bluuebunny/crossref_metadata_2025_split huggingface dataset:
Four putative pathogenic ARHGAP29 variants in patients with non-syndromic orofacial clefts (NsOFC)
Authors: Ranji Peyman , Pairet Eleonore , Helaers Raphael , Bayet Bénédicte , Gerdom Alexander , Gil-da-Silva-Lopes Vera Lúcia , Revencu Nicole , Vikkula Miikka 
Published: November 2024

AbstractThe pathophysiological basis of non-syndromic orofacial cleft (NsOFC) is still largely unclear. However, exome sequencing (ES) has led to identify several causative genes, often with reduced penetrance. Among these, the Rho GTPase activating protein 29 (ARHGAP29) has been previously implicated in 7 families with NsOFC. We investigated a cohort of 224 NsOFCs for which no genetic pathogenic variant had been identified by diagnostic testing. We used ES and bioinformatic variant filtering and identified four novel putative pathogenic variants in ARHGAP29 in four families. One was a missense variant leading to the substitution of the first methionine with threonine, two were heterozygous frameshift variants leading to a premature termination codon, and one was a nonsense variant. All variants were predicted to result in loss of function, either through mRNA decay, truncated ARHGAP29, or abnormal N-terminal initiation of translation of ARHGAP29. The truncated ARHGAP29 proteins would lack the important RhoGAP domain. The variants were either absent or rare in the control population databases, and the loss of intolerance score (pLI) of ARHGAP29 is 1.0, suggesting that ARHGAP29 haploinsufficiency is not tolerated. Phenotypes ranged from microform cleft lip (CL) to complete bilateral cleft lip and palate (CLP), with one unaffected mutation carrier. These results extend the mutational spectrum of ARHGAP29 and show that it is an important gene underlying variable NsOFC phenotypes. ARHGAP29 should be included in diagnostic genetic testing for NsOFC, especially familial cases, as it may be mutated in ∼4% of them (4/97 in our cohort) with high penetrance (89%).
Effectiveness of the intelligent hypertension excellence centers (iHEC) therapy model in the blood pressure management of older hypertensive patients: a randomized controlled trial
Authors: Jiang Yuqin , Zheng Lijun , Zhang Yunhe , Fan Zhen , Guo Jianshu , Yang Junling , Liu Peng , Zhong Ping , Xie Dili 
Published: November 2024

AbstractIntelligent hypertension excellence centers (iHEC) may improve blood pressure (BP) management in older hypertensive patients. However, this has not yet been rigorously evaluated, so we conducted a prospective randomized open-label clinical trial to verify this hypothesis. Older patients with hypertension were recruited between January and June 2022. The control group received conventional treatment and visited doctors in clinic. The intervention group received the iHEC therapy model, including remote BP management, online consultation, and follow-up services with support from the internet. Both groups received 12 months follow-up. Finally, 540 older patients with hypertension participated in the study; of these, 517 completed the follow-up. The average age was 71.4 ± 3.7years, 81 patients with frailty (15.7%). When follow-up was terminated, the SBP of the intervention group was 4.2 mmHg lower than that of the control group (95% CI, 2.0 to 6.4, P < 0.001), and the overall BP control rate in the intervention group was higher than that in the control group (60.2% vs. 48.1%, P < 0.05). During follow-up, the new-onset rate of excessive BP lowering in the intervention group was lower than that in the control group (3.8% vs. 9.0%, P < 0.05). Patients with a median age or above and high school education or above had higher numbers of online consultations and home BP measurements (P < 0.05).Our study confirmed those who received the iHEC therapy model achieved better BP reduction, higher rates of BP control, and alleviated the risk of excessive BP reduction.
3D chromatin maps of a brown alga reveal U/V sex chromosome spatial organization
Authors: Liu Pengfei , Vigneau Jeromine , Craig Rory J. , Barrera-Redondo Josué , Avdievich Elena , Martinho Claudia , Borg Michael , Haas Fabian B. , Liu Chang , Coelho Susana M. 
Published: November 2024

AbstractNuclear three dimensional (3D) folding of chromatin structure has been linked to gene expression regulation and correct developmental programs, but little is known about the 3D architecture of sex chromosomes within the nucleus, and how that impacts their role in sex determination. Here, we determine the sex-specific 3D organization of the model brown alga Ectocarpus chromosomes at 2 kb resolution, by mapping long-range chromosomal interactions using Hi-C coupled with Oxford Nanopore long reads. We report that Ectocarpus interphase chromatin exhibits a non-Rabl conformation, with strong contacts among telomeres and among centromeres, which feature centromere-specific LTR retrotransposons. The Ectocarpus chromosomes do not contain large local interactive domains that resemble TADs described in animals, but their 3D genome organization is largely shaped by post-translational modifications of histone proteins. We show that the sex determining region (SDR) within the U and V chromosomes are insulated and span the centromeres and we link sex-specific chromatin dynamics and gene expression levels to the 3D chromatin structure of the U and V chromosomes. Finally, we uncover the unique conformation of a large genomic region on chromosome 6 harboring an endogenous viral element, providing insights regarding the impact of a latent giant dsDNA virus on the host genome’s 3D chromosomal folding.
Fine-mapping and molecular characterisation of primary sclerosing cholangitis genetic risk loci
Authors: Goode Elizabeth C. , Fachal Laura , Panousis Nikolaos , Moutsianas Loukas , McIntyre Rebecca E. , Bai Benjamin Yu Hang , Kawasaki Norihito , Wittmann Alexandra , Raine Tim , Rushbrook Simon M. , Anderson Carl A. 
Published: November 2024

AbstractGenome-wide association studies of primary sclerosing cholangitis have identified 23 susceptibility loci. The majority of these loci reside in non-coding regions of the genome and are thought to exert their effect by perturbing the regulation of nearby genes. Here, we aim to identify these genes to improve the biological understanding of primary sclerosing cholangitis, and nominate potential drug targets. We first build an eQTL map for six primary sclerosing cholangitis-relevant T-cell subsets obtained from the peripheral blood of primary sclerosing cholangitis and ulcerative colitis patients. These maps identify 10,459 unique eGenes, 87% of which are shared across all six primary sclerosing cholangitis T-cell types. We then search for colocalisations between primary sclerosing cholangitis loci and eQTLs and undertake Bayesian fine-mapping to identify disease-causing variants. In this work, colocalisation analyses nominate likely primary sclerosing cholangitis effector genes and biological mechanisms at five non-coding (UBASH3A, PRKD2, ETS2 and AP003774.1/CCDC88B) and one coding (SH2B3) primary sclerosing cholangitis loci. Through fine-mapping we identify likely causal variants for a third of all primary sclerosing cholangitis-associated loci, including two to single variant resolution.
Nucleotidyltransferase toxin MenT extends aminoacyl acceptor ends of serine tRNAs to control Mycobacterium tuberculosis growth
Authors: Xu Xibing , Barriot Roland , Voisin Bertille , Arrowsmith Tom J. , Usher Ben , Gutierrez Claude , Han Xue , Pagès Carine , Redder Peter , Blower Tim R. , Neyrolles Olivier , Genevaux Pierre 
Published: November 2024

AbstractToxins of toxin-antitoxin systems use diverse mechanisms to inhibit bacterial growth. In this study, we characterize the translation inhibitor toxin MenT3 of Mycobacterium tuberculosis, the bacterium responsible for tuberculosis in humans. We show that MenT3 is a robust cytidine specific tRNA nucleotidyltransferase in vitro, capable of modifying the aminoacyl acceptor ends of most tRNA but with a marked preference for tRNASer, to which long stretches of cytidines are added. Furthermore, transcriptomic-wide analysis of MenT3 targets in M. tuberculosis identifies tRNASer as the sole target of MenT3 and reveals significant detoxification attempts by the essential CCA-adding enzyme PcnA in response to MenT3. Finally, under physiological conditions, only in the presence the native menAT3 operon, an active pool of endogenous MenT3 targeting tRNASer in M. tuberculosis is detected, likely reflecting the importance of MenT3 during infection.
Why models underestimate West African tropical forest primary productivity
Authors: Zhang-Zheng Huanyuan , Deng Xiongjie , Aguirre-Gutiérrez Jesús , Stocker Benjamin D. , Thomson Eleanor , Ding Ruijie , Adu-Bredu Stephen , Duah-Gyamfi Akwasi , Gvozdevaite Agne , Moore Sam , Oliveras Menor Imma , Prentice I. Colin , Malhi Yadvinder 
Published: November 2024

AbstractTropical forests dominate terrestrial photosynthesis, yet there are major contradictions in our understanding due to a lack of field studies, especially outside the tropical Americas. A recent field study indicated that West African forests have among the highest forests gross primary productivity (GPP) yet observed, contradicting models that rank them lower than Amazonian forests. Here, we show possible reasons for this data-model mismatch. We found that biometric GPP measurements are on average 56.3% higher than multiple global GPP products at the study sites. The underestimation of GPP largely disappears when a standard photosynthesis model is informed by local field-measured values of (a) fractional absorbed photosynthetic radiation (fAPAR), and (b) photosynthetic traits. Remote sensing products systematically underestimate fAPAR (33.9% on average at study sites) due to cloud contamination issues. The study highlights the potential widespread underestimation of tropical forests GPP and carbon cycling and hints at the ways forward for model and input data improvement.
Cohort studies on 71 outcomes among people with atopic eczema in UK primary care data
Authors: Matthewman Julian , Schultze Anna , Strongman Helen , Bhaskaran Krishnan , Roberts Amanda , Denaxas Spiros , Mansfield Kathryn E. , Langan Sinéad M. 
Published: November 2024

AbstractAtopic eczema may be related to multiple subsequent adverse health outcomes. Here, we provide evidence to judge and compare associations between eczema and a comprehensive set of outcomes. We conducted 71 cohort studies (age, sex, general practice-matched) using Clinical Practice Research Datalink Aurum primary care records (1997−2023), comparing up to 3.6 million people with eczema to 16.8 million without. Eczema was associated with subsequent diagnosis of outcomes with adjusted hazard ratios (99% confidence intervals) from Cox regression of up to 4.02(3.95–4.10) for food allergy (rate difference [RD] per 1,000 person-years of 1.5). Besides strong associations with atopic and allergic conditions (e.g., asthma 1.87[1.39–1.82], RD5.4) and skin infections (e.g., molluscum contagiosum 1.81[1.64–1.96], RD1.8), the strongest associations were with Hodgkin’s lymphoma (1.85[1.66–2.06], RD0.02), Alopecia Areata (1.77[1.71–1.83], RD0.2), Crohn’s disease (1.62[1.54–1.69], RD0.1), Urticaria (1.58[1.57–1.60], RD1.9), Coeliac disease (1.42[1.37–1.47], RD0.1), Ulcerative colitis (1.40[1.34–1.46], RD0.1), Autoimmune liver disease (1.32[1.21–1.43], RD0.01), and Irritable bowel syndrome (1.31[1.29–1.32], RD0.7). Sensitivity analyses revealed the impact of consultation bias or choice of cohort age cut-off on findings. Comparatively large HRs in severe eczema were seen for some liver, gastrointestinal and cardiovascular conditions, osteoporosis, and fractures. Most cancers and neurological conditions were not associated with eczema.
Coordinated inheritance of extrachromosomal DNAs in cancer cells
Authors: Hung King L. , Jones Matthew G. , Wong Ivy Tsz-Lo , Curtis Ellis J. , Lange Joshua T. , He Britney Jiayu , Luebeck Jens , Schmargon Rachel , Scanu Elisa , Brückner Lotte , Yan Xiaowei , Li Rui , Gnanasekar Aditi , Chamorro González Rocío , Belk Julia A. , Liu Zhonglin , Melillo Bruno , Bafna Vineet , Dörr Jan R. , Werner Benjamin , Huang Weini , Cravatt Benjamin F. , Henssen Anton G. , Mischel Paul S. , Chang Howard Y. 
Published: November 2024

AbstractThe chromosomal theory of inheritance dictates that genes on the same chromosome segregate together while genes on different chromosomes assort independently1. Extrachromosomal DNAs (ecDNAs) are common in cancer and drive oncogene amplification, dysregulated gene expression and intratumoural heterogeneity through random segregation during cell division2,3. Distinct ecDNA sequences, termed ecDNA species, can co-exist to facilitate intermolecular cooperation in cancer cells4. How multiple ecDNA species within a tumour cell are assorted and maintained across somatic cell generations is unclear. Here we show that cooperative ecDNA species are coordinately inherited through mitotic co-segregation. Imaging and single-cell analyses show that multiple ecDNAs encoding distinct oncogenes co-occur and are correlated in copy number in human cancer cells. ecDNA species are coordinately segregated asymmetrically during mitosis, resulting in daughter cells with simultaneous copy-number gains in multiple ecDNA species before any selection. Intermolecular proximity and active transcription at the start of mitosis facilitate the coordinated segregation of ecDNA species, and transcription inhibition reduces co-segregation. Computational modelling reveals the quantitative principles of ecDNA co-segregation and co-selection, predicting their observed distributions in cancer cells. Coordinated inheritance of ecDNAs enables co-amplification of specialized ecDNAs containing only enhancer elements and guides therapeutic strategies to jointly deplete cooperating ecDNA oncogenes. Coordinated inheritance of ecDNAs confers stability to oncogene cooperation and novel gene regulatory circuits, allowing winning combinations of epigenetic states to be transmitted across cell generations.
Selective ion transport through hydrated micropores in polymer membranes
Authors: Wang Anqi , Breakwell Charlotte , Foglia Fabrizia , Tan Rui , Lovell Louie , Wei Xiaochu , Wong Toby , Meng Naiqi , Li Haodong , Seel Andrew , Sarter Mona , Smith Keenan , Alvarez‐Fernandez Alberto , Furedi Mate , Guldin Stefan , Britton Melanie M. , McKeown Neil B. , Jelfs Kim E. , Song Qilei 
Published: November 2024

AbstractIon-conducting polymer membranes are essential in many separation processes and electrochemical devices, including electrodialysis1, redox flow batteries2, fuel cells3 and electrolysers4,5. Controlling ion transport and selectivity in these membranes largely hinges on the manipulation of pore size. Although membrane pore structures can be designed in the dry state6, they are redefined upon hydration owing to swelling in electrolyte solutions. Strategies to control pore hydration and a deeper understanding of pore structure evolution are vital for accurate pore size tuning. Here we report polymer membranes containing pendant groups of varying hydrophobicity, strategically positioned near charged groups to regulate their hydration capacity and pore swelling. Modulation of the hydrated micropore size (less than two nanometres) enables direct control over water and ion transport across broad length scales, as quantified by spectroscopic and computational methods. Ion selectivity improves in hydration-restrained pores created by more hydrophobic pendant groups. These highly interconnected ion transport channels, with tuned pore gate sizes, show higher ionic conductivity and orders-of-magnitude lower permeation rates of redox-active species compared with conventional membranes, enabling stable cycling of energy-dense aqueous organic redox flow batteries. This pore size tailoring approach provides a promising avenue to membranes with precisely controlled ionic and molecular transport functions.
Nucleosome flipping drives kinetic proofreading and processivity by SWR1
Authors: Girvan Paul , Jalal Adam S. B. , McCormack Elizabeth A. , Skehan Michael T. , Knight Carol L. , Wigley Dale B. , Rueda David S. 
Published: November 2024

AbstractThe yeast SWR1 complex catalyses the exchange of histone H2A–H2B dimers in nucleosomes, with Htz1–H2B dimers1–3. Here we used single-molecule analysis to demonstrate two-step double exchange of the two H2A–H2B dimers in a canonical yeast nucleosome with Htz1–H2B dimers, and showed that double exchange can be processive without release of the nucleosome from the SWR1 complex. Further analysis showed that bound nucleosomes flip between two states, with each presenting a different face, and hence histone dimer, to SWR1. The bound dwell time is longer when an H2A–H2B dimer is presented for exchange than when presented with an Htz1–H2B dimer. A hexasome intermediate in the reaction is bound to the SWR1 complex in a single orientation with the ‘empty’ site presented for dimer insertion. Cryo-electron microscopy analysis revealed different populations of complexes showing nucleosomes caught ‘flipping’ between different conformations without release, each placing a different dimer into position for exchange, with the Swc2 subunit having a key role in this process. Together, the data reveal a processive mechanism for double dimer exchange that explains how SWR1 can ‘proofread’ the dimer identities within nucleosomes.
Investigating the electronic properties and reactivity of polyaniline emeraldine base functionalized with metal oxides
Authors: Badry Rania , Elhaes Hanan , Ibrahim Asmaa , Refaat Ahmed , Ibrahim Medhat A. 
Published: November 2024

AbstractDue to its appealing qualities, such as its miniature size and the ability to modify physical properties through chemical synthesis and molecular design, polymer material offers considerable advantages over traditional inorganic material-based electronics. Conjugate polymers are particularly interesting because of their molecular design capabilities, which enable the synthesis of conducting polymers with a variety of ionization potentials and electron affinities (EA), and their ability to control the energy gap and electronegativity (χ). Accordingly, density functional theory (DFT) at the B3LYP/SDD model was used to present possible interactions between polyaniline (PANi) and both alkali and heavy metal oxides. Total dipole moment (TDM), HOMO–LUMO band gap energy (ΔE), ionization energy (IE), EA, chemical hardness (η), chemical potential (μ), electrophilicity index (ω), chemical softness (S), and χ are calculated. TDM of PANi increased while ΔE decreased due to functionalization. The distribution of electronic charge density in molecular electrostatic potential (MESP) maps together with the results of ω reflected the electrophilic nature. The obtained results confirmed that the addition of metal oxides significantly improves the TDM, ΔE, and reactivity descriptors. A strong correlation between the experimental and calculated IR spectra was observed. Additionally, PANi–2MgO and PANi–2MnO model molecules exhibited the highest reactivity. Accordingly, PANi functionalized with MgO and MnO are promising candidates for energy storage devices.
Syntactic and semantic specialization in 9- to 10-year-old children during auditory sentence processing
Authors: Wang Jin , Wagley Neelima , Rice Mabel , Gaab Nadine , Booth James R. 
Published: November 2024

AbstractPrior literature has debated whether syntax is separable from semantics in the brain. Using functional magnetic resonance imaging and multi-voxel pattern analysis, our previous studies investigated brain activity during morpho-syntactic versus semantic processing. These studies only detected semantic specialization in activation patterns and no syntactic specialization in 5- to 6-year-old and 7- to 8-year-old children. To examine if older children who have mastered morpho-syntactic skills would show specialization for syntax, the current study examined 64 9- to 10-year-old children using the same design and analyses. We observed that only the left IFG pars opercularis was sensitive to syntactic but not semantic information, supporting the hypothesis that this region serves as a core region for syntax. In addition, the left STG which has been implicated in the integration of semantics and syntax, as well as the left MTG and IFG pars triangularis which have been implicated in semantics, were sensitive to both semantic and syntactic information with no evidence of specialization. These findings suggest a lexicalized view of syntax, which argues that semantically sensitive regions are also critical regions for syntactic processing during language comprehension.
The USP12/46 deubiquitinases protect integrins from ESCRT-mediated lysosomal degradation
Authors: Yu Kaikai , Wang Guan M , Guo Shiny Shengzhen , Bassermann Florian , Fässler Reinhard 
Published: November 2024

AbstractThe functions of integrins are tightly regulated via multiple mechanisms including trafficking and degradation. Integrins are repeatedly internalized, routed into the endosomal system and either degraded by the lysosome or recycled back to the plasma membrane. The ubiquitin system dictates whether internalized proteins are degraded or recycled. Here, we use a genetic screen and proximity-dependent biotin identification to identify deubiquitinase(s) that control integrin surface levels. We find that a ternary deubiquitinating complex, comprised of USP12 (or the homologous USP46), WDR48 and WDR20, stabilizes β1 integrin (Itgb1) by preventing ESCRT-mediated lysosomal degradation. Mechanistically, the USP12/46-WDR48-WDR20 complex removes ubiquitin from the cytoplasmic tail of internalized Itgb1 in early endosomes, which in turn prevents ESCRT-mediated sorting and Itgb1 degradation.
Consistency of HFrEF treatment effect in underrepresented groups in randomized clinical trials
Authors: Baudry Guillaume , Monzo Luca , Petrie Mark C. , Girerd Nicolas , Piña Ileana L. , Mebazaa Alexandre , Butler Javed , Abid Leila , Zannad Faiez , Van Spall Harriette G. C. 
Published: November 2024

Abstract
Despite the established efficacy of heart failure (HF) guideline-directed medical therapies, implementation varies across demographic groups, including Black, Indigenous, and people of color, older adults, females, and those who are socioeconomically deprived. This review synthesizes the representativeness of trial participants and describes subgroup analyses from pivotal trials in HF with reduced ejection fraction (HFrEF). It reviews the largely consistent treatment effect of medical therapies across the demographic groups represented in trials. It makes arguments for broad implementation of therapies based on these data, while calling for more representative trials to improve research and health equity in HF.
Bisbenzothieno[b]-fused BODIPYs in panchromatic photoinitiation for free radical and cationic photopolymerization and application in 3D printing
Authors: Xu Yangyang , Tang Wenlong , Deng Hui , Zhang Jianjun , Zhu Zhongquan , Yu Changjiang , Zhu Haiguang , Sun Ke , Li Jiazhu , Lalevée Jacques 
Published: November 2024

A family of BODIPY derivatives were reported to exhibit panchromatic behavior for the effective induction of polymerization reactions at both ends of the visible spectrum, e.g. LED@405 nm and LED@660 nm, with practical applications in 3D printing.