bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased Biogenic Calcification and Burial Under Elevated pCO2 During the Miocene: A Model‐Data Comparison
Authors: Si Weimin , Herbert Timothy , Wu Mengxi , Rosenthal Yair 
Published: May 2023

AbstractOcean acidification due to anthropogenic CO2 emission reduces ocean pH and carbonate saturation, with the projection that marine calcifiers and associated ecosystems will be negatively affected in the future. On longer time scale, however, recent studies of deep‐sea carbonate sediments suggest significantly increased carbonate production and burial in the open ocean during the warm Middle Miocene. Here, we present new model simulations in comparison to published Miocene carbonate accumulation rates to show that global biogenic carbonate production in the pelagic environment was approximately doubled relative to present‐day values when elevated atmospheric pCO2 led to substantial global warming ∼13–15 million years ago. Our analysis also finds that although high carbonate production was associated with high dissolution in the deep‐sea, net pelagic carbonate burial was approximately 30%–45% higher than modern. At the steady state of the long‐term carbon cycle, this requires an equivalent increase in riverine carbonate alkalinity influx during the Middle Miocene, attributable to enhanced chemical weathering under a warmer climate. Elevated biogenic carbonate production resulted in a Miocene ocean that had carbon (dissolved inorganic carbon) and alkalinity (total alkalinity) inventories similar to modern values but was poorly buffered and less saturated in both the surface and the deep ocean relative to modern.
Quantifying 3D Gravity Wave Drag in a Library of Tropical Convection‐Permitting Simulations for Data‐Driven Parameterizations
Authors: Sun Y. Qiang , Hassanzadeh Pedram , Alexander M. Joan , Kruse Christopher G. 
Published: May 2023

AbstractAtmospheric gravity waves (GWs) span a broad range of length scales. As a result, the un‐resolved and under‐resolved GWs have to be represented using a sub‐grid scale (SGS) parameterization in general circulation models (GCMs). In recent years, machine learning (ML) techniques have emerged as novel methods for SGS modeling of climate processes. In the widely used approach of supervised (offline) learning, the true representation of the SGS terms have to be properly extracted from high‐fidelity data (e.g., GW‐resolving simulations). However, this is a non‐trivial task, and the quality of the ML‐based parameterization significantly hinges on the quality of these SGS terms. Here, we compare three methods to extract 3D GW fluxes and the resulting drag (Gravity Wave Drag [GWD]) from high‐resolution simulations: Helmholtz decomposition, and spatial filtering to compute the Reynolds stress and the full SGS stress. In addition to previous studies that focused only on vertical fluxes by GWs, we also quantify the SGS GWD due to lateral momentum fluxes. We build and utilize a library of tropical high‐resolution (Δx = 3 km) simulations using weather research and forecasting model. Results show that the SGS lateral momentum fluxes could have a significant contribution to the total GWD. Moreover, when estimating GWD due to lateral effects, interactions between the SGS and the resolved large‐scale flow need to be considered. The sensitivity of the results to different filter type and length scale (dependent on GCM resolution) is also explored to inform the scale‐awareness in the development of data‐driven parameterizations.
FBXW7β loss-of-function enhances FASN-mediated lipogenesis and promotes colorectal cancer growth
Authors: Wei Wenxia , Qin Baifu , Wen Weijie , Zhang Boyu , Luo Haidan , Wang Yuzhi , Xu Hui , Xie Xiaoshan , Liu Sicheng , Jiang Xin , Wang Mengan , Tang Qin , Zhang Jiayu , Yang Runxiang , Fan Zongmin , Lyu Haiwen , Lin Junzhong , Li Kai , Lee Mong-Hong 
Published: May 2023

AbstractContinuous de novo fatty acid synthesis is required for the biosynthetic demands of tumor. FBXW7 is a highly mutated gene in CRC, but its biological functions in cancer are not fully characterized. Here, we report that FBXW7β, a FBXW7 isoform located in the cytoplasm and frequently mutated in CRC, is an E3 ligase of fatty acid synthase (FASN). Cancer-specific FBXW7β mutations that could not degrade FASN can lead to sustained lipogenesis in CRC. COP9 signalosome subunit 6 (CSN6), an oncogenic marker of CRC, increases lipogenesis via interacting with and stabilizing FASN. Mechanistic studies show that CSN6 associates with both FBXW7β and FASN, and antagonizes FBXW7β’s activity by enhancing FBXW7β autoubiquitination and degradation, which in turn prevents FBXW7β-mediated FASN ubiquitination and degradation, thereby regulating lipogenesis positively. Both CSN6 and FASN are positively correlated in CRC, and CSN6-FASN axis, regulated by EGF, is responsible for poor prognosis of CRC. The EGF-CSN6-FASN axis promotes tumor growth and implies a treatment strategy of combination of orlistat and cetuximab. Patient-derived xenograft experiments prove the effectiveness of employing orlistat and cetuximab combination in suppressing tumor growth for CSN6/FASN-high CRC. Thus, CSN6-FASN axis reprograms lipogenesis to promote tumor growth and is a target for cancer intervening strategy in CRC.
Radiation-induced tumor immune microenvironments and potential targets for combination therapy
Authors: Guo Siyu , Yao Yihan , Tang Yang , Xin Zengfeng , Wu Dang , Ni Chao , Huang Jian , Wei Qichun , Zhang Ting 
Published: May 2023

AbstractAs one of the four major means of cancer treatment including surgery, radiotherapy (RT), chemotherapy, immunotherapy, RT can be applied to various cancers as both a radical cancer treatment and an adjuvant treatment before or after surgery. Although RT is an important modality for cancer treatment, the consequential changes caused by RT in the tumor microenvironment (TME) have not yet been fully elucidated. RT-induced damage to cancer cells leads to different outcomes, such as survival, senescence, or death. During RT, alterations in signaling pathways result in changes in the local immune microenvironment. However, some immune cells are immunosuppressive or transform into immunosuppressive phenotypes under specific conditions, leading to the development of radioresistance. Patients who are radioresistant respond poorly to RT and may experience cancer progression. Given that the emergence of radioresistance is inevitable, new radiosensitization treatments are urgently needed. In this review, we discuss the changes in irradiated cancer cells and immune cells in the TME under different RT regimens and describe existing and potential molecules that could be targeted to improve the therapeutic effects of RT. Overall, this review highlights the possibilities of synergistic therapy by building on existing research.
Novel insights into the METTL3-METTL14 complex in musculoskeletal diseases
Authors: Xu Yeqiu , Zhang Yuanzhuang , Luo Yinzhou , Qiu Guanzhen , Lu Jie , He Ming , Wang Yong 
Published: May 2023

AbstractN6-methyladenosine (m6A) modification, catalyzed by methyltransferase complexes (MTCs), plays many roles in multifaceted biological activities. As the most important subunit of MTCs, the METTL3-METTL14 complex is reported to be the initial factor that catalyzes the methylation of adenosines. Recently, accumulating evidence has indicated that the METTL3-METTL14 complex plays a key role in musculoskeletal diseases in an m6A-dependent or -independent manner. Although the functions of m6A modifications in a variety of musculoskeletal diseases have been widely recognized, the critical role of the METTL3-METTL14 complex in certain musculoskeletal disorders, such as osteoporosis, osteoarthritis, rheumatoid arthritis and osteosarcoma, has not been systematically revealed. In the current review, the structure, mechanisms and functions of the METTL3-METTL14 complex and the mechanisms and functions of its downstream pathways in the aforementioned musculoskeletal diseases are categorized and summarized.
Unidirectional rotation of micromotors on water powered by pH-controlled disassembly of chiral molecular crystals
Authors: Carmeli Itai , Bounioux Celine M. , Mickel Philip , Richardson Mark B. , Templeman Yael , Scofield Joel M. P. , Qiao Greg G. , Rosen Brian Ashley , Yusupov Yelena , Meshi Louisa , Voelcker Nicolas H. , Diéguez Oswaldo , Miloh Touvia , Král Petr , Cohen Hagai , Richter Shachar E. 
Published: May 2023

AbstractBiological and synthetic molecular motors, fueled by various physical and chemical means, can perform asymmetric linear and rotary motions that are inherently related to their asymmetric shapes. Here, we describe silver-organic micro-complexes of random shapes that exhibit macroscopic unidirectional rotation on water surface through the asymmetric release of cinchonine or cinchonidine chiral molecules from their crystallites asymmetrically adsorbed on the complex surfaces. Computational modeling indicates that the motor rotation is driven by a pH-controlled asymmetric jet-like Coulombic ejection of chiral molecules upon their protonation in water. The motor is capable of towing very large cargo, and its rotation can be accelerated by adding reducing agents to the water.
Long-wave infrared transparent sulfur polymers enabled by symmetric thiol cross-linker
Authors: Lee Miyeon , Oh Yuna , Yu Jaesang , Jang Se Gyu , Yeo Hyeonuk , Park Jong-Jin , You Nam-Ho 
Published: May 2023

AbstractInfrared (IR) transmissive polymeric materials for optical elements require a balance between their optical properties, including refractive index (n) and IR transparency, and thermal properties such as glass transition temperature (Tg). Achieving both a high refractive index (n) and IR transparency in polymer materials is a very difficult challenge. In particular, there are significant complexities and considerations to obtaining organic materials that transmit in the long-wave infrared (LWIR) region, because of high optical losses due to the IR absorption of the organic molecules. Our differentiated strategy to extend the frontiers of LWIR transparency is to reduce the IR absorption of the organic moieties. The proposed approach synthesized a sulfur copolymer via the inverse vulcanization of 1,3,5-benzenetrithiol (BTT), which has a relatively simple IR absorption because of its symmetric structure, and elemental sulfur, which is mostly IR inactive. This strategy resulted in approximately 1 mm thick windows with an ultrahigh refractive index (nav > 1.9) and high mid−wave infrared (MWIR) and LWIR transmission, without any significant decline in thermal properties. Furthermore, we demonstrated that our IR transmissive material was sufficiently competitive with widely used optical inorganic and polymeric materials.
A map of single-phase high-entropy alloys
Authors: Chen Wei , Hilhorst Antoine , Bokas Georgios , Gorsse Stéphane , Jacques Pascal J. , Hautier Geoffroy 
Published: May 2023

AbstractHigh-entropy alloys have exhibited unusual materials properties. The stability of equimolar single-phase solid solution of five or more elements is supposedly rare and identifying the existence of such alloys has been challenging because of the vast chemical space of possible combinations. Herein, based on high-throughput density-functional theory calculations, we construct a chemical map of single-phase equimolar high-entropy alloys by investigating over 658,000 equimolar quinary alloys through a binary regular solid-solution model. We identify 30,201 potential single-phase equimolar alloys (5% of the possible combinations) forming mainly in body-centered cubic structures. We unveil the chemistries that are likely to form high-entropy alloys, and identify the complex interplay among mixing enthalpy, intermetallics formation, and melting point that drives the formation of these solid solutions. We demonstrate the power of our method by predicting the existence of two new high-entropy alloys, i.e. the body-centered cubic AlCoMnNiV and the face-centered cubic CoFeMnNiZn, which are successfully synthesized.
Plasma metabolite profile for primary open-angle glaucoma in three US cohorts and the UK Biobank
Authors: Zeleznik Oana A. , Kang Jae H. , Lasky-Su Jessica , Eliassen A. Heather , Frueh Lisa , Clish Clary B. , Rosner Bernard A. , Elze Tobias , Hysi Pirro , Khawaja Anthony , Wiggs Janey L. , Pasquale Louis R. ,   UK Biobank Eye and Vision Consortium
Published: May 2023

AbstractGlaucoma is a progressive optic neuropathy and a leading cause of irreversible blindness worldwide. Primary open-angle glaucoma is the most common form, and yet the etiology of this multifactorial disease is poorly understood. We aimed to identify plasma metabolites associated with the risk of developing POAG in a case-control study (599 cases and 599 matched controls) nested within the Nurses’ Health Studies, and Health Professionals’ Follow-Up Study. Plasma metabolites were measured with LC-MS/MS at the Broad Institute (Cambridge, MA, USA); 369 metabolites from 18 metabolite classes passed quality control analyses. For comparison, in a cross-sectional study in the UK Biobank, 168 metabolites were measured in plasma samples from 2,238 prevalent glaucoma cases and 44,723 controls using NMR spectroscopy (Nightingale, Finland; version 2020). Here we show higher levels of diglycerides and triglycerides are adversely associated with glaucoma in all four cohorts, suggesting that they play an important role in glaucoma pathogenesis.
ERK and USP5 govern PD-1 homeostasis via deubiquitination to modulate tumor immunotherapy
Authors: Xiao Xiangling , Shi Jie , He Chuan , Bu Xia , Sun Yishuang , Gao Minling , Xiang Bolin , Xiong Wenjun , Dai Panpan , Mao Qi , Xing Xixin , Yao Yingmeng , Yu Haisheng , Xu Gaoshan , Li Siqi , Ren Yan , Chen Baoxiang , Jiang Congqing , Meng Geng , Lee Yu-Ru , Wei Wenyi , Freeman Gordon J. , Xie Conghua , Zhang Jinfang 
Published: May 2023

AbstractThe programmed cell death protein 1 (PD-1) is an inhibitory receptor on T cells and plays an important role in promoting cancer immune evasion. While ubiquitin E3 ligases regulating PD-1 stability have been reported, deubiquitinases governing PD-1 homeostasis to modulate tumor immunotherapy remain unknown. Here, we identify the ubiquitin-specific protease 5 (USP5) as a bona fide deubiquitinase for PD-1. Mechanistically, USP5 interacts with PD-1, leading to deubiquitination and stabilization of PD-1. Moreover, extracellular signal-regulated kinase (ERK) phosphorylates PD-1 at Thr234 and promotes PD-1 interaction with USP5. Conditional knockout of Usp5 in T cells increases the production of effector cytokines and retards tumor growth in mice. USP5 inhibition in combination with Trametinib or anti-CTLA-4 has an additive effect on suppressing tumor growth in mice. Together, this study describes a molecular mechanism of ERK/USP5-mediated regulation of PD-1 and identifies potential combinatorial therapeutic strategies for enhancing anti-tumor efficacy.
Independent rediploidization masks shared whole genome duplication in the sturgeon-paddlefish ancestor
Authors: Redmond Anthony K. , Casey Dearbhaile , Gundappa Manu Kumar , Macqueen Daniel J. , McLysaght Aoife 
Published: May 2023

AbstractWhole genome duplication (WGD) is a dramatic evolutionary event generating many new genes and which may play a role in survival through mass extinctions. Paddlefish and sturgeon are sister lineages that both show genomic evidence for ancient WGD. Until now this has been interpreted as two independent WGD events due to a preponderance of duplicate genes with independent histories. Here we show that although there is indeed a plurality of apparently independent gene duplications, these derive from a shared genome duplication event occurring well over 200 million years ago, likely close to the Permian-Triassic mass extinction period. This was followed by a prolonged process of reversion to stable diploid inheritance (rediploidization), that may have promoted survival during the Triassic-Jurassic mass extinction. We show that the sharing of this WGD is masked by the fact that paddlefish and sturgeon lineage divergence occurred before rediploidization had proceeded even half-way. Thus, for most genes the resolution to diploidy was lineage-specific. Because genes are only truly duplicated once diploid inheritance is established, the paddlefish and sturgeon genomes are thus a mosaic of shared and non-shared gene duplications resulting from a shared genome duplication event.
Universal quantum control of an atomic spin qubit on a surface
Authors: Wang Yu , Haze Masahiro , Bui Hong T. , Soe We-hyo , Aubin Herve , Ardavan Arzhang , Heinrich Andreas J. , Phark Soo-hyon 
Published: May 2023

AbstractScanning tunneling microscopy (STM) enables the bottom-up fabrication of tailored spin systems on a surface that are engineered with atomic precision. When combining STM with electron spin resonance (ESR), these single atomic and molecular spins can be controlled quantum-coherently and utilized as electron-spin qubits. Here we demonstrate universal quantum control of such a spin qubit on a surface by employing coherent control along two distinct directions, achieved with two consecutive radio-frequency (RF) pulses with a well-defined phase difference. We first show transformations of each Cartesian component of a Bloch vector on the quantization axis, followed by ESR-STM detection. Then we demonstrate the ability to generate an arbitrary superposition state of a single spin qubit by using two-axis control schemes, in which experimental data show excellent agreement with simulations. Finally, we present an implementation of two-axis control in dynamical decoupling. Our work extends the scope of STM-based pulsed ESR, highlighting the potential of this technique for quantum gate operations of electron-spin qubits on a surface.
Calibration of a serum reference standard for Group B streptococcal polysaccharide conjugate vaccine development using surface plasmon resonance
Authors: Esadze Alexandre , Grube Christopher D. , Wellnitz Sabine , Singh Suddham , Nguyen Ha H. , Gaylord Michelle A. , Zhu Aiping , Gribenko Alexey , Tan Charles Y. , Anderson Annaliesa S. , Simon Raphael 
Published: May 2023

AbstractGroup B streptococcus (GBS) is a leading cause of neonatal morbidity and mortality worldwide. Development of a maternal vaccine to protect newborns through placentally transferred antibody is considered feasible based on the well-established relationship between anti-GBS capsular polysaccharide (CPS) IgG levels at birth and reduced risk of neonatal invasive GBS. An accurately calibrated serum reference standard that can be used to measure anti-CPS concentrations is critical for estimation of protective antibody levels across serotypes and potential vaccine performance. For this, precise weight-based measurement of anti-CPS IgG in sera is required. Here, we report an improved approach for determining serum anti-CPS IgG levels using surface plasmon resonance with monoclonal antibody standards, coupled with a direct Luminex-based immunoassay. This technique was used to quantify serotype-specific anti-CPS IgG levels in a human serum reference pool derived from subjects immunized with an investigational six-valent GBS glycoconjugate vaccine.
Rapid and efficient ambient temperature X-ray crystal structure determination at Turkish Light Source
Authors: Gul Mehmet , Ayan Esra , Destan Ebru , Johnson J. Austin , Shafiei Alaleh , Kepceoğlu Abdullah , Yilmaz Merve , Ertem Fatma Betül , Yapici İlkin , Tosun Bilge , Baldir Nilüfer , Tokay Nurettin , Nergiz Zeliş , Karakadioğlu Gözde , Paydos Seyide Seda , Kulakman Cahine , Ferah Cengiz Kaan , Güven Ömür , Atalay Necati , Akcan Enver Kamil , Cetinok Haluk , Arslan Nazlı Eylül , Şabanoğlu Kardelen , Aşci Bengisu , Tavli Serra , Gümüsboğa Helin , Altuntaş Sevde , Otsuka Masami , Fujita Mikako , Teki̇n Şaban , Çi̇ftçi̇ Halilibrahim , Durdaği Serdar , Karaca Ezgi , Kaplan Türköz Burcu , Kabasakal Burak Veli , Kati Ahmet , DeMi̇rci̇ Hasan 
Published: May 2023

AbstractHigh-resolution biomacromolecular structure determination is essential to better understand protein function and dynamics. Serial crystallography is an emerging structural biology technique which has fundamental limitations due to either sample volume requirements or immediate access to the competitive X-ray beamtime. Obtaining a high volume of well-diffracting, sufficient-size crystals while mitigating radiation damage remains a critical bottleneck of serial crystallography. As an alternative, we introduce the plate-reader module adapted for using a 72-well Terasaki plate for biomacromolecule structure determination at a convenience of a home X-ray source. We also present the first ambient temperature lysozyme structure determined at the Turkish light source (Turkish DeLight). The complete dataset was collected in 18.5 min with resolution extending to 2.39 Å and 100% completeness. Combined with our previous cryogenic structure (PDB ID: 7Y6A), the ambient temperature structure provides invaluable information about the structural dynamics of the lysozyme. Turkish DeLight provides robust and rapid ambient temperature biomacromolecular structure determination with limited radiation damage.
Information load dynamically modulates functional brain connectivity during narrative listening
Authors: Mastrandrea Rossana , Cecchetti Luca , Lettieri Giada , Handjaras Giacomo , Leo Andrea , Papale Paolo , Gili Tommaso , Martini Nicola , Latta Daniele Della , Chiappino Dante , Pietrini Pietro , Ricciardi Emiliano 
Published: May 2023

AbstractNarratives are paradigmatic examples of natural language, where nouns represent a proxy of information. Functional magnetic resonance imaging (fMRI) studies revealed the recruitment of temporal cortices during noun processing and the existence of a noun-specific network at rest. Yet, it is unclear whether, in narratives, changes in noun density influence the brain functional connectivity, so that the coupling between regions correlates with information load. We acquired fMRI activity in healthy individuals listening to a narrative with noun density changing over time and measured whole-network and node-specific degree and betweenness centrality. Network measures were correlated with information magnitude with a time-varying approach. Noun density correlated positively with the across-regions average number of connections and negatively with the average betweenness centrality, suggesting the pruning of peripheral connections as information decreased. Locally, the degree of the bilateral anterior superior temporal sulcus (aSTS) was positively associated with nouns. Importantly, aSTS connectivity cannot be explained by changes in other parts of speech (e.g., verbs) or syllable density. Our results indicate that the brain recalibrates its global connectivity as a function of the information conveyed by nouns in natural language. Also, using naturalistic stimulation and network metrics, we corroborate the role of aSTS in noun processing.