bluuebunny/crossref_metadata_2025 huggingface dataset:
14-3-3 binding regulates Tau assembly and microtubule association
Authors: Hochmair Janine , van den Oetelaar Maxime C. M. , Diez Lisa , Lemmens Lenne J. M. , Ponce Renata , Ravatt Leandre , Franck Maximilian W. , Semenova Ekaterina , Mohapatra Satabdee , Ottmann Christian , Brunsveld Luc , Wegmann Susanne
Published: March 2024

14-3-3 proteins are among the most abundant proteins in the brain and bind a large number of proteins in a phosphorylation dependent manner, including proteins prone to aggregate in neurodegenerative diseases. Binding of 14-3-3 is reported to facilitate the function, promote solubility, and coordinate the assembly of client proteins. For the microtubule-associated protein Tau, a neuronal client of 14-3-3, we show that phosphorylation-dependent stoichiometric binding of 14-3-3ζ dimers inhibits Tau assembling into biomolecular condensates, prevents its aggregation, and realizes efficient dissociation of Tau from microtubules. In contrast, at sub-stoichiometric 14-3-3 concentrations, multivalent electrostatic interactions promote the co-condensation of 14-3-3ζ with Tau in a phosphorylation-independent manner, offering an additional level in regulating the interactions of both proteins. These findings offer long-sought mechanistic insights into how 14-3-3 proteins regulate substrate solubility and highlight their importance for maintaining Tau protein functionality in the brain.
Undruggable oncoproteins cMyc and NMyc bind to mediator of transcription with superior high affinity
Authors: Knight Andrea , Houser Josef , Otasevic Tomas , Juran Vilem , Vybihal Vaclav , Smrcka Martin , Piskacek Martin
Published: March 2024

The overexpression of MYC genes is frequently found in many human cancers including adult and pediatric malignant brain tumors. Targeting MYC genes continues to be challenging due to their undruggable nature. The nine-amino-acid activation domain (9aaTAD) has been identified using our prediction algorithm in all four Yamanaka factors including c-Myc and showed to activate transcription as short peptides. We generated a set of c-Myc constructs (1-108, 69-108 and 98-108) in the N-terminal regions and tested their ability to initiate transcription. We discovered strong interactions in nanomolar scale between the 9aaTAD of c-Myc and N-Myc proteins with the KIX domain of CBP coactivator. The c-Myc 9aaTAD (region 98-108) was not overlapping with the MBII (region 128-143) and therefore represents TRRAP independent activation region. Next, we showed the 9aaTADs in human c-Myc and N-Myc conservation within the MYC family. Interestingly, the loss of the 9aaTAD in L-Myc paralogs was identified in higher metazoans suggesting the deletions had occurred in early tetrapod evolution. In summary, as c-Myc is largely intrinsically disordered protein and therefore difficult to target by small molecule inhibitors, our finding of the c-Myc 9aaTAD in complex with the KIX domain represents a promising druggable target for development of new peptide inhibitors in MYC-driven tumors.
ADMA-histones define genomic loading of Rhino at the initial step of piRNA cluster formation
Authors: Saito Raku , Ishizu Hirotsugu , Harigai Ritsuko , Murano Kensaku , Siomi Mikiko C.
Published: March 2024

InDrosophilagerm cells, piRNAs arise from dual-strand piRNA clusters. These clusters are occupied by H3K9me3, but are transcribed from internal sites in a manner dependent on the binding of HP1 homolog Rhino to H3K9me3 on the clusters. However, how initial loading of Rhino onto the clusters occurs remains unknown. Here, we used cultured ovarian somatic cells (OSCs), which lack endogenous Rhino and Rhino stabilizer Kipferl, the absence of which renders the dual-strand clusters inert, and found that exogenous Rhino tends to bind to the ends of dual-strand clusters with asymmetric dimethylarginine histones (ADMA-histones). Depletion of the arginine methyltransferases responsible for ADMA modification affected the genomic localization of Rhino in OSCs and in the ovary. We also identified genomic regions, termed INSECTs, where ADMA-dependent Rhino propagation begins. We propose that ADMA-histones define the initial genomic loading of Rhino and stabilize Rhino−genome association during cluster formation.
A functional circadian clock regulates composition and daily bacterial load of the gut microbiome inDrosophila melanogaster
Authors: Battistolli Matteo , Varponi Irene , Romoli Ottavia , Sandrelli Federica
Published: March 2024

WhileDrosophila melanogasterserves as a crucial model for investigating both the circadian clock and gut microbiome, our understanding of their relationship in this organism is still limited. Recent analyses suggested that theDrosophilagut microbiome modulates the host circadian tran-scriptome to minimize rapid oscillations in response to changing environments. To delve deeper into the potential relationship between the gut microbiota and circadian clock inDrosophila, we examined the composition and abundance of the gut microbiota in wild-type and arrhythmicper01flies, under 12 h:12 h light: dark (12:12 LD) and constant darkness (DD) conditions. The gut microbiota of wild-type andper01flies showed differences in composition, suggesting that theD. melanogastercircadian clock has a role in shaping the gut microbiome. In 12:12 LD and DD conditions,per01mutants showed significant daily variations in gut bacterial quantity, unlike wild-type flies. This suggests that the circadian clock inD. melanogasterplays a role in maintaining daily stability in gut microbiome load. Finally, some gut bacteria exhibited significant 24 h fluctuations in their relative abundance, which appeared independent from the fly circadian clock, suggesting that certain gut commensal bacteria inDrosophilamay possess a host-independent circadian clock.
Heterochromatin protein 1 (HP1) ofSchistosoma mansoni: non-canonical chromatin landscape and fitness effects
Authors: da Trindade Natália S. , Valentini Marilia Bergamini , Rognon Anne , Mendes Tiago Manuel Fernandes , Allegretti Silmara Marques , Grunau Christoph , Cabral Fernanda J.
Published: March 2024

Heterochromatin protein 1 (HP1) is widespread in several organisms playing a role in control of gene expression by heterochromatin formation and maintenance of silent chromatin.Schistosoma mansoniis a human parasite that is responsible for Schistosomiasis, a tropical neglected disease in the tropical and subtropical areas in the world, where the intermediate hostBiomphalaria glabratais present. In this study we attempted to investigate if theSmHP1 is enriched inS. mansonichromatin in cercariae larvae stage, compared with another larvae stage sporocysts and it’s importance forS. mansonilife cycle progression and parasite fitness. We used ChIPmentation with commercial antibody ab109028 that passed in-house quality control. Our data show thatS. mansoniHP1 enrichment is non-canonical with a peak at the transcription end sites of protein coding genes. We did not find strong differences inSmHP1 chromatin landscapes between sporocysts and cercariae. Knock-down ofSmHP1 in schistosomula andin vivoexperiments in mice unexpectedly increased parasite fitness. Our results suggest thatSmHP1 may influence chromatin structure in a non-canonical way inS. mansonistages and may play a role in regulation of parasite fitness.
ONE HEALTH APPROACH ON SARS-COV-2 – USING SHEEP AS SENTINEL ANIMALS TO INCREASE FUTURE PANDEMIC PREPAREDNESS – a pilot study
Authors: Samojlović Milena , Mesquita João , Santos-Silva Sérgio , Neptin Malin , Esbjörnsson Joakim
Published: March 2024

Coronaviruses are a family of viruses that can infect a number of species of birds and mammals with great zoonotic potential to cross species barriers and cause spill-over events. SARS-CoV-2 has been shown to cause clinical and inapparent disease and mortality in several animals cohabitating with humans. Sheep are also susceptible to SARS-CoV-2 and have potential to harbor and spread the virus, as well as develop neutralising antibodies due to similarities of virus-receptor interactions to those in humans. The main aim of this study was to investigate the prevalence of SARS-CoV-2 neutralising antibodies in sentinel animals after natural exposure to the virus. The serum samples were collected from sheep in Central Portugal, Serra da Estrela region, both prior to and during the COVID-19 pandemic. The sheep were kept on dairy farms for production of Serra da Estrela cheese, in small herds and in constant contact with farm workers. The sera were tested using already established SARS-CoV-2 pseudovirus systems for multiple SARS-CoV-2 variants including Wuhan, Delta and Omicron. Partial neutralisation activity towards Wuhan and Delta variants was observed, while neutralisating antibody escape was observed in all Omicron variants tested due to the mutations present . Our results indicate that potential SARS-CoV-2 virus cross-species transmission could have been established through contacts between people and animals on sheep farms. Using farm animals as sentinels is of great importance for implementing One Health Approach in zoonotic virus surveillance and control towards increasing future pandemic preparedness.
Erosion of X-Chromosome Inactivation in female hiPSCs is heterogeneous and persists during differentiation
Authors: Raposo Ana Cláudia , Caldas Paulo , Arez Maria , Jeremias Joana , Barbosa Pedro , Sousa-Luís Rui , Água Frederico , Oxley David , Mupo Annalisa , Eckersley-Maslin Melanie , Casanova Miguel , Grosso Ana Rita , da Rocha Simão Teixeira
Published: March 2024

During culture, female human pluripotent stem cells (hPSCs), including human induced PSCs (hiPSCs) exhibit a propensity for erosion of X-chromosome inactivation (XCI). This phenomenon is characterized by the loss of XIST RNA expression and reactivation of a subset of X-linked genes from the inactive X chromosome (Xi). XCI erosion, despite its common occurrence, is often overlooked by the stem cell community, hindering a complete understanding of its impact on both fundamental and translational applications of hiPSCs. Investigating erosion dynamics in female hiPSCs, our study reveals that XCI erosion is a frequent yet heterogeneous phenomenon, resulting in the reactivation of several X-linked genes. The likelihood of a gene to erode increases for those located on the short arm of the X chromosome and within H3K27me3-enriched domains. Paradoxically, genes that typically escape XCI are hypersensitive to loss of XIST RNA and XCI erosion. This implies that XIST RNA normally restrains expression levels of these genes on the Xi. Importantly, increased X-linked gene expression upon erosion does not globally impact (hydroxy)methylation levels in hiPSCs or at imprinted regions. By exploring diverse differentiation paradigms, such as trilineage commitment and cardiac differentiation, our study reveals the persistence of abnormal XCI patterns throughout differentiation. This finding has significant implications for fundamental research, translational applications, and clinical use of stem cells. We underscore the importance of raising awareness within the stem cell community regarding XCI erosion and advocate for its inclusion in comprehensive hiPSC quality control.
TheToxoplasma gondiimitochondrial transporter ABCB7 is essential for cytosolic iron-sulfur cluster biogenesis and protein translation
Authors: Maclean Andrew E. , Sloan Megan A. , Renaud Eléa A. , Demolombe Vincent , Besteiro Sébastien , Sheiner Lilach
Published: March 2024

Iron-sulfur (Fe-S) clusters are ubiquitous inorganic cofactors required for numerous essential cellular pathways. Since they cannot be scavenged from the environment, Fe-S clusters are synthesised de novo in cellular compartments such as the apicoplast, mitochondrion and cytosol. The cytosolic Fe-S cluster biosynthesis pathway relies on transport of an intermediate from the mitochondrial pathway. An ATP binding cassette (ABC) transporter called ABCB7 is responsible for this role in numerous commonly studied organisms, but its role in the medically important apicomplexan parasites has not yet been studied. Here we identify and characterise theToxoplasma gondiiABCB7 homolog. Genetic depletion shows that it is essential for parasite growth, and that disruption triggers partial stage conversion. Characterisation of the knock-down line highlights a defect in cytosolic Fe-S cluster biogenesis leading to defects in protein translation and other pathways including DNA and RNA replication and metabolism. Our work provides support for a broad conservation of the connection between mitochondrial and cytosolic in Fe-S cluster biosynthesis and reveal its importance for parasite survival.
R6G narrows BmrA conformational spectrum for a more efficient use of ATP
Authors: Gobet A , Moissonnier L , Zarkadas E , Magnard S , Bettler E , Martin J , Terreux R , Schoehn G , Orelle C , Jault JM , Falson P , Chaptal V
Published: March 2024

Multidrug ABC transporters harness the energy of ATP binding and hydrolysis to change conformation and thereby translocate substrates out of the cell to detoxify them. While this general access mechanism scheme is well accepted, molecular details of this interplay is still elusive. Rhodamine6G binding on a catalytic mutant of the homodimeric multidrug ABC transporter BmrA triggers a cooperative binding of ATP on the two identical nucleotide-binding-sites, otherwise Michaelian. We investigated this asymmetric behavior via a structural-enzymology approach, solving cryoEM structure of BmrA at defined ATP ratio along the enzymatic transition, highlighting the plasticity of BmrA as it undergoes the transition from inward to outward facing conformations. Analysis of continuous heterogeneity within cryoEM data and structural dynamics, revealed that Rhodamine6G narrows the conformational spectrum explored by the nucleotide-binding-domains, describing the allosteric effect of drug binding that optimizes the ATP-dependent conversion of the transporter to the outward-facing state. Following on these findings, the effect of drug-binding showed an ATPase stimulation and a maximal transport activity of the wild-type protein at the concentration-range where the allosteric transition occurs. Drug diffusion rate is the likely rate-limiting step of the reaction, while drug transport and ATPase activities are in effect uncoupled.
OCTOPUS: Disk-based, Multiplatform, Mobile-friendly Metagenomics Classifier
Authors: Marini Simone , Barquero Alexander , Wadhwani Anisha Ashok , Bian Jiang , Ruiz Jaime , Boucher Christina , Prosperi Mattia
Published: March 2024

Portable genomic sequencers such as Oxford Nanopore’s MinION enable real-time applications in clinical and environmental health. However, there is a bottleneck in the downstream analytics when bioinformatics pipelines are unavailable, e.g., when cloud processing is unreachable due to absence of Internet connection, or only low-end computing devices can be carried on site. Here we present a platform-friendly software for portable metagenomic analysis of Nanopore data, the Oligomer-based Classifier of Taxonomic Operational and Pan-genome Units via Singletons (OCTOPUS). OCTOPUS is written in Java, reimplements several features of the popular Kraken2 and KrakenUniq software, with original components for improving metagenomics classification on incomplete/sampled reference databases, making it ideal for running on smartphones or tablets. OCTOPUS obtains sensitivity and precision comparable to Kraken2, while dramatically decreasing (4-to 16-fold) the false positive rate, and yielding high correlation on real-word data. OCTOPUS is available along with customized databases athttps://github.com/DataIntellSystLab/OCTOPUSandhttps://github.com/Ruiz-HCI-Lab/OctopusMobile.
N-acyl homoserine lactone signaling modulates bacterial community associated with human dental plaque
Authors: Sikdar Rakesh , Beauclaire Mai V. , Lima Bruno P. , Herzberg Mark C. , Elias Mikael H.
Published: March 2024

N-acyl homoserine lactones (AHLs) are small diffusible signaling molecules that mediate a cell density-dependent bacterial communication system known as quorum sensing (QS). AHL-mediated QS regulates gene expression to control many critical bacterial behaviors including biofilm formation, pathogenicity, and antimicrobial resistance. Dental plaque is a complex multispecies oral biofilm formed by successive colonization of the tooth surface by groups of commensal, symbiotic, and pathogenic bacteria, which can contribute to tooth decay and periodontal diseases. While the existence and roles of AHL-mediated QS in oral microbiota have been debated, recent evidence indicates that AHLs play significant roles in oral biofilm development and community dysbiosis. The underlying mechanisms, however, remain poorly characterized. To better understand the importance of AHL signaling in dental plaque formation, we manipulated AHL signaling by adding AHL lactonases or exogenous AHL signaling molecules. We find that AHLs can be detected in dental plaque grown under 5% CO2conditions, but not when grown under anaerobic conditions, and yet anaerobic cultures are still responsive to AHLs. QS signal disruption using lactonases leads to changes in microbial population structures in both planktonic and biofilm states, changes that are dependent on the substrate preference of the used lactonase but mainly result in the increase in the abundance of commensal and pioneer colonizer species. Remarkably, the opposite manipulation, that is the addition of exogenous AHLs increases the abundance of late colonizer bacterial species. Hence, this work highlights the importance of AHL-mediated QS in dental plaque communities, its potential different roles in anaerobic and aerobic parts of dental plaque, and underscores the potential of QS interference in the control of periodontal diseases
An expanded genetic toolkit for inducible expression and targeted gene silencing inRickettsia parkeri
Authors: McGinn Jon , Wen Annie , Edwards Desmond L. , Brinkley David M. , Lamason Rebecca L.
Published: March 2024

Pathogenic species within theRickettsiagenus are transmitted to humans through arthropod vectors and cause a spectrum of diseases ranging from mild to life-threatening. Despite rickettsiae posing an emerging global health risk, the genetic requirements of their infectious life cycles remain poorly understood. A major hurdle toward building this understanding has been the lack of efficient tools for genetic manipulation, owing to the technical difficulties associated with their obligate intracellular nature. To this end, we implemented the Tet-On system to enable conditional gene expression inRickettsia parkeri. Using Tet-On, we show inducible expression of antibiotic resistance and a fluorescent reporter. We further used this inducible promoter to screen the ability ofR. parkerito express four variants of the catalytically dead Cas9 (dCas9). We demonstrate that all four dCas9 variants can be expressed inR. parkeriand used for CRISPR interference (CRISPRi)-mediated targeted gene knockdown. We show targeted knockdown of an antibiotic resistance gene as well as the endogenous virulence factorsca2. Altogether, we have developed systems for inducible gene expression and CRISPRi-mediated gene knockdown for the first time in rickettsiae, laying the groundwork for more scalable, targeted mechanistic investigations into their infectious life cycles.

IMPORTANCE

The spotted fever group ofRickettsiacontains vector-borne pathogenic bacteria that are neglected and emerging threats to public health. Due to the obligate intracellular nature of rickettsiae, the development of tools for genetic manipulation has been stunted, and the molecular and genetic underpinnings of their infectious lifecycle remain poorly understood. Here, we expand the genetic toolkit by introducing systems for conditional gene expression and CRISPRi-mediated gene knockdown. These systems allow for relatively easy manipulation of rickettsial gene expression. We demonstrate the effectiveness of these tools by disrupting the intracellular life cycle using CRISPRi to deplete thesca2virulence factor. These tools will be crucial for building a more comprehensive and detailed understanding of rickettsial biology and pathogenesis.
Phase separation of polyubiquitinated proteins in UBQLN2 condensates controls substrate fate
Authors: Valentino Isabella M. , Llivicota-Guaman Jeniffer G. , Dao Thuy P. , Mulvey Erin O. , Lehman Andrew M. , Galagedera Sarasi K. K. , Mallon Erica L. , Castañeda Carlos A. , Kraut Daniel A.
Published: March 2024

Ubiquitination is one of the most common post-translational modifications in eukaryotic cells. Depending on the architecture of polyubiquitin chains, substrate proteins can meet different cellular fates, but our understanding of how chain linkage controls protein fate remains limited. UBL-UBA shuttle proteins, such as UBQLN2, bind to ubiquitinated proteins and to the proteasome or other protein quality control machinery elements and play a role in substrate fate determination. Under physiological conditions, UBQLN2 forms biomolecular condensates through phase separation, a physicochemical phenomenon in which multivalent interactions drive the formation of a macromolecule-rich dense phase. Ubiquitin and polyubiquitin chains modulate UBQLN2’s phase separation in a linkage-dependent manner, suggesting a possible link to substrate fate determination, but polyubiquitinated substrates have not been examined directly. Using sedimentation assays and microscopy we show that polyubiquitinated substrates induce UBQLN2 phase separation and incorporate into the resulting condensates. This substrate effect is strongest with K63-linked substrates, intermediate with mixed-linkage substrates, and weakest with K48-linked substrates. Proteasomes can be recruited to these condensates, but proteasome activity towards K63-linked and mixed linkage substrates is inhibited in condensates. Substrates are also protected from deubiquitinases by UBQLN2-induced phase separation. Our results suggest that phase separation could regulate the fate of ubiquitinated substrates in a chain-linkage dependent manner, thus serving as an interpreter of the ubiquitin code.

Significance

Covalent attachment of polyubiquitin chains to eukaryotic proteins is a common protein quality control signal. Ubiquitination often marks proteins for degradation by the proteasome, but can also drive non-degradative outcomes. Proteins, including UBQLN2, that bind both polyubiquitin and the proteasome can either enhance or inhibit degradation. The ALS-related UBQLN2 is recruited to membraneless organelles, including stress granules, and undergoes phase separationin vitro, but the effects of phase separation on substrate fate are unknown. Herein we show that UBQLN2 phase separation is modulated by polyubiquitinated substrates in a linkage-dependent fashion. We show that two functional outcomes, degradation and deubiquitination, are differentially affected by phase separation. Our results suggest that phase separation of substrates and UBQLN2 could control protein fates.
Advancing microbial isolation: The impact of leaf mold extract agar on soil samples
Authors: Miyashita Atsushi , Mikami Kazuhiro , Ishii Masaki , Miyauchi Masanobu , Tabuchi Fumiaki
Published: March 2024

In this study, we developed a new agar medium using leaf mold extract and evaluated its microbial cultivation performance with soil samples. As a control for performance evaluation, the general-purpose nutrient medium YME agar was used. For YME agar, isolated microbes were confirmed to belong mainly to theBacillusgenus through 16S rRNA gene sequencing. In contrast, for the leaf mold agar, bacteria belonging to eitherStreptomycesorRhizobiumwere frequently isolated. Also, of the 51 sequenced isolates on the leaf mold agar medium, an unidentified species (i.e., not listed in databases) with 16S rRNA sequence identity below 98.7% was found. The unidentified species did not grow in standard nutrient media (YME, BHI, LB10, or TSB) but grew in 10% leaf mold extract. The findings of this study suggest that the use of leaf mold agar medium can effectively isolate soil microbes that are difficult to culture in general-purpose nutrient media such as YME. Moreover, this approach indicates a viable method for discovering unknown, previously-uncultured microbial species from soil samples.
Solvation Free Energy in Governing Equations for DNA Hybridization, Protein–Ligand Binding, and Protein Folding
Authors: Harmon Caroline , Bui Austin , Espejo Jasmin M. , Gancayco Marc , Le Jennifer M. , Rangel Juan , Eggers Daryl K.
Published: March 2024

This work examines the thermodynamics of model biomolecular interactions using a governing equation that accounts for the participation of bulk water in the balanced reaction. In the first example, the binding affinities of two model DNA duplexes, one of nine and one of ten base pairs in length, are measured and characterized by isothermal titration calorimetry as a function of concentration. The results indicate that the change in solvation free energy that accompanies duplex formation (ΔGS) is large and unfavorable. When normalized to the number of base pairs, the duplex with the larger number of G:C pairings yields the largest change in solvation free energy, ΔGS= +460 kcal/mol/base pair at 25 °C. A modelling study demonstrates how the solvation free energy alters the output of a typical titration experiment. Hybridization measurements are completed at four different temperatures, however a van’t Hoff analysis of the data is complicated by the varying degree of intramolecular base stacking within each DNA strand as a function of temperature. The same thermodynamic framework is applied to a model protein– ligand interaction, the binding of ribonuclease A with the nucleotide inhibitor 3’-UMP, and to a conformational equilibrium, the change in tertiary structure of α-lactalbumin in molar guanidinium chloride solutions. The ribonuclease study yields a value of ΔGS= +160 kcal/mol, whereas the folding equilibrium yields ΔGS≈ 0, an apparent characteristic of hydrophobic interactions. These examples complement previous applications of the governing equation to the interaction of smaller molecules and demonstrate the importance of solvation energy in biothermodynamics.
Repatterning of mammalian backbone regionalization in cetaceans
Authors: Gillet Amandine , Jones Katrina E. , Pierce Stephanie E.
Published: March 2024

The reinvasion of the aquatic realm by cetaceans is one of the most iconic ecological transitions that led to drastic modifications of the mammalian body plan, especially the axial skeleton. Relative to the vertebral column of other mammals that is subdivided into numerous anatomical regions, regional boundaries of the cetacean backbone appear obscured. Whether the traditional mammalian regions are present in cetaceans but hard to detect due to anatomical homogenization or if regions have been entirely repatterned remains unresolved. Here we combine a segmented linear regression approach with spectral clustering to quantitatively investigate the number, position, and homology of vertebral regions across species from all major cetacean clades. We propose the new “Nested Regions” hypothesis under which the cetacean backbone is composed of six homologous modules subdivided into six to nine post-cervical regions, with the degree of regionalization dependent on vertebral count and ecology. Compared to terrestrial mammals, the cetacean backbone is less regionalized in the precaudal segment but more regionalized in the caudal segment, indicating repatterning of the vertebral column associated with the transition from limb-powered to axial-driven locomotion.
Biochemical analysis of the endoribonuclease activity of the human mitochondrial topoisomerase 1
Authors: Bader Cyrielle P. J. , Kasho Erika , Forslund Josefin M. E. , Wessels Malgorzata , Wanrooij Paulina H.
Published: March 2024

The incorporation of ribonucleotides (rNMPs) into the nuclear genome leads to severe genomic instability, including strand breaks and short 2-5 bp deletions at repetitive sequences. Curiously, the detrimental effects of rNMPs are not observed for the human mitochondrial genome (mtDNA) that typically contains several rNMPs per molecule. Given that the nuclear genome instability phenotype is dependent on the activity of the nuclear topoisomerase 1 enzyme (hTop1), and mammalian mitochondria contain a distinct topoisomerase 1 paralog (hTop1mt), we hypothesized that the differential effects of rNMPs on the two genomes may reflect differing properties of the two cellular topoisomerase 1 enzymes. Here, we characterized the endoribonuclease activity of hTop1mt and found it to be less efficient than that of its nuclear counterpart, a finding that was partly explained by its substrate binding properties. While hTop1 and yeast Top1 showed higher affinity for an rNMP-containing substrate and were able to cleave at an rNMP located outside of the consensus cleavage site, hTop1mt showed no preference for rNMPs. As a consequence, hTop1mt was inefficient at producing the short rNMP-dependent deletions that are characteristic of Top1-driven genome instability. These findings help explain the tolerance of rNMPs in the mitochondrial genome.
Consumer xenocentrism when domestic products are better
Authors: Thoumrungroje Amonrat , Diamantopoulos Adamantios , Scherer Nathalie Caroline
Published: March 2024

Purpose

Drawing on cue utilization theory and the theory of motivated reasoning, we investigate the impact of consumer xenocentrism on product preferences in a situation where domestic products objectively outperform their foreign counterparts.

Design/methodology/approach

We develop and test a model linking xenocentrism to consumers’ preference towards domestic vs. foreign products by (1) examining the mediating role of consumers’ ability to identify the superior product and (2) assessing the role of product involvement in potentially moderating this relationship. An experimental design was employed, whereby respondents (Thai consumers, N = 579) were asked to compare two products in the same product category, one foreign and one domestic. In one condition, the foreign product outperformed the domestic one on a range of relevant product attributes, whereas in a second condition, the opposite was the case.

Findings

Our findings provide clear evidence that xenocentric consumers often cannot recognize the superiority of domestic products and, even if they do, they still exhibit preferences toward (inferior) foreign products. Thus, for xenocentric consumers, it seems that the country of origin (COO) overrides other cues and often results in suboptimal product choices.

Originality/value

Our study adds to our theoretical understanding of the functioning of the consumer xenocentrism construct and has important implications for foreign companies targeting xenocentric consumers as well as for local firms seeking to counteract xenocentric tendencies.
Real Estate Insights AI: real estate’s new roommate – the good, the bad and the algorithmic
Authors: Szumilo Nikodem , Wiegelmann Thomas
Published: March 2024

Purpose

This paper aims to provide a comprehensive analysis of the transformative impact of Artificial Intelligence (AI) and Large Language Models (LLMs), such as GPT-4, on the real estate industry. It explores how these technologies are reshaping various aspects of the sector, from market analysis and valuation to customer interactions and evaluates the balance between technological efficiency and the preservation of human elements in business.

Design/methodology/approach

The study is based on an analysis of the strengths and weaknesses of AI as a technology in applications for real estate. It uses this framework to assess the potential of this technology in different use cases. This is supplemented by an emerging literature on the topic, practical insights and industry expert opinions to provide a balanced perspective on the subject.

Findings

The paper reveals that AI and LLMs offer significant benefits in real estate, including enhanced data-driven decision-making, predictive analytics and operational efficiency. However, it also uncovers critical challenges, such as potential biases in AI algorithms and the risk of depersonalising customer interactions.

Practical implications

The paper advocates for a balanced approach to adopting AI, emphasising the importance of understanding its strengths and limitations while ensuring ethical usage in the diverse and complex landscape of real estate.

Originality/value

This work stands out for its balanced examination of both the advantages and limitations of AI in real estate. It introduces the novel concept of the “jagged technological frontier” in real estate, providing a unique framework for understanding the interplay between AI and human expertise in the industry.
Conclusion: what should be the role of tourism education social structures to create and support collaborative learning environments and the tourism sector?
Authors: Guden Nafiya , Safaeimanesh Farzad
Published: March 2024

Purpose

This theme issue sought to find answers to the question: What should be the role of tourism education social structures to create and support collaborative learning environments and the tourism sector?

Design/methodology/approach

A thematic analysis of the articles in this collection draws together the key outcomes related to the strategic question, with particular reference to the contribution to knowledge, important to generate ideas and conceptual researches that will support institutions teaching tourism and hospitality. Archive research results and recommendations to encourage the collaboration of different stakeholders involved in sustainable tourism development. Most importantly to raise awareness of the question of what educators are doing in tourism education for social, organizational structures in learning environments and the actual tourism sector.

Findings

Two key players, the educator and sector has been challenged to consider their roles in education as well as depicting the role of social and organizational structures that support the students, institutions and the tourism sector. The main findings have proven the important role education plays for a truly sustainable tourism model, suggesting that it is not possible to create awareness of the sustainable development goals without incorporating them in the tourism education system with the support of information computer technology.

Originality/value

This paper reflects on the strategic question discussed in this theme issue, and it contains valid reviews, research studies by practitioners who are experienced in the field of tourism education with an opportunity to research, reflect and develop new possibilities in learning, mitigate negative points and increase positive tourism education roles for sustainable tourism development, in the destination and industry.
Soil microbial gene abundance rather than diversity and network complexity predominantly determines soil multifunctionality in Tibetan alpine grasslands along a precipitation gradient
Authors: Pan Junxiao , Li Yang , Zhang Ruiyang , Tian Dashuan , Wang Peiyan , Song Lei , Quan Quan , Chen Chen , Niu Shuli , Zhang Xinyu , Wang Jinsong
Published: March 2024

The relationship between biodiversity and ecosystem functioning has mainly focused on plant communities, with comparably little known about soil microbial‐driven ecosystem functions. Climate change severely threatens soil microbial roles, but how soil microbial communities determine soil multifunctionality under climate change is poorly understood.

Here, we evaluated the effects of diverse bacterial and fungal properties, including microbial gene abundance, diversity and network complexity, on soil multifunctionality (nine soil functions) across a 3000 km transect along a natural precipitation gradient in Tibetan alpine grasslands. Variation partitioning analyses were performed to disentangle the relative importance of bacterial and fungal properties to the variation of soil multifunctionality. Moreover, structural equation modelling was adopted to explore the influencing pathways of precipitation‐induced changes in plant and edaphic factors to soil microbial properties and, consequently, soil multifunctionality.

Soil multifunctionality was positively associated with bacterial and fungal gene abundance, diversity and network complexity. Microbial gene abundance was the more important driver influencing soil multifunctionality than microbial diversity and network complexity. In addition, microbial gene abundance was mainly determined by precipitation‐induced changes in soil pH. Meanwhile, the effects of bacterial properties on soil multifunctionality were much larger than those of fungi. Soil multifunctionality was closely associated with different bacterial (cellulolysis, ligninolysis, nitrogen reduction, denitrification and nitrate fixation etc.) and fungal (soil saprotrophs, arbuscular mycorrhizal and plant pathogens etc.) functional guilds, which exert vital regulations on an array of soil biogeochemical cycling processes.

Our results provide the large‐scale evidence of the relative contribution of soil microbial gene abundance, diversity and network complexity to the variation of soil multifunctionality in alpine grasslands with changing precipitation, which is pivotal for understanding microbial roles in modulating and predicting soil multifunctionality under future precipitation changes.

Read the free Plain Language Summary for this article on the Journal blog.
How are the impacts of multiple anthropogenic drivers considered in marine ecosystem service research? A systematic literature review
Authors: Solé Figueras Liliana , Zandt Emma I. , Buschbaum Christian , Meunier Cédric Léo
Published: March 2024

In recent decades, great research efforts have been made to understand how specific anthropogenic drivers impact coastal marine ecosystems and their services. Nevertheless, we still lack a synthesis of the existing knowledge on single and multiple anthropogenic drivers impacts to coastal marine systems, which is necessary to guide future work.

The objective of this paper is to assess the current knowledge on the impacts of anthropogenic drivers and their interactions on coastal marine ecosystem services, with emphasis on abiotic drivers as dissolved nutrients (eutrophication or de‐eutrophication), temperature (warming), pH (acidification) and oxygen (hypoxia). We performed a systematic review of the literature consisting of 164 papers using the PRISMA method (Preferred Reporting Items for Systematic Reviews and Meta‐Analyses). We only include English‐written papers, we exclude non‐English papers to avoid potential errors in representing or interpreting scientific information due to language limitations among the authors.

The results show that coastal marine ecosystem service research has largely focused on single drivers, while multiple driver assessments are less common.

Assessments partially integrate multiple driver complexity, but they do not consider (1) relations and feedbacks between drivers; 2() social processes dynamics; and (3) temporal and spatial scales.

Synthesis and applications. We have reviewed the current scientific knowledge on how human drivers affect coastal marine ecosystem services. We found that understanding the combined effects of different drivers and considering various time and space scales is still a pending issue. Ignoring multiple drivers, their interactions and time and space scales limits our understanding of reality, and results in high levels of uncertainty. This affects policies and actions, as they rely on uncertain information. Thus, incomplete knowledge leads to poor management of coastal ecosystem services. To improve this, we propose research framework to better consider multiple drivers and time and space factors.
Tropical agroforestry supports insect pollinators and improves bean yield
Authors: Kingazi Nanyika , Temu Ruwa‐Aichi , Sirima Agnes , Jonsson Mattias
Published: March 2024

Pollination services contribute to crop productivity worldwide, but insect pollinators are declining in most agricultural landscapes, mainly due to agricultural expansion and an increase in intensive agricultural practices. To reduce the negative effects of agricultural expansion and intensification, farmers can adopt ecological interventions, such as diversifying agricultural systems through agroforestry. However, there have been variable results on the effectiveness of agroforestry in enhancing pollinators and pollination services. Furthermore, most of the information has been generated in temperate regions, while the impact of agroforestry in tropical East Africa is largely unknown.

Using common beans (Phaseolus vulgaris L.) as the focal crop, this study tested whether a tropical agroforestry system called Chagga home gardens supports pollinator communities and improves pollination and crop yield. We examined 16 agroforestry plots paired with 16 non‐agroforestry plots located along a gradient of woody (trees and shrubs) cover within a 1‐km radius to document the abundance, species richness and visitation rates of pollinating insects on bean flowers and how they contributed to bean yield.

The beans planted in the agroforestry plots had almost twice the abundance of insect pollinators, three times the richness of the species and almost twice the visitation rates than those planted in non‐agroforestry plots. We also found a significant positive effect of woody cover in the surrounding landscape on insect pollinator abundances, but not on species richness and visitation rates. Additionally, the abundance and richness of insect pollinators increased significantly with flower abundance, while the overall plant richness in a plot significantly increased insect pollinator abundance and their visitation rate. The difference in bean yield between unbagged flowers (in which insect pollinators were allowed to access bean flowers) and bagged flowers and the total yield were higher in agroforestry than in non‐agroforestry plots.

Synthesis and applications. This study showed that, compared to monoculture, agroforestry generally promotes pollination services in a tropical context. Furthermore, we found that agroforestry is likely to be particularly helpful for pollinators when it increases flower abundance and plant richness and if it is coordinated so that woody cover also increases at the landscape scale.
Rationalising Mid‐Century Choice of Law: Legal Technique and its Limits in the ‘Dark Science’ of Conflicts
Authors: Bomhoff Jacco
Published: March 2024

Under the common banner of a search for a ‘more rational’ approach to choice of law, US conflict‐of‐laws scholars of the late 1950s and the 1960s produced an impressive array of new technical instruments for their discipline. This article situates their work in the broader contexts of innovations in the social‐ and behavioural sciences and in legal‐ and political theory of this period. On this contextual reading, the methodological clashes of the so‐called ‘choice‐of‐law revolution’ change in shape and become part of a much larger story – one with relevance also outside the discipline and beyond the United States. That story is about different degrees of faith in the capacities of technical instruments and practices, like legal doctrine, to manage and resolve conflict, by making disparate factors commensurable, and by affording outcomes that optimise all competing interests in play. By revisiting these mid‐century battles over conflicts methods in light of contemporaneous understandings of ‘rationality’ and ‘legitimacy’ in other fields, the article contributes to our understanding of the genealogy of post‐war choice of law, as well as of the history of these ideals – and their technical means – in modern legal thought.
Adverse pregnancy outcomes in pregnant women with chronic kidney disease: A systematic review and meta‐analysis
Authors: Jeyaraman Deepthika , Walters Ben , Bramham Kate , Fish Richard , Lambie Mark , Wu Pensée
Published: March 2024

Background

Chronic kidney disease (CKD) is associated with an increased risk of adverse pregnancy outcomes, but the risk at different stages of CKD (defined by estimated glomerular filtration rate, eGFR) compared with women without CKD has not been quantified in large cohorts.

Objectives

To quantify the association between CKD and adverse pregnancy outcomes according to CKD definition, CKD stage and presence or absence of diabetes.

Search strategy

A systematic search of EMBASE and MEDLINE from inception to 5 January 2023.

Selection criteria

English‐language randomised controlled trials as well as cohort and case–control studies investigating adverse pregnancy outcomes in pregnant women with CKD.

Data collection and analysis

Two reviewers conducted independent data extractions. A random‐effects model was used to estimate risk.

Main results

We included 19 studies with 3 251 902 women. Defining CKD using eGFR or serum creatinine produced results with greater effect size but wider confidence intervals. Compared with CKD stages 1–2, women with CKD stages 3–5 have a greater risk, but also greater imprecision in the risk estimate, of the following outcomes: pre‐eclampsia (OR 55.18, 95% CI 2.63–1157.68, vs OR 24.74, 95% CI 1.75–348.70), preterm birth (OR 20.24, 95% CI 2.85–143.75, vs OR 8.18, 95% CI 1.54–43.46) and neonatal intensive care unit admission (OR 19.32, 95% CI 3.07–121.68, vs OR 9.77, 95% CI 2.49–38.39). Women with diabetic kidney disease, compared with women without diabetic kidney disease, have higher risks of maternal mortality, small‐for‐gestational‐age neonates, pre‐eclampsia and gestational hypertension.

Conclusions

There is heterogeneity in the definition of CKD in pregnancy. Future studies should consider ways to standardise its definition and measurement in pregnancy.
Fetal growth in IVF/ICSI pregnancies from fresh/thawed embryo transfer and natural conception
Authors: Cavoretto Paolo Ivo
Published: March 2024

Linked article: This is a mini commentary on Ageheim et al., pp. 1229–1237 in this issue. To view this article visit https://doi.org/10.1111/1471‐0528.17786.
Comparative genomics provides insights into molecular adaptation to hypermetamorphosis and cantharidin metabolism in blister beetles (Coleoptera: Meloidae)
Authors: RICCIERI Alessandra , SPAGONI Lucrezia , LI Ming , FRANCHINI Paolo , ROSSI Marianna N. , FRATINI Emiliano , CERVELLI Manuela , BOLOGNA Marco A. , MANCINI Emiliano
Published: March 2024

Blister beetles (Coleoptera: Meloidae) are currently subdivided into three subfamilies: Eleticinae (a basal group), Nemognathinae, and Meloinae. These are all characterized by the endogenous production of the defensive terpene cantharidin (CA), whereas the two most derived subfamilies show a hypermetamorphic larval development. Here, we provide novel draft genome assemblies of five species sampled across the three blister beetle subfamilies (Iselma pallidipennis, Stenodera caucasica, Zonitis immaculata, Lydus trimaculatus, and Mylabris variabilis) and performed a comparative analysis with other available Meloidae genomes and the closely‐related canthariphilous species (Pyrochroa serraticornis) to disclose adaptations at a molecular level. Our results highlighted the expansion and selection of genes potentially responsible for CA production and metabolism, as well as its mobilization and vesicular compartmentalization. Furthermore, we observed adaptive selection patterns and gain of genes devoted to epigenetic regulation, development, and morphogenesis, possibly related to hypermetamorphosis. We hypothesize that most genetic adaptations occurred to support both CA biosynthesis and hypermetamorphosis, two crucial aspects of Meloidae biology that likely contributed to their evolutionary success.