bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolic network construction reveals probiotic-specific alterations in the metabolic activity of a synthetic small intestinal community
Authors: Jansma Jack , Chatziioannou Anastasia Chrysovalantou , Castricum Kitty , Hemert Saskia van , Aidy Sahar El 
Published: March 2023

AbstractThe gut microbiota plays a crucial role in maintaining overall health and probiotics have emerged as a promising microbiota-targeted therapy for improving human health. However, the molecular mechanisms of probiotics action in general and the targeting of small intestinal microbiota by probiotics are not well understood. To address this, we constructed a synthetic community of three species, which resembles the upper small intestinal microbiota. Our results indicate that probiotic supplementation can directly affect the metabolism of the community, resulting in colonization resistance in a probiotic specific manner. Supplementation withStreptococcus thermophilusled to increased lactate production and a decrease in pH, whileLactobacillus caseisupplementation increased the resistance to perturbations and nutrient utilization without affecting lactate production or pH. Additionally, when combined with kynurenine,Lactobacillus caseienhanced the kynurenine pathway metabolism resulting in elevated kynurenic acid levels and possibly indirect colonization resistance. Overall, our study reveals how selecting probiotics with distinct functional capacities can unlock the full potential of microbiota-targeted therapies.ImportanceThe development of probiotic therapies targeted at the small intestinal microbiota represents a significant advancement in the field of probiotic interventions. This region poses unique opportunities due to its low number of gut microbiota, along with the presence of heightened immune and metabolic host responses. However, progress in this area has been hindered by a lack of detailed understanding regarding the molecular mechanisms through which probiotics exert their effects in the small intestine. Our study, utilizing a synthetic community of three small intestinal bacterial strains and the addition of two different probiotic species, and kynurenine as a representative dietary or endogenously produced compound, highlights the importance of selecting probiotic species with diverse genetic capabilities that complement the functional capacity of the resident microbiota, or alternatively, constructing a multispecies formula. This approach holds great promise for the development of effective probiotic therapies and underscores the need to consider the functional capacity of probiotic species when designing interventions.
Optimised protocol for production and analysis of recombinant protein-filled vesicles fromE. coli.
Authors: Streather Bree R. , Baker Karen , Eastwood Tara A. , Mulvihill Daniel P. 
Published: March 2023

AbstractWe have developed an innovative system that exports diverse recombinant proteins in membrane bound vesicles fromE. coli1. These recombinant vesicles compartmentalise proteins within a micro-environment that enables production of otherwise challenging insoluble, toxic, or disulphide-bond containing proteins from bacteria. The release of vesicle-packaged proteins supports isolation from the culture and allows long-term storage of active protein. This technology results in high yields of vesicle-packaged, functional proteins for efficient downstream processing for a wide range of applications from discovery science to applied biotechnology and medicine. In this article, and associated video, we provide a detailed protocol of the method, and highlight key steps in the methodology to maximise recombinant protein filled vesicle production.SummaryThis protocol describes a detailed method for the bacterial production of recombinant proteins, including typically insoluble or disulphide-bond containing proteins, packaged inside extracellular membrane-bound vesicles. This has the potential to applied to many areas of scientific research including applied biotechnology and medicine.
Mitochondrial H2O2release does not directly cause genomic DNA damage
Authors: van Soest Daan M.K. , Polderman Paulien E. , den Toom Wytze T. F. , Zwakenberg Susan , de Henau Sasha , Burgering Boudewijn M. T. , Dansen Tobias B. 
Published: March 2023

AbstractReactive Oxygen Species (ROS) derived from mitochondrial respiration are frequently cited as a major source of genomic DNA damage and subsequent mutations that contribute to cancer development and aging. However, experimental evidence showing that ROS released by mitochondrial can directly damage nuclear DNA under (patho)physiological conditions has been largely lacking. In this study we modeled the effects of mitochondrial H2O2release and compared this to H2O2production at the nucleosomes in an untransformed human cell line. We used a chemogenetic approach to produce localized H2O2and combined it with a new method we developed to directly quantify the amount of H2O2produced. This enabled us to precisely investigate to what extent DNA damage occurs downstream of near- and supraphysiological amounts of localized H2O2generation. Nuclear H2O2production gives rise to DNA strand breaks, subsequent activation of the DNA damage response, cell cycle arrest and eventually senescence. Release of H2O2from mitochondria on the other hand shows none of these effects, even at levels that are orders of magnitude higher than what mitochondria normally produce. Artificially high levels of mitochondrial H2O2release do result in DNA strand breaks, but in parallel invariably cause ferroptosis-mediated cell death, preventing propagation of DNA damage-induced mutations. This study shows that H2O2released from mitochondria is unlikely to directly damage genomic DNA, limiting its contribution to oncogenic transformation and aging.
Population-level transposable element expression dynamics influence trait evolution in a fungal crop pathogen
Authors: Abraham Leen Nanchira , Oggenfuss Ursula , Croll Daniel 
Published: March 2023

AbstractRapid adaptive evolution is driven by strong selection pressure acting on standing genetic variation within populations. How adaptive genetic variation is generated within species and how such variation influences phenotypic trait expression is often not well understood though. Here, we focused on recent activity of transposable elements (TEs) using deep population genomics and transcriptomics analyses of a fungal plant pathogen with a highly active content of TEs in the genome.Zymoseptoria triticicauses one of the most damaging diseases on wheat, with recent adaptation to the host and environment being facilitated by TE-associated mutations. We obtained genomic and RNA-sequencing data from 146 isolates collected from a single wheat field. We established a genome-wide map of TE insertion polymorphisms in the population by analyzing recent TE insertions among individuals. We quantified the locus-specific transcription of individual TEs within the population and revealed considerable variation in transcription across individual TE loci. About 20% of all TE copies show activity in the genome implying that genomic defenses such as repressive epigenetic marks and repeat-induced polymorphisms are ineffective at preventing the proliferation of TEs in the genome. A quarter of recent TE insertions are associated with expression variation of neighboring genes providing broad potential to influence trait expression. We indeed found that TE insertions are likely responsible for variation in virulence on the host and secondary metabolite production. Our study emphasizes how TE-derived polymorphisms segregate even in individual populations and broadly underpin transcription and adaptive trait variation in a species.
Turing pattern prediction in three-dimensional domains: the role of initial conditions and growth
Authors: Ben Tahar Soha , Muñoz Jose J , Shefelbine Sandra J , Comellas Ester 
Published: March 2023

AbstractReaction-diffusion systems have been widely used to model pattern formation in biological systems. However, the emergence of Turing patterns in three-dimensional (3D) domains remains relatively unexplored. A few studies on this topic have shown that extending pattern formation from 2D to 3D is not straightforward. Linear stability analysis, which is commonly used to associate admissible wave modes with predicted patterns in 1D and 2D, has yet to be applied in 3D. We have used this approach, together with finite element modelling of a Turing system with Schnakenberg kinetics, to investigate the effects of initial conditions and growing domains on the competition between admissible modes in 3D Turing pattern emergence. Our results reveal that non-random initial conditions on the activator play a stronger role than those of the inhibitor. We also observe a path dependency of the evolving pattern within a growing domain. Our findings shed new light on the mechanisms ensuring reliable pattern formation in 3D domains and have important implications for the development of more robust models of morphogen patterning in developmental processes.
The Kinetochore Protein KNL-1 Regulates the Actin Cytoskeleton to Control Dendrite Branching
Authors: Domingos Henrique Alves , Green Mattie , Ouzounidis Vasileios R. , Finlayson Cameron , Prevo Bram , Cheerambathur Dhanya K. 
Published: March 2023

ABSTRACTThe function of the nervous system is intimately tied to its complex and highly inter-connected architecture. Precise control of dendritic branching in individual neurons is central to building the complex structure of the nervous system. Here we show that the kinetochore protein KNL-1 and its associated KMN (Knl1/Mis12/Ndc80 complex) network partners, typically known for their role in chromosome-microtubule coupling during mitosis, control dendrite branching in theC. elegansmechanosensory PVD neuron. KNL-1 restrains excess dendritic branching and promotes contact-dependent repulsion events, ensuring robust sensory behavior and preventing premature neurodegeneration. Unexpectedly, KNL-1 loss resulted in significant alterations of the actin cytoskeleton alongside changes in microtubule dynamics within dendrites. We show that KNL-1 modulates F-actin dynamics to generate proper dendrite architecture, and that its N-terminus can initiate F-actin assembly. These findings reveal that the post-mitotic neuronal KMN network acts to shape the developing nervous system by regulating the actin cytoskeleton and provide new insight into the mechanisms controlling dendrite architecture.
Baicalin Ameliorates Defective Decidualization in URSA by Regulating Mitochondrial Fission Induced Necroptosis
Authors: Zhao Xiaoxuan , Zhao Ying , Yang Qujia , Ma Jing , Zhao Yang , Wang Suxia , Jiang Yuepeng , Zhang Qin 
Published: March 2023

AbstractDefective decidualization is a significant pathological feature of URSA. And the potential relationship between mitochondrial fission, necroptosis and defective decidualization remains unknown. Baicalin plays an important role in regulating mitochondrial fission and programmed cell death. However, whether baicalin has a protective effect on defective decidualization in URSA has not been reported thus far. This study aims to explore the mechanisms of mitochondrial fission induced necroptosis in defective decidualization in URSA and the regulation of baicalin. First, decidual tissues were collected from URSA and health controls. And then, T-hESC was treated with lipopolysaccharide (LPS), Tyrphostin A9 (TA9), TA9+necrostatin-1(Nec-1) and TA9+baicalin during in vitro decidualization. Besides, URSA mice were established and randomly administrated with low, medium, and high doses of baicalin as well as saline. Results showed that decidualization markers prolactin (PRL) and insulin-like growth factor-binding protein-1 (IGFBP1) in patients with URSA were significantly decreased (P<0.05). The incidence of cell necroptosis was increased, manifested with increased Annexin V and PI positive cells, high level of pRIP3 T231(P<0.01) and pMLKL S358 (P<0.05). Moreover, mitochondrial fission was also hyperactive, featured by elevated level of Fis1 (P<0.01) and Drp1 (P<0.05). In vitro experiments, LPS was induced to trigger necroptosis of T-hESC during induced decidualization, and IGFBP1 and PRL were subsequently decreased (P<0.05). Besides, mitochondrial fission inducer TA9 promoted the level of necroptosis (P<0.05) and induced defective decidualization, which could be rescued by necroptosis inhibitor Nec-1 (P<0.05). In addition, baicalin could reduce mitochondrial fission (P<0.05), necroptosis (P<0.05) and ameliorate defective decidualization in vivo and in vitro (P<0.05). In conclusion, hyperactive mitochondrial fission could promote necroptosis, thus inducing defective decidualization. And baicalin could ameliorates defective decidualization in URSA by regulating mitochondrial fission induced necroptosis.
Statistical examination of shared loci in neuropsychiatric diseases using genome-wide association study summary statistics
Authors: Spargo Thomas P , Gilchrist Lachlan , Hunt Guy P , Dobson Richard JB , Proitsi Petroula , Al-Chalabi Ammar , Pain Oliver , Iacoangeli Alfredo 
Published: March 2023

AbstractContinued methodological advances have enabled numerous statistical approaches for the analysis of summary statistics from genome-wide association studies. Genetic correlation analysis within specific regions enables a new strategy for identifying pleiotropy. Genomic regions with significant ‘local’ genetic correlations can be investigated further using state-of-the-art methodologies for statistical fine-mapping and variant colocalisation. We explored the utility of a genome-wide local genetic correlation analysis approach for identifying genetic overlaps between the candidate neuropsychiatric disorders, Alzheimer’s disease, amyotrophic lateral sclerosis, frontotemporal dementia, Parkinson’s disease, and schizophrenia. The correlation analysis identified several associations between traits, the majority of which were loci in the human leukocyte antigen (HLA) region. Colocalisation analysis suggested that disease-implicated variants in these loci often differ between traits and, in one locus, indicated a shared causal variant between amyotrophic lateral sclerosis and Alzheimer’s disease. Our study identified candidate loci that might play a role in multiple neuropsychiatric diseases and suggested the role of distinct mechanisms across diseases despite shared loci. The fine-mapping and colocalisation analysis protocol designed for this study has been implemented in a flexible analysis pipeline that produces HTML reports and is available at:https://github.com/ThomasPSpargo/COLOC-reporter.
Characterisation of the SUF FeS cluster machinery in the amitochondriate eukaryoteMonocercomonoides exilis
Authors: Peña-Diaz Priscila , Braymer Joseph J. , Vacek Vojtěch , Zelená Marie , Lometto Stefano , Hrdý Ivan , Treitli Sebastian C. , Hochberg Georg , Py Béatrice , Lill Roland , Hampl Vladimír 
Published: March 2023

AbstractMonocercomonoides exilisis the first eukaryotic organism described as a complete amitochondriate, yet it shares common features with heterotrophic anaerobic/microaerophilic protists, some of which bear divergent mitochondrion-related organelles or MROs. It has been postulated that the retention of these organelles stems from their involvement in the assembly of essential cytosolic and nuclear FeS proteins, whose maturation requires the evolutionarily conserved mitochondrial ISC and cytosolic CIA machineries. The amitochondriateM. exilislacks genes encoding the ISC machinery yet contains a bacteria-derived SUF system (MeSuf), composed of the cysteine desulphurase SufS fused to SufD and SufU, as well as the FeS scaffolding components MeSufB and MeSufC. Here, we show that expression of the M. exilis SUFgenes, either individually or in tandem, can restore the maturation of the FeS protein IscR in theEscherichia colidouble mutants of ΔsufSΔiscSand ΔsufBΔiscUA. In vivoandin vitrostudies indicate that purified MeSufB, MeSufC and MeSufDSU proteins interact suggesting that they act as a complex in the protist. MeSufBC can undergo conformational changes in the presence of ATP and assemble FeS clusters under anaerobic conditions in presence and absence of ATPin vitro. Altogether, these results indicate that the dynamically interacting MeSufDSUBC proteins may function as an FeS cluster assembly complex inM. exilisthereby being capable of replacing the organelle-enclosed ISC system of canonical eukaryotes.
Green innovation and the cost of equity: evidence from China
Authors: Alkebsee Radwan , Habib Ahsan , Li Junyan 
Published: March 2023

PurposeThis paper aims to examine the association between green innovation and the cost of equity in China. This study relies on the investors’ base perspective and shareholders’ perceived risk perspective to investigate the relation between green innovation and the cost of equity in China.Design/methodology/approachThe paper uses firm-fixed effect regression for a sample of Chinese public companies for the period 2008–2018.FindingsThe authors find a negative relationship between green innovation and the cost of equity capital. This negative association is found to be more pronounced for less financially constrained firms, during periods of high economic policy uncertainty, and for firms with a strong internal control environment. Finally, the paper shows that the negative association became more pronounced after the passage of the Environmental Protection Law of China in 2012. The results remain robust to possible endogeneity concerns.Originality/valueThis study contributes to the green innovation literature by documenting that shareholders favorably view firms implementing green innovation policies. The study also has policy implications for Chinese regulators in improving the green credit policy.
Does personal data protection matter for ISO 9001 certification and firm performance?
Authors: Siougle Efrosini , Dimelis Sophia , Malevris Nikolaos 
Published: March 2023

PurposeThis study explores the link between ISO 9001 certification, personal data protection and firm performance using financial balance sheet and survey data. The security aspect of data protection is analyzed based on the major requirements of the General Data Protection Regulation and mapped to the relevant controls of the ISO/IEC 27001/27002 standards.Design/methodology/approachThe research analysis is based on 96 ISO 9001–certified and non-certified publicly traded manufacturing and service firms that responded to a structured questionnaire. The authors develop and empirically test their theoretical model using the structural equation modeling technique and follow a difference-in-differences econometric modeling approach to estimate financial performance differences between certified and non-certified firms accounting for the level of data protection.FindingsThe estimates indicate three core dimensions in the areas of “policies, procedures and responsibilities,” “access control management” and “risk-reduction techniques” as desirable components in establishing the concept of data security. The estimates also suggest that the data protection level has significantly impacted the performance of certified firms relative to the non-certified. Controlling for the effect of industry-level factors reveals a positive relationship between data security and high-technological intensity.Practical implicationsThe results imply that improving the level of compliance to data protection enhances the link between certification and firm performance.Originality/valueThis study fills a gap in the literature by empirically testing the influence of data protection on the relationship between quality certification and firm performance.
Collation of best practices for preparedness: lessons from disasters in Pakistan and Japan
Authors: Schwarz Jonas , Kascel Valentina , Azmat Muhammad , Kummer Sebastian 
Published: March 2023

PurposeThis study aims to compare the humanitarian supply chains and logistics of two countries in earthquake preparedness by modifying and using a previously established preparedness evaluation framework.Design/methodology/approachA European flood emergency management system (FEMS) is a seven-dimensional framework to assess a country’s preparedness for flood emergencies. The FEMS framework was modified to apply to earthquakes. Leveraging a multiple explanatory case study approach with data analysis, the authors reconstructed the events of the earthquakes in Pakistan (2005) and Japan (2011) with an applied grading (1–5). Findings were evaluated within the adopted FEMS framework. From a practitioner’s perspective, the framework is applicable and can accelerate support in the field.FindingsPakistan lacked emergency plans before the 2005 earthquake. In contrast, Japan possessed emergency plans before the disaster, helping minimise casualties. Overall, Japan demonstrated considerably better emergency management effectiveness. However, both countries significantly lacked the distribution of responsibilities among actors.Originality/valuePractical factors in the humanitarian supply chain are well understood. However, synthesising individual factors into a comprehensive framework is difficult, which the study solves by applying and adopting the FEMS framework to earthquakes. The developed framework allows practitioners a structured baseline for prioritising measures in the field. Furthermore, this study exemplifies the usefulness of cross-hazard research within emergency management and preparedness in a real-world scenario.