bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bone morphogenetic protein 1.3 inhibition decreases scar formation and supports cardiomyocyte survival after myocardial infarction
Authors: Vukicevic Slobodan , Colliva Andrea , Kufner Vera , Martinelli Valentina , Moimas Silvia , Vodret Simone , Rumenovic Viktorija , Milosevic Milan , Brkljacic Boris , Delic-Brkljacic Diana , Correa Ricardo , Giacca Mauro , Maglione Manuel , Bordukalo-Niksic Tatjana , Dumic-Cule Ivo , Zacchigna Serena 
Published: January 2022

AbstractDespite the high prevalence of ischemic heart diseases worldwide, no antibody-based treatment currently exists. Starting from the evidence that a specific isoform of the Bone Morphogenetic Protein 1 (BMP1.3) is particularly elevated in both patients and animal models of myocardial infarction, here we assess whether its inhibition by a specific monoclonal antibody reduces cardiac fibrosis. We find that this treatment reduces collagen deposition and cross-linking, paralleled by enhanced cardiomyocyte survival, both in vivo and in primary cultures of cardiac cells. Mechanistically, we show that the anti-BMP1.3 monoclonal antibody inhibits Transforming Growth Factor β pathway, thus reducing myofibroblast activation and inducing cardioprotection through BMP5. Collectively, these data support the therapeutic use of anti-BMP1.3 antibodies to prevent cardiomyocyte apoptosis, reduce collagen deposition and preserve cardiac function after ischemia.
Polyply; a python suite for facilitating simulations of macromolecules and nanomaterials
Authors: Grünewald Fabian , Alessandri Riccardo , Kroon Peter C. , Monticelli Luca , Souza Paulo C. T. , Marrink Siewert J. 
Published: January 2022

AbstractMolecular dynamics simulations play an increasingly important role in the rational design of (nano)-materials and in the study of biomacromolecules. However, generating input files and realistic starting coordinates for these simulations is a major bottleneck, especially for high throughput protocols and for complex multi-component systems. To eliminate this bottleneck, we present the polyply software suite that provides 1) a multi-scale graph matching algorithm designed to generate parameters quickly and for arbitrarily complex polymeric topologies, and 2) a generic multi-scale random walk protocol capable of setting up complex systems efficiently and independent of the target force-field or model resolution. We benchmark quality and performance of the approach by creating realistic coordinates for polymer melt simulations, single-stranded as well as circular single-stranded DNA. We further demonstrate the power of our approach by setting up a microphase-separated block copolymer system, and by generating a liquid-liquid phase separated system inside a lipid vesicle.
Mechanical force promotes dimethylarginine dimethylaminohydrolase 1-mediated hydrolysis of the metabolite asymmetric dimethylarginine to enhance bone formation
Authors: Xie Ziang , Hou Lei , Shen Shuying , Wu Yizheng , Wang Jian , Jie Zhiwei , Zhao Xiangde , Li Xiang , Zhang Xuyang , Chen Junxin , Xu Wenbin , Ning Lei , Ma Qingliang , Wang Shiyu , Wang Haoming , Yuan Putao , Fang Xiangqian , Qin An , Fan Shunwu 
Published: January 2022

AbstractMechanical force is critical for the development and remodeling of bone. Here we report that mechanical force regulates the production of the metabolite asymmetric dimethylarginine (ADMA) via regulating the hydrolytic enzyme dimethylarginine dimethylaminohydrolase 1 (Ddah1) expression in osteoblasts. The presence of -394 4 N del/ins polymorphism of Ddah1 and higher serum ADMA concentration are negatively associated with bone mineral density. Global or osteoblast-specific deletion of Ddah1 leads to increased ADMA level but reduced bone formation. Further molecular study unveils that mechanical stimulation enhances TAZ/SMAD4-induced Ddah1 transcription. Deletion of Ddah1 in osteoblast-lineage cells fails to respond to mechanical stimulus-associated bone formation. Taken together, the study reveals mechanical force is capable of down-regulating ADMA to enhance bone formation.
Interfacial-confined coordination to single-atom nanotherapeutics
Authors: Qin Limei , Gan Jie , Niu Dechao , Cao Yueqiang , Duan Xuezhi , Qin Xing , Zhang Hao , Jiang Zheng , Jiang Yongjun , Dai Sheng , Li Yongsheng , Shi Jianlin 
Published: January 2022

AbstractPursuing and developing effective methodologies to construct highly active catalytic sites to maximize the atomic and energy efficiency by material engineering are attractive. Relative to the tremendous researches of carbon-based single atom systems, the construction of bio-applicable single atom materials is still in its infancy. Herein, we propose a facile and general interfacial-confined coordination strategy to construct high-quality single-atom nanotherapeutic agent with Fe single atoms being anchored on defective carbon dots confined in a biocompatible mesoporous silica nanoreactor. Furthermore, the efficient energy conversion capability of silica-based Fe single atoms system has been demonstrated on the basis of the exogenous physical photo irradiation and endogenous biochemical reactive oxygen species stimulus in the confined mesoporous network. More importantly, the highest photothermal conversion efficiency with the mechanism of increased electron density and narrow bandgap of this single atom structure in defective carbon was proposed by the theoretical DFT calculations. The present methodology provides a scientific paradigm to design and develop versatile single atom nanotherapeutics with adjustable metal components and tune the corresponding reactions for safe and efficient tumor therapeutic strategy.
Climate changes modulated the history of Arctic iodine during the Last Glacial Cycle
Authors: Corella Juan Pablo , Maffezzoli Niccolo , Spolaor Andrea , Vallelonga Paul , Cuevas Carlos A. , Scoto Federico , Müller Juliane , Vinther Bo , Kjær Helle A. , Cozzi Giulio , Edwards Ross , Barbante Carlo , Saiz-Lopez Alfonso 
Published: January 2022

AbstractIodine has a significant impact on promoting the formation of new ultrafine aerosol particles and accelerating tropospheric ozone loss, thereby affecting radiative forcing and climate. Therefore, understanding the long-term natural evolution of iodine, and its coupling with climate variability, is key to adequately assess its effect on climate on centennial to millennial timescales. Here, using two Greenland ice cores (NEEM and RECAP), we report the Arctic iodine variability during the last 127,000 years. We find the highest and lowest iodine levels recorded during interglacial and glacial periods, respectively, modulated by ocean bioproductivity and sea ice dynamics. Our sub-decadal resolution measurements reveal that high frequency iodine emission variability occurred in pace with Dansgaard/Oeschger events, highlighting the rapid Arctic ocean-ice-atmosphere iodine exchange response to abrupt climate changes. Finally, we discuss if iodine levels during past warmer-than-present climate phases can serve as analogues of future scenarios under an expected ice-free Arctic Ocean. We argue that the combination of natural biogenic ocean iodine release (boosted by ongoing Arctic warming and sea ice retreat) and anthropogenic ozone-induced iodine emissions may lead to a near future scenario with the highest iodine levels of the last 127,000 years.
Latency reversal plus natural killer cells diminish HIV reservoir in vivo
Authors: Kim Jocelyn T. , Zhang Tian-Hao , Carmona Camille , Lee Bryanna , Seet Christopher S. , Kostelny Matthew , Shah Nisarg , Chen Hongying , Farrell Kylie , Soliman Mohamed S. A. , Dimapasoc Melanie , Sinani Michelle , Blanco Kenia Yazmin Reyna , Bojorquez David , Jiang Hong , Shi Yuan , Du Yushen , Komarova Natalia L. , Wodarz Dominik , Wender Paul A. , Marsden Matthew D. , Sun Ren , Zack Jerome A. 
Published: January 2022

AbstractHIV is difficult to eradicate due to the persistence of a long-lived reservoir of latently infected cells. Previous studies have shown that natural killer cells are important to inhibiting HIV infection, but it is unclear whether the administration of natural killer cells can reduce rebound viremia when anti-retroviral therapy is discontinued. Here we show the administration of allogeneic human peripheral blood natural killer cells delays viral rebound following interruption of anti-retroviral therapy in humanized mice infected with HIV-1. Utilizing genetically barcoded virus technology, we show these natural killer cells efficiently reduced viral clones rebounding from latency. Moreover, a kick and kill strategy comprised of the protein kinase C modulator and latency reversing agent SUW133 and allogeneic human peripheral blood natural killer cells during anti-retroviral therapy eliminated the viral reservoir in a subset of mice. Therefore, combinations utilizing latency reversal agents with targeted cellular killing agents may be an effective approach to eradicating the viral reservoir.
Brain-inspired global-local learning incorporated with neuromorphic computing
Authors: Wu Yujie , Zhao Rong , Zhu Jun , Chen Feng , Xu Mingkun , Li Guoqi , Song Sen , Deng Lei , Wang Guanrui , Zheng Hao , Ma Songchen , Pei Jing , Zhang Youhui , Zhao Mingguo , Shi Luping 
Published: January 2022

AbstractThere are two principle approaches for learning in artificial intelligence: error-driven global learning and neuroscience-oriented local learning. Integrating them into one network may provide complementary learning capabilities for versatile learning scenarios. At the same time, neuromorphic computing holds great promise, but still needs plenty of useful algorithms and algorithm-hardware co-designs to fully exploit its advantages. Here, we present a neuromorphic global-local synergic learning model by introducing a brain-inspired meta-learning paradigm and a differentiable spiking model incorporating neuronal dynamics and synaptic plasticity. It can meta-learn local plasticity and receive top-down supervision information for multiscale learning. We demonstrate the advantages of this model in multiple different tasks, including few-shot learning, continual learning, and fault-tolerance learning in neuromorphic vision sensors. It achieves significantly higher performance than single-learning methods. We further implement the model in the Tianjic neuromorphic platform by exploiting algorithm-hardware co-designs and prove that the model can fully utilize neuromorphic many-core architecture to develop hybrid computation paradigm.
Structural mechanism for tyrosine hydroxylase inhibition by dopamine and reactivation by Ser40 phosphorylation
Authors: Bueno-Carrasco María Teresa , Cuéllar Jorge , Flydal Marte I. , Santiago César , Kråkenes Trond-André , Kleppe Rune , López-Blanco José R. , Marcilla Miguel , Teigen Knut , Alvira Sara , Chacón Pablo , Martinez Aurora , Valpuesta José M. 
Published: January 2022

AbstractTyrosine hydroxylase (TH) catalyzes the rate-limiting step in the biosynthesis of dopamine (DA) and other catecholamines, and its dysfunction leads to DA deficiency and parkinsonisms. Inhibition by catecholamines and reactivation by S40 phosphorylation are key regulatory mechanisms of TH activity and conformational stability. We used Cryo-EM to determine the structures of full-length human TH without and with DA, and the structure of S40 phosphorylated TH, complemented with biophysical and biochemical characterizations and molecular dynamics simulations. TH presents a tetrameric structure with dimerized regulatory domains that are separated 15 Å from the catalytic domains. Upon DA binding, a 20-residue α-helix in the flexible N-terminal tail of the regulatory domain is fixed in the active site, blocking it, while S40-phosphorylation forces its egress. The structures reveal the molecular basis of the inhibitory and stabilizing effects of DA and its counteraction by S40-phosphorylation, key regulatory mechanisms for homeostasis of DA and TH.
Size compatibility and concentration dependent supramolecular host–guest interactions at interfaces
Authors: Park Jintae , Park Jinwoo , Lee Jinhoon , Lim Chanoong , Lee Dong Woog 
Published: January 2022

AbstractThe quantification of supramolecular host–guest interactions is important for finely modulating supramolecular systems. Previously, most host–guest interactions quantified using force spectroscopic techniques have been reported in force units. However, accurately evaluating the adhesion energies of host–guest pairs remains challenging. Herein, using a surface forces apparatus, we directly quantify the interaction energies between cyclodextrin (CD)-modified surfaces and ditopic adamantane (DAd) molecules in water as a function of the DAd concentration and the CD cavity size. The adhesion energy of the β-CD–DAd complex drastically increased with increasing DAd concentration and reached saturation. Moreover, the molecular adhesion energy of a single host–guest inclusion complex was evaluated to be ~9.51 kBT. This approach has potential for quantifying fundamental information toward furthering the understanding of supramolecular chemistry and its applications, such as molecular actuators, underwater adhesives, and biosensors, which require precise tuning of specific host–guest interactions.
Structure-dynamics relationships in cryogenically deformed bulk metallic glass
Authors: Spieckermann Florian , Şopu Daniel , Soprunyuk Viktor , Kerber Michael B. , Bednarčík Jozef , Schökel Alexander , Rezvan Amir , Ketov Sergey , Sarac Baran , Schafler Erhard , Eckert Jürgen 
Published: January 2022

AbstractThe atomistic mechanisms occurring during the processes of aging and rejuvenation in glassy materials involve very small structural rearrangements that are extremely difficult to capture experimentally. Here we use in-situ X-ray diffraction to investigate the structural rearrangements during annealing from 77 K up to the crystallization temperature in Cu44Zr44Al8Hf2Co2 bulk metallic glass rejuvenated by high pressure torsion performed at cryogenic temperatures and at room temperature. Using a measure of the configurational entropy calculated from the X-ray pair correlation function, the structural footprint of the deformation-induced rejuvenation in bulk metallic glass is revealed. With synchrotron radiation, temperature and time resolutions comparable to calorimetric experiments are possible. This opens hitherto unavailable experimental possibilities allowing to unambiguously correlate changes in atomic configuration and structure to calorimetrically observed signals and can attribute those to changes of the dynamic and vibrational relaxations (α-, β- and γ-transition) in glassy materials. The results suggest that the structural footprint of the β-transition is related to entropic relaxation with characteristics of a first-order transition. Dynamic mechanical analysis data shows that in the range of the β-transition, non-reversible structural rearrangements are preferentially activated. The low-temperature γ-transition is mostly triggering reversible deformations and shows a change of slope in the entropic footprint suggesting second-order characteristics.
Coordination modulation of iridium single-atom catalyst maximizing water oxidation activity
Authors: Lei Zhanwu , Cai Wenbin , Rao Yifei , Wang Kuan , Jiang Yuyuan , Liu Yang , Jin Xu , Li Jianming , Lv Zhengxing , Jiao Shuhong , Zhang Wenhua , Yan Pengfei , Zhang Shuo , Cao Ruiguo 
Published: January 2022

AbstractSingle-atom catalysts (SACs) have attracted tremendous research interests in various energy-related fields because of their high activity, selectivity and 100% atom utilization. However, it is still a challenge to enhance the intrinsic and specific activity of SACs. Herein, we present an approach to fabricate a high surface distribution density of iridium (Ir) SAC on nickel-iron sulfide nanosheet arrays substrate (Ir1/NFS), which delivers a high water oxidation activity. The Ir1/NFS catalyst offers a low overpotential of ~170 mV at a current density of 10 mA cm−2 and a high turnover frequency of 9.85 s−1 at an overpotential of 300 mV in 1.0 M KOH solution. At the same time, the Ir1/NFS catalyst exhibits a high stability performance, reaching a lifespan up to 350 hours at a current density of 100 mA cm−2. First-principles calculations reveal that the electronic structures of Ir atoms are significantly regulated by the sulfide substrate, endowing an energetically favorable reaction pathway. This work represents a promising strategy to fabricate high surface distribution density single-atom catalysts with high activity and durability for electrochemical water splitting.
Cross-reactive memory T cells associate with protection against SARS-CoV-2 infection in COVID-19 contacts
Authors: Kundu Rhia , Narean Janakan Sam , Wang Lulu , Fenn Joseph , Pillay Timesh , Fernandez Nieves Derqui , Conibear Emily , Koycheva Aleksandra , Davies Megan , Tolosa-Wright Mica , Hakki Seran , Varro Robert , McDermott Eimear , Hammett Sarah , Cutajar Jessica , Thwaites Ryan S. , Parker Eleanor , Rosadas Carolina , McClure Myra , Tedder Richard , Taylor Graham P. , Dunning Jake , Lalvani Ajit 
Published: January 2022

AbstractCross-reactive immune responses to SARS-CoV-2 have been observed in pre-pandemic cohorts and proposed to contribute to host protection. Here we assess 52 COVID-19 household contacts to capture immune responses at the earliest timepoints after SARS-CoV-2 exposure. Using a dual cytokine FLISpot assay on peripheral blood mononuclear cells, we enumerate the frequency of T cells specific for spike, nucleocapsid, membrane, envelope and ORF1 SARS-CoV-2 epitopes that cross-react with human endemic coronaviruses. We observe higher frequencies of cross-reactive (p = 0.0139), and nucleocapsid-specific (p = 0.0355) IL-2-secreting memory T cells in contacts who remained PCR-negative despite exposure (n = 26), when compared with those who convert to PCR-positive (n = 26); no significant difference in the frequency of responses to spike is observed, hinting at a limited protective function of spike-cross-reactive T cells. Our results are thus consistent with pre-existing non-spike cross-reactive memory T cells protecting SARS-CoV-2-naïve contacts from infection, thereby supporting the inclusion of non-spike antigens in second-generation vaccines.
Tartrate-resistant acid phosphatase 5 promotes pulmonary fibrosis by modulating β-catenin signaling
Authors: Hu Yinan , Wang Qi , Yu Jun , Zhou Qing , Deng Yanhan , Liu Juan , Zhang Lei , Xu Yongjian , Xiong Weining , Wang Yi 
Published: January 2022

AbstractIdiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease with limited therapeutic options. Tartrate-resistant acid phosphatase 5 (ACP5) performs a variety of functions. However, its role in IPF remains unclear. Here, we demonstrate that the levels of ACP5 are increased in IPF patient samples and mice with bleomycin (BLM)-induced pulmonary fibrosis. In particular, higher levels of ACP5 are present in the sera of IPF patients with a diffusing capacity of the lungs for carbonmonoxide (DLCO) less than 40% of the predicted value. Additionally, Acp5 deficiency protects mice from BLM-induced lung injury and fibrosis coupled with a significant reduction of fibroblast differentiation and proliferation. Mechanistic studies reveal that Acp5 is upregulated by transforming growth factor-β1 (TGF-β1) in a TGF-β receptor 1 (TGFβR1)/Smad family member 3 (Smad3)-dependent manner, after which Acp5 dephosphorylates p-β-catenin at serine 33 and threonine 41, inhibiting the degradation of β-catenin and subsequently enhancing β-catenin signaling in the nucleus, which promotes the differentiation, proliferation and migration of fibroblast. More importantly, the treatment of mice with Acp5 siRNA-loaded liposomes or Acp5 inhibitor reverses established lung fibrosis. In conclusions, Acp5 is involved in the initiation and progression of pulmonary fibrosis and strategies aimed at silencing or suppressing Acp5 could be considered as potential therapeutic approaches against pulmonary fibrosis.
Prefrontal cortical plasticity during learning of cognitive tasks
Authors: Tang Hua , Riley Mitchell R. , Singh Balbir , Qi Xue-Lian , Blake David T. , Constantinidis Christos 
Published: January 2022

AbstractTraining in working memory tasks is associated with lasting changes in prefrontal cortical activity. To assess the neural activity changes induced by training, we recorded single units, multi-unit activity (MUA) and local field potentials (LFP) with chronic electrode arrays implanted in the prefrontal cortex of two monkeys, throughout the period they were trained to perform cognitive tasks. Mastering different task phases was associated with distinct changes in neural activity, which included recruitment of larger numbers of neurons, increases or decreases of their firing rate, changes in the correlation structure between neurons, and redistribution of power across LFP frequency bands. In every training phase, changes induced by the actively learned task were also observed in a control task, which remained the same across the training period. Our results reveal how learning to perform cognitive tasks induces plasticity of prefrontal cortical activity, and how activity changes may generalize between tasks.
Transient neuronal suppression for exploitation of new sensory evidence
Authors: Shinn Maxwell , Lee Daeyeol , Murray John D. , Seo Hyojung 
Published: January 2022

AbstractIn noisy but stationary environments, decisions should be based on the temporal integration of sequentially sampled evidence. This strategy has been supported by many behavioral studies and is qualitatively consistent with neural activity in multiple brain areas. By contrast, decision-making in the face of non-stationary sensory evidence remains poorly understood. Here, we trained monkeys to identify and respond via saccade to the dominant color of a dynamically refreshed bicolor patch that becomes informative after a variable delay. Animals’ behavioral responses were briefly suppressed after evidence changes, and many neurons in the frontal eye field displayed a corresponding dip in activity at this time, similar to that frequently observed after stimulus onset but sensitive to stimulus strength. Generalized drift-diffusion models revealed consistency of behavior and neural activity with brief suppression of motor output, but not with pausing or resetting of evidence accumulation. These results suggest that momentary arrest of motor preparation is important for dynamic perceptual decision making.
Chirality transmission in macromolecular domains
Authors: Pandey Shankar , Mandal Shankar , Danielsen Mathias Bogetoft , Brown Asha , Hu Changpeng , Christensen Niels Johan , Kulakova Alina Vitaliyivna , Song Shixi , Brown Tom , Jensen Knud J. , Wengel Jesper , Lou Chenguang , Mao Hanbin 
Published: January 2022

AbstractChiral communications exist in secondary structures of foldamers and copolymers via a network of noncovalent interactions within effective intermolecular force (IMF) range. It is not known whether long-range chiral communication exists between macromolecular tertiary structures such as peptide coiled-coils beyond the IMF distance. Harnessing the high sensitivity of single-molecule force spectroscopy, we investigate the chiral interaction between covalently linked DNA duplexes and peptide coiled-coils by evaluating the binding of a diastereomeric pair of three DNA-peptide conjugates. We find that right-handed DNA triple helices well accommodate peptide triple coiled-coils of the same handedness, but not with the left-handed coiled-coil stereoisomers. This chiral communication is effective in a range (<4.5 nm) far beyond canonical IMF distance. Small-angle X-ray scattering and molecular dynamics simulation indicate that the interdomain linkers are tightly packed via hydrophobic interactions, which likely sustains the chirality transmission between DNA and peptide domains. Our findings establish that long-range chiral transmission occurs in tertiary macromolecular domains, explaining the presence of homochiral pairing of superhelices in proteins.