bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chronic UCN2 treatment desensitizes CRHR2 and improves insulin sensitivity
Authors: Flaherty Stephen E. , Bezy Olivier , Zheng Wei , Yan Dong , Li Xiangping , Jagarlapudi Srinath , Albuquerque Bina , Esquejo Ryan M. , Peloquin Matthew , Semache Meriem , Mancini Arturo , Kang Liya , Drujan Doreen , Breitkopf Susanne B. , Griffin John D. , Jean Beltran Pierre M. , Xue Liang , Stansfield John , Pashos Evanthia , Shakey Quazi , Pehmøller Christian , Monetti Mara , Birnbaum Morris J. , Fortin Jean-Philippe , Wu Zhidan 
Published: July 2023

AbstractUrocortin 2 (UCN2) acts as a ligand for the G protein-coupled receptor corticotropin-releasing hormone receptor 2 (CRHR2). UCN2 has been reported to improve or worsen insulin sensitivity and glucose tolerance in vivo. Here we show that acute dosing of UCN2 induces systemic insulin resistance in male mice and skeletal muscle. Inversely, chronic elevation of UCN2 by injection with adenovirus encoding UCN2 resolves metabolic complications, improving glucose tolerance. CRHR2 recruits Gs in response to low concentrations of UCN2, as well as Gi and β-Arrestin at high concentrations of UCN2. Pre-treating cells and skeletal muscle ex vivo with UCN2 leads to internalization of CRHR2, dampened ligand-dependent increases in cAMP, and blunted reductions in insulin signaling. These results provide mechanistic insights into how UCN2 regulates insulin sensitivity and glucose metabolism in skeletal muscle and in vivo. Importantly, a working model was derived from these results that unifies the contradictory metabolic effects of UCN2.
Ozone-enabled fatty acid discovery reveals unexpected diversity in the human lipidome
Authors: Menzel Jan Philipp , Young Reuben S. E. , Benfield Aurélie H. , Scott Julia S. , Wongsomboon Puttandon , Cudlman Lukáš , Cvačka Josef , Butler Lisa M. , Henriques Sónia T. , Poad Berwyck L. J. , Blanksby Stephen J. 
Published: July 2023

AbstractFatty acid isomers are responsible for an under-reported lipidome diversity across all kingdoms of life. Isomers of unsaturated fatty acids are often masked in contemporary analysis by incomplete separation and the absence of sufficiently diagnostic methods for structure elucidation. Here, we introduce a comprehensive workflow, to discover unsaturated fatty acids through coupling liquid chromatography and mass spectrometry with gas-phase ozonolysis of double bonds. The workflow encompasses semi-automated data analysis and enables de novo identification in complex media including human plasma, cancer cell lines and vernix caseosa. The targeted analysis including ozonolysis enables structural assignment over a dynamic range of five orders of magnitude, even in instances of incomplete chromatographic separation. Thereby we expand the number of identified plasma fatty acids two-fold, including non-methylene-interrupted fatty acids. Detection, without prior knowledge, allows discovery of non-canonical double bond positions. Changes in relative isomer abundances reflect underlying perturbations in lipid metabolism.
High-speed scanless entire bandwidth mid-infrared chemical imaging
Authors: Zhao Yue , Kusama Shota , Furutani Yuji , Huang Wei-Hong , Luo Chih-Wei , Fuji Takao 
Published: July 2023

AbstractMid-infrared spectroscopy probes molecular vibrations to identify chemical species and functional groups. Therefore, mid-infrared hyperspectral imaging is one of the most powerful and promising candidates for chemical imaging using optical methods. Yet high-speed and entire bandwidth mid-infrared hyperspectral imaging has not been realized. Here we report a mid-infrared hyperspectral chemical imaging technique that uses chirped pulse upconversion of sub-cycle pulses at the image plane. This technique offers a lateral resolution of 15 µm, and the field of view is adjustable between 800 µm × 600 µm to 12 mm × 9 mm. The hyperspectral imaging produces a 640 × 480 pixel image in 8 s, which covers a spectral range of 640–3015 cm–1, comprising 1069 wavelength points and offering a wavenumber resolution of 2.6–3.7 cm–1. For discrete frequency mid-infrared imaging, the measurement speed reaches a frame rate of 5 kHz, the repetition rate of the laser. As a demonstration, we effectively identified and mapped different components in a microfluidic device, plant cell, and mouse embryo section. The great capacity and latent force of this technique in chemical imaging promise to be applied to many fields such as chemical analysis, biology, and medicine.
Polar Solomon rings in ferroelectric nanocrystals
Authors: Wang Jing , Liang Deshan , Ma Jing , Fan Yuanyuan , Ma Ji , Jafri Hasnain Mehdi , Yang Huayu , Zhang Qinghua , Wang Yue , Guo Changqing , Dong Shouzhe , Liu Di , Wang Xueyun , Hong Jiawang , Zhang Nan , Gu Lin , Yi Di , Zhang Jinxing , Lin Yuanhua , Chen Long-Qing , Huang Houbing , Nan Ce-Wen 
Published: July 2023

AbstractSolomon rings, upholding the symbol of wisdom with profound historical roots, were widely used as decorations in ancient architecture and clothing. However, it was only recently discovered that such topological structures can be formed by self-organization in biological/chemical molecules, liquid crystals, etc. Here, we report the observation of polar Solomon rings in a ferroelectric nanocrystal, which consist of two intertwined vortices and are mathematically equivalent to a $${4}_{1}^{2}$$

4

1

2

link in topology. By combining piezoresponse force microscopy observations and phase-field simulations, we demonstrate the reversible switching between polar Solomon rings and vertex textures by an electric field. The two types of topological polar textures exhibit distinct absorption of terahertz infrared waves, which can be exploited in infrared displays with a nanoscale resolution. Our study establishes, both experimentally and computationally, the existence and electrical manipulation of polar Solomon rings, a new form of topological polar structures that may provide a simple way for fast, robust, and high-resolution optoelectronic devices.
A mechanical-coupling mechanism in OSCA/TMEM63 channel mechanosensitivity
Authors: Zhang Mingfeng , Shan Yuanyue , Cox Charles D. , Pei Duanqing 
Published: July 2023

AbstractMechanosensitive (MS) ion channels are a ubiquitous type of molecular force sensor sensing forces from the surrounding bilayer. The profound structural diversity in these channels suggests that the molecular mechanisms of force sensing follow unique structural blueprints. Here we determine the structures of plant and mammalian OSCA/TMEM63 proteins, allowing us to identify essential elements for mechanotransduction and propose roles for putative bound lipids in OSCA/TMEM63 mechanosensation. Briefly, the central cavity created by the dimer interface couples each subunit and modulates dimeric OSCA/TMEM63 channel mechanosensitivity through the modulating lipids while the cytosolic side of the pore is gated by a plug lipid that prevents the ion permeation. Our results suggest that the gating mechanism of OSCA/TMEM63 channels may combine structural aspects of the ‘lipid-gated’ mechanism of MscS and TRAAK channels and the calcium-induced gating mechanism of the TMEM16 family, which may provide insights into the structural rearrangements of TMEM16/TMC superfamilies.
A soft, self-sensing tensile valve for perceptive soft robots
Authors: Choe Jun Kyu , Kim Junsoo , Song Hyeonseo , Bae Joonbum , Kim Jiyun 
Published: July 2023

AbstractSoft inflatable robots are a promising paradigm for applications that benefit from their inherent safety and adaptability. However, for perception, complex connections of rigid electronics both in hardware and software remain the mainstay. Although recent efforts have created soft analogs of individual rigid components, the integration of sensing and control systems is challenging to achieve without compromising the complete softness, form factor, or capabilities. Here, we report a soft self-sensing tensile valve that integrates the functional capabilities of sensors and control valves to directly transform applied tensile strain into distinctive steady-state output pressure states using only a single, constant pressure source. By harnessing a unique mechanism, “helical pinching”, we derive physical sharing of both sensing and control valve structures, achieving all-in-one integration in a compact form factor. We demonstrate programmability and applicability of our platform, illustrating a pathway towards fully soft, electronics-free, untethered, and autonomous robotic systems.
In vitro and in vivo characterization of SARS-CoV-2 strains resistant to nirmatrelvir
Authors: Kiso Maki , Furusawa Yuri , Uraki Ryuta , Imai Masaki , Yamayoshi Seiya , Kawaoka Yoshihiro 
Published: July 2023

AbstractNirmatrelvir, an oral antiviral agent that targets a SARS-CoV-2 main protease (3CLpro), is clinically useful against infection with SARS-CoV-2 including its omicron variants. Since most omicron subvariants have reduced sensitivity to many monoclonal antibody therapies, potential SARS-CoV-2 resistance to nirmatrelvir is a major public health concern. Several amino acid substitutions have been identified as being responsible for reduced susceptibility to nirmatrelvir. Among them, we selected L50F/E166V and L50F/E166A/L167F in the 3CLpro because these combinations of substitutions are unlikely to affect virus fitness. We prepared and characterized delta variants possessing Nsp5-L50F/E166V and Nsp5-L50F/E166A/L167F. Both mutant viruses showed decreased susceptibility to nirmatrelvir and their growth in VeroE6/TMPRSS2 cells was delayed. Both mutant viruses showed attenuated phenotypes in a male hamster infection model, maintained airborne transmissibility, and were outcompeted by wild-type virus in co-infection experiments in the absence of nirmatrelvir, but less so in the presence of the drug. These results suggest that viruses possessing Nsp5-L50F/E166V and Nsp5-L50F/E166A/L167F do not become dominant in nature. However, it is important to closely monitor the emergence of nirmatrelvir-resistant SARS-CoV-2 variants because resistant viruses with additional compensatory mutations could emerge, outcompete the wild-type virus, and become dominant.
Generation of the transgene-free canker-resistant Citrus sinensis using Cas12a/crRNA ribonucleoprotein in the T0 generation
Authors: Su Hang , Wang Yuanchun , Xu Jin , Omar Ahmad A. , Grosser Jude W. , Calovic Milica , Zhang Liyang , Feng Yu , Vakulskas Christopher A. , Wang Nian 
Published: July 2023

AbstractCitrus canker caused by Xanthomonas citri subsp. citri (Xcc) is a destructive citrus disease worldwide. Generating disease-resistant cultivars is the most effective, environmentally friendly and economic approach for disease control. However, citrus traditional breeding is lengthy and laborious. Here, we develop transgene-free canker-resistant Citrus sinensis lines in the T0 generation within 10 months through transformation of embryogenic protoplasts with Cas12a/crRNA ribonucleoprotein to edit the canker susceptibility gene CsLOB1. Among the 39 regenerated lines, 38 are biallelic/homozygous mutants, demonstrating a 97.4% biallelic/homozygous mutation rate. No off-target mutations are detected in the edited lines. Canker resistance of the cslob1-edited lines results from both abolishing canker symptoms and inhibiting Xcc growth. The transgene-free canker-resistant C. sinensis lines have received regulatory approval by USDA APHIS and are exempted from EPA regulation. This study provides a sustainable and efficient citrus canker control solution and presents an efficient transgene-free genome-editing strategy for citrus and other crops.
An immunostimulatory glycolipid that blocks SARS-CoV-2, RSV, and influenza infections in vivo
Authors: Tsuji Moriya , Nair Manoj S. , Masuda Kazuya , Castagna Candace , Chong Zhenlu , Darling Tamarand L. , Seehra Kuljeet , Hwang Youngmin , Ribeiro Ágata Lopes , Ferreira Geovane Marques , Corredor Laura , Coelho-dos-Reis Jordana Grazziela Alves , Tsuji Yukiko , Mori Munemasa , Boon Adrianus C. M. , Diamond Michael S. , Huang Yaoxing , Ho David D. 
Published: July 2023

AbstractProphylactic vaccines for SARS-CoV-2 have lowered the incidence of severe COVID-19, but emergence of viral variants that are antigenically distinct from the vaccine strains are of concern and additional, broadly acting preventive approaches are desirable. Here, we report on a glycolipid termed 7DW8-5 that exploits the host innate immune system to enable rapid control of viral infections in vivo. This glycolipid binds to CD1d on antigen-presenting cells and thereby stimulates NKT cells to release a cascade of cytokines and chemokines. The intranasal administration of 7DW8-5 prior to virus exposure significantly blocked infection by three different authentic variants of SARS-CoV-2, as well as by respiratory syncytial virus and influenza virus, in mice or hamsters. We also found that this protective antiviral effect is both host-directed and mechanism-specific, requiring both the CD1d molecule and interferon-$$\gamma$$
γ
. A chemical compound like 7DW8-5 that is easy to administer and cheap to manufacture may be useful not only in slowing the spread of COVID-19 but also in responding to future pandemics long before vaccines or drugs are developed.
Cryo-EM structure of GABA transporter 1 reveals substrate recognition and transport mechanism
Authors: Nayak Smruti Ranjan , Joseph Deepthi , Höfner Georg , Dakua Archishman , Athreya Arunabh , Wanner Klaus T. , Kanner Baruch I. , Penmatsa Aravind 
Published: July 2023

AbstractThe inhibitory neurotransmitter γ-aminobutyric acid (GABA) is cleared from the synaptic cleft by the sodium- and chloride-coupled GABA transporter GAT1. Inhibition of GAT1 prolongs the GABAergic signaling at the synapse and is a strategy to treat certain forms of epilepsy. In this study, we present the cryo-electron microscopy structure of Rattus norvegicus GABA transporter 1 (rGAT1) at a resolution of 3.1 Å. The structure elucidation was facilitated by epitope transfer of a fragment-antigen binding (Fab) interaction site from the Drosophila dopamine transporter (dDAT) to rGAT1. The structure reveals rGAT1 in a cytosol-facing conformation, with a linear density in the primary binding site that accommodates a molecule of GABA, a displaced ion density proximal to Na site 1 and a bound chloride ion. A unique insertion in TM10 aids the formation of a compact, closed extracellular gate. Besides yielding mechanistic insights into ion and substrate recognition, our study will enable the rational design of specific antiepileptics.
Extracellular tau stimulates phagocytosis of living neurons by activated microglia via Toll-like 4 receptor–NLRP3 inflammasome–caspase-1 signalling axis
Authors: Pampuscenko Katryna , Morkuniene Ramune , Krasauskas Lukas , Smirnovas Vytautas , Brown Guy C. , Borutaite Vilmante 
Published: July 2023

AbstractIn tauopathies, abnormal deposition of intracellular tau protein followed by gradual elevation of tau in cerebrospinal fluids and neuronal loss has been documented, however, the mechanism how actually neurons die under tau pathology is largely unknown. We have previously shown that extracellular tau protein (2N4R isoform) can stimulate microglia to phagocytose live neurons, i.e. cause neuronal death by primary phagocytosis, also known as phagoptosis. Here we show that tau protein induced caspase-1 activation in microglial cells via ‘Toll-like’ 4 (TLR4) receptors and neutral sphingomyelinase. Tau-induced neuronal loss was blocked by caspase-1 inhibitors (Ac-YVAD-CHO and VX-765) as well as by TLR4 antibodies. Inhibition of caspase-1 by Ac-YVAD-CHO prevented tau-induced exposure of phosphatidylserine on the outer leaflet of neuronal membranes and reduced microglial phagocytic activity. We also show that suppression of NLRP3 inflammasome, which is down-stream of TLR4 receptors and mediates caspase-1 activation, by a specific inhibitor (MCC550) also prevented tau-induced neuronal loss. Moreover, NADPH oxidase is also involved in tau-induced neurotoxicity since neuronal loss was abolished by its pharmacological inhibitor. Overall, our data indicate that extracellular tau protein stimulates microglia to phagocytose live neurons via Toll-like 4 receptor–NLRP3 inflammasome–caspase-1 axis and NADPH oxidase, each of which may serve as a potential molecular target for pharmacological treatment of tauopathies.
An explorative cross-sectional analysis of mental health shame and help-seeking intentions in different lifestyles
Authors: Helmert Claudia , Fleischer Toni , Speerforck Sven , Ulke Christine , Altweck Laura , Hahm Stefanie , Muehlan Holger , Schmidt Silke , Grabe Hans J. , Völzke Henry , Schomerus Georg 
Published: July 2023

AbstractTo identify und support particular target groups for mental health prevention, we explore the links between shame and help-seeking intentions concerning mental health in different lifestyles (based on socioeconomic status as well as health-related behaviors). Lifestyles were operationalized by nine confirmatory, homogenous clusters of the sample. These clusters are based on individuals’ similarities in sociodemographic aspects and health behavior. Analyses included t tests, Chi-square, ANOVA, regressions investigating in sociodemographic characteristics. Hierarchical linear models examining cross-sectional associations of shame and willingness to seek help for different lifestyles of participants of the Study of Health in Pomerania (SHIP-START-1 and SHIP-START-3, data collected 2002–2006 and 2014–2016; n = 1630). Hierarchical linear models showed small context effects for lifestyle-related associations of shame and willingness to seek help. For younger as well as male participants, lifestyles indicated different associations of shame and help-seeking intentions: Especially the lifestyles with unhealthy behaviors and high as well as low socioeconomic status resulted in higher shame being associated with low help-seeking intentions in case of mental illness. Lifestyle clusters might be a useful tool to identify marginalized groups with unhealthy behaviors, which should be addressed by interventions and prevention programs.
Homozygosity mapping in the Kazakh national dog breed Tazy
Authors: Perfilyeva Anastassiya , Bespalova Kira , Bespalov Sergey , Begmanova Mamura , Kuzovleva Yelena , Vishnyakova Olga , Nazarenko Inna , Abylkassymova Gulnar , Perfilyeva Yuliya , Plakhov Konstantin , Djansugurova Leyla , Bekmanov Bakhytzhan 
Published: July 2023

AbstractThe Tazy is a breed of sighthound common in Kazakhstan. The identification of runs of homozygosity (ROH) is an informative approach to assessing the history and possible patterns of directional selection pressure. To our knowledge, the present study is the first to provide an overview of the ROH pattern in the Tazy dogs from a genome-wide perspective. The ROH of the Tazy was found to be mainly composed of shorter segments (1–2 Mb), accounting for approximately 67% of the total ROH. The estimated ROH-based inbreeding coefficients (FROH) ranged from 0.028 to 0.058 with a mean of 0.057. Five genomic regions under positive selection were identified on chromosomes 18, 22, and 25. The regions on chromosomes 18 and 22 may be breed specific, while the region on chromosome 22 overlaps with regions of hunting traits in other hunting dog breeds. Among the 12 candidate genes located in these regions, the gene CAB39L may be a candidate that affects running speed and endurance of the Tazy dog. Eight genes could belong to an evolutionarily conserved complex as they were clustered in a large protein network with strong linkages. The results may enable effective interventions when incorporated into conservation planning and selection of the Tazy breed.
Thickness-stiffness trade-off improves lodging resistance in rice
Authors: Tsugawa Satoru , Shima Hiroyuki , Ishimoto Yukitaka , Ishikawa Kazuya 
Published: July 2023

AbstractLodging of cereal crops significantly reduces grain yield and quality, making lodging resistance a prime target for breeding programs. However, lodging resistance among different rice (Oryza sativa L.) cultivars in the field remains largely unknown, as is the relationship between the major properties of culms such as their morphological and mechanical properties. Here, we investigated the morphological and mechanical properties of 12 rice cultivars by considering different internodes within culms. We detected variation in these two traits among cultivars: one set of cultivars had thicker but softer culms (thickness-type), while the other set of cultivars showed stiffer but thinner culms (stiffness-type). We designate this variation as a thickness-stiffness trade-off. We then constructed a mechanical model to dissect the mechanical and/or morphological constraints of rice culms subjected to their own weight (self-weight load). Through modeling, we discovered that ear weight and the morphology of the highest internode were important for reducing deflection, which may be important factors to achieve higher lodging resistance. The mechanical theory devised in this study could be used to predict the deflection of rice culms and may open new avenues for novel mechanics-based breeding techniques.
The role of water in the laboratory thermal advancement of immature type I kerogen from the Cretaceous Qingshankou Formation in China
Authors: Safaei-Farouji Majid , Gentzis Thomas , Liu Bo , Ma Zhongliang , Wang Liu , Xu Yaohui , Ostadhassan Mehdi 
Published: July 2023

AbstractTo understand variations in geochemistry, organic petrology, and chemical composition of crude oil and byproducts, an immature sample from the Cretaceous Qingshankou Formation in the Songliao Basin, China, was analyzed by anhydrous and hydrous pyrolysis (AHP/HP) at a wide range of temperatures ranging from 300 °C to 450 °C. The geochemical parameters: TOC, S2, HI, and Tmax obtained from Rock–Eval pyrolysis showed both a decrease and an increase as thermal maturity progressed under HP and AHP conditions. Gas chromatography (GC) analysis showed the presence of n-alkanes in the C14 to C36 range in both expelled and residual byproducts, a Delta-shaped configuration although many samples had a gradually reducing (tapering) trend toward the high range. Gas chromatography-mass spectrometry (GC–MS) analysis revealed both an increase and a decrease in biomarker and very small changes in aromatic compound variations with increasing temperature during pyrolysis. To be more specific, C29Ts biomarker increased with temperature for the expelled byproduct, while the opposite trend was observed for the residual one. Next, The Ts/Tm ratio initially increased and then decreased with temperature while the C29H/C30H ratio fluctuated for the expelled byproduct but increased for the residual. Moreover, the GI and C30 rearranged hopane to C30 hopane ratio remained unchanged whereas the C23 tricyclic terpane/C24 tetracyclic terpane ratio and the C23/C24 tricyclic terpane ratio showed varying trends with maturity alike the C19/C23 and C20/C23 tricyclic terpane. Ultimately, based on organic petrography observations, increasing the temperature resulted in higher bitumen reflectance (%Bro, r) and optical and structural alterations in the macerals. The findings of this study provide valuable insights for future exploration endeavors in the studied region. Moreover, they contribute to our understanding of the significant role of water in the generation and expulsion of petroleum and associated byproducts, thereby facilitating the development of updated models in this field.
Ligand leaching enabling improved electrocatalytic oxygen evolution performance
Authors: Zhou Hongbo , Wei Zi , Nyaaba Albert Akeno , Kang Ziliang , Liu Yashu , Chen Caiyao , Zhu Jun , Ji Xiafang , Zhu Guoxing 
Published: July 2023

Nanosheet-like organic frameworks composed by [Fe(CN)6]3− and amine coordinated Ni ions were prepared, the ligand leaching of which induced improved catalytic activity for oxygen evolution.