We suggest implications for theory and future research as well as for practitioners responsible for developing crisis leadership in organisations.