bluuebunny/crossref_metadata_2025_split huggingface dataset:
NIMA-related kinase 9 regulates the phosphorylation of the essential myosin light chain in the heart
Authors: Müller Marion , Eghbalian Rose , Boeckel Jes-Niels , Frese Karen S. , Haas Jan , Kayvanpour Elham , Sedaghat-Hamedani Farbod , Lackner Maximilian K. , Tugrul Oguz F. , Ruppert Thomas , Tappu Rewati , Martins Bordalo Diana , Kneuer Jasmin M. , Piekarek Annika , Herch Sabine , Schudy Sarah , Keller Andreas , Grammes Nadja , Bischof Cornelius , Klinke Anna , Cardoso-Moreira Margarida , Kaessmann Henrik , Katus Hugo A. , Frey Norbert , Steinmetz Lars M. , Meder Benjamin 
Published: October 2022

AbstractTo adapt to changing hemodynamic demands, regulatory mechanisms modulate actin-myosin-kinetics by calcium-dependent and -independent mechanisms. We investigate the posttranslational modification of human essential myosin light chain (ELC) and identify NIMA-related kinase 9 (NEK9) to interact with ELC. NEK9 is highly expressed in the heart and the interaction with ELC is calcium-dependent. Silencing of NEK9 results in blunting of calcium-dependent ELC-phosphorylation. CRISPR/Cas9-mediated disruption of NEK9 leads to cardiomyopathy in zebrafish. Binding to ELC is mediated via the protein kinase domain of NEK9. A causal relationship between NEK9 activity and ELC-phosphorylation is demonstrated by genetic sensitizing in-vivo. Finally, we observe significantly upregulated ELC-phosphorylation in dilated cardiomyopathy patients and provide a unique map of human ELC-phosphorylation-sites. In summary, NEK9-mediated ELC-phosphorylation is a calcium-dependent regulatory system mediating cardiac contraction and inotropy.
Tuning the many-body interactions in a helical Luttinger liquid
Authors: Jia Junxiang , Marcellina Elizabeth , Das Anirban , Lodge Michael S. , Wang BaoKai , Ho Duc-Quan , Biswas Riddhi , Pham Tuan Anh , Tao Wei , Huang Cheng-Yi , Lin Hsin , Bansil Arun , Mukherjee Shantanu , Weber Bent 
Published: October 2022

AbstractIn one-dimensional (1D) systems, electronic interactions lead to a breakdown of Fermi liquid theory and the formation of a Tomonaga-Luttinger Liquid (TLL). The strength of its many-body correlations can be quantified by a single dimensionless parameter, the Luttinger parameter K, characterising the competition between the electrons’ kinetic and electrostatic energies. Recently, signatures of a TLL have been reported for the topological edge states of quantum spin Hall (QSH) insulators, strictly 1D electronic structures with linear (Dirac) dispersion and spin-momentum locking. Here we show that the many-body interactions in such helical Luttinger Liquid can be effectively controlled by the edge state’s dielectric environment. This is reflected in a tunability of the Luttinger parameter K, distinct on different edges of the crystal, and extracted to high accuracy from the statistics of tunnelling spectra at tens of tunnelling points. The interplay of topology and many-body correlations in 1D helical systems has been suggested as a potential avenue towards realising non-Abelian parafermions.
A BDNF-TrkB autocrine loop enhances senescent cell viability
Authors: Anerillas Carlos , Herman Allison B. , Munk Rachel , Garrido Amanda , Lam Kwan-Wood Gabriel , Payea Matthew J. , Rossi Martina , Tsitsipatis Dimitrios , Martindale Jennifer L. , Piao Yulan , Mazan-Mamczarz Krystyna , Fan Jinshui , Cui Chang-Yi , De Supriyo , Abdelmohsen Kotb , de Cabo Rafael , Gorospe Myriam 
Published: October 2022

AbstractCellular senescence is characterized by cell cycle arrest, resistance to apoptosis, and a senescence-associated secretory phenotype (SASP) whereby cells secrete pro-inflammatory and tissue-remodeling factors. Given that the SASP exacerbates age-associated pathologies, some aging interventions aim at selectively eliminating senescent cells. In this study, a drug library screen uncovered TrkB (NTRK2) inhibitors capable of triggering apoptosis of several senescent, but not proliferating, human cells. Senescent cells expressed high levels of TrkB, which supported senescent cell viability, and secreted the TrkB ligand BDNF. The reduced viability of senescent cells after ablating BDNF signaling suggested an autocrine function for TrkB and BDNF, which activated ERK5 and elevated BCL2L2 levels, favoring senescent cell survival. Treatment with TrkB inhibitors reduced the accumulation of senescent cells in aged mouse organs. We propose that the activation of TrkB by SASP factor BDNF promotes cell survival and could be exploited therapeutically to reduce the senescent-cell burden.
Direct observation of photoinduced carrier blocking in mixed-dimensional 2D/3D perovskites and the origin
Authors: Yu Dejian , Cao Fei , Liao Jinfeng , Wang Bingzhe , Su Chenliang , Xing Guichuan 
Published: October 2022

AbstractMixed-dimensional 2D/3D halide perovskite solar cells promise high stability but practically deliver poor power conversion efficiency, and the 2D HP component has been held as the culprit because its intrinsic downsides (ill charge conductivity, wider bandgap, and strong exciton binding) were intuitively deemed to hinder carrier transport. Herein, we show that the 2D HP fragments, in fact, allow free migration of carriers in darkness but only block the carrier transport under illumination. While surely limiting the photovoltaic performance, such photoinduced carrier blocking effect is unexplainable by the traditional understanding above but is found to stem from the trap-filling-enhanced built-in potential of the 2D/3D HP interface. By parsing the depth-profile nanoscopic phase arrangement of the mixed-dimensional 2D/3D HP film for solar cells and revealing a photoinduced potential barrier up to several hundred meV, we further elucidate how the photoinduced carrier blocking mechanism jeopardizes the short-circuit current and fill factor.
Exhumation and tectonic history of inaccessible subglacial interior East Antarctica from thermochronology on glacial erratics
Authors: Fitzgerald Paul G. , Goodge John W. 
Published: October 2022

AbstractThe geology, tectonic history and landscape evolution of ice-covered East Antarctica are the least known of any continent. Lithic boulders eroded from the continental interior and deposited in glacial moraines flanking the Transantarctic Mountains provide rare constraints on the geological history of central interior East Antarctica. Crystallization ages and ice velocities indicate these glacial erratics are not sourced locally from the Transantarctic Mountains but rather originate from the continental interior, possibly as far inland as the enigmatic Gamburtsev Subglacial Mountains. We apply low-temperature thermochronology to these boulders, including multi-kinetic inverse thermal modeling, to constrain a multi-stage episodic exhumation history. Cambro-Ordovician and Jurassic rapid-cooling episodes correlate with significant exhumation events accompanying Pan-African convergence and Gondwanan supercontinent rifting, respectively. Here we show that while Cretaceous rapid cooling overlaps temporally with Transantarctic Mountains formation, a lack of discrete younger rapid-cooling pulses precludes significant Cenozoic tectonic or glacial exhumation of central interior East Antarctica.
Synthetic biology-instructed transdermal microneedle patch for traceable photodynamic therapy
Authors: He Gang , Li Yashi , Younis Muhammad Rizwan , Fu Lian-Hua , He Ting , Lei Shan , Lin Jing , Huang Peng 
Published: October 2022

Abstract5-Aminolevulinic acid-based photodynamic therapy heavily depends on the biological transformation efficiency of 5-aminolevulinic acid to protoporphyrin IX, while the lack of an effective delivery system and imaging navigation are major hurdles in improving the accumulation of protoporphyrin IX and optimizing therapeutic parameters. Herein, we leverage a synthetic biology approach to construct a transdermal theranostic microneedle patch integrated with 5-aminolevulinic acid and catalase co-loaded tumor acidity-responsive copper-doped calcium phosphate nanoparticles for efficient 5-aminolevulinic acid-based photodynamic therapy by maximizing the enrichment of intratumoral protoporphyrin IX. We show that continuous oxygen generation by catalase in vivo reverses tumor hypoxia, enhances protoporphyrin IX accumulation by blocking protoporphyrin IX efflux (downregulating hypoxia-inducible factor-1α and ferrochelatase) and upregulates protoporphyrin IX biosynthesis (providing exogenous 5-aminolevulinic acid and upregulating ALA-synthetase). In vivo fluorescence/photoacoustic duplex imaging can monitor intratumoral oxygen saturation and protoporphyrin IX metabolic kinetics simultaneously. This approach thus facilitates the optimization of therapeutic parameters for different cancers to realize Ca2+/Cu2+-interferences-enhanced repeatable photodynamic therapy, making this theranostic patch promising for clinical practice.
Structural insight into the ligand binding mechanism of aryl hydrocarbon receptor
Authors: Dai Shuyan , Qu Lingzhi , Li Jun , Zhang Ye , Jiang Longying , Wei Hudie , Guo Ming , Chen Xiaojuan , Chen Yongheng 
Published: October 2022

AbstractThe aryl hydrocarbon receptor (AHR), a member of the basic helix–loop–helix (bHLH) Per–Arnt–Sim (PAS) family of transcription factors, plays important roles in regulating xenobiotic metabolism, cellular differentiation, stem cell maintenance, as well as immunity. More recently, AHR has gained significant interest as a drug target for the development of novel cancer immunotherapy drugs. Detailed understanding of AHR-ligand binding has been hampered for decades by the lack of a three-dimensional structure of the AHR PAS-B domain. Here, we present multiple crystal structures of the Drosophila AHR PAS-B domain, including its apo, ligand-bound, and AHR nuclear translocator (ARNT) PAS-B-bound forms. Together with biochemical and cellular assays, our data reveal structural features of the AHR PAS-B domain, provide insights into the mechanism of AHR ligand binding, and provide the structural basis for the future development of AHR-targeted therapeutics.
Flexible learning of quantum states with generative query neural networks
Authors: Zhu Yan , Wu Ya-Dong , Bai Ge , Wang Dong-Sheng , Wang Yuexuan , Chiribella Giulio 
Published: October 2022

AbstractDeep neural networks are a powerful tool for characterizing quantum states. Existing networks are typically trained with experimental data gathered from the quantum state that needs to be characterized. But is it possible to train a neural network offline, on a different set of states? Here we introduce a network that can be trained with classically simulated data from a fiducial set of states and measurements, and can later be used to characterize quantum states that share structural similarities with the fiducial states. With little guidance of quantum physics, the network builds its own data-driven representation of a quantum state, and then uses it to predict the outcome statistics of quantum measurements that have not been performed yet. The state representations produced by the network can also be used for tasks beyond the prediction of outcome statistics, including clustering of quantum states and identification of different phases of matter.
Central role of Prominin-1 in lipid rafts during liver regeneration
Authors: Bahn Myeong-Suk , Yu Dong-Min , Lee Myoungwoo , Jo Sung-Je , Lee Ji-Won , Kim Ho-Chul , Lee Hyun , Kim Hong Lim , Kim Arum , Hong Jeong-Ho , Kim Jun Seok , Koo Seung-Hoi , Lee Jae-Seon , Ko Young-Gyu 
Published: October 2022

AbstractProminin-1, a lipid raft protein, is required for maintaining cancer stem cell properties in hepatocarcinoma cell lines, but its physiological roles in the liver have not been well studied. Here, we investigate the role of Prominin-1 in lipid rafts during liver regeneration and show that expression of Prominin-1 increases after 2/3 partial hepatectomy or CCl4 injection. Hepatocyte proliferation and liver regeneration are attenuated in liver-specific Prominin-1 knockout mice compared to wild-type mice. Detailed mechanistic studies reveal that Prominin-1 interacts with the interleukin-6 signal transducer glycoprotein 130, confining it to lipid rafts so that STAT3 signaling by IL-6 is effectively activated. The overexpression of the glycosylphosphatidylinsositol-anchored first extracellular domain of Prominin-1, which is the domain that binds to GP130, rescued the proliferation of hepatocytes and liver regeneration in liver-specific Prominin-1 knockout mice. In summary, Prominin-1 is upregulated in hepatocytes during liver regeneration where it recruits GP130 into lipid rafts and activates the IL6-GP130-STAT3 axis, suggesting that Prominin-1 might be a promising target for therapeutic applications in liver transplantation.
Cryo-EM structures of thermostabilized prestin provide mechanistic insights underlying outer hair cell electromotility
Authors: Futamata Haon , Fukuda Masahiro , Umeda Rie , Yamashita Keitaro , Tomita Atsuhiro , Takahashi Satoe , Shikakura Takafumi , Hayashi Shigehiko , Kusakizako Tsukasa , Nishizawa Tomohiro , Homma Kazuaki , Nureki Osamu 
Published: October 2022

AbstractOuter hair cell elecromotility, driven by prestin, is essential for mammalian cochlear amplification. Here, we report the cryo-EM structures of thermostabilized prestin (PresTS), complexed with chloride, sulfate, or salicylate at 3.52-3.63 Å resolutions. The central positively-charged cavity allows flexible binding of various anion species, which likely accounts for the known distinct modulations of nonlinear capacitance (NLC) by different anions. Comparisons of these PresTS structures with recent prestin structures suggest rigid-body movement between the core and gate domains, and provide mechanistic insights into prestin inhibition by salicylate. Mutations at the dimeric interface severely diminished NLC, suggesting that stabilization of the gate domain facilitates core domain movement, thereby contributing to the expression of NLC. These findings advance our understanding of the molecular mechanism underlying mammalian cochlear amplification.
Force-triggered rapid microstructure growth on hydrogel surface for on-demand functions
Authors: Mu Qifeng , Cui Kunpeng , Wang Zhi Jian , Matsuda Takahiro , Cui Wei , Kato Hinako , Namiki Shotaro , Yamazaki Tomoko , Frauenlob Martin , Nonoyama Takayuki , Tsuda Masumi , Tanaka Shinya , Nakajima Tasuku , Gong Jian Ping 
Published: October 2022

AbstractLiving organisms share the ability to grow various microstructures on their surface to achieve functions. Here we present a force stamp method to grow microstructures on the surface of hydrogels based on a force-triggered polymerisation mechanism of double-network hydrogels. This method allows fast spatial modulation of the morphology and chemistry of the hydrogel surface within seconds for on-demand functions. We demonstrate the oriented growth of cells and directional transportation of water droplets on the engineered hydrogel surfaces. This force-triggered method to chemically engineer the hydrogel surfaces provides a new tool in addition to the conventional methods using light or heat, and will promote the wide application of hydrogels in various fields.
Myogenic tissue nanotransfection improves muscle torque recovery following volumetric muscle loss
Authors: Clark Andrew , Ghatak Subhadip , Guda Poornachander Reddy , El Masry Mohamed S. , Xuan Yi , Sato Amy Y. , Bellido Teresita , Sen Chandan K. 
Published: October 2022

AbstractThis work rests on our non-viral tissue nanotransfection (TNT) platform to deliver MyoD (TNTMyoD) to injured tissue in vivo. TNTMyoD was performed on skin and successfully induced expression of myogenic factors. TNTMyoD was then used as a therapy 7 days following volumetric muscle loss (VML) of rat tibialis anterior and rescued muscle function. TNTMyoD is promising as VML intervention.
CCRT and aerobic exercise: a randomised controlled study of processing speed, cognitive flexibility, and serum BDNF expression in schizophrenia
Authors: Dai Yuanyuan , Ding Hongyan , Lu Xiaozi , Wu Xiumei , Xu Chunhua , Jiang Tingting , Ming Liang , Xia Zhong , Song Chuanfu , Shen Hongxian , Hao Wei , Huang Shucai 
Published: October 2022

AbstractComputerised cognitive remediation therapy (CCRT) and aerobic exercise are often used to rehabilitate social functioning in patients with schizophrenia. However, there is limited knowledge regarding the effects of CCRT combined with aerobic exercise on cognitive function and brain-derived neurotrophic factor (BDNF) levels in patients with schizophrenia and cognitive impairment. Ninety-six patients with schizophrenia and cognitive impairment were included in this study and randomly divided into control, aerobic exercise (AE), and CCRT combined with aerobic exercise (CAE) groups. Changes in processing speed and cognitive flexibility at week 8 were evaluated as primary and secondary cognitive outcomes using the Trail Making Test: Part A, the Brief Assessment of Cognition in Schizophrenia: Symbol Coding Test, and the Stroop Colour-Word Test. Positive and Negative Syndrome Scale (PANSS) scores and serum BDNF expression were determined as other secondary outcomes. The CAE group showed significantly better performance in terms of changes in processing speed and cognitive flexibility than the control and AE groups at week 8 (p < 0.05); however, no significant improvements in processing speed and cognitive flexibility were found between the control and AE groups. The CAE group showed significant improvements in the PANSS negative symptoms than the control group at week 8 (p < 0.05), but the AE group showed no significant difference in the changes of PANSS negative symptoms when compared with the other two groups. The CAE group and AE group showed a greater increase in serum BDNF levels than the control group (p < 0.01), but there was no significant difference in serum BDNF expression between the CAE group and AE group. In conclusion, 8-week CCRT combined with aerobic exercise may improve some cognitive performance and negative symptoms in patients with schizophrenia. Aerobic exercise may have an immediate effect on serum BDNF levels rather than cognitive function.
IL-17D-induced inhibition of DDX5 expression in keratinocytes amplifies IL-36R-mediated skin inflammation
Authors: Ni Xinhui , Xu Yi , Wang Wang , Kong Baida , Ouyang Jian , Chen Jiwei , Yan Man , Wu Yawei , Chen Qi , Wang Xinxin , Li Hongquan , Gao Xiaoguang , Guo Hongquan , Cui Lian , Chen Zeyu , Shi Yuling , Zhu Ronghui , Li Wei , Shi Tieliu , Wang Lin-Fa , Huang Jinling , Dong Chen , Lai Yuping 
Published: October 2022

AbstractAberrant RNA splicing in keratinocytes drives inflammatory skin disorders. In the present study, we found that the RNA helicase DDX5 was downregulated in keratinocytes from the inflammatory skin lesions in patients with atopic dermatitis and psoriasis, and that mice with keratinocyte-specific deletion of Ddx5 (Ddx5∆KC) were more susceptible to cutaneous inflammation. Inhibition of DDX5 expression in keratinocytes was induced by the cytokine interleukin (IL)-17D through activation of the CD93–p38 MAPK–AKT–SMAD2/3 signaling pathway and led to pre-messenger RNA splicing events that favored the production of membrane-bound, intact IL-36 receptor (IL-36R) at the expense of soluble IL-36R (sIL-36R) and to the selective amplification of IL-36R-mediated inflammatory responses and cutaneous inflammation. Restoration of sIL-36R in Ddx5∆KC mice with experimental atopic dermatitis or psoriasis suppressed skin inflammation and alleviated the disease phenotypes. These findings indicate that IL-17D modulation of DDX5 expression controls inflammation in keratinocytes during inflammatory skin diseases.
Web and social media searches highlight menstrual irregularities as a global concern in COVID-19 vaccinations
Authors: Katz Ariel , Tepper Yoav , Birk Ohad , Eran Alal 
Published: October 2022

AbstractDelineation of public concerns that prevent vaccine compliance is a major step in generating assurances and enhancing the success of COVID-19 prevention programs. We therefore sought to identify public concerns associated with COVID-19 vaccines, as reflected by web and social media searches, with a focus on menstrual irregularities. We used trajectory analyses of web and social media search data in combination with global COVID-19 data to reveal time-dependent correlations between vaccination rates and the relative volume of vaccine and period related searches. A surge of period and vaccine related Google searches followed the introduction of Covid vaccines around the world, and the commencement of vaccination programs in English speaking countries and across the United States. The relative volume of searches such as “Covid vaccine menstrual irregularities”, “Covid vaccine menstrual period”, “Pfizer vaccine menstruation”, and “Moderna vaccine menstruation” was each significantly correlated with vaccination rates (Spearman r = 0.42–0.88, P = 4.33 × 10–34–1.55 × 10–5), and significantly different before and after the introduction of Covid vaccines (Mann–Whitney P = 2.00 × 10–21–7.10 × 10–20). TikTok users were more engaged in period problems in 2021 than ever before. International, national, and state-level correlations between COVID-19 vaccinations and online activity demonstrate a global major concern of vaccine-related menstrual irregularities. Whether it is a potential side effect or an unfounded worry, monitoring of web and social media activity could reveal the public perception of COVID-19 prevention efforts, which could then be directly addressed and translated into insightful public health strategies.
Multi-species occupancy modeling suggests interspecific interaction among the three ungulate species
Authors: Singh Hemant , Sharief Amira , Joshi Bheem Dutt , Kumar Vineet , Mukherjee Tanoy , Chandra Kailash , Bhardwaj Nitin , Thakur Mukesh , Sharma Lalit Kumar 
Published: October 2022

AbstractSpecies with sympatric distribution influence ecosystem dynamics and are impacted by the presence of other co-existing species. Assessing the coexistence and the role of interspecific interactions with the landscape variables is necessary to know the species co-occurrence in space. In the Indian Himalayan region, such studies are completely lacking due to limited efforts being made, mainly because of complex terrains and inaccessible landscape features. We used camera trapping and sign survey in a multi-species occupancy framework to understand the influence of environmental variables on occupancy and detection probability of species-specific and pair-wise interaction of the three ungulates in Uttarkashi. Our results concluded that individual species' occupancy probabilities were related both to the environmental variables and the presence or absence of other interacting species. Our top model showed evidence of interspecific interaction among species pairs, and the occupancy probability of species one varied in the presence or absence of another species. The overall activity patterns were similar among all the three species and were found active throughout the day. The activity overlap between sambar—barking deer (Dhat1 value = 0.85) was considerably higher than barking deer—goral (Dhat1 value = 0.78). The findings of the present study will be useful for the conservation and management of ungulates in the Indian Himalayan and adjoining regions.