bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel scheme for ultrashort terahertz pulse generation over a gapless wide spectral range: Raman-resonance-enhanced four-wave mixing
Authors: Le Jiaming , Su Yudan , Tian Chuanshan , Kung A. H. , Shen Y. Ron 
Published: February 2023

AbstractUltrashort energetic terahertz (THz) pulses have created an exciting new area of research on light interactions with matter. For material studies in small laboratories, widely tunable femtosecond THz pulses with peak field strength close to MV cm−1 are desired. Currently, they can be largely acquired by optical rectification and difference frequency generation in crystals without inversion symmetry. We describe in this paper a novel scheme of THz pulse generation with no frequency tuning gap based on Raman-resonance-enhanced four-wave mixing in centrosymmetric media, particularly diamond. We show that we could generate highly stable, few-cycle pulses with near-Gaussian spatial and temporal profiles and carrier frequency tunable from 5 to >20 THz. They had a stable and controllable carrier-envelop phase and carried ~15 nJ energy per pulse at 10 THz (with a peak field strength of ~1 MV cm−1 at focus) from a 0.5-mm-thick diamond. The measured THz pulse characteristics agreed well with theoretical predictions. Other merits of the scheme are discussed, including the possibility of improving the THz output energy to a much higher level.
Rabi oscillations in a stretching molecule
Authors: Pan Shengzhe , Hu Chenxi , Zhang Wenbin , Zhang Zhaohan , Zhou Lianrong , Lu Chenxu , Lu Peifen , Ni Hongcheng , Wu Jian , He Feng 
Published: February 2023

AbstractRabi oscillation is an elementary laser-driven physical process in atoms and artificial atoms from solid-state systems, while it is rarely demonstrated in molecules. Here, we investigate the bond-length-dependent Rabi oscillations with varying Rabi frequencies in strong-laser-field dissociation of H2+. The coupling of the bond stretching and Rabi oscillations makes the nuclei gain different kinetic energies while the electron is alternatively absorbing and emitting photons. The resulting proton kinetic energy spectra show rich structures beyond the prediction of the Floquet theorem and the well-accepted resonant one-photon dissociation pathway. Our study shows that the laser-driven Rabi oscillations accompanied by nuclear motions are essential to understanding the bond-breaking mechanism and provide a time-resolved perspective to manipulate rich dynamics of the strong-laser-field dissociation of molecules.
Loss of 5-hydroxymethylcytosine induces chemotherapy resistance in hepatocellular carcinoma via the 5-hmC/PCAF/AKT axis
Authors: Guo Xiao-Jun , Huang Xiao-Yong , Yang Xuan , Lu Jia-Cheng , Wei Chuan-Yuan , Gao Chao , Pei Yan-Zi , Chen Yi , Sun Qi-Man , Cai Jia-Bin , Zhou Jian , Fan Jia , Ke Ai-Wu , Shi Yujiang G. , Shen Ying-Hao , Zhang Peng-Fei , Shi Guo-Ming , Yang Guo-Huan 
Published: February 2023

AbstractMultidrug resistance is a major challenge in treating advanced hepatocellular carcinoma (HCC). Although recent studies have reported that the multidrug resistance phenotype is associated with abnormal DNA methylation in cancer cells, the epigenetic mechanism underlying multidrug resistance remains unknown. Here, we reported that the level of 5-hydroxymethylcytosine (5-hmC) in human HCC tissues was significantly lower than that in adjacent liver tissues, and reduced 5-hmC significantly correlated with malignant phenotypes, including poor differentiation and microvascular invasion; additionally, loss of 5-hmC was related to chemotherapy resistance in post-transplantation HCC patients. Further, the 5-hmC level was regulated by ten-eleven translocation 2 (TET2), and the reduction of TET2 in HCC contributes to chemotherapy resistance through histone acetyltransferase P300/CBP-associated factor (PCAF) inhibition and AKT signaling hyperactivation. In conclusion, loss of 5-hmC induces chemotherapy resistance through PCAF/AKT axis and is a promising chemosensitivity prediction biomarker and therapeutic target for HCC patients.
ERCC6L facilitates the progression of laryngeal squamous cell carcinoma by the binding of FOXM1 and KIF4A
Authors: Cui Meng , Chang Yu , Wang Jiheng , Wu Junfu , Li Gang , Tan Jie 
Published: February 2023

AbstractThe role of excision repair cross-complementation group 6-like (ERCC6L) has been reported in several cancers, but little is known about its expression and function in laryngeal squamous cell carcinoma (LSCC). In this study, the expression of ERCC6L in LSCC was determined by immunohistochemistry and its correlation with prognostic factors was analyzed. Furthermore, cytological functional validation elucidated the role and underlying mechanisms of ERCC6L dysregulation in LSCC. Our data revealed that ERCC6L expression was elevated in LSCC and it’s correlated with TNM stage. In addition, ERCC6L knockdown LSCC cells showed decreased proliferation and migration, increased apoptosis, and reactive oxygen species (ROS). Mechanically, overexpression of ERCC6L promoted nuclear translocation of FOXM1 to facilitate direct binding to the KIF4A promoter and upregulated KIF4A expression. Furthermore, KIF4A knockdown attenuated the role of ERCC6L overexpression in promoting proliferation, migration, and tumorigenesis of LSCC cells. In summary, ERCC6L promoted the binding of FOXM1 and KIF4A in LSCC cells to drive their progression, which may be a promising target for precision therapy in this disease.
GRIA3 p.Met661Thr variant in a female with developmental epileptic encephalopathy
Authors: Okano Satomi , Makita Yoshio , Miyamoto Akie , Taketazu Genya , Kimura Kayano , Fukuda Ikue , Tanaka Hajime , Yanagi Kumiko , Kaname Tadashi 
Published: February 2023

AbstractThe X-linked human glutamate receptor subunit 3 (GRIA3) gene (MIM *305915, Xq25) encodes ionotropic α amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)-type glutamate receptor subunit 3, which mediates postsynaptic neurotransmission. Variants in this gene can cause a variety of neurological disorders, primarily reported in male patients. Here, we report a female patient with developmental and epileptic encephalopathy who carries the novel de novo GRIA3 variant NM_007325.5: c.1982T > C: p.Met661Thr.
Pathogenic variants of Alport syndrome and monogenic diabetes identified by exome sequencing in a family
Authors: Watanabe Hirofumi , Goto Shin , Hosojima Michihiro , Kabasawa Hideyuki , Imai Naofumi , Ito Yumi , Narita Ichiei 
Published: February 2023

AbstractWe present a family of two female Alport syndrome patients with a family history of impaired glucose tolerance. Whole exome sequencing identified a novel heterozygous variant of COL4A5 NM_033380.3: c.2636 C > A (p.S879*) and a rare variant of GCK NM_001354800.1: c.1135 G > A (p.A379T) as the causes of Alport syndrome and monogenic diabetes, respectively. Two independent pathogenic variants affected the clinical phenotypes. Clinical next-generation sequencing is helpful for identifying the causes of patients’ manifestations.
Direct observation of cation diffusion driven surface reconstruction at van der Waals gaps
Authors: Cui Wenjun , Lin Weixiao , Lu Weichao , Liu Chengshan , Gao Zhixiao , Ma Hao , Zhao Wen , Van Tendeloo Gustaaf , Zhao Wenyu , Zhang Qingjie , Sang Xiahan 
Published: February 2023

AbstractWeak interlayer van der Waals (vdW) bonding has significant impact on the surface/interface structure, electronic properties, and transport properties of vdW layered materials. Unraveling the complex atomistic dynamics and structural evolution at vdW surfaces is therefore critical for the design and synthesis of the next-generation vdW layered materials. Here, we show that Ge/Bi cation diffusion along the vdW gap in layered GeBi2Te4 (GBT) can be directly observed using in situ heating scanning transmission electron microscopy (STEM). The cation concentration variation during diffusion was correlated with the local Te6 octahedron distortion based on a quantitative analysis of the atomic column intensity and position in time-elapsed STEM images. The in-plane cation diffusion leads to out-of-plane surface etching through complex structural evolutions involving the formation and propagation of a non-centrosymmetric GeTe2 triple layer surface reconstruction on fresh vdW surfaces, and GBT subsurface reconstruction from a septuple layer to a quintuple layer. Our results provide atomistic insight into the cation diffusion and surface reconstruction in vdW layered materials.
The AAA+ chaperone VCP disaggregates Tau fibrils and generates aggregate seeds in a cellular system
Authors: Saha Itika , Yuste-Checa Patricia , Da Silva Padilha Miguel , Guo Qiang , Körner Roman , Holthusen Hauke , Trinkaus Victoria A. , Dudanova Irina , Fernández-Busnadiego Rubén , Baumeister Wolfgang , Sanders David W. , Gautam Saurabh , Diamond Marc I. , Hartl F. Ulrich , Hipp Mark S. 
Published: February 2023

AbstractAmyloid-like aggregates of the microtubule-associated protein Tau are associated with several neurodegenerative disorders including Alzheimer’s disease. The existence of cellular machinery for the removal of such aggregates has remained unclear, as specialized disaggregase chaperones are thought to be absent in mammalian cells. Here we show in cell culture and in neurons that the hexameric ATPase valosin-containing protein (VCP) is recruited to ubiquitylated Tau fibrils, resulting in their efficient disaggregation. Aggregate clearance depends on the functional cooperation of VCP with heat shock 70 kDa protein (Hsp70) and the ubiquitin-proteasome machinery. While inhibition of VCP activity stabilizes large Tau aggregates, disaggregation by VCP generates seeding-active Tau species as byproduct. These findings identify VCP as a core component of the machinery for the removal of neurodegenerative disease aggregates and suggest that its activity can be associated with enhanced aggregate spreading in tauopathies.
HIV vaccine candidate efficacy in female macaques mediated by cAMP-dependent efferocytosis and V2-specific ADCC
Authors: Bissa Massimiliano , Kim Sohyoung , Galli Veronica , Fourati Slim , Sarkis Sarkis , Arakelyan Anush , de Castro Isabela Silva , Rahman Mohammad Arif , Fujiwara Saori , Vaccari Monica , Tomalka Jeffrey A. , Stamos James D. , Schifanella Luca , Gorini Giacomo , Moles Ramona , Gutowska Anna , Ferrari Guido , Lobanov Alexei , Montefiori David C. , Nelson George W. , Cam Margaret C. , Chakhtoura Marita , Haddad Elias K. , Doster Melvin N. , McKinnon Katherine , Brown Sophia , Venzon David J. , Choo-Wosoba Hyoyoung , Breed Matthew W. , Killoran Kristin E. , Kramer Joshua , Margolis Leonid , Sekaly Rafick P. , Hager Gordon L. , Franchini Genoveffa 
Published: February 2023

AbstractThe development of an effective vaccine to protect against HIV acquisition will be greatly bolstered by in-depth understanding of the innate and adaptive responses to vaccination. We report here that the efficacy of DNA/ALVAC/gp120/alum vaccines, based on V2-specific antibodies mediating apoptosis of infected cells (V2-ADCC), is complemented by efferocytosis, a cyclic AMP (cAMP)-dependent antiphlogistic engulfment of apoptotic cells by CD14+ monocytes. Central to vaccine efficacy is the engagement of the CCL2/CCR2 axis and tolerogenic dendritic cells producing IL-10 (DC-10). Epigenetic reprogramming in CD14+ cells of the cyclic AMP/CREB pathway and increased systemic levels of miRNA-139-5p, a negative regulator of expression of the cAMP-specific phosphodiesterase PDE4D, correlated with vaccine efficacy. These data posit that efferocytosis, through the prompt and effective removal of apoptotic infected cells, contributes to vaccine efficacy by decreasing inflammation and maintaining tissue homeostasis.
G9a/GLP inhibition during ex vivo lymphocyte expansion increases in vivo cytotoxicity of engineered T cells against hepatocellular carcinoma
Authors: Lam Maxine S. Y. , Reales-Calderon Jose Antonio , Ow Jin Rong , Aw Joey J. Y. , Tan Damien , Vijayakumar Ragavi , Ceccarello Erica , Tabaglio Tommaso , Lim Yan Ting , Chien Wang Loo , Lai Fritz , Tanoto Anthony Tan , Chen Qingfeng , Sobota Radoslaw M. , Adriani Giulia , Bertoletti Antonio , Guccione Ernesto , Pavesi Andrea 
Published: February 2023

AbstractEngineered T cells transiently expressing tumor-targeting receptors are an attractive form of engineered T cell therapy as they carry no risk of insertional mutagenesis or long-term adverse side-effects. However, multiple rounds of treatment are often required, increasing patient discomfort and cost. To mitigate this, we sought to improve the antitumor activity of transient engineered T cells by screening a panel of small molecules targeting epigenetic regulators for their effect on T cell cytotoxicity. Using a model for engineered T cells targetting hepatocellular carcinoma, we find that short-term inhibition of G9a/GLP increases T cell antitumor activity in in vitro models and an orthotopic mouse model. G9a/GLP inhibition increases granzyme expression without terminal T cell differentiation or exhaustion and results in specific changes in expression of genes and proteins involved in pro-inflammatory pathways, T cell activation and cytotoxicity.
FMO rewires metabolism to promote longevity through tryptophan and one carbon metabolism in C. elegans
Authors: Choi Hyo Sub , Bhat Ajay , Howington Marshall B. , Schaller Megan L. , Cox Rebecca L. , Huang Shijiao , Beydoun Safa , Miller Hillary A. , Tuckowski Angela M. , Mecano Joy , Dean Elizabeth S. , Jensen Lindy , Beard Daniel A. , Evans Charles R. , Leiser Scott F. 
Published: February 2023

AbstractFlavin containing monooxygenases (FMOs) are promiscuous enzymes known for metabolizing a wide range of exogenous compounds. In C. elegans, fmo-2 expression increases lifespan and healthspan downstream of multiple longevity-promoting pathways through an unknown mechanism. Here, we report that, beyond its classification as a xenobiotic enzyme, fmo-2 expression leads to rewiring of endogenous metabolism principally through changes in one carbon metabolism (OCM). These changes are likely relevant, as we find that genetically modifying OCM enzyme expression leads to alterations in longevity that interact with fmo-2 expression. Using computer modeling, we identify decreased methylation as the major OCM flux modified by FMO-2 that is sufficient to recapitulate its longevity benefits. We further find that tryptophan is decreased in multiple mammalian FMO overexpression models and is a validated substrate for FMO-2. Our resulting model connects a single enzyme to two previously unconnected key metabolic pathways and provides a framework for the metabolic interconnectivity of longevity-promoting pathways such as dietary restriction. FMOs are well-conserved enzymes that are also induced by lifespan-extending interventions in mice, supporting a conserved and important role in promoting health and longevity through metabolic remodeling.
Antecedent chromatin organization determines cGAS recruitment to ruptured micronuclei
Authors: MacDonald Kate M. , Nicholson-Puthenveedu Shirony , Tageldein Maha M. , Khasnis Sarika , Arrowsmith Cheryl H. , Harding Shane M. 
Published: February 2023

AbstractMicronuclei (MN) are cytosolic bodies that sequester acentric fragments or mis-segregated chromosomes from the primary nucleus. Spontaneous rupture of the MN envelope allows recognition by the viral receptor cyclic GMP-AMP synthase (cGAS), initiating interferon signaling downstream of DNA damage. Here, we demonstrate that MN rupture is permissive but not sufficient for cGAS localization. Chromatin characteristics such as histone 3, lysine 79 dimethylation (H3K79me2) are present in the nucleus before DNA damage, retained in ruptured MN, and regulate cGAS recruitment. cGAS is further responsive to dynamic intra-MN processes occurring prior to rupture, including transcription. MN chromatin tethering via the nucleosome acidic patch is necessary for cGAS-dependent interferon signaling. Our data suggest that both damage-antecedent nuclear chromatin status and MN-contained chromatin organizational changes dictate cGAS recruitment and the magnitude of the cGAS-driven interferon cascade. Our work defines MN as integrative signaling hubs for the cellular response to genotoxic stress.
Increased levels of endogenous retroviruses trigger fibroinflammation and play a role in kidney disease development
Authors: Dhillon Poonam , Mulholland Kelly Ann , Hu Hailong , Park Jihwan , Sheng Xin , Abedini Amin , Liu Hongbo , Vassalotti Allison , Wu Junnan , Susztak Katalin 
Published: February 2023

AbstractInflammation is a common feature of all forms of chronic kidney disease; however, the underlying mechanism remains poorly understood. Evolutionarily inherited endogenous retroviruses (ERVs) have the potential to trigger an immune reaction. Comprehensive RNA-sequencing of control and diseased kidneys from human and mouse disease models indicated higher expression of transposable elements (TEs) and ERVs in diseased kidneys. Loss of cytosine methylation causing epigenetic derepression likely contributes to an increase in ERV levels. Genetic deletion/pharmacological inhibition of DNA methyltransferase 1 (DNMT1) induces ERV expression. In cultured kidney tubule cells, ERVs elicit the activation of cytosolic nucleotide sensors such as RIG-I, MDA5, and STING. ERVs expressions in kidney tubules trigger RIG-I/STING, and cytokine expression, and correlate with the presence of immune cells. Genetic deletion of RIG-I or STING or treatment with reverse transcriptase inhibitor ameliorates kidney fibroinflammation. Our data indicate an important role of epigenetic derepression-induced ERV activation triggering renal fibroinflammation.
Quantifying PON1 on HDL with nanoparticle-gated electrokinetic membrane sensor for accurate cardiovascular risk assessment
Authors: Kumar Sonu , Maniya Nalin , Wang Ceming , Senapati Satyajyoti , Chang Hsueh-Chia 
Published: February 2023

AbstractCardiovascular disease-related deaths (one-third of global deaths) can be reduced with a simple screening test for better biomarkers than the current lipid and lipoprotein profiles. We propose using a highly atheroprotective subset of HDL with colocalized PON1 (PON1-HDL) for superior cardiovascular risk assessment. However, direct quantification of HDL proteomic subclasses are complicated by the peroxides/antioxidants associated with HDL interfering with redox reactions in enzymatic calorimetric and electrochemical immunoassays. Hence, we developed an enzyme-free Nanoparticle-Gated Electrokinetic Membrane Sensor (NGEMS) platform for quantification of PON1-HDL in plasma within 60 min, with a sub-picomolar limit of detection, 3–4 log dynamic range and without needing sample pretreatment or individual-sample calibration. Using NGEMS, we report our study on human plasma PON1-HDL as a cardiovascular risk marker with AUC~0.99 significantly outperforming others (AUC~0.6–0.8), including cholesterol/triglycerides tests. Validation for a larger cohort can establish PON1-HDL as a biomarker that can potentially reshape cardiovascular landscape.
Sample multiplexing-based targeted pathway proteomics with real-time analytics reveals the impact of genetic variation on protein expression
Authors: Yu Qing , Liu Xinyue , Keller Mark P. , Navarrete-Perea Jose , Zhang Tian , Fu Sipei , Vaites Laura P. , Shuken Steven R. , Schmid Ernst , Keele Gregory R. , Li Jiaming , Huttlin Edward L. , Rashan Edrees H. , Simcox Judith , Churchill Gary A. , Schweppe Devin K. , Attie Alan D. , Paulo Joao A. , Gygi Steven P. 
Published: February 2023

AbstractTargeted proteomics enables hypothesis-driven research by measuring the cellular expression of protein cohorts related by function, disease, or class after perturbation. Here, we present a pathway-centric approach and an assay builder resource for targeting entire pathways of up to 200 proteins selected from >10,000 expressed proteins to directly measure their abundances, exploiting sample multiplexing to increase throughput by 16-fold. The strategy, termed GoDig, requires only a single-shot LC-MS analysis, ~1 µg combined peptide material, a list of up to 200 proteins, and real-time analytics to trigger simultaneous quantification of up to 16 samples for hundreds of analytes. We apply GoDig to quantify the impact of genetic variation on protein expression in mice fed a high-fat diet. We create several GoDig assays to quantify the expression of multiple protein families (kinases, lipid metabolism- and lipid droplet-associated proteins) across 480 fully-genotyped Diversity Outbred mice, revealing protein quantitative trait loci and establishing potential linkages between specific proteins and lipid homeostasis.
Genetic and pharmacologic inhibition of ALDH1A3 as a treatment of β-cell failure
Authors: Son Jinsook , Du Wen , Esposito Mark , Shariati Kaavian , Ding Hongxu , Kang Yibin , Accili Domenico 
Published: February 2023

AbstractType 2 diabetes (T2D) is associated with β-cell dedifferentiation. Aldehyde dehydrogenase 1 isoform A3 (ALHD1A3) is a marker of β-cell dedifferentiation and correlates with T2D progression. However, it is unknown whether ALDH1A3 activity contributes to β-cell failure, and whether the decrease of ALDH1A3-positive β-cells (A+) following pair-feeding of diabetic animals is due to β-cell restoration. To tackle these questions, we (i) investigated the fate of A+ cells during pair-feeding by lineage-tracing, (ii) somatically ablated ALDH1A3 in diabetic β-cells, and (iii) used a novel selective ALDH1A3 inhibitor to treat diabetes. Lineage tracing and functional characterization show that A+ cells can be reconverted to functional, mature β-cells. Genetic or pharmacological inhibition of ALDH1A3 in diabetic mice lowers glycemia and increases insulin secretion. Characterization of β-cells following ALDH1A3 inhibition shows reactivation of differentiation as well as regeneration pathways. We conclude that ALDH1A3 inhibition offers a therapeutic strategy against β-cell dysfunction in diabetes.
Achiral organoiodine-functionalized helical polyisocyanides for multiple asymmetric dearomative oxidations
Authors: Wu Zong-Quan , Song Xue , Li Yan-Xiang , Zhou Li , Zhu Yuan-Yuan , Chen Zheng , Liu Na 
Published: February 2023

AbstractImmobilizing organocatalyst onto helical polymers not only facilitates the catalyst recycling from homogeneous reactions, but also boosts enantioselectivity. In this work, achiral organoiodine-functionalized single left- and right-handed helical polyisocyanides were prepared from the same monomers, which catalyzed three asymmetric oxidations gave the desired products in high yields and excellent enantioselectivity. The enantiomeric excess of the target products was up to 95%. Remarkably, the enantioselectivity can be switched by reversing the helicity of the polymer backbone. The polymer catalysts can be facilely recovered and recycled in different asymmetric oxidations with maintained excellent activity and enantioselectivity.