bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reconciling the Apparent Discrepancy Between Cenozoic Deep‐Sea Temperatures From Proxies and From Benthic Oxygen Isotope Deconvolution
Authors: Rohling E. J. , Gernon T. M. , Heslop D. , Reichart G. J. , Roberts A. P. , Yu J. 
Published: November 2024

AbstractUnderstanding past deep‐sea temperature and sea‐water oxygen isotope ratios is fundamental to environmental Earth science. For example, it provides crucial insight into past ice‐volume variations, an important climate system feedback. Moreover, deep‐sea temperature is important to deep‐sea ecology and biogeochemical cycling. Here we compare deep‐sea temperature and sea‐water oxygen isotope ratios from model‐based deconvolution of benthic foraminiferal carbonate δ18O with clumped isotope‐based deep‐sea temperature data in 1000‐year timesteps over the Cenozoic. To assess wider implications of the observed differences, we quantitatively evaluate a range of potential explanatory hypotheses—such as diagenetic overprints, carbonate ion effects, ice‐sheet morphology changes, and warm saline deep‐water admixture—but find that, individually, none can explain the observed differences satisfactorily. We then evaluate the implications of possible combined effects and recent advances in clumped isotope temperature calibration. We find that combined consideration of a recently proposed cool clumped isotope calibration and possible carbonate ion or pH influences can provide results that approximate deep‐sea temperature reconstructions based on conventional δ18Oc deconvolution. The match can be further improved if modest warm saline deep‐water contributions are considered during past warm periods. This contrasts with ice‐volume and ice‐sheet morphology changes, which appear unrealistic or insignificant, respectively. Our quantitative comparison offers a means toward formulation of a comprehensive and internally consistent understanding of Cenozoic variability in sea level (ice volume), GIA‐corrected ice‐sheet heights and mean ice δ18O, sea‐water δ18O, sea‐water δ18Ow, deep‐sea temperature, and deep‐sea [CO32−] variations.
Learning Regionalization Using Accurate Spatial Cost Gradients Within a Differentiable High‐Resolution Hydrological Model: Application to the French Mediterranean Region
Authors: Huynh Ngo Nghi Truyen , Garambois Pierre‐André , Colleoni François , Renard Benjamin , Roux Hélène , Demargne Julie , Jay‐Allemand Maxime , Javelle Pierre 
Published: November 2024

AbstractEstimating spatially distributed hydrological parameters in ungauged catchments poses a challenging regionalization problem and requires imposing spatial constraints given the sparsity of discharge data. A possible approach is to search for a transfer function that quantitatively relates physical descriptors to conceptual model parameters. This paper introduces a Hybrid Data Assimilation and Parameter Regionalization (HDA‐PR) approach incorporating learnable regionalization mappings, based on either multi‐linear regression or artificial neural networks (ANNs), into a differentiable hydrological model. This approach demonstrates how two differentiable codes can be linked and their gradients chained, enabling the exploitation of heterogeneous data sets across extensive spatio‐temporal computational domains within a high‐dimensional regionalization context, using accurate adjoint‐based gradients. The inverse problem is tackled with a multi‐gauge calibration cost function accounting for information from multiple observation sites. HDA‐PR was tested on high‐resolution, hourly and kilometric regional modeling of 126 flash‐flood‐prone catchments in the French Mediterranean region. The results highlight a strong regionalization performance of HDA‐PR especially in the most challenging upstream‐to‐downstream extrapolation scenario with ANN, achieving median Nash‐Sutcliffe efficiency (NSE) scores from 0.6 to 0.71 for spatial, temporal, spatio‐temporal validations, and improving NSE by up to 30% on average compared to the baseline model calibrated with lumped parameters. Multiple evaluation metrics based on flood‐oriented hydrological signatures also indicate that the use of an ANN leads to better performances than a multi‐linear regression in a validation context. ANN enables to learn a non‐linear descriptors‐to‐parameters mapping which provides better model controllability than a linear mapping for complex calibration cases.
Longitudinal analysis of genetic and epigenetic changes in human pluripotent stem cells in the landscape of culture-induced abnormality
Authors: Kim Yun-Jeong , Kang Byunghee , Kweon Solbi , Oh Sejin , Kim Dayeon , Gil Dayeon , Lee Hyeonji , Kim Jung-Hyun , Ju Ji Hyeon , Roh Tae-Young , Hong Chang Pyo , Cha Hyuk-Jin 
Published: November 2024

AbstractHuman embryonic stem cells (hESCs) are naturally equipped to maintain genome integrity to minimize genetic mutations during early embryo development. However, genetic aberration risks and subsequent cellular changes in hESCs during in vitro culture pose a significant threat to stem cell therapy. While a few studies have reported specific somatic mutations and copy number variations (CNVs), the molecular mechanisms underlying the acquisition of ‘culture-adapted phenotypes’ by hESCs are largely unknown. Therefore, we conducted comprehensive genomic, single-cell transcriptomic, and single-cell ATAC-seq analyses of an isogenic hESC model displaying definitive ‘culture-adapted phenotypes’. We found that hESCs lacking TP53, in which loss-of-function mutations were identified in human pluripotent stem cells (hPSCs), presented a surge in somatic mutations. Notably, hPSCs with a copy number gain of 20q11.21 during early passage did not present ‘culture-adapted phenotypes’ or BCL2L1 induction. Single-cell RNA-seq and ATAC-seq analyses revealed active transcriptional regulation at the 20q11.21 locus. Furthermore, the induction of BCL2L1 and TPX2 to trigger ‘culture-adapted phenotypes’ was associated with epigenetic changes facilitating TEA domain (TEAD) binding. These results suggest that 20q11.21 copy number gain and additional epigenetic changes are necessary for expressing ‘culture-adapted phenotypes’ by activating gene transcription at this specific locus.
MYH1 deficiency disrupts outer hair cell electromotility, resulting in hearing loss
Authors: Jung Jinsei , Joo Sun Young , Min Hyehyun , Roh Jae Won , Kim Kyung Ah , Ma Ji-Hyun , Rim John Hoon , Kim Jung Ah , Kim Se Jin , Jang Seung Hyun , Koh Young Ik , Kim Hye-Youn , Lee Ho , Kim Byoung Choul , Gee Heon Yung , Bok Jinwoong , Choi Jae Young , Seong Je Kyung 
Published: November 2024

AbstractMyh1 is a mouse deafness gene with an unknown function in the auditory system. Hearing loss in Myh1-knockout mice is characterized by an elevated threshold for the auditory brainstem response and the absence of a threshold for distortion product otoacoustic emission. Here, we investigated the role of MYH1 in outer hair cells (OHCs), crucial structures in the organ of Corti responsible for regulating cochlear amplification. Direct whole-cell voltage-clamp recordings of OHCs revealed that prestin activity was lower in Myh1-knockout mice than in wild-type mice, indicating abnormal OHC electromotility. We analyzed whole-exome sequencing data from 437 patients with hearing loss of unknown genetic causes and identified biallelic missense variants of MYH1 in five unrelated families. Hearing loss in individuals harboring biallelic MYH1 variants was non-progressive, with an onset ranging from congenital to childhood. Three of five individuals with MYH1 variants displayed osteopenia. Structural prediction by AlphaFold2 followed by molecular dynamic simulations revealed that the identified variants presented structural abnormalities compared with wild-type MYH1. In a heterogeneous overexpression system, MYH1 variants, particularly those in the head domain, abolished MYH1 functions, such as by increasing prestin activity and modulating the membrane traction force. Overall, our findings suggest an essential function of MYH1 in OHCs, as observed in Myh1-deficient mice, and provide genetic evidence linking biallelic MYH1 variants to autosomal recessive hearing loss in humans.
GLP-1 and its derived peptides mediate pain relief through direct TRPV1 inhibition without affecting thermoregulation
Authors: Go Eun Jin , Hwang Sung-Min , Jo Hyunjung , Rahman Md. Mahbubur , Park Jaeik , Lee Ji Yeon , Jo Youn Yi , Lee Byung-Gil , Jung YunJae , Berta Temugin , Kim Yong Ho , Park Chul-Kyu 
Published: November 2024

AbstractHormonal regulation during food ingestion and its association with pain prompted the investigation of the impact of glucagon-like peptide-1 (GLP-1) on transient receptor potential vanilloid 1 (TRPV1). Both endogenous and synthetic GLP-1, as well as a GLP-1R antagonist, exendin 9–39, reduced heat sensitivity in naïve mice. GLP-1-derived peptides (liraglutide, exendin-4, and exendin 9–39) effectively inhibited capsaicin (CAP)-induced currents and calcium responses in cultured sensory neurons and TRPV1-expressing cell lines. Notably, exendin 9–39 alleviated CAP-induced acute pain, as well as chronic pain induced by complete Freund’s adjuvant (CFA) and spared nerve injury (SNI), in mice without causing hyperthermia associated with other TRPV1 inhibitors. Electrophysiological analyses revealed that exendin 9–39 binds to the extracellular side of TRPV1, functioning as a noncompetitive inhibitor of CAP. Exendin 9–39 did not affect proton-induced TRPV1 activation, suggesting its selective antagonism. Among the exendin 9–39 fragments, exendin 20–29 specifically binds to TRPV1, alleviating pain in both acute and chronic pain models without interfering with GLP-1R function. Our study revealed a novel role for GLP-1 and its derivatives in pain relief, suggesting exendin 20–29 as a promising therapeutic candidate.
The MCP-3/Ccr3 axis contributes to increased bone mass by affecting osteoblast and osteoclast differentiation
Authors: Kim Jung Ha , Kim Kabsun , Kim Inyoung , Seong Semun , Che Xiangguo , Choi Je-Yong , Koh Jeong-Tae , Kim Nacksung 
Published: November 2024

AbstractSeveral CC subfamily chemokines have been reported to regulate bone metabolism by affecting osteoblast or osteoclast differentiation. However, the role of monocyte chemotactic protein 3 (MCP-3), a CC chemokine, in bone remodeling is not well understood. Here, we show that MCP-3 regulates bone remodeling by promoting osteoblast differentiation and inhibiting osteoclast differentiation. In a Ccr3-dependent manner, MCP-3 promoted osteoblast differentiation by stimulating p38 phosphorylation and suppressed osteoclast differentiation by upregulating interferon beta. MCP-3 increased bone morphogenetic protein 2-induced ectopic bone formation, and mice with MCP-3-overexpressing osteoblast precursor cells presented increased bone mass. Moreover, MCP-3 exhibited therapeutic effects by abrogating receptor activator of nuclear factor kappa-B ligand-induced bone loss. Therefore, MCP-3 has therapeutic potential for diseases involving bone loss due to its positive role in osteoblast differentiation and negative role in osteoclast differentiation.
Organoids in the oral and maxillofacial region: present and future
Authors: Wu Yufei , Li Xiang , Liu Hanzhe , Yang Xiao , Li Rui , Zhao Hui , Shang Zhengjun 
Published: November 2024

AbstractThe oral and maxillofacial region comprises a variety of organs made up of multiple soft and hard tissue, which are anatomically vulnerable to the pathogenic factors of trauma, inflammation, and cancer. The studies of this intricate entity have been long-termly challenged by a lack of versatile preclinical models. Recently, the advancements in the organoid industry have provided novel strategies to break through this dilemma. Here, we summarize the existing biological and engineering approaches that were employed to generate oral and maxillofacial organoids. Then, we detail the use of modified co-culture methods, such as cell cluster co-inoculation and air-liquid interface culture technology to reconstitute the vascular network and immune microenvironment in assembled organoids. We further retrospect the existing oral and maxillofacial assembled organoids and their potential to recapitulate the homeostasis in parental tissues such as tooth, salivary gland, and mucosa. Finally, we discuss how the next-generation organoids may benefit to regenerative and precision medicine for treatment of oral-maxillofacial illness.
Sex-dependent differences in hematopoietic stem cell aging and leukemogenic potential
Authors: Zhang Chunxiao , Hao Taisen , Bortoluzzi Alessia , Chen Min-Hsuan , Wu Xiwei , Wang Jinhui , Ermel Richard , Kim Young , Chen Shiuan , Chen WenYong 
Published: November 2024

AbstractSex influences many biological outcomes, but how sex affects hematopoietic stem cell (HSC) aging and hematological disorders is poorly understood. The widespread use of young animal models to study age-related diseases further complicates these matters. Using aged and long-lived BALB/c mouse models, we discovered that aging mice exhibit sex-dependent disparities, mirroring aging humans, in developing myeloid skewing, anemia, and leukemia. These disparities are underlined by sex-differentiated HSC aging characteristics across the population, single-cell, and molecular levels. The HSC population expanded significantly with aging and longevity in males, but this occurred to a much lesser degree in aging females that instead expanded committed progenitors. Aging male HSCs are more susceptible to BCR-ABL1 transformation with faster development of chronic myeloid leukemia (CML) than female HSCs. Additionally, the loss of the aging regulator Sirt1 inhibited CML development in aging male but not female mice. Our results showed for the first time that sex-differentiated HSC aging impacts hematopoiesis, leukemogenesis, and certain gene functions. This discovery provides insights into understanding age-dependent hematological diseases and sex-targeted strategies for the treatment and prevention of certain blood disorders and cancer.
Targeting the HECTD3-p62 axis increases the radiosensitivity of triple negative breast cancer cells
Authors: Huang Maobo , Liu Wenjing , Cheng Zhuo , Li Fubing , Kong Yanjie , Yang Chuanyu , Tang Yu , Jiang Dewei , Li Wenhui , Hu Yudie , Hu Jinhui , Puno PemaTenzin , Chen Ceshi 
Published: November 2024

AbstractTriple negative breast cancer is the most malignant subtype of breast cancer and current treatment options are limited. Radiotherapy is one of the primary therapeutic options for patients with TNBC. In this study, we discovered that the E3 ubiquitin ligase, HECTD3, promoted TNBC cell survival after irradiation. HECTD3 collaborated with UbcH5b to promote p62 ubiquitination and autophagy while HECTD3 deletion led to p62 accumulation in the nucleus in response to irradiation, thus inhibiting RNF168 mediated DNA damage repair. Furthermore, the HECTD3/UbcH5b inhibitor, PC3-15, increased the radiosensitivity of TNBC cells by inhibiting DNA damage repair. Taken together, we conclude that HECTD3 promotes autophagy and DNA damage repair in response to irradiation in a p62-denpendent manner, and that inhibition of the HECTD3-p62 axis could be a potential therapeutic strategy for patients with TNBC in addition to radiotherapy.
Risk of developing hyperkalemia in patients with hypertension treated with combination antihypertensive therapy – a retrospective register-based study
Authors: Al-Janabi Fatma Luai Mahdi , Moussa Fatme , Taleb Sarah , Leutscher Peter Derek Christian , Søndergaard Marc Meller , Melgaard Dorte , Søgaard Peter , Torp-Pedersen Christian , Kragholm Kristian , Krogager Maria Lukács 
Published: October 2024

AbstractThe risk of hyperkalemia in relation to different combinations of antihypertensive therapy remains to be elucidated. In this Danish register-based study, we aimed to investigate the risk of developing hyperkalemia in relation to different combinations of antihypertensive therapy. Using incidence density matching, we matched a hyperkalemic patient to five normokalemic patients on eGFR groups, age, sex, and time between study entry and date of potassium measurement. Combination therapies were subdivided into eight groups: beta blockers (BB) + calcium channel blockers (CCB), BB + renin angiotensin system inhibitors (RASi), BB + RASi + mineralocorticoid receptor antagonists (MRA), CCB + RASi, CCB + RASi + thiazides, CCB + thiazides, RASi + thiazides, and other combinations. Multivariable conditional logistic regression was used to estimate the odds of hyperkalemia within 90 days for each of the eight antihypertensive combination therapies. A total of 793 patients with hyperkalemia were matched to 3598 normokalemic patients. In multivariable analysis, odds of developing hyperkalemia when being treated with BB + RASi + MRA was 1.95 (95% CI, 1.39–2.72) compared to RASi + thiazides (reference). CCB + thiazides (OR, 0.76 [95% CI, 0.45–1.28]) and CCB + RASi + Thiazid (OR 0.81 [95% CI, 0.51–1.28]) were among the others not significantly associated with hyperkalemia. Combinations of BB + RASi + MRA were significantly associated with an increased risk of developing hyperkalemia within 90 days of initiating treatment.
A hole-selective hybrid TiO2 layer for stable and low-cost photoanodes in solar water oxidation
Authors: Bae Sanghyun , Moehl Thomas , Service Erin , Kim Minjung , Adams Pardis , Wang Zhenbin , Choi Yuri , Ryu Jungki , Tilley S. David 
Published: November 2024

AbstractThe use of conductive and corrosion-resistant protective layers represents a key strategy for improving the durability of light absorber materials in photoelectrochemical water splitting. For high performance photoanodes such as Si, GaAs, and GaP, amorphous TiO2 protective overlayers, deposited by atomic layer deposition, are conductive for holes via a defect band in the TiO2. However, when coated on simply prepared, low-cost photoanodes such as metal oxides, no charge transfer is observed through amorphous TiO2. Here, we report a hybrid polyethyleneimine/TiO2 layer that facilitates hole transfer from model oxides BiVO4 and Fe2O3, enabling access to a broader scope of available materials for practical water oxidation. A thin polyethyleneimine layer between the light absorber and the hybrid polyethyleneimine/TiO2 acts as a hole-selective interface, improving the optoelectronic properties of the photoanode devices. These polyethyleneimine/TiO2 modified photoanodes exhibit high photostability for solar water oxidation over 400 h.
Brain structural associations of syntactic complexity and diversity across schizophrenia spectrum and major depressive disorders, and healthy controls
Authors: Schneider Katharina , Alexander Nina , Jansen Andreas , Nenadić Igor , Straube Benjamin , Teutenberg Lea , Thomas-Odenthal Florian , Usemann Paula , Dannlowski Udo , Kircher Tilo , Nagels Arne , Stein Frederike 
Published: November 2024

AbstractDeviations in syntax production have been well documented in schizophrenia spectrum disorders (SSD). Recently, we have shown evidence for transdiagnostic subtypes of syntactic complexity and diversity. However, there is a lack of studies exploring brain structural correlates of syntax across diagnoses. We assessed syntactic complexity and diversity of oral language production using four Thematic Apperception Test pictures in a sample of N = 87 subjects (n = 24 major depressive disorder (MDD), n = 30 SSD patients both diagnosed according to DSM-IV-TR, and n = 33 healthy controls (HC)). General linear models were used to investigate the association of syntax with gray matter volume (GMV), fractional anisotropy (FA), axial (AD), radial (RD), and mean diffusivity (MD). Age, sex, total intracranial volume, group, interaction of group and syntax were covariates of no interest. Syntactic diversity was positively correlated with the GMV of the right medial pre- and postcentral gyri and with the FA of the left superior-longitudinal fasciculus (temporal part). Conversely, the AD of the left cingulum bundle and the forceps minor were negatively correlated with syntactic diversity. The AD of the right inferior-longitudinal fasciculus was positively correlated with syntactic complexity. Negative associations were observed between syntactic complexity and the FA of the left cingulum bundle, the right superior-longitudinal fasciculus, and the AD of the forceps minor and the left uncinate fasciculus. Our study showed brain structural correlates of syntactic complexity and diversity across diagnoses and HC. This contributes to a comprehensive understanding of the interplay between linguistic and neural substrates in syntax production in psychiatric disorders and HC.
Carbonic anhydrase inhibition ameliorates tau toxicity via enhanced tau secretion
Authors: Lopez Ana , Siddiqi Farah H. , Villeneuve Julien , Ureshino Rodrigo Portes , Jeon Hee-Yeon , Koulousakis Philippos , Keeling Sophie , McEwan William A. , Fleming Angeleen , Rubinsztein David C. 
Published: October 2024

AbstractTauopathies are neurodegenerative diseases that manifest with intracellular accumulation and aggregation of tau protein. These include Pick’s disease, progressive supranuclear palsy, corticobasal degeneration and argyrophilic grain disease, where tau is believed to be the primary disease driver, as well as secondary tauopathies, such as Alzheimer’s disease. There is a need to develop effective pharmacological therapies. Here we tested >1,400 clinically approved compounds using transgenic zebrafish tauopathy models. This revealed that carbonic anhydrase (CA) inhibitors protected against tau toxicity. CRISPR experiments confirmed that CA depletion mimicked the effects of these drugs. CA inhibition promoted faster clearance of human tau by promoting lysosomal exocytosis. Importantly, methazolamide, a CA inhibitor used in the clinic, also reduced total and phosphorylated tau levels, increased neuronal survival and ameliorated neurodegeneration in mouse tauopathy models at concentrations similar to those seen in people. These data underscore the feasibility of in vivo drug screens using zebrafish models and suggest serious consideration of CA inhibitors for treating tauopathies.
Massively parallel sequencing of mitochondrial genome in primary open angle glaucoma identifies somatically acquired mitochondrial mutations in ocular tissue
Authors: Vallabh Neeru Amrita , Lane Brian , Simpson David , Fuchs Marc , Choudhary Anshoo , Criddle David , Cheeseman Robert , Willoughby Colin 
Published: November 2024

AbstractGlaucoma is a sight threatening neurodegenerative condition of the optic nerve head associated with ageing and marked by the loss of retinal ganglion cells. Mitochondrial dysfunction plays a crucial role in the pathogenesis of neurodegeneration in the most prevalent type of glaucoma: primary open angle glaucoma (POAG). All previous mitochondrial genome sequencing studies in POAG analyzed mitochondrial DNA (mtDNA) isolated from peripheral blood leukocytes and have not evaluated cells derived from ocular tissue, which better represent the glaucomatous disease context. In this study, we evaluated mitochondrial genome variation and heteroplasmy using massively parallel sequencing of mtDNA in a cohort of patients with POAG, and in a subset assess the role of somatic mitochondrial genome mutations in disease pathogenesis using paired samples of peripheral blood leukocytes and ocular tissue (Tenon’s ocular fibroblasts). An enrichment of potentially pathogenic nonsynonymous mtDNA variants was identified in Tenon’s ocular fibroblasts from participants with POAG. The absence of oxidative DNA damage and predominance of transition variants support the concept that errors in mtDNA replication represent the predominant mutation mechanism in Tenon’s ocular fibroblasts from patients with POAG. Pathogenic somatic mitochondrial genome mutations were observed in people with POAG. This supports the role of somatic mitochondrial genome variants in the etiology of glaucoma.