bluuebunny/crossref_metadata_2025_split huggingface dataset:
Machine Learning‐Based New Earthquake Catalog Illuminates On‐Fault and Off‐Fault Seismicity Patterns at the Discovery Transform Fault, East Pacific Rise
Authors: Gong Jianhua , Fan Wenyuan , Parnell‐Turner Ross 
Published: September 2023

AbstractOceanic transform faults connect spreading centers and are imprinted with previous tectonic events. However, their tectonic interactions are not well understood due to limited observations. The Discovery transform fault system at 4°S, East Pacific Rise (EPR), represents a young transform system, offering a unique opportunity to study the interplay between faulting and other tectonic events at an early phases of an oceanic transform system. Discovery regularly hosts M5–6 characteristic earthquakes, and the seafloor north of Discovery includes a 35 km‐long rift zone that records a complex history of rifting, faulting and volcanism, suggesting that the transform faults likely interact with regional tectonic activity. We apply a machine‐learning enabled workflow to locate 21,391 earthquakes recorded during a 1‐year ocean bottom seismometer experiment in 2008. Our results indicate that seismicity on the western Discovery fault is separated into seven patches with distinct aseismic and seismic slip modes. Additionally, we observe a patch of off‐fault seismicity near where seafloor abyssal hills intersect the rift zone. This seismicity may have been caused by varying opening rates as spreading rate decreases from north to south in the rift zone. Our findings suggest that the Discovery system is still evolving, and that system equilibrium has not been reached between rifting and faulting. These results reflect the complex yet rarely observed interactions between fault slip, plate rotation, and rifting which are likely ubiquitous at oceanic transform systems.
Assessing the Effects of a Minor CIR‐HSS Geomagnetic Storm on the Brazilian Low‐Latitude Ionosphere: Ground and Space‐Based Observations
Authors: Chingarandi F. S. , Candido C. M. N. , Becker‐Guedes F. , Jonah O. F. , Moraes‐Santos S. P. , Klausner V. , Taiwo O. O. 
Published: September 2023

AbstractThis paper investigates the effects of a minor G1 Co‐rotating Interaction Region (CIR)/High‐Speed Stream (HSS)‐driven geomagnetic storm that occurred on (13–14 October 2018), during deep solar minimum. We used simultaneous observations from multiple instruments, namely; ground‐based Global Navigation Satellite Systems (GNSS) receivers, a Digisonde, ground magnetometers, and space‐based observations from the National Aeronautics and Space Administration Global‐scale Observations of Limb and Disk (GOLD) and SWARM missions. This study presents a detailed picture of the low‐latitude ionosphere response over the Brazilian sector during a minor storm. Our results showed that the minor CIR/HSS‐driven storm caused a positive ionospheric storm of over ∼20 TECU in magnitude. For the first time, periodic post‐sunset irregularities and Equatorial Plasma Bubbles, equatorial plasma bubbles, were analyzed using GOLD FUV OI 135.6 nm emission, Total Electron Content (TEC) maps, Rate of TEC index, ROTI, and TEC gradients. Fluctuations in the interplanetary magnetic field Bz and changes in the thermospheric column density ratio (∑O/N2) are discussed as the main sources of ionospheric changes during the storm. This paper highlights the importance of monitoring and understanding the impact of Sun‐Earth interactions and provides insight into the behavior of the low‐latitude ionosphere during minor geomagnetic storms.
Probabilistic Solar Proxy Forecasting With Neural Network Ensembles
Authors: Daniell Joshua D. , Mehta Piyush M. 
Published: September 2023

AbstractSpace weather indices are used commonly to drive forecasts of thermosphere density, which affects objects in low‐Earth orbit (LEO) through atmospheric drag. One commonly used space weather proxy, F10.7cm, correlates well with solar extreme ultra‐violet (EUV) energy deposition into the thermosphere. Currently, the USAF contracts Space Environment Technologies (SET), which uses a linear algorithm to forecast F10.7cm. In this work, we introduce methods using neural network ensembles with multi‐layer perceptrons (MLPs) and long‐short term memory (LSTMs) to improve on the SET predictions. We make predictions only from historical F10.7cm values. We investigate data manipulation methods (backwards averaging and lookback) as well as multi step and dynamic forecasting. This work shows an improvement over the popular persistence and the operational SET model when using ensemble methods. The best models found in this work are ensemble approaches using multi step or a combination of multi step and dynamic predictions. Nearly all approaches offer an improvement, with the best models improving between 48% and 59% on relative MSE with respect to persistence. Other relative error metrics were shown to improve greatly when ensembles methods were used. We were also able to leverage the ensemble approach to provide a distribution of predicted values; allowing an investigation into forecast uncertainty. Our work found models that produced less biased predictions at elevated and high solar activity levels. Uncertainty was also investigated through the use of a calibration error score metric (CES), our best ensemble reached similar CES as other work.
Genome-wide analysis identifies novel loci influencing plasma apolipoprotein E concentration and Alzheimer’s disease risk
Authors: Aslam M. Muaaz , Fan Kang-Hsien , Lawrence Elizabeth , Bedison Margaret Anne , Snitz Beth E. , DeKosky Steven T. , Lopez Oscar L. , Feingold Eleanor , Kamboh M. Ilyas 
Published: September 2023

AbstractThe APOE 2/3/4 polymorphism is the greatest genetic risk factor for Alzheimer’s disease (AD). This polymorphism is also associated with variation in plasma ApoE level; while APOE*4 lowers, APOE*2 increases ApoE level. Lower plasma ApoE level has also been suggested to be a risk factor for incident dementia. To our knowledge, no large genome-wide association study (GWAS) has been reported on plasma ApoE level. This study aimed to identify new genetic variants affecting plasma ApoE level as well as to test if baseline ApoE level is associated with cognitive function and incident dementia in a longitudinally followed cohort of the Ginkgo Evaluation of Memory (GEM) study. Baseline plasma ApoE concentration was measured in 3031 participants (95.4% European Americans (EAs)). GWAS analysis was performed on 2580 self-identified EAs where both genotype and plasma ApoE data were available. Lower ApoE concentration was associated with worse cognitive function, but not with incident dementia. As expected, the risk for AD increased from E2/2 through to E4/4 genotypes (P for trend = 4.8E-75). In addition to confirming the expected and opposite associations of APOE*2 (P = 4.73E-79) and APOE*4 (P = 8.73E-12) with ApoE level, GWAS analysis revealed nine additional independent signals in the APOE region, and together they explained about 22% of the variance in plasma ApoE level. We also identified seven new loci on chromosomes 1, 4, 5, 7, 11, 12 and 20 (P range = 5.49E-08 to 5.36E-10) that explained about 9% of the variance in ApoE level. Plasma ApoE level-associated independent variants, especially in the APOE region, were also associated with AD risk and amyloid deposition in the brain, indicating that genetically determined ApoE level variation may be a risk factor for developing AD. These results improve our understanding of the genetic determinants of plasma ApoE level and their potential value in affecting AD risk.
Dlk2 interacts with Syap1 to activate Akt signaling pathway during osteoclast formation
Authors: Chen Xinwei , Chen Xuzhuo , Chao Rui , Wang Yexin , Mao Yi , Fan Baoting , Zhang Yaosheng , Xu Weifeng , Qin An , Zhang Shanyong 
Published: September 2023

AbstractExcessive osteoclast formation and bone resorption are related to osteolytic diseases. Delta drosophila homolog-like 2 (Dlk2), a member of the epidermal growth factor (EGF)-like superfamily, reportedly regulates adipocyte differentiation, but its roles in bone homeostasis are unclear. In this study, we demonstrated that Dlk2 deletion in osteoclasts significantly inhibited osteoclast formation in vitro and contributed to a high-bone-mass phenotype in vivo. Importantly, Dlk2 was shown to interact with synapse-associated protein 1 (Syap1), which regulates Akt phosphorylation at Ser473. Dlk2 deletion inhibited Syap1-mediated activation of the AktSer473, ERK1/2 and p38 signaling cascades. Additionally, Dlk2 deficiency exhibits increased bone mass in ovariectomized mice. Our results reveal the important roles of the Dlk2-Syap1 signaling pathway in osteoclast differentiation and osteoclast-related bone disorders.
Fine-scale collective movements reveal present, past and future dynamics of a multilevel society in Przewalski’s horses
Authors: Ozogány Katalin , Kerekes Viola , Fülöp Attila , Barta Zoltán , Nagy Máté 
Published: September 2023

AbstractStudying animal societies needs detailed observation of many individuals, but technological advances offer new opportunities in this field. Here, we present a state-of-the-art drone observation of a multilevel herd of Przewalski’s horses, consisting of harems (one-male, multifemale groups). We track, in high spatio-temporal resolution, the movements of 238 individually identified horses on drone videos, and combine movement analyses with demographic data from two decades of population monitoring. Analysis of collective movements reveals how the structure of the herd’s social network is related to kinship and familiarity of individuals. The network centrality of harems is related to their age and how long the harem stallions have kept harems previously. Harems of genetically related stallions are closer to each other in the network, and female exchange is more frequent between closer harems. High movement similarity of females from different harems predicts becoming harem mates in the future. Our results show that only a few minutes of fine-scale movement tracking combined with high throughput data driven analysis can reveal the structure of a society, reconstruct past group dynamics and predict future ones.
Control of intracellular pH and bicarbonate by CO2 diffusion into human sperm
Authors: Grahn Elena , Kaufmann Svenja V. , Askarova Malika , Ninov Momchil , Welp Luisa M. , Berger Thomas K. , Urlaub Henning , Kaupp U.Benjamin 
Published: September 2023

AbstractThe reaction of CO2 with H2O to form bicarbonate (HCO3−) and H+ controls sperm motility and fertilization via HCO3−-stimulated cAMP synthesis. A complex network of signaling proteins participates in this reaction. Here, we identify key players that regulate intracellular pH (pHi) and HCO3− in human sperm by quantitative mass spectrometry (MS) and kinetic patch-clamp fluorometry. The resting pHi is set by amiloride-sensitive Na+/H+ exchange. The sperm-specific putative Na+/H+ exchanger SLC9C1, unlike its sea urchin homologue, is not gated by voltage or cAMP. Transporters and channels implied in HCO3− transport are not detected, and may be present at copy numbers < 10 molecules/sperm cell. Instead, HCO3− is produced by diffusion of CO2 into cells and readjustment of the CO2/HCO3−/H+ equilibrium. The proton channel Hv1 may serve as a unidirectional valve that blunts the acidification ensuing from HCO3− synthesis. This work provides a new framework for the study of male infertility.
A tissue-intrinsic IL-33/EGF circuit promotes epithelial regeneration after intestinal injury
Authors: Calafiore Marco , Fu Ya-Yuan , Vinci Paola , Arnhold Viktor , Chang Winston Y. , Jansen Suze A. , Egorova Anastasiya , Takashima Shuichiro , Kuttiyara Jason , Ito Takahiro , Serody Jonathan , Nakae Susumu , Turnquist Heth , van Es Johan , Clevers Hans , Lindemans Caroline A. , Blazar Bruce R. , Hanash Alan M. 
Published: September 2023

AbstractIntestinal stem cells (ISCs) maintain the epithelial lining of the intestines, but mechanisms regulating ISCs and their niche after damage remain poorly understood. Utilizing radiation injury to model intestinal pathology, we report here that the Interleukin-33 (IL-33)/ST2 axis, an immunomodulatory pathway monitored clinically as an intestinal injury biomarker, regulates intrinsic epithelial regeneration by inducing production of epidermal growth factor (EGF). Three-dimensional imaging and lineage-specific RiboTag induction within the stem cell compartment indicated that ISCs expressed IL-33 in response to radiation injury. Neighboring Paneth cells responded to IL-33 by augmenting production of EGF, which promoted ISC recovery and epithelial regeneration. These findings reveal an unknown pathway of niche regulation and crypt regeneration whereby the niche responds dynamically upon injury and the stem cells orchestrate regeneration by regulating their niche. This regenerative circuit also highlights the breadth of IL-33 activity beyond immunomodulation and the therapeutic potential of EGF administration for treatment of intestinal injury.
Programmable RNA detection with CRISPR-Cas12a
Authors: Rananaware Santosh R. , Vesco Emma K. , Shoemaker Grace M. , Anekar Swapnil S. , Sandoval Luke Samuel W. , Meister Katelyn S. , Macaluso Nicolas C. , Nguyen Long T. , Jain Piyush K. 
Published: September 2023

AbstractCas12a, a CRISPR-associated protein complex, has an inherent ability to cleave DNA substrates and is utilized in diagnostic tools to identify DNA molecules. We demonstrate that multiple orthologs of Cas12a activate trans-cleavage in the presence of split activators. Specifically, the PAM-distal region of the crRNA recognizes RNA targets provided that the PAM-proximal seed region has a DNA target. Our method, Split Activator for Highly Accessible RNA Analysis (SAHARA), detects picomolar concentrations of RNA without sample amplification, reverse-transcription, or strand-displacement by simply supplying a short DNA sequence complementary to the seed region. Beyond RNA detection, SAHARA outperforms wild-type CRISPR-Cas12a in specificity towards point-mutations and can detect multiple RNA and DNA targets in pooled crRNA/Cas12a arrays via distinct PAM-proximal seed DNAs. In conclusion, SAHARA is a simple, yet powerful nucleic acid detection platform based on Cas12a that can be applied in a multiplexed fashion and potentially be expanded to other CRISPR-Cas enzymes.
The COMPASS subunit Spp1 protects nascent DNA at the Tus/Ter replication fork barrier by limiting DNA availability to nucleases
Authors: Ghaddar Nagham , Corda Yves , Luciano Pierre , Galli Martina , Doksani Ylli , Géli Vincent 
Published: September 2023

AbstractHomologous recombination factors play a crucial role in protecting nascent DNA during DNA replication, but the role of chromatin in this process is largely unknown. Here, we used the bacterial Tus/Ter barrier known to induce a site-specific replication fork stalling in S. cerevisiae. We report that the Set1C subunit Spp1 is recruited behind the stalled replication fork independently of its interaction with Set1. Spp1 chromatin recruitment depends on the interaction of its PHD domain with H3K4me3 parental histones deposited behind the stalled fork. Its recruitment prevents the accumulation of ssDNA at the stalled fork by restricting the access of Exo1. We further show that deleting SPP1 increases the mutation rate upstream of the barrier favoring the accumulation of microdeletions. Finally, we report that Spp1 protects nascent DNA at the Tus/Ter stalled replication fork. We propose that Spp1 limits the remodeling of the fork, which ultimately limits nascent DNA availability to nucleases.
Cis P-tau is a central circulating and placental etiologic driver and therapeutic target of preeclampsia
Authors: Jash Sukanta , Banerjee Sayani , Cheng Shibin , Wang Bin , Qiu Chenxi , Kondo Asami , Ernerudh Jan , Zhou Xiao Zhen , Lu Kun Ping , Sharma Surendra 
Published: September 2023

AbstractPreeclampsia (PE) is the leading cause of maternal and fetal mortality globally and may trigger dementia later in life in mothers and their offspring. However, the etiological drivers remain elusive. Cis P-tau is an early etiological driver and blood biomarker in pre-clinical Alzheimer’s and after vascular or traumatic brain injury, which can be targeted by stereo-specific antibody, with clinical trials ongoing. Here we find significant cis P-tau in the placenta and serum of PE patients, and in primary human trophoblasts exposed to hypoxia or sera from PE patients due to Pin1 inactivation. Depletion of cis P-tau from PE patient sera by the antibody prevents their ability to disrupt trophoblast invasion and endovascular activity and to cause the PE-like pathological and clinical features in pregnant humanized tau mice. Our studies uncover that cis P-tau is a central circulating etiological driver and its stereo-specific antibody is valuable for early PE diagnosis and treatment.
MKP1 promotes nonalcoholic steatohepatitis by suppressing AMPK activity through LKB1 nuclear retention
Authors: Qiu Bin , Lawan Ahmed , Xirouchaki Chrysovalantou E. , Yi Jae-Sung , Robert Marie , Zhang Lei , Brown Wendy , Fernández-Hernando Carlos , Yang Xiaoyong , Tiganis Tony , Bennett Anton M. 
Published: September 2023

AbstractNonalcoholic steatohepatitis (NASH) is triggered by hepatocyte death through activation of caspase 6, as a result of decreased adenosine monophosphate (AMP)-activated protein kinase-alpha (AMPKα) activity. Increased hepatocellular death promotes inflammation which drives hepatic fibrosis. We show that the nuclear-localized mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP1) is upregulated in NASH patients and in NASH diet fed male mice. The focus of this work is to investigate whether and how MKP1 is involved in the development of NASH. Under NASH conditions increased oxidative stress, induces MKP1 expression leading to nuclear p38 MAPK dephosphorylation and decreases liver kinase B1 (LKB1) phosphorylation at a site required to promote LKB1 nuclear exit. Hepatic deletion of MKP1 in NASH diet fed male mice releases nuclear LKB1 into the cytoplasm to activate AMPKα and prevents hepatocellular death, inflammation and NASH. Hence, nuclear-localized MKP1-p38 MAPK-LKB1 signaling is required to suppress AMPKα which triggers hepatocyte death and the development of NASH.
The self-association equilibrium of DNAJA2 regulates its interaction with unfolded substrate proteins and with Hsc70
Authors: Velasco-Carneros Lorea , Cuéllar Jorge , Dublang Leire , Santiago César , Maréchal Jean-Didier , Martín-Benito Jaime , Maestro Moisés , Fernández-Higuero José Ángel , Orozco Natalia , Moro Fernando , Valpuesta José María , Muga Arturo 
Published: September 2023

AbstractJ-domain proteins tune the specificity of Hsp70s, engaging them in precise functions. Despite their essential role, the structure and function of many J-domain proteins remain largely unknown. We explore human DNAJA2, finding that it reversibly forms highly-ordered, tubular structures that can be dissociated by Hsc70, the constitutively expressed Hsp70 isoform. Cryoelectron microscopy and mutational studies reveal that different domains are involved in self-association. Oligomer dissociation into dimers potentiates its interaction with unfolded client proteins. The J-domains are accessible to Hsc70 within the tubular structure. They allow binding of closely spaced Hsc70 molecules that could be transferred to the unfolded substrate for its cooperative remodelling, explaining the efficient recovery of DNAJA2-bound clients. The disordered C-terminal domain, comprising the last 52 residues, regulates its holding activity and productive interaction with Hsc70. These in vitro findings suggest that the association equilibrium of DNAJA2 could regulate its interaction with client proteins and Hsc70.
Cryo-EM structure of a bacteriophage M13 mini variant
Authors: Jia Qi , Xiang Ye 
Published: September 2023

AbstractFilamentous bacteriophages package their circular, single stranded DNA genome with the major coat protein pVIII and the minor coat proteins pIII, pVII, pVI, and pIX. Here, we report the cryo-EM structure of a ~500 Å long bacteriophage M13 mini variant. The distal ends of the mini phage are sealed by two cap-like complexes composed of the minor coat proteins. The top cap complex consists of pVII and pIX, both exhibiting a single helix structure. Arg33 of pVII and Glu29 of pIX, located on the inner surface of the cap, play a key role in recognizing the genome packaging signal. The bottom cap complex is formed by the hook-like structures of pIII and pVI, arranged in helix barrels. Most of the inner ssDNA genome adopts a double helix structure with a similar pitch to that of the A-form double-stranded DNA. These findings provide insights into the assembly of filamentous bacteriophages.
Topological magneto-optical effect from skyrmion lattice
Authors: Kato Yoshihiro D. , Okamura Yoshihiro , Hirschberger Max , Tokura Yoshinori , Takahashi Youtarou 
Published: September 2023

AbstractThe magnetic skyrmion is a spin-swirling topological object characterized by its nontrivial winding number, holding potential for next-generation spintronic devices. While optical readout has become increasingly important towards the high integration and ultrafast operation of those devices, the optical response of skyrmions has remained elusive. Here, we show the magneto-optical Kerr effect (MOKE) induced by the skyrmion formation, i.e., topological MOKE, in Gd2PdSi3. The significantly enhanced optical rotation found in the skyrmion phase demonstrates the emergence of topological MOKE, exemplifying the light-skyrmion interaction arising from the emergent gauge field. This gauge field in momentum space causes a dramatic reconstruction of the electronic band structure, giving rise to magneto-optical activity ranging up to the sub-eV region. The present findings pave a way for photonic technology based on skyrmionics.
Single cell multiomic analysis reveals diabetes-associated β-cell heterogeneity driven by HNF1A
Authors: Weng Chen , Gu Anniya , Zhang Shanshan , Lu Leina , Ke Luxin , Gao Peidong , Liu Xiaoxiao , Wang Yuntong , Hu Peinan , Plummer Dylan , MacDonald Elise , Zhang Saixian , Xi Jiajia , Lai Sisi , Leskov Konstantin , Yuan Kyle , Jin Fulai , Li Yan 
Published: September 2023

AbstractBroad heterogeneity in pancreatic β-cell function and morphology has been widely reported. However, determining which components of this cellular heterogeneity serve a diabetes-relevant function remains challenging. Here, we integrate single-cell transcriptome, single-nuclei chromatin accessibility, and cell-type specific 3D genome profiles from human islets and identify Type II Diabetes (T2D)-associated β-cell heterogeneity at both transcriptomic and epigenomic levels. We develop a computational method to explicitly dissect the intra-donor and inter-donor heterogeneity between single β-cells, which reflect distinct mechanisms of T2D pathogenesis. Integrative transcriptomic and epigenomic analysis identifies HNF1A as a principal driver of intra-donor heterogeneity between β-cells from the same donors; HNF1A expression is also reduced in β-cells from T2D donors. Interestingly, HNF1A activity in single β-cells is significantly associated with lower Na+ currents and we nominate a HNF1A target, FXYD2, as the primary mitigator. Our study demonstrates the value of investigating disease-associated single-cell heterogeneity and provides new insights into the pathogenesis of T2D.