bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcription factor Foxp1 stimulates angiogenesis in adult rats after myocardial infarction
Authors: Wang Dinghui , Liu Bin , Xiong Tianhua , Yu Wenlong , Yang Huiping , Wang Jing , Jing Xiaodong , She Qiang 
Published: September 2022

AbstractForkhead box protein P1 (FoxP1) is essential for cardiac development and the regulation of neovascularization, but its potential for cardiac angiogenesis has not been explored. This study aims to investigate the angiogenic role of FoxP1 in a rat model of myocardial infarction (MI). Adult male rats were subjected to MI, and Foxp1 was knocked down with lentivirus FoxP1 siRNA. Endothelial cell proliferation, angiogenesis, and cardiac function were also assessed. Cell scratch assay and tubule formation analysis were used to detect the migration ability and tube formation ability of human umbilical vein endothelial cells (HUVECs). Compared with that in the sham group, results showed that the expression of FoxP1 was significantly increased in the MI group. Foxp1 knockdown decreases FoxP1 expression, reduces angiogenesis, and increases collagen deposition. When Foxp1 was knocked down in HUVECs using FoxP1 siRNA lentivirus, cell proliferation, migration, and tube formation abilities decreased significantly. Our study showed that FoxP1 elicits pleiotropic beneficial actions on angiogenesis in the post-MI heart by promoting the proliferation of endothelial cells. FoxP1 should be considered a candidate for therapeutic cardiac angiogenesis.
Diverse cell-specific patterns of alternative polyadenylation in Drosophila
Authors: Lee Seungjae , Chen Yen-Chung ,   FCA Consortium, Gillen Austin E. , Taliaferro J. Matthew , Deplancke Bart , Li Hongjie , Lai Eric C. 
Published: September 2022

AbstractMost genes in higher eukaryotes express isoforms with distinct 3’ untranslated regions (3’ UTRs), generated by alternative polyadenylation (APA). Since 3’ UTRs are predominant locations of post-transcriptional regulation, APA can render such programs conditional, and can also alter protein sequences via alternative last exon (ALE) isoforms. We previously used 3’-sequencing from diverseDrosophilasamples to define multiple tissue-specific APA landscapes. Here, we exploit comprehensive single nucleus RNA-sequencing data (Fly Cell Atlas) to elucidate cell-type expression of 3’ UTRs across >250 adultDrosophilacell types. We reveal the cellular bases of multiple tissue-specific APA/ALE programs, such as 3’ UTR lengthening in differentiated neurons and 3’ UTR shortening in spermatocytes and spermatids. We trace dynamic 3’ UTR patterns across cell lineages, including in the male germline, and discover new APA patterns in the intestinal stem cell lineage. Finally, we correlate expression of RNA binding proteins (RBPs), miRNAs and global levels of cleavage and polyadenylation (CPA) factors in several cell types that exhibit characteristic APA landscapes, yielding candidate regulators of transcriptome complexity. These analyses provide a comprehensive foundation for future investigations of mechanisms and biological impacts of alternative 3’ isoforms across the major cell types of this widely-studied model organism.
Therapeutic high affinity T cell receptor targeting a KRASG12D cancer neoantigen
Authors: Poole Andrew , Karuppiah Vijaykumar , Hartt Annabelle , Haidar Jaafar N. , Moureau Sylvie , Dobrzycki Tomasz , Hayes Conor , Rowley Christopher , Dias Jorge , Harper Stephen , Barnbrook Keir , Hock Miriam , Coles Charlotte , Yang Wei , Aleksic Milos , Lin Aimee Bence , Robinson Ross , Dukes Joe D. , Liddy Nathaniel , Van der Kamp Marc , Plowman Gregory D. , Vuidepot Annelise , Cole David K. , Whale Andrew D. , Chillakuri Chandramouli 
Published: September 2022

AbstractNeoantigens derived from somatic mutations are specific to cancer cells and are ideal targets for cancer immunotherapy. KRAS is the most frequently mutated oncogene and drives the pathogenesis of several cancers. Here we show the identification and development of an affinity-enhanced T cell receptor (TCR) that recognizes a peptide derived from the most common KRAS mutant, KRASG12D, presented in the context of HLA-A*11:01. The affinity of the engineered TCR is increased by over one million-fold yet fully able to distinguish KRASG12D over KRASWT. While crystal structures reveal few discernible differences in TCR interactions with KRASWT versus KRASG12D, thermodynamic analysis and molecular dynamics simulations reveal that TCR specificity is driven by differences in indirect electrostatic interactions. The affinity enhanced TCR, fused to a humanized anti-CD3 scFv, enables selective killing of cancer cells expressing KRASG12D. Our work thus reveals a molecular mechanism that drives TCR selectivity and describes a soluble bispecific molecule with therapeutic potential against cancers harboring a common shared neoantigen.
Wilkes subglacial basin ice sheet response to Southern Ocean warming during late Pleistocene interglacials
Authors: Crotti Ilaria , Quiquet Aurélien , Landais Amaelle , Stenni Barbara , Wilson David J. , Severi Mirko , Mulvaney Robert , Wilhelms Frank , Barbante Carlo , Frezzotti Massimo 
Published: September 2022

AbstractThe response of the East Antarctic Ice Sheet to past intervals of oceanic and atmospheric warming is still not well constrained but is critical for understanding both past and future sea-level change. Furthermore, the ice sheet in the Wilkes Subglacial Basin appears to have undergone thinning and ice discharge events during recent decades. Here we combine glaciological evidence on ice sheet elevation from the TALDICE ice core with offshore sedimentological records and ice sheet modelling experiments to reconstruct the ice dynamics in the Wilkes Subglacial Basin over the past 350,000 years. Our results indicate that the Wilkes Subglacial Basin experienced an extensive retreat 330,000 years ago and a more limited retreat 125,000 years ago. These changes coincide with warmer Southern Ocean temperatures and elevated global mean sea level during those interglacial periods, confirming the sensitivity of the Wilkes Subglacial Basin ice sheet to ocean warming and its potential role in sea-level change.
An analysis modality for vascular structures combining tissue-clearing technology and topological data analysis
Authors: Takahashi Kei , Abe Ko , Kubota Shimpei I. , Fukatsu Noriaki , Morishita Yasuyuki , Yoshimatsu Yasuhiro , Hirakawa Satoshi , Kubota Yoshiaki , Watabe Tetsuro , Ehata Shogo , Ueda Hiroki R. , Shimamura Teppei , Miyazono Kohei 
Published: September 2022

AbstractThe blood and lymphatic vasculature networks are not yet fully understood even in mouse because of the inherent limitations of imaging systems and quantification methods. This study aims to evaluate the usefulness of the tissue-clearing technology for visualizing blood and lymphatic vessels in adult mouse. Clear, unobstructed brain/body imaging cocktails and computational analysis (CUBIC) enables us to capture the high-resolution 3D images of organ- or area-specific vascular structures. To evaluate these 3D structural images, signals are first classified from the original captured images by machine learning at pixel base. Then, these classified target signals are subjected to topological data analysis and non-homogeneous Poisson process model to extract geometric features. Consequently, the structural difference of vasculatures is successfully evaluated in mouse disease models. In conclusion, this study demonstrates the utility of CUBIC for analysis of vascular structures and presents its feasibility as an analysis modality in combination with 3D images and mathematical frameworks.
Inhibition of interleukin-1β reduces myelofibrosis and osteosclerosis in mice with JAK2-V617F driven myeloproliferative neoplasm
Authors: Rai Shivam , Grockowiak Elodie , Hansen Nils , Luque Paz Damien , Stoll Cedric B. , Hao-Shen Hui , Mild-Schneider Gabriele , Dirnhofer Stefan , Farady Christopher J. , Méndez-Ferrer Simón , Skoda Radek C. 
Published: September 2022

AbstractInterleukin-1β (IL-1β) is a master regulator of inflammation. Increased activity of IL-1β has been implicated in various pathological conditions including myeloproliferative neoplasms (MPNs). Here we show that IL-1β serum levels and expression of IL-1 receptors on hematopoietic progenitors and stem cells correlate withJAK2-V617F mutant allele fraction in peripheral blood of patients with MPN. We show that the source of IL-1β overproduction in a mouse model of MPN areJAK2-V617F expressing hematopoietic cells. Knockout ofIL-1βin hematopoietic cells ofJAK2-V617F mice reduces inflammatory cytokines, prevents damage to nestin-positive niche cells and reduces megakaryopoiesis, resulting in decrease of myelofibrosis and osteosclerosis. Inhibition of IL-1β inJAK2-V617F mutant mice by anti-IL-1β antibody also reduces myelofibrosis and osteosclerosis and shows additive effects with ruxolitinib. These results suggest that inhibition of IL-1β with anti-IL-1β antibody alone or in combination with ruxolitinib could have beneficial effects on the clinical course in patients with myelofibrosis.
Wide field imaging of van der Waals ferromagnet Fe3GeTe2 by spin defects in hexagonal boron nitride
Authors: Huang Mengqi , Zhou Jingcheng , Chen Di , Lu Hanyi , McLaughlin Nathan J. , Li Senlei , Alghamdi Mohammed , Djugba Dziga , Shi Jing , Wang Hailong , Du Chunhui Rita 
Published: September 2022

AbstractEmergent color centers with accessible spins hosted by van der Waals materials have attracted substantial interest in recent years due to their significant potential for implementing transformative quantum sensing technologies. Hexagonal boron nitride (hBN) is naturally relevant in this context due to its remarkable ease of integration into devices consisting of low-dimensional materials. Taking advantage of boron vacancy spin defects in hBN, we report nanoscale quantum imaging of low-dimensional ferromagnetism sustained in Fe3GeTe2/hBN van der Waals heterostructures. Exploiting spin relaxometry methods, we have further observed spatially varying magnetic fluctuations in the exfoliated Fe3GeTe2 flake, whose magnitude reaches a peak value around the Curie temperature. Our results demonstrate the capability of spin defects in hBN of investigating local magnetic properties of layered materials in an accessible and precise way, which can be extended readily to a broad range of miniaturized van der Waals heterostructure systems.
Record high-Tc and large practical utilization level of electric polarization in metal-free molecular antiferroelectric solid solutions
Authors: Xu Haojie , Guo Wuqian , Ma Yu , Liu Yi , Hu Xinxin , Hua Lina , Han Shiguo , Liu Xitao , Luo Junhua , Sun Zhihua 
Published: September 2022

AbstractMetal-free antiferroelectric materials are holding a promise for energy storage application, owing to their unique merits of wearability, environmental friendliness, and structure tunability. Despite receiving great interests, metal-free antiferroelectrics are quite limited and it is a challenge to acquire new soft antiferroelectric candidates. Here, we have successfully exploited binary CMBrxI1-x and CMBrxCl1-x solid solution as single crystals (0 ≤ x ≤ 1, where CM is cyclohexylmethylammonium). A molecule-level modification can effectively enhance Curie temperature. Emphatically, the binary CM-chloride salt shows the highest antiferroelectric-to-paraelectric Curie temperature of ~453 K among the known molecular antiferroelectrics. Its characteristic double electrical hysteresis loops provide a large electric polarization up to ~11.4 μC/cm2, which endows notable energy storage behaviors. To our best knowledge, this work provides an effective solid-solution methodology to the targeted design of new metal-free antiferroelectric candidates toward biocompatible energy storage devices.
Identifying and tailoring C–N coupling site for efficient urea synthesis over diatomic Fe–Ni catalyst
Authors: Zhang Xiaoran , Zhu Xiaorong , Bo Shuowen , Chen Chen , Qiu Mengyi , Wei Xiaoxiao , He Nihan , Xie Chao , Chen Wei , Zheng Jianyun , Chen Pinsong , Jiang San Ping , Li Yafei , Liu Qinghua , Wang Shuangyin 
Published: September 2022

AbstractElectrocatalytic urea synthesis emerged as the promising alternative of Haber–Bosch process and industrial urea synthetic protocol. Here, we report that a diatomic catalyst with bonded Fe–Ni pairs can significantly improve the efficiency of electrochemical urea synthesis. Compared with isolated diatomic and single-atom catalysts, the bonded Fe–Ni pairs act as the efficient sites for coordinated adsorption and activation of multiple reactants, enhancing the crucial C–N coupling thermodynamically and kinetically. The performance for urea synthesis up to an order of magnitude higher than those of single-atom and isolated diatomic electrocatalysts, a high urea yield rate of 20.2 mmol h−1 g−1 with corresponding Faradaic efficiency of 17.8% has been successfully achieved. A total Faradaic efficiency of about 100% for the formation of value-added urea, CO, and NH3 was realized. This work presents an insight into synergistic catalysis towards sustainable urea synthesis via identifying and tailoring the atomic site configurations.
The primeval optical evolving matter by optical binding inside and outside the photon beam
Authors: Huang Chih-Hao , Louis Boris , Bresolí-Obach Roger , Kudo Tetsuhiro , Camacho Rafael , Scheblykin Ivan G. , Sugiyama Teruki , Hofkens Johan , Masuhara Hiroshi 
Published: September 2022

AbstractOptical binding has recently gained considerable attention because it enables the light-induced assembly of many-body systems; however, this phenomenon has only been described between directly irradiated particles. Here, we demonstrate that optical binding can occur outside the focal spot of a single tightly focused laser beam. By trapping at an interface, we assemble up to three gold nanoparticles with a linear arrangement which fully-occupies the laser focus. The trapping laser is efficiently scattered by this linear alignment and interacts with particles outside the focus area, generating several discrete arc-shape potential wells with a half-wavelength periodicity. Those external nanoparticles inside the arcs show a correlated motion not only with the linear aligned particles, but also between themselves even both are not directly illuminated. We propose that the particles are optically bound outside the focal spot by the back-scattered light and multi-channel light scattering, forming a dynamic optical binding network.
Chang’E-5 samples reveal high water content in lunar minerals
Authors: Zhou Chuanjiao , Tang Hong , Li Xiongyao , Zeng Xiaojia , Mo Bing , Yu Wen , Wu Yanxue , Zeng Xiandi , Liu Jianzhong , Wen Yuanyun 
Published: September 2022

AbstractThe formation and distribution of lunar surficial water remains ambiguous. Here, we show the prominence of water (OH/H2O) attributed to solar wind implantation on the uppermost surface of olivine, plagioclase, and pyroxene grains from Chang’E-5 samples. The results of spectral and microstructural analyses indicate that solar wind-derived water is affected by exposure time, crystal structure, and mineral composition. Our estimate of a minimum of 170 ppm water content in lunar soils in the Chang’E-5 region is consistent with that reported by the Moon Minerology Mapper and Chang’E-5 lander. By comparing with remote sensing data and through lunar soil maturity analysis, the amount of water in Chang’E-5 provides a reference for the distribution of surficial water in middle latitude of the Moon. We conclude that minerals in lunar soils are important reservoirs of water, and formation and retention of water originating from solar wind occurs on airless bodies.
Holocene seasonal temperature evolution and spatial variability over the Northern Hemisphere landmass
Authors: Zhang Wenchao , Wu Haibin , Cheng Jun , Geng Junyan , Li Qin , Sun Yong , Yu Yanyan , Lu Huayu , Guo Zhengtang 
Published: September 2022

AbstractThe origin of the temperature divergence between Holocene proxy reconstructions and model simulations remains controversial, but it possibly results from potential biases in the seasonality of reconstructions or in the climate sensitivity of models. Here we present an extensive dataset of Holocene seasonal temperatures reconstructed using 1310 pollen records covering the Northern Hemisphere landmass. Our results indicate that both summer and winter temperatures warmed from the early to mid-Holocene (~11–7 ka BP) and then cooled thereafter, but with significant spatial variability. Strong early Holocene warming trend occurred mainly in Europe, eastern North America and northern Asia, which can be generally captured by model simulations and is likely associated with the retreat of continental ice sheets. The subsequent cooling trend is pervasively recorded except for northern Asia and southeastern North America, which may reflect the cross-seasonal impact of the decreasing summer insolation through climatic feedbacks, but the cooling in winter season is not well reproduced by climate models. Our results challenge the proposal that seasonal biases in proxies are the main origin of model–data discrepancies and highlight the critical impact of insolation and associated feedbacks on temperature changes, which warrant closer attention in future climate modelling.
Unconventional interfacial water structure of highly concentrated aqueous electrolytes at negative electrode polarizations
Authors: Li Chao-Yu , Chen Ming , Liu Shuai , Lu Xinyao , Meng Jinhui , Yan Jiawei , Abruña Héctor D. , Feng Guang , Lian Tianquan 
Published: September 2022

AbstractWater-in-salt electrolytes are an appealing option for future electrochemical energy storage devices due to their safety and low toxicity. However, the physicochemical interactions occurring at the interface between the electrode and the water-in-salt electrolyte are not yet fully understood. Here, via in situ Raman spectroscopy and molecular dynamics simulations, we investigate the electrical double-layer structure occurring at the interface between a water-in-salt electrolyte and an Au(111) electrode. We demonstrate that most interfacial water molecules are bound with lithium ions and have zero, one, or two hydrogen bonds to feature three hydroxyl stretching bands. Moreover, the accumulation of lithium ions on the electrode surface at large negative polarizations reduces the interfacial field to induce an unusual “hydrogen-up” structure of interfacial water and blue shift of the hydroxyl stretching frequencies. These physicochemical behaviours are quantitatively different from aqueous electrolyte solutions with lower concentrations. This atomistic understanding of the double-layer structure provides key insights for designing future aqueous electrolytes for electrochemical energy storage devices.
Immunologically “cold” triple negative breast cancers engraft at a higher rate in patient derived xenografts
Authors: Petrosyan Varduhi , Dobrolecki Lacey E. , LaPlante Emily L. , Srinivasan Ramakrishnan Rajaram , Bailey Matthew H. , Welm Alana L. , Welm Bryan E. , Lewis Michael T. , Milosavljevic Aleksandar 
Published: September 2022

AbstractTNBC is a heterogeneous subtype of breast cancer, and only a subset of TNBC can be established as PDXs. Here, we show that there is an engraftment bias toward TNBC with low levels of immune cell infiltration. Additionally, TNBC that failed to engraft show gene expression consistent with a cancer-promoting immunological state, leading us to hypothesize that the immunological state of the tumor and possibly the state of the immune system of the host may be essential for engraftment.
A flexible and scalable scheme for mixing computed formation energies from different levels of theory
Authors: Kingsbury Ryan S. , Rosen Andrew S. , Gupta Ayush S. , Munro Jason M. , Ong Shyue Ping , Jain Anubhav , Dwaraknath Shyam , Horton Matthew K. , Persson Kristin A. 
Published: September 2022

AbstractComputational materials discovery efforts are enabled by large databases of properties derived from high-throughput density functional theory (DFT), which now contain millions of calculations at the generalized gradient approximation (GGA) level of theory. It is now feasible to carry out high-throughput calculations using more accurate methods, such as meta-GGA DFT; however recomputing an entire database with a higher-fidelity method would not effectively leverage the enormous investment of computational resources embodied in existing (GGA) calculations. Instead, we propose here a general procedure by which higher-fidelity, low-coverage calculations (e.g., meta-GGA calculations for selected chemical systems) can be combined with lower-fidelity, high-coverage calculations (e.g., an existing database of GGA calculations) in a robust and scalable manner. We then use legacy PBE(+U) GGA calculations and new r2SCAN meta-GGA calculations from the Materials Project database to demonstrate that our scheme improves solid and aqueous phase stability predictions, and discuss practical considerations for its implementation.
Long-term inhibition of mutant LRRK2 hyper-kinase activity reduced mouse brain α-synuclein oligomers without adverse effects
Authors: Ho Philip Wing-Lok , Chang Eunice Eun-Seo , Leung Chi-Ting , Liu Huifang , Malki Yasine , Pang Shirley Yin-Yu , Choi Zoe Yuen-Kiu , Liang Yingmin , Lai Weng Seng , Ruan Yuefei , Leung Kenneth Mei-Yee , Yung Susan , Mak Judith Choi-Wo , Kung Michelle Hiu-Wai , Ramsden David B. , Ho Shu-Leong 
Published: September 2022

AbstractParkinson’s disease (PD) is characterized by dopaminergic neurodegeneration in nigrostriatal and cortical brain regions associated with pathogenic α-synuclein (αSyn) aggregate/oligomer accumulation. LRRK2 hyperactivity is a disease-modifying therapeutic target in PD. However, LRRK2 inhibition may be associated with peripheral effects, albeit with unclear clinical consequences. Here, we significantly reduced αSyn oligomer accumulation in mouse striatum through long-term LRRK2 inhibition using GNE-7915 (specific brain-penetrant LRRK2 inhibitor) without causing adverse peripheral effects. GNE-7915 concentrations in wild-type (WT) mouse sera and brain samples reached a peak at 1 h, which gradually decreased over 24 h following a single subcutaneous (100 mg/kg) injection. The same dose in young WT and LRRK2R1441G mutant mice significantly inhibited LRRK2 kinase activity (Thr73-Rab10 and Ser106-Rab12 phosphorylation) in the lung, which dissipated by 72 h post-injection. 14-month-old mutant mice injected with GNE-7915 twice weekly for 18 weeks (equivalent to ~13 human years) exhibited reduced striatal αSyn oligomer and cortical pSer129-αSyn levels, correlating with inhibition of LRRK2 hyperactivity in brain and lung to WT levels. No GNE-7915-treated mice showed increased mortality or morbidity. Unlike reports of abnormalities in lung and kidney at acute high doses of LRRK2 inhibitors, our GNE-7915-treated mice did not exhibit swollen lamellar bodies in type II pneumocytes or abnormal vacuolation in the kidney. Functional and histopathological assessments of lung, kidney and liver, including whole-body plethysmography, urinary albumin-creatinine ratio (ACR), serum alanine aminotransferase (ALT) and serum interleukin-6 (inflammatory marker) did not reveal abnormalities after long-term GNE-7915 treatment. Long-term inhibition of mutant LRRK2 hyper-kinase activity to physiological levels presents an efficacious and safe disease-modifying therapy to ameliorate synucleinopathy in PD.