bluuebunny/crossref_metadata_2025 huggingface dataset:
Spectral Analysis of Hydrological Signals to Estimate Watershed Properties Considering Impacts of Unsaturated Zone
Authors: Zhou Yunqiu , Liang Xiuyu , Ma Enze , Chen Kewei , Schilling Keith , Zheng Tianyuan , Zheng Yuhu , Zhang You‐Kuan , Zheng Chunmiao
Published: November 2024

Understanding responses of stream discharge to precipitation in a watershed is important in gaining insights into watershed hydrology and estimating hydraulic parameters. Transfer functions in the spectral domain are commonly used to quantify the relationship between precipitation and discharge, and estimate watershed hydraulic parameters. However, previous models have not adequately accounted for the impact of the unsaturated zone. To address this, we have developed a novel analytical model that considers the effect of the unsaturated zone to obtain transfer functions within watersheds. These transfer functions are derived by the spectral method and verified through numerical simulations. The results indicate that the transfer functions are influenced significantly by the relative hydraulic conductivity exponent αk in the moisture characteristic curve. A higher αk results in a lower transfer function, indicating more robust filtering of hydrological signals. A thicker unsaturated zone results in lower transfer functions at higher frequencies. The traditional transfer functions, which neglect the retention capacity of the unsaturated zone, tend to overestimate hydrological responses at high frequencies. Our transfer functions agree well with integrated watershed‐scale flow models and are also applied to observed data from four watersheds in Iowa, providing reasonable estimates for the hydraulic parameters. This study contributes to a deeper understanding of watershed behavior and offers an enhanced tool for estimating hydraulic parameters with practical applications.
A Comprehensive Analysis of Air‐Sea CO2 Flux Uncertainties Constructed From Surface Ocean Data Products
Authors: Ford Daniel J. , Blannin Josh , Watts Jennifer , Watson Andrew J. , Landschützer Peter , Jersild Annika , Shutler Jamie D.
Published: November 2024

Increasing anthropogenic CO2 emissions to the atmosphere are partially sequestered into the global oceans through the air‐sea exchange of CO2 and its subsequent movement to depth, commonly referred to as the global ocean carbon sink. Quantifying this ocean carbon sink provides a key component for closing the global carbon budget, which is used to inform and guide policy decisions. These estimates are typically accompanied by an uncertainty budget built by selecting what are perceived as critical uncertainty components based on selective experimentation. However, there is a growing realization that these budgets are incomplete and may be underestimated, which limits their power as a constraint within global budgets. In this study, we present a methodology for quantifying spatially and temporally varying uncertainties in the air‐sea CO2 flux calculations for the fCO2‐product based assessments that allows an exhaustive assessment of all known sources of uncertainties, including decorrelation length scales between gridded measurements, and the approach follows standard uncertainty propagation methodologies. The resulting standard uncertainties are higher than previously suggested budgets, but the component contributions are largely consistent with previous work. The uncertainties presented in this study identify how the significance and importance of key components change in space and time. For an exemplar method (the UExP‐FNN‐U method), the work identifies that we can currently estimate the annual ocean carbon sink to a precision of ±0.70 Pg C yr−1 (1σ uncertainty). Because this method has been built on established uncertainty propagation and approaches, it appears that applicable to all fCO2‐product assessments of the ocean carbon sink.
Investigating the Effect of Lithosphere Thickness and Viscosity on Mantle Dynamics Throughout the Supercontinent Cycle
Authors: Plimmer A. , Davies J. H. , Panton J.
Published: November 2024

The relationship between the lithosphere and the mantle during the supercontinent cycle is complex and poorly constrained. The processes which drive dispersal are often simplified to two end members: slab pull and plume push. We aim to explore how lithosphere thickness and viscosity during supercontinent assembly may affect the interaction of deep mantle structures throughout the supercontinent cycle. We consider supercontinental lithosphere structure as one of many potential processes which may affect the evolution of upwellings and downwellings and therefore systematically vary the properties of continental and cratonic lithosphere, respectively within our 3D spherical simulations. The viscosity and thickness of the lithosphere alters the dip and trajectory of downwelling material beneath the supercontinent as it assembles. Focusing on Pangea, we observe that plumes evolve and are swept beneath the center of the supercontinent by circum‐continental subduction. The proximity of these upwelling and downwelling structures beneath the supercontinent interior varies with lithosphere thickness and viscosity. Where slabs impinge on the top of an evolving plume head (when continental and cratonic lithosphere are thick and viscous in our simulations), the cold slabs can reduce the magnitude of an evolving plume. Conversely, when the continental lithosphere is thin and weak in our simulations, slab dips shallow in the upper mantle and descend adjacent to the evolving plume, sweeping it laterally near the core‐mantle boundary. These contrasting evolutions alter the magnitude of the thermal anomaly and the degree to which the plume can thin the lithosphere prior to breakup.
Opposite Trends in the Northern Hemisphere Stratosphere Between Mid‐Winter and Early Spring Linked to Surface Temperature Anomalies
Authors: Rivière Gwendal , D’Andrea Fabio , Domeisen Daniela I. V. , Portal Alice
Published: November 2024

Trends in the coupled stratosphere‐troposphere system during the 1979–2022 period are investigated in the Northern Hemisphere using reanalysis datasets. More upward planetary wave propagation in December is shown to precede the deceleration of the stratospheric polar vortex in January. This deceleration prevents the waves from continuing to propagate upward in February and favors an acceleration of the stratospheric polar vortex in March. This is associated with an increased Northern Hemisphere annular mode in March in the stratosphere and the troposphere. Trends show a moderate significance level because of strong interannual variability. Recent seasons whose anomalies project onto the trends are those for which wave‐1 anomaly constructively interferes with wave‐1 climatology in December, which occurs when there is warming in an area extending from Eastern Canada to Greenland and slight cooling over Eurasia. It shows the potential for predicting the springtime stratospheric polar vortex from wintertime wave‐1 anomalies.
Identification of Continental Mantle Earthquakes Using Regional Waves Propagating Into a Thinned Continental Crust
Authors: Wang Shiqi , Klemperer Simon L.
Published: November 2024

We evaluate three identifiers of continental mantle earthquakes (CMEs) motivated by surface‐wave normal‐mode theory: the amplitude ratio of Sn to Lg, and the frequency content of Sn and of Lg, after wave propagation through continental crustal thinning. These flexible and easily applicable methods allow for potential new discoveries of CMEs. They rely on guided waves whose propagation is dependent on the uniformity of their waveguides. For a range of Moho models, we perform 2.5D axisymmetric simulations that reach the conventional distance and frequency ranges of observational studies; we compare results from four different source depths straddling the Moho. Our synthetics, and six south‐Tibet earthquakes recorded by an array in Bangladesh, show our Sn/Lg identifier is robust in the presence of crustal thinning, but the identifying frequency contents of Sn and Lg are easily obscured. These results strengthen the utility of Sn/Lg methods for global studies of CMEs.
Electron Scattering Due To Asymmetric Drift‐Orbit Bifurcation: Geometric Jumps of Adiabatic Invariant
Authors: Kamaletdinov S. R. , Artemyev A. V. , Angelopoulos V. , Neishtadt A. I.
Published: November 2024

Radial transport of energetic electrons is one of the key processes responsible for the variability of the outer radiation belt. This transport amounts to a violation of the drift motion. One of the mechanisms that can lead to such violation and associated radial transport is drift‐orbit bifurcation. This arises naturally from solar wind compression of the dayside magnetosphere, which results in a local maximum of the field strength at the equator and two off‐equatorial minima at the north and south segments of the field line. Azimuthally drifting, near‐equatorially mirroring electrons can be trapped, bouncing along the field line in either of those minima for a portion of their drift orbit around Earth. Trapping and the ensuing de‐trapping are associated with jumps of the second adiabatic invariant, making the third adiabatic invariant undefined and the drift orbit open. Drift‐orbit bifurcation has been previously investigated for north‐south and dawn‐dusk symmetric configurations of the magnetospheric magnetic field. Here we study the implications of an asymmetry in the drift‐orbit bifurcation due to a large IMF field. Using the theory of separatrix crossings in Hamiltonian systems with a slow and a fast variable, we demonstrate that there are geometric (in phase space) jumps of adiabatic invariants due to the asymmetry of the magnetic field configuration. These jumps have magnitudes comparable to the initial invariant magnitudes and are dictated by the topology of the magnetic field. We develop a technique that allows estimation of the jumps in a given magnetic field configuration. We also assess the radial transport expected from asymmetric drift‐orbit bifurcation. We find that such transport can reach (Earth's radius) per drift period, depending on the magnitude of the IMF .
More Than Deoxygenation: Linking Iodate Reduction to Nitrogen, Iron, and Sulfur Chemistry in Reducing Regimes
Authors: Evans Natalya , Johnson Emma , Taing Amanda , Schnur Alexi A. , Chace Peter J. , Richards Samantha , Hardisty Dalton S. , Moffett James W.
Published: November 2024

A striking feature of Oxygen Deficient Zones (ODZs) on the eastern boundary of the Pacific Ocean are large subsurface plumes of iodide. Throughout the oceans, iodate is the predominant and thermodynamically favored species of dissolved iodine, but iodate is depleted within these plumes. The origin of iodide plumes and mechanism of reduction of iodate to iodide remains unclear but is thought to arise from a combination of in situ reduction and inputs from reducing shelf sediments. To distinguish between these sources, we investigated iodine redox speciation along the Oregon continental shelf. This upwelling system resembles ODZs but exhibits episodic hypoxia, rather than a persistently denitrifying water column. We observed elevated iodide in the benthic boundary layer overlying shelf sediments, but to a much smaller extent than within ODZs. There was no evidence of offshore plumes of iodide or increases in total dissolved iodine. Results suggest that an anaerobic water column dominated by denitrification, such as in ODZs, is required for iodate reduction. However, re‐analysis of iodine redox data from previous ODZ work suggests that most iodate reduction occurs in sediments, not the water column, and is also decoupled from denitrification. The underlying differences between these regimes have yet to be resolved, but could indicate a role for reduced sulfur in iodate reduction if the sulfate reduction zone is closer to the sediment‐water interface in ODZ shelf sediments than in Oregon sediments. Iodate reduction is not a simple function of oxygen depletion, which has important implications for its application as a paleoredox tracer.
Sources and Fates of Sedimentary Polycyclic Aromatic Hydrocarbons in the East Siberian Arctic Shelf: Implications for Input Pathways and Black Carbon Constraint
Authors: Yu Wenxiu , Hu Limin , Zhang Yuying , Du Jiazong , Bai Yazhi , Lin Tian , Yu Huimin , Guo Zhigang , Bosin Alexander , Astakhov Anatolii , Shi Xuefa
Published: November 2024

The Arctic region is experiencing more rapid climate changes than the other parts of the world and serves as a sink for semi‐volatile persistent organic pollutants, such as polycyclic aromatic hydrocarbons (PAHs), which can be utilized as molecular markers for pyrogenic carbon, such as black carbon (BC). As the sea ice retreats and increased terrestrial inputs with widespread wildfires, the PAH concentrations in the Arctic Ocean are rising. In this study, the sources and fates of PAHs together with BC in surface sediments from the East Siberian Arctic Shelf (ESAS) were analyzed. Positive matrix factorization (PMF) elucidated a mixed petrogenic and pyrogenic sources and distinct PAH fates associated with diverse input pathways including coastal permafrost erosion contribution (∼30%), petrogenic‐related emission (∼34%), fossil fuel combustion (∼26%), and biomass burning (∼10%). Correlation analysis indicated that BC plays a key role in affecting the behavior and fates of PAHs. In the Chukchi Sea, PAHs are closely associated with soot‐BC, whereas in the Laptev Sea (LS) and west East Siberian Sea (W‐ESS), they exhibit a coupling process with char‐BC. The presence of these carbonaceous materials in the sediments of CS is likely influenced by atmospheric deposition and biological activity, whereas the LS and W‐ESS regions are mainly affected by long‐distance river transport and direct deposition from coastal permafrost. As global warming continues, permafrost thawing induces the remobilization and retranslocation of PAHs, thereby becoming a significant PAH contributor and input pathway in the rapidly changing Arctic coastal margin.
Massive Ice Sheet Basal Melting Triggered by Atmospheric Collapse on Mars, Leading to Formation of an Overtopped, Ice‐Covered Argyre Basin Paleolake Fed by 1,000‐km Rivers
Authors: Buhler P. B.
Published: November 2024

Near the Noachian‐Hesperian boundary (∼3.6 billion years ago), most of Mars' near‐surface water inventory was likely frozen in large southern ice sheets and Mars' CO2 atmosphere had eroded enough that it began to periodically collapse. Here, I report model results showing that thermal blanketing of a southern H2O ice sheet by a CO2 ice cap formed during atmospheric collapse would produce melt equivalent to ∼0.2–2.0 × Mars' present‐day global near‐surface H2O inventory. I then model downstream flow, demonstrating the likely development of an ice‐covered fluviolacustrine system with 1,000s‐of‐kilometer‐long rivers, an overtopped Mediterranean‐Sea‐sized lake in Argyre Basin, and substantial water delivery into Margaritifer Terra and potentially Chryse Planitia. This study shows that a steady‐state hydrologic cycle driven by pole‐to‐equator melt and equator‐to‐pole sublimation and atmospheric transport lasting 105–107 year could occur multiple times throughout a ∼108‐year window during which atmospheric pressure was low enough to collapse yet CO2 and H2O inventories and geothermal heat output were high enough to produce substantial meltwater. The nature of this proposed hydrologic cycle is consistent with estimates of the timing, duration, and intermittency of Noachian‐Hesperian fluvial activity. Thus, meltwater release triggered by atmospheric collapse potentially played an important role in the intense pulse of Noachian‐Hesperian fluvial activity: directly so for the Argyre‐Margaritifer‐Chryse system and perhaps indirectly for other catchments. Finally, this study demonstrates that large amounts of water can mobilize in a cold climate, driven by the same atmospheric collapse process occurring on Mars today, without invoking late‐stage warming processes.
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

Understanding 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

Estimating 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

Human 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

Myh1 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

Hormonal 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

Several 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

The 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

Sex 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

Triple 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

The 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

The 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

Deviations 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

Tauopathies 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

Glaucoma 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.
Lateral lamina V projection neuron axon collaterals connect sensory processing across the dorsal horn of the mouse spinal cord
Authors: Browne Tyler J. , Smith Kelly M. , Gradwell Mark A. , Dayas Christopher V. , Callister Robert J. , Hughes David I. , Graham Brett A.
Published: November 2024

Spinal projection neurons (PNs) are defined by long axons that travel from their origin in the spinal cord to the brain where they relay sensory information from the body. The existence and function of a substantial axon collateral network, also arising from PNs and remaining within the spinal cord, is less well appreciated. Here we use a retrograde viral transduction strategy to characterise a novel subpopulation of deep dorsal horn spinoparabrachial neurons. Brainbow assisted analysis confirmed that virally labelled PN cell bodies formed a discrete cell column in the lateral part of Lamina V (LVlat) and the adjoining white matter. These PNs exhibited large dendritic territories biased to regions lateral and ventral to the cell body column and extending considerable rostrocaudal distances. Optogenetic activation of LVLat PNs confirmed this population mediates widespread signalling within spinal cord circuits, including activation in the superficial dorsal horn. This signalling was also demonstrated with patch clamp recordings during LVLat PN photostimulation, with a range of direct and indirect connections identified and evidence of a postsynaptic population of inhibitory interneurons. Together, these findings confirm a substantial role for PNs in local spinal sensory processing, as well as relay of sensory signals to the brain.
Acclimation and size influence predation, growth, and survival of sexually produced Diploria labyrinthiformis used in restoration
Authors: Ladd Mark C. , Shantz Andrew A. , Harrell Cailin , Hayes Nicole K. , Gilliam David S. , Muller Erinn M. , O’Neil Keri L. , Reckenbeil Brian , Craig Zachary , Lirman Diego
Published: November 2024

Stony coral tissue loss disease (SCTLD) has swept through Florida reefs and caused mass mortality of numerous coral species. In the wake of these losses, efforts are underway to propagate coral species impacted by SCTLD and promote population recovery. However, numerous knowledge gaps must be addressed to effectively grow, outplant, and restore populations of the slower growing, massive species that were lost. Here, we used sexual recruits of Diploria labyrinthiformis spawned in captivity to understand how conditioning, coral size, and nutritional status at outplanting affect coral survivorship, growth, and susceptibility to predation. We found that ex situ conditioning with supplemental feeding increased coral growth rates, resulting in larger sized corals at the time of outplanting. In turn, these corals had higher growth rates in the field and a lower probability of being removed by predators than outplants that were conditioned in in situ nurseries. Additionally, we found that coral size was an important predictor of survivorship, suggesting that hastening the speed at which young corals grow and outplanting larger juveniles can improve restoration outcomes. Taken together, our results suggest that providing supplemental food to corals at ex situ facilities confers benefits that could help restore populations of massive coral species impacted by SCTLD.
Socioeconomic inequalities linked to the transitioning to neurocognitive disorders and mortality
Authors: Gireesh Aswathikutty , Sacker Amanda , McMunn Anne , Bhatt Rikesh , Cadar Dorina
Published: November 2024

Research on socioeconomic position (SEP) and mild neurocognitive impairment, considered a transient state between normal cognitive function and dementia is limited. The purpose of this study was to determine the role of SEP in transitioning between different cognitive states and mortality risk. Using nationally representative English data and utilising a multistate model association between SEP and the risk of transitioning from no cognitive impairment (NOCI) to Cognitive impairment no dementia (CIND), dementia and death were investigated. The potential reverse transition from CIND to NOCI was also explored. The probabilities of transitioning between cognitive states and time spent in each state differed significantly between those with lower and higher levels of SEP. Higher wealth was associated with a reverse transition from CIND to NOCI [HR = 1.56, CI (1.42,1.72)]. Socioeconomic advantage might protect against the progression to the early stages of neurocognitive disorders (CIND) and facilitate the potential reversion from mild cognitive impairment to a healthy cognitive state in later life. Lower levels of education affect the risk of mortality after the onset of dementia.
Optimizing resource utilization for large scale problems through architecture aware scheduling
Authors: Elsawwaf Ali M , Aly Gamal M , Faheem Hossam M , Fayez Mahmoud
Published: November 2024

Rapid development realms of parallel architectures and its heterogeneity have inspired researchers to invent new scheduling strategies to efficiently distribute workloads among these architectures in a way that may lead to better performance. This paper presents a comprehensive study on optimizing resource utilization for large-scale problems by employing architecture-aware scheduling techniques. We conducted a series of experiments to measure the execution times of various architectures with different problem sizes. These experiments have been conducted multiple times to minimize measurement variance. The findings from these experiments are utilized to develop a scheduling strategy that enables faster completion of larger data-parallel problems while maximizing resource utilization. The proposed approach makes performance enhancement with 16.7% for large data size. It has a significant impact on enhancing computational efficiency and reducing costs in high-performance computing environments.
Effect of explosives charges types on the jet characteristics, penetration performance and fragmentation patterns of shaped charges
Authors: Elshenawy Tamer , Abdo Gamal M. , Elbeih Ahmed
Published: November 2024

Different explosive materials have been studied numerically and experimentally to assess the efficiency of a small diameter shaped charge in terms of produced jet characteristics and penetration depth into RHA steel targets. 26 different explosives have been simulated numerically using Autodyn hydrocode, whereas recommended explosives have been loaded into small diameter shaped charges by pressing technique and tested by static firing against RHA targets in order to validate the numerical calculations. The numerical analysis has presented an intensive global view about the variation of the shaped charge jets as a potential of the loaded explosive charge efficiencies. A successful trial has been performed to measure the shaped charge jet velocity using detonation velocity VOD 812 apparatus, where its measured value was only 3.6% different from the numerical one for HMX-V5 explosive. Besides, TITAN (L3) flash X-ray radiograph has also been implemented to explore the jet profile using the same explosive type and to measure its jet tip velocity, which has only 2.1% different from that estimated numerically. Extensive fragmentation analysis has been presented, which showed increase in both the fragment number and the fragment speed when the used explosive charge is of high detonation velocity. CL-20 explosive exhibited the largest jet tip velocity and its scaled collapse velocity was found to be 140% of TNT explosive. The calculated average fragment speed has been validated and the measured fragment speed has only 2.3% difference when compared to the SPH calculations.