bluuebunny/crossref_metadata_2025_split huggingface dataset:
DUSP5P1 promotes gastric cancer metastasis and platinum drug resistance
Authors: Wang Xiaohong , Zhang Lianhai , Liang Qiaoyi , Wong Chi Chun , Chen Huarong , Gou Hongyan , Dong Yujuan , Liu Weixin , Li Ziyu , Ji Jiafu , Yu Jun 
Published: October 2022

AbstractWe elucidated the functional significance and molecular mechanisms of DUSP5P1 lncRNA (dual specificity phosphatase 5 pseudogene 1) in gastric carcinogenesis. We demonstrated that gastric cancer (GC) patients with high DUSP5P1 expression had shortened survival in two independent cohorts. DUSP5P1 promoted GC cell migration and invasion in vitro and metastasis in vivo. Mechanistically, DUSP5P1 activated ARHGAP5 transcription by directly binding to the promoter of ARHGAP5 with a binding motif of TATGTG. RNA-seq revealed that ARHGAP5 activated focal adhesion and MAPK signaling pathways to promote GC metastasis. DUSP5P1 also dysregulated platinum drug resistance pathway. Consistently, DUSP5P1 overexpression in GC cells antagonized cytotoxic effect of Oxaliplatin, and shDUSP5P1 plus Oxaliplatin exerted synergistic effect on inhibiting GC metastasis in vitro and in vivo. DUSP5P1 depletion also suppressed the growth of platinum drug-resistant PDO models. In conclusion, DUSP5P1 promoted GC metastasis by directly modulating ARHGAP5 expression to activate focal adhesion and MAPK pathways, serves as therapeutic target for platinum drug resistant GC, and is an independent prognostic factor in GC.
Dental management of patients with sensory impairments
Authors: Ahmed Tasnim Aniqa , Bradley Natalie , Fenesan Stephanie 
Published: October 2022

AbstractThis article discusses the different types of sensory impairments and their aetiology. It considers how the oral health status in patients with sensory impairments is impacted by their disability and the barriers these patients face in dental care. It also discusses legislation relevant to dental care professionals when caring for patients with disabilities, including the Mental Capacity Act (2005), the Equality Act (2010) and the Accessible Information Standard (2016). Finally, it provides recommendations to dental care professionals on how they can best manage patients with sensory impairments and communicate with them effectively in order to provide them with quality dental care.
Understanding the impact of COVID-19 on dental antibiotic prescribing across England: 'it was a minefield'
Authors: Thompson Wendy , Shah Sagar , Wordley Valerie , Edwards David 
Published: October 2022

AbstractIntroduction The COVID-19 pandemic impacted significantly on dental service delivery across England.Objective To explore how and why the pandemic affected antibiotic prescribing by primary care dentists.Methods Mixed-methods study: secondary analysis of routinely collected NHS dental antibiotic prescribing data from before and during the pandemic; and an online survey of dentists (NHS and private) across England's regions.Results Dental antibiotic prescribing increased 22% in the pandemic's first year, with regional variation from a 12.1% increase in London to 29.1% in East of England. Of 159 dentists surveyed, 60% had prescribed 'many more' antibiotics. Some urgent dental centres required antibiotics before accepting referrals, irrespective of clinical appropriateness. Diagnosing remotely was hard. Antibiotics were used to delay aerosol generating procedures and fill gaps in services. Widespread frustration existed.Discussion Maintaining access to urgent dental care during a future pandemic would include availability of high-grade personal protective equipment for dental teams. Everyone must understand the impact of restricted dental access on antibiotic overprescribing and hence antibiotic resistance.Conclusion Reduced dental access and changes in dental service delivery because of the pandemic increased antibiotic prescribing. Ensuring uninterrupted access for all to effective urgent dental care is an important element of global efforts to tackle antibiotic resistance.
OPA1 drives macrophage metabolism and functional commitment via p65 signaling
Authors: Sánchez-Rodríguez Ricardo , Tezze Caterina , Agnellini Andrielly H. R. , Angioni Roberta , Venegas Francisca C. , Cioccarelli Chiara , Munari Fabio , Bertoldi Nicole , Canton Marcella , Desbats Maria Andrea , Salviati Leonardo , Gissi Rosanna , Castegna Alessandra , Soriano Maria Eugenia , Sandri Marco , Scorrano Luca , Viola Antonella , Molon Barbara 
Published: October 2022

AbstractMacrophages are essential players for the host response against pathogens, regulation of inflammation and tissue regeneration. The wide range of macrophage functions rely on their heterogeneity and plasticity that enable a dynamic adaptation of their responses according to the surrounding environmental cues. Recent studies suggest that metabolism provides synergistic support for macrophage activation and elicitation of desirable immune responses; however, the metabolic pathways orchestrating macrophage activation are still under scrutiny. Optic atrophy 1 (OPA1) is a mitochondria-shaping protein controlling mitochondrial fusion, cristae biogenesis and respiration; clear evidence shows that the lack or dysfunctional activity of this protein triggers the accumulation of metabolic intermediates of the TCA cycle. In this study, we show that OPA1 has a crucial role in macrophage activation. Selective Opa1 deletion in myeloid cells impairs M1-macrophage commitment. Mechanistically, Opa1 deletion leads to TCA cycle metabolite accumulation and defective NF-κB signaling activation. In an in vivo model of muscle regeneration upon injury, Opa1 knockout macrophages persist within the damaged tissue, leading to excess collagen deposition and impairment in muscle regeneration. Collectively, our data indicate that OPA1 is a key metabolic driver of macrophage functions.
Epigallocatechin-3-gallate inhibits osteoclastic differentiation by modulating mitophagy and mitochondrial functions
Authors: Sarkar Jaganmay , Das Manjusri , Howlader Md Sariful Islam , Prateeksha Prateeksha , Barthels Derek , Das Hiranmoy 
Published: October 2022

AbstractA natural plant product, epigallocatechin-3-gallate (EGCG), was evaluated for its effectiveness in the regulation of osteoclastogenesis. We found that EGCG inhibited the osteoclast (OC) differentiation in vitro, and in primary bone marrow cells in a dose-dependent manner. Quantitative RT-PCR studies showed that the EGCG reduced the expression of OC differentiation markers. DCFDA, MitoSOX, and JC-1 staining revealed that the EGCG attenuated the reactive oxygen species (ROS), and mitochondrial membrane potential; and flux analysis corroborated the effect of EGCG. We further found that the EGCG inhibited mRNA and protein expressions of mitophagy-related molecules. We confirmed that the OC differentiation was inhibited by EGCG by modulating mitophagy through AKT and p38MAPK pathways. Furthermore, in silico analysis revealed that the binding of RANK and RANKL was blocked by EGCG. Overall, we defined the mechanisms of osteoclastogenesis during arthritis for developing a new therapy using a natural compound besides the existing therapeutics.
Endothelial deletion of TBK1 contributes to BRB dysfunction via CXCR4 phosphorylation suppression
Authors: Zhao Bowen , Ni Yueqi , Zhang Hong , Zhao Yin , Li Lu 
Published: October 2022

AbstractBlood-retinal barrier (BRB) dysfunction has been recognized as an early pathological feature in common eye diseases that cause blindness. The breakdown of endothelial cell-to-cell junctions is the main reason for BRB dysfunction, yet our understanding of junctional modulation remains limited. Here, we demonstrated that endothelial-specific deletion of TBK1 (Tbk1ΔEC) disrupted retinal vascular development, and induced vascular leakage. LC-MS/MS proteomic analysis was used to identify candidate substrates of TBK1. We found that TBK1 interacted with CXCR4, and the phosphorylation level of CXCR4-Serine 355 (Ser355) was decreased inTbk1ΔECretina samples. Furthermore, TBK1-mediated phosphorylation of CXCR4 at Ser355 played an indispensable role in maintaining endothelial junctions. Interestingly, we also detected an increased expression of TBK1 in diabetic retinopathy samples, which suggested an association between TBK1 and the disease. Taken together, these results provided insight into the mechanisms involved in the regulation of endothelial cell-to-cell junctions via TBK1-dependent CXCR4 phosphorylation.
Dearomatization of aromatic asmic isocyanides to complex cyclohexadienes
Authors: Altundas Bilal , Alwedi Embarek , Song Zhihui , Gogoi Achyut Ranjan , Dykstra Ryan , Gutierrez Osvaldo , Fleming Fraser F. 
Published: October 2022

AbstractA dearomatization-dislocation-coupling cascade rapidly transforms aromatic isocyanides into highly functionalized cyclohexadienes. The facile cascade installs an exceptional degree of molecular complexity: three carbon-carbon bonds, two quaternary stereocenters, and three orthogonal functionalities, a cyclohexadiene, a nitrile, and an isocyanide. The tolerance of arylisocyanides makes the method among the mildest dearomatizations ever reported, typically occurring within minutes at −78 °C. Experimental and computational analyses implicate an electron transfer-initiated mechanism involving an unprecedented isocyanide rearrangement followed by radical-radical anion coupling. The dearomatization is fast, proceeds via a complex cascade mechanism supported by experimental and computational insight, and provides complex, synthetically valuable cyclohexadienes.
Improving public support for climate action through multilateralism
Authors: Bechtel Michael M. , Scheve Kenneth F. , van Lieshout Elisabeth 
Published: October 2022

AbstractFor decades, policymakers have been attempting to negotiate multilateral climate agreements. One of the motivations for securing cooperation among multiple states is the belief that the public will be more supportive of adopting costly climate policies if other countries do so, both because this makes it more likely that important sustainability goals will be reached and because those efforts resonate with widely held fairness norms. However, some recent research suggests that public approval of climate action is independent of the policy choices made by other countries. Here, we present two different experimental studies fielded in multiple countries showing that multilateralism significantly increases public approval of costly climate action. Multilateralism makes climate policy more appealing by improving effectiveness beliefs and the policy’s perceived fairness. Pursuing climate action within a multilateral setting does not only promise improved policy impacts, but may also generate higher levels of public support. Preregistration: This study has been pre-registered at AEA RCT Registry under #AEARCTR-0004090.
Nebulized fusion inhibitory peptide protects cynomolgus macaques from measles virus infection
Authors: Reynard Olivier , Gonzalez Claudia , Dumont Claire , Iampietro Mathieu , Ferren Marion , Le Guellec Sandrine , Laurie Lajoie , Mathieu Cyrille , Carpentier Gabrielle , Roseau Georges , Bovier Francesca T. , Zhu Yun , Le Pennec Deborah , Montharu Jérome , Addetia Amin , Greninger Alexander L. , Alabi Christopher A. , Brisebard Elise , Moscona Anne , Vecellio Laurent , Porotto Matteo , Horvat Branka 
Published: October 2022

AbstractMeasles is the most contagious airborne viral infection and the leading cause of child death among vaccine-preventable diseases. We show here that aerosolized lipopeptide fusion inhibitor, derived from heptad-repeat regions of the measles virus (MeV) fusion protein, blocks respiratory MeV infection in a non-human primate model, the cynomolgus macaque. We use a custom-designed mesh nebulizer to ensure efficient aerosol delivery of peptide to the respiratory tract and demonstrate the absence of adverse effects and lung pathology in macaques. The nebulized peptide efficiently prevents MeV infection, resulting in the complete absence of MeV RNA, MeV-infected cells, and MeV-specific humoral responses in treated animals. This strategy provides an additional means to fight against respiratory infection in non-vaccinated people, that can be readily translated to human trials. It presents a proof-of-concept for the aerosol delivery of fusion inhibitory peptides to protect against measles and other airborne viruses, including SARS-CoV-2, in case of high-risk exposure.
A doxycycline- and light-inducible Cre recombinase mouse model for optogenetic genome editing
Authors: Vizoso Miguel , E. J. Pritchard Colin , Bombardelli Lorenzo , van den Broek Bram , Krimpenfort Paul , Beijersbergen Roderick L. , Jalink Kees , van Rheenen Jacco 
Published: October 2022

AbstractThe experimental need to engineer the genome both in time and space, has led to the development of several photoactivatable Cre recombinase systems. However, the combination of inefficient and non-intentional background recombination has prevented thus far the wide application of these systems in biological and biomedical research. Here, we engineer an optimized photoactivatable Cre recombinase system that we refer to as doxycycline- and light-inducible Cre recombinase (DiLiCre). Following extensive characterization in cancer cell and organoid systems, we generate a DiLiCre mouse line, and illustrated the biological applicability of DiLiCre for light-induced mutagenesis in vivo and positional cell-tracing by intravital microscopy. These experiments illustrate how newly formed HrasV12 mutant cells follow an unnatural movement towards the interfollicular dermis. Together, we develop an efficient photoactivatable Cre recombinase mouse model and illustrate how this model is a powerful genome-editing tool for biological and biomedical research.
Non-classical correlations over 1250 modes between telecom photons and 979-nm photons stored in 171Yb3+:Y2SiO5
Authors: Businger M. , Nicolas L. , Mejia T. Sanchez , Ferrier A. , Goldner P. , Afzelius Mikael 
Published: October 2022

AbstractQuantum repeaters based on heralded entanglement require quantum nodes that are able to generate multimode quantum correlations between memories and telecommunication photons. The communication rate scales linearly with the number of modes, yet highly multimode quantum storage remains challenging. In this work, we demonstrate an atomic frequency comb quantum memory with a time-domain mode capacity of 1250 modes and a bandwidth of 100 MHz. The memory is based on a Y2SiO5 crystal doped with 171Yb3+ ions, with a memory wavelength of 979 nm. The memory is interfaced with a source of non-degenerate photon pairs at 979 and 1550 nm, bandwidth-matched to the quantum memory. We obtain strong non-classical second-order cross correlations over all modes, for storage times of up to 25 μs. The telecommunication photons propagated through 5 km of fiber before the release of the memory photons, a key capability for quantum repeaters based on heralded entanglement and feed-forward operations. Building on this experiment should allow distribution of entanglement between remote quantum nodes, with enhanced rates owing to the high multimode capacity.
A toxin-deformation dependent inhibition mechanism in the T7SS toxin-antitoxin system of Gram-positive bacteria
Authors: Wang Yongjin , Zhou Yang , Shi Chaowei , Liu Jiacong , Lv Guohua , Huang Huisi , Li Shengrong , Duan Liping , Zheng Xinyi , Liu Yue , Zhou Haibo , Wang Yonghua , Li Zhengqiu , Ding Ke , Sun Pinghua , Huang Yun , Lu Xiaoyun , Zhang Zhi-Min 
Published: October 2022

AbstractToxin EsaD secreted by some S. aureus strains through the type VII secretion system (T7SS) specifically kills those strains lacking the antitoxin EsaG. Here we report the structures of EsaG, the nuclease domain of EsaD and their complex, which together reveal an inhibition mechanism that relies on significant conformational change of the toxin. To inhibit EsaD, EsaG breaks the nuclease domain of EsaD protein into two independent fragments that, in turn, sandwich EsaG. The originally well-folded ββα-metal finger connecting the two fragments is stretched to become a disordered loop, leading to disruption of the catalytic site of EsaD and loss of nuclease activity. This mechanism is distinct from that of the other Type II toxin-antitoxin systems, which utilize an intrinsically disordered region on the antitoxins to cover the active site of the toxins. This study paves the way for developing therapeutic approaches targeting this antagonism.
The emergence and development of behavioral individuality in clonal fish
Authors: Laskowski Kate L. , Bierbach David , Jolles Jolle W. , Doran Carolina , Wolf Max 
Published: October 2022

AbstractBehavioral individuality is a ubiquitous phenomenon in animal populations, yet the origins and developmental trajectories of individuality, especially very early in life, are still a black box. Using a high-resolution tracking system, we mapped the behavioral trajectories of genetically identical fish (Poecilia formosa), separated immediately after birth into identical environments, over the first 10 weeks of their life at 3 s resolution. We find that (i) strong behavioral individuality is present at the very first day after birth, (ii) behavioral differences at day 1 of life predict behavior up to at least 10 weeks later, and (iii) patterns of individuality strengthen gradually over developmental time. Our results establish a null model for how behavioral individuality can develop in the absence of genetic and environmental variation and provide experimental evidence that later-in-life individuality can be strongly shaped by factors pre-dating birth like maternal provisioning, epigenetics and pre-birth developmental stochasticity.
Structures of the CcmABCD heme release complex at multiple states
Authors: Li Jiao , Zheng Wan , Gu Ming , Han Long , Luo Yanmei , Yu Koukou , Sun Mengxin , Zong Yuliang , Ma Xiuxiu , Liu Bing , Lowder Ethan P. , Mendez Deanna L. , Kranz Robert G. , Zhang Kai , Zhu Jiapeng 
Published: October 2022

AbstractCytochromes c use heme as a cofactor to carry electrons in respiration and photosynthesis. The cytochrome c maturation system I, consisting of eight membrane proteins (CcmABCDEFGH), results in the attachment of heme to cysteine residues of cytochrome c proteins. Since all c-type cytochromes are periplasmic, heme is first transported to a periplasmic heme chaperone, CcmE. A large membrane complex, CcmABCD has been proposed to carry out this transport and linkage to CcmE, yet the structural basis and mechanisms underlying the process are unknown. We describe high resolution cryo-EM structures of CcmABCD in an unbound form, in complex with inhibitor AMP-PNP, and in complex with ATP and heme. We locate the ATP-binding site in CcmA and the heme-binding site in CcmC. Based on our structures combined with functional studies, we propose a hypothetic model of heme trafficking, heme transfer to CcmE, and ATP-dependent release of holoCcmE from CcmABCD. CcmABCD represents an ABC transporter complex using the energy of ATP hydrolysis for the transfer of heme from one binding partner (CcmC) to another (CcmE).
Natural variation of Dt2 determines branching in soybean
Authors: Liang Qianjin , Chen Liyu , Yang Xia , Yang Hui , Liu Shulin , Kou Kun , Fan Lei , Zhang Zhifang , Duan Zongbiao , Yuan Yaqin , Liang Shan , Liu Yucheng , Lu Xingtong , Zhou Guoan , Zhang Min , Kong Fanjiang , Tian Zhixi 
Published: October 2022

AbstractShoot branching is fundamentally important in determining soybean yield. Here, through genome-wide association study, we identify one predominant association locus on chromosome 18 that confers soybean branch number in the natural population. Further analyses determine that Dt2 is the corresponding gene and the natural variations in Dt2 result in significant differential transcriptional levels between the two major haplotypes. Functional characterization reveals that Dt2 interacts with GmAgl22 and GmSoc1a to physically bind to the promoters of GmAp1a and GmAp1d and to activate their transcription. Population genetic investigation show that the genetic differentiation of Dt2 display significant geographic structure. Our study provides a predominant gene for soybean branch number and may facilitate the breeding of high-yield soybean varieties.
The gate injection-based field-effect synapse transistor with linear conductance update for online training
Authors: Seo Seokho , Kim Beomjin , Kim Donghoon , Park Seungwoo , Kim Tae Ryong , Park Junkyu , Jeong Hakcheon , Park See-On , Park Taehoon , Shin Hyeok , Kim Myung-Su , Choi Yang-Kyu , Choi Shinhyun 
Published: October 2022

AbstractNeuromorphic computing, an alternative for von Neumann architecture, requires synapse devices where the data can be stored and computed in the same place. The three-terminal synapse device is attractive for neuromorphic computing due to its high stability and controllability. However, high nonlinearity on weight update, low dynamic range, and incompatibility with conventional CMOS systems have been reported as obstacles for large-scale crossbar arrays. Here, we propose the CMOS compatible gate injection-based field-effect transistor employing thermionic emission to enhance the linear conductance update. The dependence of the linearity on the conduction mechanism is examined by inserting an interfacial layer in the gate stack. To demonstrate the conduction mechanism, the gate current measurement is conducted under varying temperatures. The device based on thermionic emission achieves superior synaptic characteristics, leading to high performance on the artificial neural network simulation as 93.17% on the MNIST dataset.
Synthesis of N-acyl sulfenamides via copper catalysis and their use as S-sulfenylating reagents of thiols
Authors: Bai Ziqian , Zhu Shiyang , Hu Yiyao , Yang Peng , Chu Xin , He Gang , Wang Hao , Chen Gong 
Published: October 2022

AbstractSulfur–heteroatom bonds such as S–S and S–N are found in a variety of natural products and often play important roles in biological processes. Despite their widespread applications, the synthesis of sulfenamides, which feature S–N bonds that may be cleaved under mild conditions, remains underdeveloped. Here, we report a method for synthesis ofN-acyl sulfenamides via copper-catalyzed nitrene-mediatedS-amidation reaction of thiols with dioxazolones. This method is efficient, convenient, and broadly applicable. Moreover, the resultingN-acetyl sulfenamides are highly effectiveS-sulfenylation reagents for the synthesis of unsymmetrical disulfides under mild conditions. TheS-sulfenylation protocol enables facile access to sterically demanding disulfides that are difficult to synthesize by other means.