bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Spring Phenology on Grassland Growth in Qilian Mountains Across Multiple Spatiotemporal Scales
Authors: Sun Yunfan , Guan Qingyu , Du Qinqin , Wang Qingzheng , Yang Xinyue , Zhang Erya
Published: November 2023

Investigating the differences in grassland growth and its response to advancing spring phenology and climate change across various spatiotemporal scales is crucial for the sustainable development of alpine mountain regions under a warming and wetting climate. This study analyzed the growth dynamics of grassland in the Qilian Mountains from 2000 to 2019 at seasonal and periodic scales. Using partial wavelet coherency and partial correlation analysis, we investigated the influence of temperature, precipitation, and spring phenology on grassland growth. Additionally, we quantified the dominant factors affecting grassland growth in different ecological zones and elevational gradient. The results indicated that the mean normalized difference vegetation index increased at an average rate of 1.1 and 2.8 × 10−3/year for grassland in spring and summer, respectively. Furthermore, the start of vegetation growing season (SOS) has advanced 6.0 days during 2000–2019. The dominant factor for grassland growth shifted from spring temperature to summer precipitation. The importance of SOS ranked second, significantly influencing 29.3% and 25.1% of grassland during spring and summer, respectively. Grasslands situated above 4,000 m above sea level (ASL) were more sensitive to climate change, with SOS exerting the greatest influence within the elevation range of 2,800–4,000 m ASL. Additionally, the phase difference in the time‐frequency scale of partial wavelet coherency revealed a lag effect of approximately 1 month for summer grassland growth to respond to precipitation. These findings can provide a scientific basis for optimizing global vegetation models and predicting the productivity of alpine mountain grasslands.
Geomagnetically Induced Current Mitigation in New Zealand: Operational Mitigation Method Development With Industry Input
Authors: Mac Manus D. H. , Rodger C. J. , Renton A. , Ronald J. , Harper D. , Taylor C. , Dalzell M. , Divett T. , Clilverd M. A.
Published: November 2023

Reducing the impact of Geomagnetically induced currents (GICs) on electrical power networks is an essential step to protect network assets and maintain reliable power transmission during and after storm events. In this study, multiple mitigation strategies are tested during worst‐case extreme storm scenarios in order to investigate their effectiveness for the New Zealand transmission network. By working directly with our industry partners, Transpower New Zealand Ltd, a mitigation strategy in the form of targeted line disconnections has been developed. This mitigation strategy proved more effective than previous strategies at reducing GIC magnitudes and durations at transformers at most risk to GIC while still maintaining the continuous supply of power throughout New Zealand. Under this mitigation plan, the average 60‐min mean GIC decreased for 27 of the top 30 at‐risk transformers, and the total network GIC was reduced by 16%. This updated mitigation has been adopted as an operational procedure in the New Zealand national control room to manage GIC. In addition, simulations show that the installation of 14 capacitor blocking devices at specific transformers reduces the total GIC sum in the network by an additional 16%. As a result of this study Transpower is considering further mitigation in the form of capacitor blockers. We strongly recommend collaborating with the relevant power network providers to develop effective mitigation strategies that reduce GIC and have a minimal impact on power distribution.
Groundwater Sensitivity to Climate Variations Across Australia
Authors: Fan Xinyang , Peterson Tim J. , Henley Benjamin J. , Arora Meenakshi
Published: November 2023

Groundwater response to climate variations is often pivotal to managing groundwater sustainably. However, this relationship is rarely explicitly examined because of the complexity of surface to subsurface processes and the diverse impacts of multiple drivers, such as groundwater pumping and land use changes. In this paper, we address this challenge by proposing methods to quantify the sensitivity of groundwater level and recharge to temporal climate variability across Australia. Using the HydroSight groundwater hydrograph toolbox we first identify 1,143 out of a total of 4,350 bores as climate‐driven, where historically, head was primarily driven by climate variations. Streamflow elasticity measures are then adapted to groundwater to quantify the long‐term head and recharge sensitivity. We find that the national median sensitivity of head and recharge to precipitation change are 42 and 0.43 mm mm−1, respectively (interquartiles: 20–77 and 0.30–0.55 mm mm−1); both of which are ∼8 times that of potential evapotranspiration. Nationally, the results are spatially correlated, suggestive of large‐scale effects. The responses of head and recharge appear to be primarily related to climate type and hydrogeology. The more arid the climate, the higher the head sensitivity but the lower the recharge sensitivity. Porous media generally show higher head sensitivity than fractured media due to smaller aquifer specific yield, and again contrarily for that of recharge. These findings contribute to understanding the long‐term impact of climate change on groundwater and thus provide valuable insights for sustainable groundwater management.
Constraining Plant Hydraulics With Microwave Radiometry in a Land Surface Model: Impacts of Temporal Resolution
Authors: Holtzman Nataniel , Wang Yujie , Wood Jeffrey D. , Frankenberg Christian , Konings Alexandra G.
Published: November 2023

Vegetation water content (VWC) plays a key role in transpiration, plant mortality, and wildfire risk. Although land surface models now often contain plant hydraulics schemes, there are few direct VWC measurements to constrain these models at global scale. One proposed solution to this data gap is passive microwave remote sensing, which is sensitive to temporal changes in VWC. Here, we test that approach by using synthetic microwave observations to constrain VWC and surface soil moisture within the Climate Modeling Alliance Land model. We further investigate the possible utility of sub‐daily observations of VWC, which could be obtained through a satellite in geostationary orbit or combinations of multiple satellites. These high‐temporal‐resolution observations could allow for improved determination of ecosystem parameters, carbon and water fluxes, and subsurface hydraulics, relative to the currently available twice‐daily sun‐synchronous observational patterns. We find that incorporating observations at four different times in the diurnal cycle (such as could be available from two sun‐synchronous satellites) provides a significantly better constraint on water and carbon fluxes than twice‐daily observations do. For example, the root mean square error of projected evapotranspiration and gross primary productivity during drought periods was reduced by approximately 40%, when using four‐times‐daily relative to twice‐daily observations. Adding hourly observations of the entire diurnal cycle did not further improve the inferred parameters and fluxes. Our comparison of observational strategies may be informative in the design of future satellite missions to study plant hydraulics, as well as when using existing remotely sensed data to study vegetation water stress response.
Study of Supercooling Phenomena in Soil‐Water Systems Based on Nucleation Theory: Quantifying Supercooling Degree
Authors: Wang Chong , Li Kunyu , Cai Honghong , Wu Yumo , Lin Zhikun , Li Shuangyang
Published: November 2023

Determining the minimum supercooling temperature (Tsc) of unsaturated saline soils is the key scientific problem in cold‐region agricultural and engineering, and theoretical models with good predictability are urgently needed. This study establishes a framework for pore solution freezing nucleation in unsaturated saline soils, the chemical potential energy balance equation was established by determining phase transition driving force and potential energy barrier for the formation of stable crystal embryos. Finally, the physical model was constructed. By citing 46 sets of data from different researchers, the validity of the prediction results of this paper's model under different soil types and cooling rates is demonstrated, and the microscopic mechanism of supercooling occurring in the pore solution of positive permafrost is elucidated. The analysis found that electrolyte action restricts the free diffusion of molecules and promotes nucleation to occur, so that a maximum value of Tsc exists during the growth of salinity (in NaCl saline soils occurs at a solution concentration of 0.26 mol/L). Too fast cooling rate will lead to a lag in crystallization time and an increase in supercooling. The combined water content determines the Tsc when rc < 1 μm (pore size), and the effect of changes in water content and cooling rate on supercooling is more significant in small pores; the electrolyte concentration determines the Tsc when rc > 1 μm, Tsc‐max from concentration changes will be more significant in large pores. This study can provide theoretical reserves for controlling the freezing process of soils, studying the mechanism of freezing‐thawing hysteresis, and improving the related numerical calculation models.
Sex-associated differences in frequencies and prognostic impact of recurrent genetic alterations in adult acute myeloid leukemia (Alliance, AMLCG)
Authors: Ozga Michael , Nicolet Deedra , Mrózek Krzysztof , Yilmaz Ayse S. , Kohlschmidt Jessica , Larkin Karilyn T. , Blachly James S. , Oakes Christopher C. , Buss Jill , Walker Christopher J. , Orwick Shelley , Jurinovic Vindi , Rothenberg-Thurley Maja , Dufour Annika , Schneider Stephanie , Sauerland Maria Cristina , Görlich Dennis , Krug Utz , Berdel Wolfgang E. , Woermann Bernhard J. , Hiddemann Wolfgang , Braess Jan , Subklewe Marion , Spiekermann Karsten , Carroll Andrew J. , Blum William G. , Powell Bayard L. , Kolitz Jonathan E. , Moore Joseph O. , Mayer Robert J. , Larson Richard A. , Uy Geoffrey L. , Stock Wendy , Metzeler Klaus H. , Grimes H. Leighton , Byrd John C. , Salomonis Nathan , Herold Tobias , Mims Alice S. , Eisfeld Ann-Kathrin
Published: November 2023

Clinical outcome of patients with acute myeloid leukemia (AML) is associated with demographic and genetic features. Although the associations of acquired genetic alterations with patients’ sex have been recently analyzed, their impact on outcome of female and male patients has not yet been comprehensively assessed. We performed mutational profiling, cytogenetic and outcome analyses in 1726 adults with AML (749 female and 977 male) treated on frontline Alliance for Clinical Trials in Oncology protocols. A validation cohort comprised 465 women and 489 men treated on frontline protocols of the German AML Cooperative Group. Compared with men, women more often had normal karyotype, FLT3-ITD, DNMT3A, NPM1 and WT1 mutations and less often complex karyotype, ASXL1, SRSF2, U2AF1, RUNX1, or KIT mutations. More women were in the 2022 European LeukemiaNet intermediate-risk group and more men in adverse-risk group. We found sex differences in co-occurring mutation patterns and prognostic impact of select genetic alterations. The mutation-associated splicing events and gene-expression profiles also differed between sexes. In patients aged <60 years, SF3B1 mutations were male-specific adverse outcome prognosticators. We conclude that sex differences in AML-associated genetic alterations and mutation-specific differential splicing events highlight the importance of patients’ sex in analyses of AML biology and prognostication.
Chronic lymphocytic leukemia patient-derived xenografts recapitulate clonal evolution to Richter transformation
Authors: Playa-Albinyana Heribert , Arenas Fabian , Royo Romina , Giró Ariadna , López-Oreja Irene , Aymerich Marta , López-Guerra Mònica , Frigola Gerard , Beà Sílvia , Delgado Julio , Garcia-Roves Pablo M. , Campo Elías , Nadeu Ferran , Colomer Dolors
Published: November 2023

Chronic lymphocytic leukemia (CLL) is a B-cell neoplasm with a heterogeneous clinical behavior. In 5–10% of patients the disease transforms into a diffuse large-B cell lymphoma known as Richter transformation (RT), which is associated with dismal prognosis. Here, we aimed to establish patient-derived xenograft (PDX) models to study the molecular features and evolution of CLL and RT. We generated two PDXs by injecting CLL (PDX12) and RT (PDX19) cells into immunocompromised NSG mice. Both PDXs were morphologically and phenotypically similar to RT. Whole-genome sequencing analysis at different time points of the PDX evolution revealed a genomic landscape similar to RT tumors from both patients and uncovered an unprecedented RT subclonal heterogeneity and clonal evolution during PDX generation. In PDX12, the transformed cells expanded from a very small subclone already present at the CLL stage. Transcriptomic analysis of PDXs showed a high oxidative phosphorylation (OXPHOS) and low B-cell receptor (BCR) signaling similar to the RT in the patients. IACS-010759, an OXPHOS inhibitor, reduced proliferation, and circumvented resistance to venetoclax. In summary, we have generated new RT-PDX models, one of them from CLL cells that mimicked the evolution of CLL to RT uncovering intrinsic features of RT cells of therapeutical value.
Investigation into the role of the MITA-TRIM38 interaction in regulating pyroptosis and maintaining immune tolerance at the maternal-fetal interface
Authors: Liu Jun , Deng Yan , Wang An , Liu Bowen , Zhou Xi , Yin Tailang , Wang Yan , Tang Tao , Qiu Yang , Chen Jiao , Yang Jing
Published: November 2023

The maternal-fetal interface shares similarities with tumor tissues in terms of the immune microenvironment. Normal pregnancy is maintained due to the immunosuppressed state, but pyroptosis induced by MITA can trigger the body’s immune response and disrupt the immunosuppressed state of the maternal-fetal interface, leading to abortion. In this study, we explored the role of MITA and TRIM38 in regulating pyroptosis and maintaining the immune tolerance of the maternal-fetal interface during pregnancy. Our findings show that the interaction between MITA and TRIM38 plays a crucial role in maintaining the immunosuppressed state of the maternal-fetal interface. Specifically, we observed that TRIM38-mediated K48 ubiquitination of MITA was higher in M2 macrophages, leading to low expression levels of MITA and thus inhibiting pyroptosis. Conversely, in M1 macrophages, the ubiquitination of K48 was lower, resulting in higher expression levels of MITA and promoting pyroptosis. Our results also indicated that pyroptosis played an important role in hindering the transformation of M1 to M2 and maintaining the immunosuppressed state of the maternal-fetal interface. These discoveries help elucidate the mechanisms that support the preservation of the immune tolerance microenvironment at the maternal-fetal interface, playing a vital role in ensuring successful pregnancy.
sFlt-1/PIGF ratio positive associated with non-dipper type change in ambulatory blood pressure monitoring(ABPM) for preeclampsia development
Authors: Chen Yunshan , Di Xiaodan , Xiang Guochun , Liu Yunfeng , Pan Xiuyu , Deng Wenfeng , Zhu Xiongjie , Lei Ming , Zhang Guozheng , Liu Huishu
Published: November 2023

In order to explore relationship of ambulatory blood pressure monitoring (ABPM) and soluble fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PlGF) in suspected preeclampsia(PE), suspected PE participants in 28 + 0 to 33 + 6 weeks underwent ABPM and sFlt-1/PlGF from July 2020 to July 2022 were included(N = 476) in study. ABPM parameters were compared between sFlt-1/PlGF ≥38 and <38 groups. Correlation analysis was performed between ABPM and sFlt-1/PlGF, and logistic regression was used to explore prediction value for PE in 2 weeks. One hundred eighteen cases developed PE in 2 weeks with 114 from sFlt-1/PlGF ≥38 group. Daytime and nighttime BP were all increased,with increased non-dipper (58.4% vs. 30.3%), riser (22.1% vs. 13.1%) and and decreased Dipper (15.4% vs. 45.9%) type of ABPM in sFlt-1/PlGF ≥38 groups (P < 0.05).The riser group had the highest sFlt-1 and lowest PlGF. sFlt-1/PlGF and sFlt-1 were all positively correlated with systolic (SBP) & diastolic blood pressure(DBP)(P < 0.01), in which correlation coefficients of daytime and nighttime BP with sFlt-1 were β = 150.05 & 157.67 for SBP, β = 234 and 199.01 for DBP, respectively. However, PlGF was only negatively associated with nighttime SBP and DBP(P < 0.05), with no correlation with daytime BP (P > 0.05).Combining sFlt-1/PlGF and ABPM model, showed sFlt-1/PlGF (aOR = 2.01 (1.69–2.36)), Nighttime DBP (aOR = 1.14 (1.02–1.28)) contributed to preeclampsia prediction, and had improved predictive value compared to ABPM or sFlt-1/PlGF models alone(P < 0.05). sFlt-1/PlGF ratio was positively correlated with BP parameters, whereas PIGF was only negatively correlated with nocturnal BP and increased non-dipper type change in ABPM, which had a synergistic effect with sFlt-1/PlGF on PE prediction.
Emulator-based Bayesian inference on non-proportional scintillation models by compton-edge probing
Authors: Breitenmoser David , Cerutti Francesco , Butterweck Gernot , Kasprzak Malgorzata Magdalena , Mayer Sabine
Published: November 2023

Scintillator detector response modeling has become an essential tool in various research fields such as particle and nuclear physics, astronomy or geophysics. Yet, due to the system complexity and the requirement for accurate electron response measurements, model inference and calibration remains a challenge. Here, we propose Compton edge probing to perform non-proportional scintillation model (NPSM) inference for inorganic scintillators. We use laboratory-based gamma-ray radiation measurements with a NaI(Tl) scintillator to perform Bayesian inference on a NPSM. Further, we apply machine learning to emulate the detector response obtained by Monte Carlo simulations. We show that the proposed methodology successfully constrains the NPSM and hereby quantifies the intrinsic resolution. Moreover, using the trained emulators, we can predict the spectral Compton edge dynamics as a function of the parameterized scintillation mechanisms. The presented framework offers a simple way to infer NPSMs for any inorganic scintillator without the need for additional electron response measurements.
Xylose and shikimate transporters facilitates microbial consortium as a chassis for benzylisoquinoline alkaloid production
Authors: Gao Meirong , Zhao Yuxin , Yao Zhanyi , Su Qianhe , Van Beek Payton , Shao Zengyi
Published: November 2023

Plant-sourced aromatic amino acid (AAA) derivatives are a vast group of compounds with broad applications. Here, we present the development of a yeast consortium for efficient production of (S)-norcoclaurine, the key precursor for benzylisoquinoline alkaloid biosynthesis. A xylose transporter enables the concurrent mixed-sugar utilization in Scheffersomyces stipitis, which plays a crucial role in enhancing the flux entering the highly regulated shikimate pathway located upstream of AAA biosynthesis. Two quinate permeases isolated from Aspergillus niger facilitates shikimate translocation to the co-cultured Saccharomyces cerevisiae that converts shikimate to (S)-norcoclaurine, resulting in the maximal titer (11.5 mg/L), nearly 110-fold higher than the titer reported for an S. cerevisiae monoculture. Our findings magnify the potential of microbial consortium platforms for the economical de novo synthesis of complex compounds, where pathway modularization and compartmentalization in distinct specialty strains enable effective fine-tuning of long biosynthetic pathways and diminish intermediate buildup, thereby leading to increases in production.
Temporal morphogen gradient-driven neural induction shapes single expanded neuroepithelium brain organoids with enhanced cortical identity
Authors: Pagliaro Anna , Finger Roxy , Zoutendijk Iris , Bunschuh Saskia , Clevers Hans , Hendriks Delilah , Artegiani Benedetta
Published: November 2023

Pluripotent stem cell (PSC)-derived human brain organoids enable the study of human brain development in vitro. Typically, the fate of PSCs is guided into subsequent specification steps through static medium switches. In vivo, morphogen gradients are critical for proper brain development and determine cell specification, and associated defects result in neurodevelopmental disorders. Here, we show that initiating neural induction in a temporal stepwise gradient guides the generation of brain organoids composed of a single, self-organized apical-out neuroepithelium, termed ENOs (expanded neuroepithelium organoids). This is at odds with standard brain organoid protocols in which multiple and independent neuroepithelium units (rosettes) are formed. We find that a prolonged, decreasing gradient of TGF-β signaling is a determining factor in ENO formation and allows for an extended phase of neuroepithelium expansion. In-depth characterization reveals that ENOs display improved cellular morphology and tissue architectural features that resemble in vivo human brain development, including expanded germinal zones. Consequently, cortical specification is enhanced in ENOs. ENOs constitute a platform to study the early events of human cortical development and allow interrogation of the complex relationship between tissue architecture and cellular states in shaping the developing human brain.
Nuclear actin polymerization rapidly mediates replication fork remodeling upon stress by limiting PrimPol activity
Authors: Palumbieri Maria Dilia , Merigliano Chiara , González-Acosta Daniel , Kuster Danina , Krietsch Jana , Stoy Henriette , von Känel Thomas , Ulferts Svenja , Welter Bettina , Frey Joël , Doerdelmann Cyril , Sanchi Andrea , Grosse Robert , Chiolo Irene , Lopes Massimo
Published: November 2023

Cells rapidly respond to replication stress actively slowing fork progression and inducing fork reversal. How replication fork plasticity is achieved in the context of nuclear organization is currently unknown. Using nuclear actin probes in living and fixed cells, we visualized nuclear actin filaments in unperturbed S phase and observed their rapid extension in number and length upon genotoxic treatments, frequently taking contact with replication factories. Chemically or genetically impairing nuclear actin polymerization shortly before these treatments prevents active fork slowing and abolishes fork reversal. Defective fork remodeling is linked to deregulated chromatin loading of PrimPol, which promotes unrestrained and discontinuous DNA synthesis and limits the recruitment of RAD51 and SMARCAL1 to nascent DNA. Moreover, defective nuclear actin polymerization upon mild replication interference induces chromosomal instability in a PRIMPOL-dependent manner. Hence, by limiting PrimPol activity, nuclear F-actin orchestrates replication fork plasticity and is a key molecular determinant in the rapid cellular response to genotoxic treatments.
Functional Janus structured liquids and aerogels
Authors: Ghaffarkhah Ahmadreza , Hashemi Seyyed Alireza , Ahmadijokani Farhad , Goodarzi Milad , Riazi Hossein , Mhatre Sameer E. , Zaremba Orysia , Rojas Orlando J. , Soroush Masoud , Russell Thomas P. , Wuttke Stefan , Kamkar Milad , Arjmand Mohammad
Published: November 2023

Janus structures have unique properties due to their distinct functionalities on opposing faces, but have yet to be realized with flowing liquids. We demonstrate such Janus liquids with a customizable distribution of nanoparticles (NPs) throughout their structures by joining two aqueous streams of NP dispersions in an apolar liquid. Using this anisotropic integration platform, different magnetic, conductive, or non-responsive NPs can be spatially confined to opposite sides of the original interface using magnetic graphene oxide (mGO)/GO, Ti3C2Tx/GO, or GO suspensions. The resultant Janus liquids can be used as templates for versatile, responsive, and mechanically robust aerogels suitable for piezoresistive sensing, human motion monitoring, and electromagnetic interference (EMI) shielding with a tuned absorption mechanism. The EMI shields outperform their current counterparts in terms of wave absorption, i.e., SET ≈ 51 dB, SER ≈ 0.4 dB, and A = 0.91, due to their high porosity ranging from micro- to macro-scales along with non-interfering magnetic and conductive networks imparted by the Janus architecture.
Data-driven grading of acute graft-versus-host disease
Authors: Bayraktar Evren , Graf Theresa , Ayuk Francis A. , Beutel Gernot , Penack Olaf , Luft Thomas , Brueder Nicole , Castellani Gastone , Reinhardt H. Christian , Kröger Nicolaus , Beelen Dietrich W. , Turki Amin T.
Published: November 2023

Despite advances in allogeneic hematopoietic cell transplantation, acute graft-versus-host disease (aGVHD) remains its leading complication, yet with heterogeneous outcomes. Here, we analyzed aGVHD phenotypes and clinical classifications in depth in large, multicenter cohorts involving 3019 patients and addressed prevailing gaps by developing data-driven models. We compared, tested and verified these along with all conventional classifications in independent cohorts and found that data-driven grading outperformed conventional grading in Akaike information criterion and concordance index metrics. Data-driven classifications refined aGVHD assessment with up to 12 severity grades, which were associated with distinct nonrelapse mortality (NRM) and confirmed the key role of intestinal aGVHD. We developed an online calculator for physicians to implement principal component-derived grading (PC1). These results provide substantial insight into the evaluation of aGVHD phenotypes and multiorgan involvement, which relegates the exclusive reporting of overall aGVHD severity grades in transplant registries and clinical trials. Data-driven aGVHD grading provides an expandable platform to refine classification and transplant risk assessment.
Compensating transport trends in the Drake Passage frontal regions yield no acceleration in net transport
Authors: Gutierrez-Villanueva Manuel O. , Chereskin Teresa K. , Sprintall Janet
Published: November 2023

Although the westerly winds that drive the Antarctic Circumpolar Current (ACC) have increased over the past several decades, the ACC response remains an open question. Here we use a 15-year time series of concurrent upper-ocean temperature, salinity, and ocean velocity with high spatial resolution across Drake Passage to analyze whether the net Drake Passage transport has accelerated in the last 15 years. We find that, although the net Drake Passage transport relative to 760 m shows insignificant acceleration, the net transport trend comprises compensating trends across the ACC frontal regions. Our results show an increase in the mesoscale eddy activity between the fronts consistent with buoyancy changes in the fronts and with an eddy saturation state. Furthermore, the increased eddy activity may play a role in redistributing momentum across the ACC frontal regions. The increase in eddy activity is expected to intensify the eddy-driven upwelling of deep warm waters around Antarctica, which has significant implications for ice-melting, sea level rise, and global climate.
Hidden magnetism uncovered in a charge ordered bilayer kagome material ScV6Sn6
Authors: Guguchia Z. , Gawryluk D. J. , Shin S. , Hao Z. , Mielke III C. , Das D. , Plokhikh I. , Liborio L. , Shenton J. Kane , Hu Y. , Sazgari V. , Medarde M. , Deng H. , Cai Y. , Chen C. , Jiang Y. , Amato A. , Shi M. , Hasan M. Z. , Yin J.-X. , Khasanov R. , Pomjakushina E. , Luetkens H.
Published: November 2023

Charge ordered kagome lattices have been demonstrated to be intriguing platforms for studying the intertwining of topology, correlation, and magnetism. The recently discovered charge ordered kagome material ScV6Sn6does not feature a magnetic groundstate or excitations, thus it is often regarded as a conventional paramagnet. Here, using advanced muon-spin rotation spectroscopy, we uncover an unexpected hidden magnetism of the charge order. We observe an enhancement of the internal field width sensed by the muon ensemble, which takes place within the charge ordered state. More importantly, the muon spin relaxation rate below the charge ordering temperature is substantially enhanced by applying an external magnetic field. Taken together with the hidden magnetism found inAV3Sb5(A= K, Rb, Cs) and FeGe kagome systems, our results suggest ubiqitous time-reversal symmetry-breaking in charge ordered kagome lattices.
The genetic relationships between brain structure and schizophrenia
Authors: Stauffer Eva-Maria , Bethlehem Richard A. I. , Dorfschmidt Lena , Won Hyejung , Warrier Varun , Bullmore Edward T.
Published: November 2023

Genetic risks for schizophrenia are theoretically mediated by genetic effects on brain structure but it has been unclear which genes are associated with both schizophrenia and cortical phenotypes. We accessed genome-wide association studies (GWAS) of schizophrenia (N = 69,369 cases; 236,642 controls), and of three magnetic resonance imaging (MRI) metrics (surface area, cortical thickness, neurite density index) measured at 180 cortical areas (N = 36,843, UK Biobank). Using Hi-C-coupled MAGMA, 61 genes were significantly associated with both schizophrenia and one or more MRI metrics. Whole genome analysis with partial least squares demonstrated significant genetic covariation between schizophrenia and area or thickness of most cortical regions. Genetic similarity between cortical areas was strongly coupled to their phenotypic covariance, and genetic covariation between schizophrenia and brain phenotypes was strongest in the hubs of structural covariance networks. Pleiotropically associated genes were enriched for neurodevelopmental processes and positionally concentrated in chromosomes 3p21, 17q21 and 11p11. Mendelian randomization analysis indicated that genetically determined variation in a posterior cingulate cortical area could be causal for schizophrenia. Parallel analyses of GWAS on bipolar disorder, Alzheimer’s disease and height showed that pleiotropic association with MRI metrics was stronger for schizophrenia compared to other disorders.
Plasma proteomic profiles predict individual future health risk
Authors: You Jia , Guo Yu , Zhang Yi , Kang Ju-Jiao , Wang Lin-Bo , Feng Jian-Feng , Cheng Wei , Yu Jin-Tai
Published: November 2023

Developing a single-domain assay to identify individuals at high risk of future events is a priority for multi-disease and mortality prevention. By training a neural network, we developed a disease/mortality-specific proteomic risk score (ProRS) based on 1461 Olink plasma proteins measured in 52,006 UK Biobank participants. This integrative score markedly stratified the risk for 45 common conditions, including infectious, hematological, endocrine, psychiatric, neurological, sensory, circulatory, respiratory, digestive, cutaneous, musculoskeletal, and genitourinary diseases, cancers, and mortality. The discriminations witnessed high accuracies achieved by ProRS for 10 endpoints (e.g., cancer, dementia, and death), with C-indexes exceeding 0.80. Notably, ProRS produced much better or equivalent predictive performance than established clinical indicators for almost all endpoints. Incorporating clinical predictors with ProRS enhanced predictive power for most endpoints, but this combination only exhibited limited improvement when compared to ProRS alone. Some proteins, e.g., GDF15, exhibited important discriminative values for various diseases. We also showed that the good discriminative performance observed could be largely translated into practical clinical utility. Taken together, proteomic profiles may serve as a replacement for complex laboratory tests or clinical measures to refine the comprehensive risk assessments of multiple diseases and mortalities simultaneously. Our models were internally validated in the UK Biobank; thus, further independent external validations are necessary to confirm our findings before application in clinical settings.
PhenoSV: interpretable phenotype-aware model for the prioritization of genes affected by structural variants
Authors: Xu Zhuoran , Li Quan , Marchionni Luigi , Wang Kai
Published: November 2023

Structural variants (SVs) represent a major source of genetic variation associated with phenotypic diversity and disease susceptibility. While long-read sequencing can discover over 20,000 SVs per human genome, interpreting their functional consequences remains challenging. Existing methods for identifying disease-related SVs focus on deletion/duplication only and cannot prioritize individual genes affected by SVs, especially for noncoding SVs. Here, we introduce PhenoSV, a phenotype-aware machine-learning model that interprets all major types of SVs and genes affected. PhenoSV segments and annotates SVs with diverse genomic features and employs a transformer-based architecture to predict their impacts under a multiple-instance learning framework. With phenotype information, PhenoSV further utilizes gene-phenotype associations to prioritize phenotype-related SVs. Evaluation on extensive human SV datasets covering all SV types demonstrates PhenoSV’s superior performance over competing methods. Applications in diseases suggest that PhenoSV can determine disease-related genes from SVs. A web server and a command-line tool for PhenoSV are available at https://phenosv.wglab.org.
Ultrasonic barrier-through imaging by Fabry-Perot resonance-tailoring panel
Authors: Park Chung Il , Choe Seungah , Lee Woorim , Choi Wonjae , Kim Miso , Seung Hong Min , Kim Yoon Young
Published: November 2023

Imaging technologies that provide detailed information on intricate shapes and states of an object play critical roles in nanoscale dynamics, bio-organ and cell studies, medical diagnostics, and underwater detection. However, ultrasonic imaging of an object hidden by a nearly impenetrable metal barrier remains intractable. Here, we present the experimental results of ultrasonic imaging of an object in water behind a metal barrier of a high impedance mismatch. In comparison to direct ultrasonic images, our method yields sufficient object information on the shapes and locations with minimal errors. While our imaging principle is based on the Fabry-Perot (FP) resonance, our strategy for reducing attenuation in our experiments focuses on customising the resonance at any desired frequency. To tailor the resonance frequency, we placed an elaborately engineered panel of a specific material and thickness, called the FP resonance-tailoring panel (RTP), and installed the panel in front of a barrier at a controlled distance. Since our RTP-based imaging technique is readily compatible with conventional ultrasound devices, it can realise underwater barrier-through imaging and communication and enhance skull-through ultrasonic brain imaging.
The ELAVL3/MYCN positive feedback loop provides a therapeutic target for neuroendocrine prostate cancer
Authors: Ji Yiyi , Zhang Weiwei , Shen Kai , Su Ruopeng , Liu Xinyu , Ma Zehua , Liu Bo , Hu Cong , Xue Yizheng , Xin Zhixiang , Yang Yi , Li Ang , Jiang Zhou , Jing Na , Zhu Helen He , Dong Liang , Zhu Yinjie , Dong Baijun , Pan Jiahua , Wang Qi , Xue Wei
Published: November 2023

Neuroendocrine prostate cancer is a rapidly progressive and lethal disease characterized by early visceral metastasis, poor prognosis, and limited treatment options. Uncovering the oncogenic mechanisms could lead to the discovery of potential therapeutic avenues. Here, we demonstrate that the RNA-binding protein ELAVL3 is specifically upregulated in neuroendocrine prostate cancer and that overexpression of ELAVL3 alone is sufficient to induce the neuroendocrine phenotype in prostate adenocarcinoma. Mechanistically, ELAVL3 is transcriptionally regulated by MYCN and subsequently binds to and stabilizes MYCN and RICTOR mRNA. Moreover, ELAVL3 is shown to be released in extracellular vesicles and induce neuroendocrine differentiation of adenocarcinoma cells via an intercellular mechanism. Pharmacological inhibition of ELAVL3 with pyrvinium pamoate, an FDA-approved drug, effectively suppresses tumor growth, reduces metastatic risk, and improves survival in neuroendocrine prostate cancer mouse models. Our results identify ELAVL3 as a critical regulator of neuroendocrine differentiation in prostate cancer and propose a drug repurposing strategy for targeted therapies.
Grammars Across Time Analyzed (GATA): a dataset of 52 languages
Authors: Blum Frederic , Barrientos Carlos , Ingunza Adriano , Blasi Damián E. , Zariquiey Roberto
Published: November 2023

Grammars Across Time Analyzed (GATA) is a resource capturing two snapshots of the grammatical structure of a diverse range of languages separated in time, aimed at furthering research on historical linguistics, language evolution, and cultural change. GATA comprises grammatical information on 52 diverse languages across all continents, featuring morphological, syntactic, and phonological information based on published grammars of the same language at two different time points. Here we introduce the coding scheme and design features of GATA, and we describe some salient patterns related to language change and the coverage of grammatical descriptions over time.
Functional trait dataset of benthic macroinvertebrates in South Korean streams
Authors: Adhurya Sagar , Lee Da-Yeong , Lee Dae-Seong , Park Young-Seuk
Published: November 2023

Functional traits are the result of evolution and adaptation, providing important ecological insights into how organisms interact with their environment. Benthic macroinvertebrates, in particular, have garnered attention as biomonitoring indicators for freshwater ecosystems. This study presents a functional trait dataset for benthic macroinvertebrates, comprising 447 taxa (393 at genus level, 53 at family level and one at class level) from five phyla (Annelida, Arthropoda, Mollusca, Nematomorpha, and Platyhelmenthes), categorized into nine traits related to life history, morphology, and habit. To account for variation in available trait information, we assigned confidence levels to each taxon and functional trait based on the level of evidence using fuzzy coding. Our dataset provides an important resource for understanding the ecology of benthic macroinvertebrates in South Korea, serving as a valuable baseline dataset for studying their biodiversity, conservation, and biomonitoring in freshwater ecosystems.
Over a decade of atmospheric mercury monitoring at Amsterdam Island in the French Southern and Antarctic Lands
Authors: Magand Olivier , Angot Hélène , Bertrand Yann , Sonke Jeroen E. , Laffont Laure , Duperray Solène , Collignon Léa , Boulanger Damien , Dommergue Aurélien
Published: November 2023

The Minamata Convention, a global and legally binding treaty that entered into force in 2017, aims to protect human health and the environment from harmful mercury (Hg) effects by reducing anthropogenic Hg emissions and environmental levels. The Conference of the Parties is to periodically evaluate the Convention’s effectiveness, starting in 2023, using existing monitoring data and observed trends. Monitoring atmospheric Hg levels has been proposed as a key indicator. However, data gaps exist, especially in the Southern Hemisphere. Here, we present over a decade of atmospheric Hg monitoring data at Amsterdam Island (37.80°S, 77.55°E), in the remote southern Indian Ocean. Datasets include gaseous elemental and oxidised Hg species ambient air concentrations from either active/continuous or passive/discrete acquisition methods, and annual total Hg wet deposition fluxes. These datasets are made available to the community to support policy-making and further scientific advancements.
TM2D3, a mammalian homologue of Drosophila neurogenic gene product Almondex, regulates surface presentation of Notch receptors
Authors: Masuda Wataru , Yamakawa Tomoko , Ajima Rieko , Miyake Katsuya , Umemiya Toshifumi , Azuma Kazuhiko , Tamaru Jun-ichi , Kiso Makoto , Das Puspa , Saga Yumiko , Matsuno Kenji , Kitagawa Motoo
Published: November 2023

Notch signaling is an evolutionarily conserved mechanism required for numerous types of cell fate decisions in metazoans. It mediates short-range communication between cells with receptors and ligands, both of which are expressed on the cell surfaces. In response to the ligand-receptor interaction, the ligand and the extracellular domain of the Notch receptor (NECD) in the complex are internalized into ligand-expressing cells by endocytosis, a prerequisite process for the conformational change of the membrane proximal region of Notch to induce critical proteolytic cleavages for its activation. Here we report that overexpression of transmembrane 2 (TM2) domain containing 3 (TM2D3), a mammalian homologue of Drosophila melanogaster Almondex (Amx), activates Notch1. This activation requires the ligand-binding domain in Notch1 and the C-terminal region containing TM2 domain in TM2D3. TM2D3 physically associates with Notch1 at the region distinct from the ligand-binding domain and enhances expression of Notch1 on the cell surface. Furthermore, cell surface expression of Notch1 and Notch2 is reduced in Tm2d3-deficient cells. Finally, amx-deficient Drosophila early embryos exhibit impaired endocytosis of NECD and Delta ligand, for which surface presentation of Notch is required. These results indicate that TM2D3 is an element involved in Notch signaling through the surface presentation.
Evaluation of the efficacy of cystinosin supplementation through CTNS mRNA delivery in experimental models for cystinosis
Authors: Bondue Tjessa , Berlingerio Sante Princiero , Siegerist Florian , Sendino-Garví Elena , Schindler Maximilian , Baelde Hans Jacobus , Cairoli Sara , Goffredo Bianca Maria , Arcolino Fanny Oliveira , Dieker Jürgen , Janssen Manoe Jacoba , Endlich Nicole , Brock Roland , Gijsbers Rik , van den Heuvel Lambertus , Levtchenko Elena
Published: November 2023

Messenger RNA (mRNA) therapies are emerging in different disease areas, but have not yet reached the kidney field. Our aim was to study the feasibility to treat the genetic defect in cystinosis using synthetic mRNA in cell models and ctns−/− zebrafish embryos. Cystinosis is a prototype lysosomal storage disorder caused by mutations in the CTNS gene, encoding the lysosomal cystine-H+ symporter cystinosin, and leading to cystine accumulation in all cells of the body. The kidneys are the first and the most severely affected organs, presenting glomerular and proximal tubular dysfunction, progressing to end-stage kidney failure. The current therapeutic standard cysteamine, reduces cystine levels, but has many side effects and does not restore kidney function. Here, we show that synthetic mRNA can restore lysosomal cystinosin expression following lipofection into CTNS−/− kidney cells and injection into ctns−/− zebrafish. A single CTNS mRNA administration decreases cellular cystine accumulation for up to 14 days in vitro. In the ctns−/− zebrafish, CTNS mRNA therapy improves proximal tubular reabsorption, reduces proteinuria, and restores brush border expression of the multi-ligand receptor megalin. Therefore, this proof-of-principle study takes the first steps in establishing an mRNA-based therapy to restore cystinosin expression, resulting in cystine reduction in vitro and in the ctns−/− larvae, and restoration of the zebrafish pronephros function.
Accurate evaluation of the progress of delivery with transperineal ultrasound may improve vaginal delivery: a single-center retrospective study
Authors: Enomoto Naosuke , Maki Shintaro , Nii Masafumi , Yamaguchi Mizuki , Tamaishi Yuya , Takakura Sho , Magawa Shoichi , Tanaka Kayo , Tanaka Hiroaki , Kondo Eiji , Katsuragi Shinji , Ikeda Tomoaki
Published: November 2023

Although digital examination of the cervix is the standard method used worldwide for evaluating the progress of delivery, it is subjective. Transperineal ultrasound (TPU) is combined with digital evaluation for accurate assessment of fetal descent and rotation of the advanced part of the fetus. This retrospective study aimed to clarify the impact of introducing TPU on perinatal outcomes at Mie University Hospital. We analyzed singleton pregnant women who underwent delivery management at our hospital between April 2020 and March 2021. Perinatal outcomes were compared between patients who used TPU (TPU+ group) and those who did not (TPU− group). The angle of progression and head direction were measured. The rate of vaginal delivery was significantly increased (90.9% vs. 71.6%; P = 0.0017), and the second stage of labor was significantly prolonged in the TPU+ group (148.1 vs. 75.8 min; P < 0.0001). A significant difference was observed in termination in the latent phase between the TPU+ group [3/8 (37.5%) cases] and TPU− group [20/25 (80.0%) cases] (P = 0.036). The rate of vaginal delivery can be increased through accurate evaluation of the progress of delivery with TPU.
3D vs. 2D simulated fetoscopy for spina bifida repair: a quantitative motion analysis
Authors: Ahmad Mirza Awais , Weiler Yolan , Joyeux Luc , Eixarch Elisenda , Vercauteren Tom , Ourselin Sebastien , Deprest Jan , Vander Poorten Emmanuel
Published: November 2023

3D imaging technology is becoming more prominent every day. However, more validation is needed to understand the actual benefit of 3D versus conventional 2D vision. This work quantitatively investigates whether experts benefit from 3D vision during minimally invasive fetoscopic spina bifida (fSB) repair. A superiority study was designed involving one expert team ($$>18$$

>
18

procedures prior) who performed six 2D and six 3D fSB repair simulations in a high-fidelity animal training model, using 3-port access. The 6D motion of the instruments was recorded. Among the motion metrics are total path length, smoothness, maximum speed, the modified Spectral Arc Length (SPARC), and Log Dimensionless Jerk (LDLJ). The primary clinical outcome is operation time (power 90%, 5% significance) using Sealed Envelope Ltd. 2012. Secondary clinical outcomes are water tightness of the repair, CO$$_2$$

2

insufflation volume, and OSATS score. Findings show that total path length and LDLJ are considerably different. Operation time during 3D vision was found to be significantly shorter compared to 2D vision ($$113\pm 9$$

113
±
9

vs. $$149\pm 19$$

149
±
19

min; p $$=$$
=
0.026). These results suggest enhanced performance with 3D vision during interrupted suturing in fetoscopic SBA repair. To confirm these results, a larger-scale follow-up study involving multiple experts and novice surgeons is recommended.