bluuebunny/crossref_metadata_2025 huggingface dataset:
Set-Off Between Solvent Parties: Equitable Set-Off
Authors: Derham Rory
Published: December 2024

This chapter discusses the set-off between solvent parties in correlation with the notion of equitable set-off. It explains that an equitable set-off has been pleaded directly as a defence in the claimant’s action since the Judicature Acts. Similar to other forms of set-off, equitable set-off is concerned with monetary demands. Thus, a person cannot retain a non-monetary asset by way of equitable set-off against a money claim. The chapter cites that an equitable set-off can take several forms before elaborating on the key concepts of implied agreement, equitable proprietary estoppel, acting by analogy with the Statutes, and substantive equitable set-off.
Set-Off Between Solvent Parties: Various Aspects
Authors: Derham Rory
Published: December 2024

This chapter explores the various aspects of set-off between solvent parties. It starts with the interplay of charterparties and bills of lading before considering the key concepts of negotiable instruments, letters of credit, and direct debits. Meanwhile, the general principle of building and construction contracts revolves around how a cross-claim for damages for delay, bad workmanship, or failure to complete is capable in principle of being employed in a set-off against an amount due for work performed under a building contract. The chapter also considers the criticisms of the state of the law of set-off in correlation with the Statutes of Set-off. It explains the undesirability of extending the defence of set-off to encompass unrelated damages cross-claims.
Set-Off in Insolvency
Authors: Derham Rory
Published: December 2024

This chapter discusses the extent of set-off in insolvency. It cites that the principal source of rights of set-off in the event of bankruptcy is section 323 of the Insolvency Act 1986. The availability of set-off may be crucial in circumstances where a bankrupt and a creditor have had prior mutual dealings giving rise to cross-demands. Additionally, the mutual credit provision extends to the situation where an insolvent partnership is wound up in accordance with the Insolvent Partnerships Order 1994. In company administration and liquidation, the relevant provision is set out, respectively, in the Insolvency (England and Wales) Rules 2016. The chapter also considers the provisions in Australia concerning bankruptcy and company liquidation.
The Rule in Cherry v Boultbee
Authors: Derham Rory
Published: December 2024

This chapter focuses on the rule in Cherry v Boultbee. It explains that the equitable principle is concerned with whether a person entitled to participate in a fund is bound to contribute to the aid of that fund. The rule, originally developed in the context of administering the estates of deceased people, illustrates a more fundamental principle of equity, that he who seeks equity must do equity. Unless an intention has been manifested to exclude the operation of the Cherry v Boultbee principle, the executor in such a case may decline to hand over anything in satisfaction of the legacy to the extent of the debt. The chapter cites that Cherry v Boultbee should be distinguished from an executor’s right of retainer.
Set-Off Agreements
Authors: Derham Rory
Published: December 2024

This chapter provides an overview of set-off agreements. It explains that parties dealing with each other may enter into an agreement for the satisfaction of their cross-demands by bringing them into an account in a set-off. Moreover, the set-off may be expressed to occur immediately or upon the happening of a specified future event. The chapter cites that an agreement for a set-off can arise by custom or be inferred from conduct. However, if a set-off agreement is terminated under a contractual right of termination, the termination may be on terms preserving the operation of the agreement in respect of matters covered by it before the termination.
Assignees, and Other Interested Third Parties
Authors: Derham Rory
Published: December 2024

This chapter elaborates on the key concepts of assignees and other interested parties. It tackles the availability of set-off in cases involving assignments, crystallized floating securities, trusts, execution creditors, and subrogation rights. When a debt is assigned, a set-off may occur between the assignee’s beneficial interest in the assigned debt and a cross-claim that the debtor has against the assignee. In some circumstances, the Contracts (Rights of Third Parties) Act 1999 allows a person not part of the contract to enforce a term in the contract purporting to confer a benefit on them. The chapter also explains that an intervening third party interest in a debt may take the form of fixed security, which commonly arises when floating security over a company’s assets and undertaking crystallizes.
Enforceability of mahr under a sharīʿa law-based contract in New Zealand: a comparison with United Kingdom, Australia, and Canada
Authors: Raman Durgeshree
Published: December 2024

Enforcement of sharīʿa-based marriage contracts, which contain provisions for the payment of mahr (dowry/dower) upon death of husband or divorce by either party, has proven to be quite challenging in jurisdictions such as the UK, Australia, and Canada. New Zealand courts are currently dealing with their first such case. In undertaking a comparative analysis, this article highlights that a statutory framework for dealing with such claims is better suited than simply enforcing it as a simple contract, which has the potential to produce unjust and inequitable results.
Evaluation of the diagnostic performance of a semi-quantitative lateral flow assay for the detection of Cryptococcus antigen in serum and cerebrospinal fluid specimens
Authors: Castañeda-Torres Maria Camila , Arango Julián , Zuluaga Alejandra , Rúa-Giraldo Álvaro , Caceres Diego H
Published: December 2024

Cryptococcosis predominantly affects immunocompromised individuals, particularly those with advanced HIV disease, with meningitis being the most severe form and linked to high mortality. Diagnosis typically relies on rapid Cryptococcus antigen (CrAg) testing, and antigen titer quantification helps in early detection and assessing disease severity. However, conventional titer methods are often more expensive than qualitative antigen detection. This study assessed the diagnostic performance of a semi-quantitative lateral flow assay (CrAgSQ LFA, IMMY™) for CrAg detection in serum and cerebrospinal fluid (CSF) collected between 2014 and 2022. The CrAgSQ LFA was compared to the standard CrAg LFA (IMMY™) and Clarus Cryptococcal Ag enzyme immunoassay (EIA-CrAg, IMMY™). The CrAgSQ LFA demonstrated 100% sensitivity and specificity in both serum and CSF, with perfect agreement (kappa 1.00) with the CrAg LFA. When comparing the CrAgSQ LFA with the titer measurement results obtained using CrAg LFA, titers ranged as follows: in category 1+, from 1:2 to 1:20; in 2+, from 1:5 to 1:40; in 3+, from 1:20 to 1:2560; and in 4+, from 1:320 to 1:2560. Titer results for the CrAgSQ LFA aligned well with CrAg LFA, and operator agreement was strong, with weighted kappa values of 0.926 and 0.966. The CrAg-EIA showed a sensitivity of 84% and specificity of 100% using the manufacture cutoff (>0.265), which improved to 96% sensitivity with an optimized cutoff value (>0.145). Overall, the CrAgSQ LFA demonstrated high accuracy and reliability, suggesting it could be a valuable tool for diagnosing cryptococcosis in the Americas.
Cosmological imprints in the filament with DisPerSE
Authors: Wu Ziyong , Luo Yu , Wang Wei , Kang Xi , Cen Renyue
Published: December 2024

In the regime of cosmology and large-scale structure formation, filaments are vital components of the cosmic web. This study employs statistical methods to examine the formation, evolution, and cosmological constraints of filaments identified by DisPerSe. We run large-sample of N-body simulations to study the filament length and its evolution. In general, the filament length distribution can be fitted by a power law with both the normalization and power index dependent on redshift and cosmological parameters. It is discovered that filament length distribution is influenced by various cosmological parameters, with σ8 and ns exhibiting slightly stronger dependence than Ωm. We also uncover a three-stage filament formation process from z ∼ 3 to z ∼ 1: rapid formation of both long and short filaments from z ∼ 3 to z ∼ 2, persistence of long filaments from z ∼ 2 to z ∼ 1, followed by fragmentation and increased prevalence of shorter filaments below z ∼ 1. Finally, we employ initial power spectrum fluctuations to elucidate the cosmological dependence on the filament length function. These insights enhance our understanding of filament evolution and their cosmological relevance and also highlight the potential cosmological applications in observations.
Phase-space Delaunay tessellation field estimator
Authors: Feldbrugge Job
Published: December 2024

The reconstruction of density and velocity fields is of central importance to the interpretation of N-body simulations. We propose a phase-space extension of the Delaunay tessellation field estimator (DTFE) that uses the mapping from Lagrangian to Eulerian space to track the dark matter fluid in phase-space. The new reconstruction scheme removes several artefacts from the conventional DTFE in multistream regions, while preserving the adaptive resolution in high-density regions and yielding continuous fields. The estimator also removes some tessellation artifacts of a previously proposed phase-space reconstruction scheme. The method is particularly suitable to the estimation of density and velocity fields of N-body simulations with multiple particle species and/or starting with glass initial conditions.
Asteroseismic masses of red giants in the Galactic Globular Clusters M9 and M19
Authors: Howell Madeline , Campbell Simon W , Kalup Csilla , Stello Dennis , De Silva Gayandhi M
Published: December 2024

Asteroseismic masses of globular cluster (GC) stars are invaluable to investigate stellar evolution. Previously, only two GCs have been seismically studied. We present new detections of solar-like oscillations in the clusters M9 and M19, focusing on two key areas: stellar mass-loss and GC multiple populations. Using K2 photometry, we detect solar-like oscillations in stars on the red giant branch and early asymptotic giant branch. We measure an integrated mass-loss for M9 of $0.16\pm 0.02$(rand)$^{+0.03}_{-0.03}$(sys)$~\mathrm{M}_{\odot }$ and M19 of $0.33\pm 0.03$(rand)$^{+0.09}_{-0.07}$(sys)$~\mathrm{M}_{\odot }$. Comparing these to the mass-loss estimates from previous seismically studied clusters, we derive a preliminary relationship between stellar mass-loss and metallicity for Type I GCs. We find that the mass-loss for M19 – a Type II GC – is significantly larger, suggesting Type II clusters follow a different mass-loss-metallicity trend. We also examine the mass distributions in each evolutionary phase for evidence of a bimodality that could indicate mass differences between sub-populations. While no clear bimodality is observed, there is tentative evidence suggesting the presence of two mass populations. Classification through spectroscopic abundances into the sub-populations is needed to verify these findings. This study reinforces that asteroseismology of GC stars provides an excellent testbed for studying stellar evolution. However, to advance the field we need high-quality photometry of more GCs, a goal that could be realised with the upcoming Roman Telescope.
CO-to-H2 conversion factor and grain size distribution through the analysis of αCO–qPAH relation
Authors: Chiang I-Da , Hirashita Hiroyuki , Chastenet Jérémy , Sandstrom Karin M , Koch Eric W , Leroy Adam K , Teng Yu-Hsuan , Williams Thomas G
Published: December 2024

The CO-to-H$_2$ conversion factor ($\alpha _\mathrm{CO}$) is expected to vary with dust abundance and grain size distribution through the efficiency of shielding gas from CO-dissociation radiation. We present a comprehensive analysis of $\alpha _\mathrm{CO}$ and grain size distribution for nearby galaxies, using the polycyclic aromatic hydrocarbon (PAH) fraction ($q_\mathrm{PAH}$) as an observable proxy of grain size distribution. We adopt the resolved observations at 2 kpc resolution in 42 nearby galaxies, where $\alpha _\mathrm{CO}$ is derived from measured metallicity and surface densities of dust and H i assuming a fixed dust-to-metal ratio. We use an analytical model for the evolution of H$_2$ and CO, in which the evolution of grain size distribution is controlled by the dense-gas fraction ($\eta$). We find that the observed level of $q_\mathrm{PAH}$ is consistent with the diffuse-gas-dominated model ($\eta =0.2$) where dust shattering is more efficient. Meanwhile, the slight decreasing trend of observed $q_\mathrm{PAH}$ with metallicity is more consistent with high-$\eta$ predictions, likely due to the more efficient loss of PAHs by coagulation. We discuss how grain size distribution (indicated by $q_\mathrm{PAH}$) and metallicity impact $\alpha _\mathrm{CO}$; we, however, did not obtain conclusive evidence that the grain size distribution affects $\alpha _\mathrm{CO}$. Observations and model predictions show similar anticorrelation between $\alpha _\mathrm{CO}$ and 12 + log(O/H). Meanwhile, there is a considerable difference in how resolved $\alpha _\mathrm{CO}$ behaves with $q_\mathrm{PAH}$. The observed $\alpha _\mathrm{CO}$ has a positive correlation with $q_\mathrm{PAH}$, while the model-predicted $\alpha _\mathrm{CO}$ does not have a definite correlation with $q_\mathrm{PAH}$. This difference is likely due to the limitation of one-zone treatment in the model.
Synoptic Wide-field EVN–e-MERLIN Public Survey (SWEEPS) – I. First steps towards commensal surveys with VLBI
Authors: Herbé-George Célestin , McKean J P , Morganti Raffaella , Radcliffe Jack F
Published: December 2024

The high angular resolution and sensitivity of Very Long Baseline Interferometry (VLBI) offer a unique tool to identify and study active galactic nuclei and star-formation activity over cosmic time. However, despite recent technical advances, such as multiple phase centre correlation, VLBI surveys have thus far been limited to either a few well-studied deep-fields or wide-areas to a relatively shallow depth. To enter the era of extensive statistical studies at high angular resolution, a significantly larger area of the sky must be observed to much better sensitivity with VLBI. The Synoptic Wide-field EVN–e-MERLIN Public Survey (SWEEPS) is a proposed commensal observing mode for the EVN and e-MERLIN, where single-target principle investigator-led observations are re-correlated at the position of known radio sources within 12 arcmin of the pointing centre. Here, we demonstrate a proof-of-concept of this methodology by detecting a 5.6 mJy core-jet object at 1.7 GHz that would have otherwise been lost from the parent data set. This is the first object to be recovered as part of the SWEEPS pilot programme, which highlights the potential for increasing sample sizes of VLBI-detected radio sources with commensal observing modes in the near future.
Phylogenetic Analysis of 590 Species Reveals Distinct Evolutionary Patterns of Intron–Exon Gene Structures Across Eukaryotic Lineages
Authors: Glick Lior , Castiglione Silvia , Loewenthal Gil , Raia Pasquale , Pupko Tal , Mayrose Itay
Published: December 2024

Introns are highly prevalent in most eukaryotic genomes. Despite the accumulating evidence for benefits conferred by the possession of introns, their specific roles and functions, as well as the processes shaping their evolution, are still only partially understood. Here, we explore the evolution of the eukaryotic intron–exon gene structure by focusing on several key features such as the intron length, the number of introns, and the intron-to-exon length ratio in protein-coding genes. We utilize whole-genome data from 590 species covering the main eukaryotic taxonomic groups and analyze them within a statistical phylogenetic framework. We found that the basic gene structure differs markedly among the main eukaryotic groups, with animals, and particularly chordates, displaying intron-rich genes, compared with plants and fungi. Reconstruction of gene structure evolution suggests that these differences evolved prior to the divergence of the main phyla and have remained mostly conserved within groups. We revisit the previously reported association between the genome size and the mean intron length and report that this association differs considerably among phyla. Analyzing a large and diverse dataset of species with whole-genome information while applying advanced modeling techniques allowed us to obtain a global evolutionary perspective. Our findings may indicate that introns play different molecular and evolutionary roles in different organisms.
Generic revision of the Recent Turridae (Neogastropoda: Conoidea)
Authors: Kantor Yuri , Bouchet Philippe , Fedosov Alexander , Puillandre Nicolas , Zaharias Paul
Published: December 2024

The family Turridae, once considered to encompass the entire diversity of Conoidea, excluding only the cone shells (family Conidae) and the auger shells (family Terebridae), has undergone significant redefinition based on both morphological and molecular data. Prior to this study, it included 15 Recent genera, comprising 209 species. However, a recent comprehensive analysis of an extensive dataset featuring 3,159 cytochrome c oxidase subunit I sequences has unveiled numerous species complexes, new species and previously undiscovered deep lineages. The newly proposed classification of Turridae based on an exon-capture phylogeny recognizes 24 clades, each worthy of genus rank, though only 13 of them had available names. As a result, 11 new genera have been described, namely Thielesyrinx n. gen., Shutogemmula n. gen., Mcleanigemmula n. gen., Pseudogemmula n. gen., Deceptigemmula n. gen., Oliveragemmula n. gen., Powelligemmula n. gen., Kilburnigemmula n. gen., Alisigemmula n. gen., Taylorigemmula n. gen. and Anisogemmula n. gen. With the exception of Thielesyrinx n. gen., species from all of these were previously classified within Gemmula, or Lophiotoma. Notably, some new genera, such as Deceptigemmula n. gen., Kilburnigemmula n. gen., Shutogemmula n. gen. and Taylorigemmula n. gen., cannot be morphologically differentiated, as similar species are found in other genera. Therefore, their distinction relies solely on molecular data. The name Eugemmula is re-instated from the synonymy of Gemmula. Purpuraturris is synonimized with Annulaturris, while Iotyrris with Xenuroturris. In total, we recognize 312 species/primary species hypotheses (PSHs) within the family. Molecular data were obtained for 212 species (among them 15 species complexes comprising in total 45 PSHs), mostly for the first time. A characteristic feature common to the entire family is the position of the relatively narrow anal sinus on the whorl periphery or immediately above it. Radula was examined in representatives of all genera. Although in several cases the radular morphology can aid genus differentiation (e.g. distinguishing Turris from Annulaturris), it is mostly a highly homoplastic structure, with very similar radular types occurring in distantly related genera.
VE-cadherin may suppress inflammation depending on the phase of inflammation of rheumatoid arthritis
Authors: Nishimi Shinichiro , Fukuse Sayaka , Miwa Yusuke , Wakabayashi Kuninobu , Isozaki Takeo
Published: December 2024

Objectives

A disintegrin and metalloproteinase (ADAM)-15 and vascular endothelial (VE)-cadherin are involved in angiogenesis. We investigated the relationship between ADAM-15 and VE-cadherin expressions in rheumatoid arthritis (RA).

Methods

VE-cadherin concentrations in the serum of patients with RA were measured using the enzyme linked immunosorbent assay. We stimulated fibroblast-like synoviocytes (RA-FLS) with VE-cadherin and measured the vascular endothelial growth factor (VEGF) and inflammatory cytokine levels using ELISA. We also examined the correlation between serum VE-cadherin levels and DAS-28ESR, and used the Matrigel assay to examine VE-cadherin involvement in angiogenesis.

Results

Serum VE-cadherin levels were significantly higher in patients with RA than in healthy controls. A negative correlation was observed between VE-cadherin and DAS-28ESR. VEGF, chemokine ligand 16, intercellular adhesion molecule-1, and interleukin-8 levels in the supernatant of RA-FLS or human umbilical vein endothelial cells stimulated with VE-cadherin were significantly lower than those in the controls. The number of intercellular bridges formed by endothelial cells using Matrigel significantly decreased in RA synovial fluids from which VE-cadherin had been removed compared to synovial fluids treated with control immunoglobulin G.

Conclusion

VE-cadherin may have an inhibitory effect on inflammation depending on the phase of RA inflammation.
Ensembl 2025
Authors: Dyer Sarah C , Austine-Orimoloye Olanrewaju , Azov Andrey G , Barba Matthieu , Barnes If , Barrera-Enriquez Vianey Paola , Becker Arne , Bennett Ruth , Beracochea Martin , Berry Andrew , Bhai Jyothish , Bhurji Simarpreet Kaur , Boddu Sanjay , Branco Lins Paulo R , Brooks Lucy , Ramaraju Shashank Budhanuru , Campbell Lahcen I , Martinez Manuel Carbajo , Charkhchi Mehrnaz , Cortes Lucas A , Davidson Claire , Denni Sukanya , Dodiya Kamalkumar , Donaldson Sarah , El Houdaigui Bilal , El Naboulsi Tamara , Falola Oluwadamilare , Fatima Reham , Genez Thiago , Martinez Jose Gonzalez , Gurbich Tatiana , Hardy Matthew , Hollis Zoe , Hunt Toby , Kay Mike , Kaykala Vinay , Lemos Diana , Lodha Disha , Mathlouthi Nourhen , Merino Gabriela Alejandra , Merritt Ryan , Mirabueno Louisse Paola , Mushtaq Aleena , Hossain Syed Nakib , Pérez-Silva José G , Perry Malcolm , Piližota Ivana , Poppleton Daniel , Prosovetskaia Irina , Raj Shriya , Salam Ahamed Imran Abdul , Saraf Shradha , Saraiva-Agostinho Nuno , Sinha Swati , Sipos Botond , Sitnik Vasily , Steed Emily , Suner Marie-Marthe , Surapaneni Likhitha , Sutinen Kyösti , Tricomi Francesca Floriana , Tsang Ian , Urbina-Gómez David , Veidenberg Andres , Walsh Thomas A , Willhoft Natalie L , Allen Jamie , Alvarez-Jarreta Jorge , Chakiachvili Marc , Cheema Jitender , da Rocha Jorge Batista , De Silva Nishadi H , Giorgetti Stefano , Haggerty Leanne , Ilsley Garth R , Keatley Jon , Loveland Jane E , Moore Benjamin , Mudge Jonathan M , Naamati Guy , Tate John , Trevanion Stephen J , Winterbottom Andrea , Flint Bethany , Frankish Adam , Hunt Sarah E , Finn Robert D , Freeberg Mallory A , Harrison Peter W , Martin Fergal J , Yates Andrew D
Published: December 2024

Ensembl (www.ensembl.org) is an open platform integrating publicly available genomics data across the tree of life with a focus on eukaryotic species related to human health, agriculture and biodiversity. This year has seen a continued expansion in the number of species represented, with >4800 eukaryotic and >31 300 prokaryotic genomes available. The new Ensembl site, currently in beta, has continued to develop, currently holding >2700 eukaryotic genome assemblies. The new site provides genome, gene, transcript, homology and variation views, and will replace the current Rapid Release site; this represents a key step towards provision of a single integrated Ensembl site. Additional activities have included developing improved regulatory annotation for human, mouse and agricultural species, and expanding the Ensembl Variant Effect Predictor tool. To learn more about Ensembl, help and documentation are available along with an extensive training program that can be accessed via our training pages.
The C-terminal PHDVC5HCH tandem domain of NSD2 is a combinatorial reader of unmodified H3K4 and tri-methylated H3K27 that regulates transcription of cell adhesion genes in multiple myeloma
Authors: Berardi Andrea , Kaestner Charlotte Leonie , Ghitti Michela , Quilici Giacomo , Cocomazzi Paolo , Li Jianping , Ballabio Federico , Zucchelli Chiara , Knapp Stefan , Licht Jonathan D , Musco Giovanna
Published: December 2024

Histone methyltransferase NSD2 (MMSET) overexpression in multiple myeloma (MM) patients plays an important role in the development of this disease subtype. Through the expansion of transcriptional activating H3K36me2 and the suppression of repressive H3K27me3 marks, NSD2 activates an aberrant set of genes that contribute to myeloma growth, adhesive and invasive activities. NSD2 transcriptional activity also depends on its non-catalytic domains, which facilitate its recruitment to chromatin through histone binding. In this study, using NMR, ITC and molecular dynamics simulations, we show that the tandem PHD domain of NSD2 (PHDVC5HCHNSD2) is a combinatorial reader of unmodified histone H3K4 and tri-methylated H3K27 (H3K27me3). This is the first PHD tandem cassette known to decode the methylation status of H3K27. Importantly, in a NSD2-dependent MM cellular model, we show that expression of NSD2 mutants, engineered to disrupt the interaction between H3K27me3 and PHDVC5HCH, display in comparison to wild-type NSD2: incomplete loss of H3K27 methylation throughout the genome, decreased activation of adhesive properties and cell adhesion genes, and a decrease of the corresponding H3K27ac signal at promoters. Collectively, these data suggest that the PHDVC5HCH domain of NSD2 plays an important role in modulating gene expression and chromatin modification, providing new opportunities for pharmacological intervention.
Comprehensive whole-genome sequencing reveals origins of mutational signatures associated with aging, mismatch repair deficiency and temozolomide chemotherapy
Authors: Hwang Taejoo , Sitko Lukasz Karol , Khoirunnisa Ratih , Navarro-Aguad Fernanda , Samuel David M , Park Hajoong , Cheon Banyoon , Mutsnaini Luthfiyyah , Lee Jaewoong , Otlu Burçak , Takeda Shunichi , Lee Semin , Ivanov Dmitri , Gartner Anton
Published: December 2024

In a comprehensive study to decipher the multi-layered response to the chemotherapeutic agent temozolomide (TMZ), we analyzed 427 genomes and determined mutational patterns in a collection of ∼40 isogenic DNA repair-deficient human TK6 lymphoblast cell lines. We first demonstrate that the spontaneous mutational background is very similar to the aging-associated mutational signature SBS40 and mainly caused by polymerase zeta-mediated translesion synthesis (TLS). MSH2-/- mismatch repair (MMR) knockout in conjunction with additional repair deficiencies uncovers cryptic mutational patterns. We next report how distinct mutational signatures are induced by TMZ upon sequential inactivation of DNA repair pathways, mirroring the acquisition of chemotherapy resistance by glioblastomas. The most toxic adduct induced by TMZ, O6-meG, is directly repaired by the O6-methylguanine-DNA methyltransferase (MGMT). In MGMT-/- cells, MMR leads to cell death and limits mutagenesis. MMR deficiency results in TMZ resistance, allowing the accumulation of ∼105 C > T substitutions corresponding to signature SBS11. Under these conditions, N3-methyladenine (3-meA), processed by base excision repair (BER), limits cell survival. Without BER, 3-meA is read through via error-prone TLS, causing T > A substitutions but not affecting survival. Blocking BER after abasic site formation results in large deletions and TMZ hypersensitization. Our findings reveal potential vulnerabilities of TMZ-resistant tumors.
An sRNA overexpression library reveals AbnZ as a negative regulator of an essential translocation module in Caulobacter crescentus
Authors: Velasco-Gomariz Manuel , Sulzer Johannes , Faber Franziska , Fröhlich Kathrin S
Published: December 2024

Small RNAs (sRNAs) play a crucial role in modulating target gene expression through short base-pairing interactions and serve as integral components of many stress response pathways and regulatory circuits in bacteria. Transcriptome analyses have facilitated the annotation of dozens of sRNA candidates in the ubiquitous environmental model bacterium Caulobacter crescentus, but their physiological functions have not been systematically investigated so far. To address this gap, we have established CauloSOEP, a multi-copy plasmid library of C. crescentus sRNAs, which can be studied in a chosen genetic background and under select conditions. Demonstrating the power of CauloSOEP, we identified sRNA AbnZ to impair cell viability and morphology. AbnZ is processed from the 3′ end of the polycistronic abn mRNA encoding the tripartite envelope-spanning efflux pump AcrAB-NodT. A combinatorial approach revealed the essential membrane translocation module TamAB as a target of AbnZ, implying that growth inhibition by AbnZ is linked to repression of this system.
Vaping-Specific Nicotine Dependence Across Days Among a National Sample of US Young Adults Who Vape
Authors: Parks Michael J , Arterberry Brooke J , Patrick Megan E
Published: December 2024

Introduction

Vaping has increased among young adults (YAs), and nicotine dependence prevalence has increased among YAs who vape, in the US. Research on nicotine dependence symptoms (NDS) among YAs who vape remains limited, and accurately measuring NDS and their severity remains a challenge. To date, no research has considered day-to-day NDS, as previous research focuses on retrospective measures.

Aims and Methods

Daily data came from the Monitoring the Future Vaping Supplement; out of 1244 YAs, we analyzed data from 150 (Mage = 19 [SE = 0.44]; 71.2% non-Hispanic white; 57.8% male) who vaped nicotine at least once during 14 daily surveys (n = 882 nicotine vaping days). The vaping-specific Hooked on Nicotine Checklist measured NDS on nicotine vaping days. Dichotomous and count measures of NDS were used at the day level and aggregated to the person level. Descriptive analyses and multilevel regression models were used. Weights ensured generalizability and adjusted for attrition.

Results

Any NDS were reported on 64.5% of nicotine vaping days (average 1.93 symptoms); 43.3% of nicotine vaping days had more than 1 NDS. Results across persons (rather than days) showed any NDS on 53.8% of nicotine vaping days, and 45.4% YAs reported between 1 and 2 symptoms per vaping day; 23.3% reported 2 + symptoms on average. Multilevel models showed nontrivial variance across days and persons in NDS, and regular vaping at baseline predicted NDS.

Conclusions

Vaping-specific NDS varied across days and persons for any NDS and NDS severity. Future research should consider daily NDS fluctuations, identifying factors that confer risk to inform NDS prevention and treatment among YAs who vape.

Implications

NDS and its severity varied across days and persons, demonstrating the utility of daily data. The results were generally similar for experiencing any NDS and NDS severity, but there was slightly more variability across days for any NDS. Intervention and treatment strategies could utilize approaches that identify and address daily symptoms to help curb nicotine dependence. Future research and treatment efforts should also consider the immediate contexts and potential factors that explain particularly elevated NDS on a given day.
Effects of a Low-Protein Diet on Kidney Function in Patients With Chronic Kidney Disease: An Umbrella Review of Systematic Reviews and Meta-analyses of Randomized Controlled Trials
Authors: Amiri Khosroshahi Reza , Zare Marzieh , Zeraattalab-Motlagh Sheida , Kiany Fatemeh , Talebi Sepide , Mohammadi Hamed
Published: December 2024

Context

Chronic kidney disease (CKD) stands out as one of the most widespread diseases globally. Dietary interventions, such as adopting a low-protein diet (LPD), play a crucial role as a key approach in impeding the advancement of CKD.

Objective

The objective of this umbrella review was to provide understanding into the effects of an LPD on kidney function among individuals with CKD, along with evaluating the certainty of the available evidence.

Data Sources

Searches for relevant studies were conducted without limitations through databases such as PubMed, Scopus, Web of Science, and Google Scholar, encompassing findings up to June 2023.

Data Extraction

The effect sizes for each meta-analysis were recalibrated using a random-effects model. The certainty of the evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach.

Data Analysis

Twenty-five meta-analyses including 47 randomized controlled trials were included in this study. Moderate certainty of the evidence suggests that LPDs may reduce glycated hemoglobin (HbA1c) and phosphorus levels, and the risk of progressing to end-stage renal disease in patients with CKD. Moreover, notable outcomes include increased glomerular filtration rate and decreased levels of serum albumin, blood urea nitrogen, and bicarbonate, although the certainty of evidence is low. In addition, LPDs can substantially decrease proteinuria, urine urea, and parathyroid hormone (PTH), although with very low certainty. The effects on serum creatinine, calcium, systolic blood pressure, and diastolic blood pressure are statistically nonsignificant, with the certainty of evidence ranging from low to moderate.

Conclusion

LPDs demonstrated beneficial effects on renal function in patients with CKD, which is supported by moderate to very low certainty evidence.

Systematic Review Registration

PROSPERO registration no. CRD42023473647.
Who lacks voter identification? The electoral implications of the Elections Act 2022
Authors: Fieldhouse Edward , Scott Ralph , Prosser Christopher , Bailey Jack , Mellon Jonathan
Published: December 2024

The Elections Act 2022 requires voters to present photo identification at general elections in Great Britain and local elections in England. In this article, we use data from the British Election Study Internet Panel to identify who does and does not own the necessary photo documents and how this affected turnout in the 2023 and 2024 local elections, as well as the 2024 General Election. We find that around 5% of the voting-age population lack valid voter identification and that this is related to age, education, socio-economic status, and social grade. The data also give us a reliable indication of the party-political impact of the photo ID requirement. We find that conservative voters are more likely to hold valid photo identification than supporters of other parties. We also find that a small but significant proportion of registered voters (between 1.2% and 2.4%) reported either being turned away or dissuaded from voting at these elections because of the requirement.
CAX-INTERACTING PROTEIN4 depletion causes early lethality and pre-mRNA missplicing in Arabidopsis
Authors: Aceituno-Valenzuela Uri , Fontcuberta-Cervera Sara , Micol-Ponce Rosa , Sarmiento-Mañús Raquel , Ruiz-Bayón Alejandro , Ponce María Rosa
Published: December 2024

Zinc knuckle (ZCCHC) motif-containing proteins are present in unicellular and multicellular eukaryotes, and most ZCCHC proteins with known functions participate in the metabolism of various classes of RNA, such as mRNAs, ribosomal RNAs, and microRNAs. The Arabidopsis (Arabidopsis thaliana) genome encodes 69 ZCCHC-containing proteins; however, the functions of most remain unclear. One of these proteins, CAX-INTERACTING PROTEIN 4 (CXIP4, encoded by AT2G28910), has been classified as a PTHR31437 family member. This family includes human Splicing regulatory glutamine/lysine-rich protein 1 (SREK1)-interacting protein 1 (SREK1IP1), which is thought to function in pre-mRNA splicing and RNA methylation. Metazoan SREK1IP1-like and plant CXIP4-like proteins only share a ZCCHC motif, and their functions remain almost entirely unknown. Here, we studied two loss-of-function alleles of Arabidopsis CXIP4: cxip4-1 is likely null and shows early lethality, and cxip4-2 is hypomorphic and viable, with pleiotropic morphological defects. The cxip4-2 mutant exhibited deregulation of defense genes and upregulation of transcription factor genes, some of which might explain its developmental defects. The cxip4-2 mutant also exhibited increased intron retention events, being more evident in cxip4-1. The specific functions of misspliced genes, such as those involved in “gene silencing by DNA methylation” and “mRNA polyadenylation factor” suggest that CXIP4 has additional functions. In cxip4-2 plants, polyadenylated RNAs accumulate in the nucleus; these could be misspliced mRNAs. The CXIP4 protein localizes to the nucleus in a pattern resembling nuclear speckles rich in splicing factors. Therefore, CXIP4 is required for plant development and survival and mRNA maturation.
A glutamine synthetase-Dof transcription factor module regulates nitrogen remobilization from source to sink tissues in tea plants
Authors: Liu Mei-Ya , Jiao Zixin , Lou Heqiang , Tang Dandan , Tian Xinyue , Zhou Bo-Wen , Ruan Jianyun , Fernie Alisdair R , Zhang Qunfeng
Published: December 2024

Nitrogen (N) remobilization from mature leaves to new shoots (NSs) is closely related to the quality of green tea in the spring season, which subsequently determines its economic value. However, the underlying N remobilization mechanism remains poorly understood. Here, we demonstrate that >80% of the recovered 15N was partitioned in the first mature leaves that supply NSs. N-remobilization efficiency (NRE) from mature leaves to NSs varied significantly among tea cultivars. N-fertilization level and NRE showed a significantly positive correlation. Based on weighted gene co-expression network analysis, glutamate metabolism-related genes, including glutamine synthetase genes, CsGSs, were dissected from the interaction network of hub genes regulating N remobilization. Gene expression patterns and the localization of CsGS1.1 in the cytosol and vascular tissue suggest its potential role in N remobilization. Consistent with these findings, source-to-sink N remobilization at the reproductive stage was enhanced in transgenic CsGS1.1-overexpressing plants. Furthermore, we demonstrated that the Dof transcription factor CsDof16 directly binds to the −526 to −426 region of the CsGS1.1 promoter, thereby activating its transcription and regulating N remobilization. Taken together, our findings suggest that the CsDof16-CsGS1.1 module regulates the remobilization of N in the form of glutamate/glutamine from mature leaves to NSs, constituting an important control point in the regulation of source-to-sink N partitioning in tea plants. Our findings can be employed to reduce fertilizer application and promote the development of sustainable tea production.
Rhizophagus irregularis regulates RiCPSI and RiCARI expression to influence plant drought tolerance
Authors: Wang Zhihao , Zhang Shiqi , Liang Jingwei , Chen Hui , Jiang Zhijian , Hu Wentao , Tang Ming
Published: December 2024

Arbuscular mycorrhizal fungi (AMF) can transfer inorganic nitrogen (N) from the soil to host plants to cope with drought stress, with arginine synthesis and NH4+ transport being pivotal processes. However, the regulatory mechanism underlying these processes remains unclear. Here, we found that drought stress upregulated expression of genes involved in the N transfer pathway and putrescine and glutathione synthesis in the mycorrhizal structures of Rhizophagus irregularis within alfalfa (Medicago sativa) roots, i.e. carbamoyl phosphate synthase (RiCPSI), arginase (RiCARI), urease (RiURE), ornithine decarboxylase (RiODC), and glutamate-cysteine ligase (RiGCL). Furthermore, we confirmed that RiCPSI is a carbamoyl phosphate synthase. Silencing RiCARI via host-induced gene silencing inhibited arbuscule formation, suppressed putrescine and glutathione synthesis, and altered arginine metabolism within R. irregularis-plant symbiosis, leading to a substantial reduction in the drought tolerance of M. sativa. Conversely, silencing RiCPSI decreased arginine, putrescine, and glutathione synthesis in R. irregularis but did not adversely affect NH4+ transfer from fungi to the host plant and drought tolerance of M. sativa. Interestingly, overexpressing RiCPSI via our host-induced gene overexpressing system enhanced arginine, putrescine, and glutathione synthesis in R. irregularis, reduced arbuscule abundance, and improved drought tolerance of M. sativa. Our findings demonstrate that under drought stress, the nitrogen transfer from AMF to the host plant was improved. This is accompanied by increased arginine, putrescine, and glutathione synthesis within R. irregularis, driven by the upregulation of RiCPSI and RiCARI expression in mycorrhizal structures within the roots. These molecular adjustments collectively contribute to enhanced drought tolerance in R. irregularis-plant symbiosis.
Propelling sustainable energy: Multi-omics analysis of pennycress FATTY ACID ELONGATION1 knockout for biofuel production
Authors: Rasoul Amira , Johnston Christopher R , LaChance Jordan , Sedbrook John C , Alonso Ana Paula
Published: December 2024

The aviation industry’s growing interest in renewable jet fuel has encouraged the exploration of alternative oilseed crops. Replacing traditional fossil fuels with a sustainable, domestically sourced crop can substantially reduce carbon emissions, thus mitigating global climate instability. Pennycress (Thlaspi arvense L.) is an emerging oilseed intermediate crop that can be grown during the offseason between maize (Zea mays) and soybean (Glycine max) to produce renewable biofuel. Pennycress is being domesticated through breeding and mutagenesis, providing opportunities for trait enhancement. Here, we employed metabolic engineering strategies to improve seed oil composition and bolster the plant's economic competitiveness. FATTY ACID ELONGATION1 (FAE1) was targeted using CRISPR-Cas 9 gene editing to eliminate very long chain fatty acids (VLCFAs) from pennycress seed oil, thereby enhancing its cold flow properties. Through an integrated multiomics approach, we investigated the impact of eliminating VLCFAs in developing and mature plant embryos. Our findings revealed improved cold-germination efficiency in fae1, with seedling emergence occurring up to 3 d earlier at 10 °C. However, these alterations led to a tradeoff between storage oil content and composition. Additionally, these shifts in lipid biosynthesis were accompanied by broad metabolic changes, such as the accumulation of glucose and ADP-glucose quantities consistent with increased starch production. Furthermore, shifts to shorter FA chains triggered the upregulation of heat shock proteins, underscoring the importance of VLCFAs in stress signaling pathways. Overall, this research provides crucial insights for optimizing pennycress seed oil while preserving essential traits for biofuel applications.
ChatGPT versus expert feedback on clinical reasoning questions and their effect on learning: a randomized controlled trial
Authors: Çiçek Feray Ekin , Ülker Müşerref , Özer Menekşe , Kıyak Yavuz Selim
Published: December 2024

Purpose

To evaluate the effectiveness of ChatGPT-generated feedback compared to expert-written feedback in improving clinical reasoning skills among first-year medical students.

Methods

This is a randomized controlled trial conducted at a single medical school and involved 129 first-year medical students who were randomly assigned to two groups. Both groups completed three formative tests with feedback on urinary tract infections (UTIs; uncomplicated, complicated, pyelonephritis) over five consecutive days as a spaced repetition, receiving either expert-written feedback (control, n = 65) or ChatGPT-generated feedback (experiment, n = 64). Clinical reasoning skills were assessed using Key-Features Questions (KFQs) immediately after the intervention and 10 days later. Students’ critical approach to artificial intelligence (AI) was also measured before and after disclosing the AI involvement in feedback generation.

Results

There was no significant difference between the mean scores of the control (immediate: 78.5 ± 20.6 delayed: 78.0 ± 21.2) and experiment (immediate: 74.7 ± 15.1, delayed: 76.0 ± 14.5) groups in overall performance on Key-Features Questions (out of 120 points) immediately (P = .26) or after 10 days (P = .57), with small effect sizes. However, the control group outperformed the ChatGPT group in complicated urinary tract infection cases (P < .001). The experiment group showed a significantly higher critical approach to AI after disclosing, with medium-large effect sizes.

Conclusions

ChatGPT-generated feedback can be an effective alternative to expert feedback in improving clinical reasoning skills in medical students, particularly in resource-constrained settings with limited expert availability. However, AI-generated feedback may lack the nuance needed for more complex cases, emphasizing the need for expert review. Additionally, exposure to the drawbacks in AI-generated feedback can enhance students’ critical approach towards AI-generated educational content.
The causal relationship between negative emotions and inflammatory dermatoses: a bidirectional Mendelian randomization study
Authors: Zhang Keyi , Zeng Mingwei , Lei Li , Fu Chuhan , Huang Jiangfeng , Zhou Shu , Wen Yaqing , Huang Jinhua , Chen Jing , Zeng Qinghai
Published: December 2024

Purpose

Observational studies have suggested a potential link between emotions and inflammatory dermatoses. However, research on the causal relationship between different types of emotions and inflammatory dermatoses is lacking. This study is aimed to investigate the causal relationship between negative emotions and inflammatory dermatoses through Mendelian randomization (MR) analysis.

Methods

Summary data of seven negative emotions were obtained from a genome-wide association study (GWAS) conducted by the MRC-IEU consortium. Seven inflammatory dermatoses including vitiligo, psoriasis, systemic lupus erythematosus, eczema, atopic dermatitis, acne, and rosacea were obtained from published GWAS. The MR analysis primarily employed the Inverse variance weighted (IVW) method, and supplemented by MR-Egger and other three MR methods.

Results

The IVW method revealed that guilty feelings have potential to increase the risk of psoriasis (OR = 1.02, 95% CI: 1.00–1.05, P = 0.019), while worrier/anxious feelings have a potential risk effect on eczema (OR = 1.07, 95% CI: 1.00–1.13, P = 0.042). Psoriasis could increase the occurrence of miserableness (OR = 1.41, 95% CI: 1.18–1.68, P = 0.0001), worrier/anxious feelings (OR = 1.26, 95% CI: 1.02–1.57, P = 0.033), nervous feelings (OR = 1.25, 95% CI: 1.05–1.49, P = 0.012), and loneliness/isolation (OR = 1.19, 95% CI: 1.04–1.36, P = 0.009). Eczema might cause an increased incidence of worrier/anxious feelings (OR = 1.038, 95% CI: 1.007–1.070, P = 0.014).

Conclusion

This MR study revealed bidirectional causality between worrier/anxious feelings and eczema. It also found that guilty feelings may elevate the risk of psoriasis, and individuals with psoriasis may experience increased rates of miserableness, worrier/anxious feelings, nervous feelings, and loneliness/isolation.