bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of autophagy modulation on phenotype and survival of cardiac stromal cells under metabolic stress
Authors: Chimenti Isotta , Picchio Vittorio , Pagano Francesca , Schirone Leonardo , Schiavon Sonia , D’Ambrosio Luca , Valenti Valentina , Forte Maurizio , di Nonno Flavio , Rubattu Speranza , Peruzzi Mariangela , Versaci Francesco , Greco Ernesto , Calogero Antonella , De Falco Elena , Frati Giacomo , Sciarretta Sebastiano 
Published: April 2022

AbstractCardiac stromal cells (CSCs) embrace multiple phenotypes and are a contributory factor in tissue homeostasis and repair. They can be exploited as therapeutic mediators against cardiac fibrosis and remodeling, but their survival and cardioprotective properties can be decreased by microenvironmental cues. We evaluated the impact of autophagy modulation by different pharmacological/genetic approaches on the viability and phenotype of murine CSCs, which had been subjected to nutrient deprivation or hyperglycemia, in order to mimic relevant stress conditions and risk factors of cardiovascular diseases. Our results show that autophagy is activated in CSCs by nutrient deprivation, and that autophagy induction by trehalose or autophagy-related protein 7 (ATG7)-overexpression can significantly preserve CSC viability. Furthermore, autophagy induction is associated with a higher proportion of primitive, non-activated stem cell antigen 1 (Sca1)-positive cells, and with a reduced fibrotic fraction (positive for the discoidin domain-containing receptor 2, DDR2) in the CSC pool after nutrient deprivation. Hyperglycemia, on the other hand, is associated with reduced autophagic flux in CSCs, and with a significant reduction in primitive Sca1+ cells. Autophagy induction by adenoviral-mediated ATG7-overexpression maintains a cardioprotective, anti-inflammatory and pro-angiogenic paracrine profile of CSCs exposed to hyperglycemia for 1 week. Finally, autophagy induction by ATG7-overexpression during hyperglycemia can significantly preserve cell viability in CSCs, which were subsequently exposed to nutrient deprivation, reducing hyperglycemia-induced impairment of cell resistance to stress. In conclusion, our results show that autophagy stimulation preserves CSC viability and function in response to metabolic stressors, suggesting that it may boost the beneficial functions of CSCs in cardiac repair mechanisms.
Cyclic 5-membered disulfides are not selective substrates of thioredoxin reductase, but are opened nonspecifically
Authors: Felber Jan G. , Poczka Lena , Scholzen Karoline C. , Zeisel Lukas , Maier Martin S. , Busker Sander , Theisen Ulrike , Brandstädter Christina , Becker Katja , Arnér Elias S. J. , Thorn-Seshold Julia , Thorn-Seshold Oliver 
Published: April 2022

AbstractThe cyclic five-membered disulfide 1,2-dithiolane has been widely used in chemical biology and in redox probes. Contradictory reports have described it either as nonspecifically reduced in cells, or else as a highly specific substrate for thioredoxin reductase (TrxR). Here we show that 1,2-dithiolane probes, such as “TRFS” probes, are nonspecifically reduced by thiol reductants and redox-active proteins, and their cellular performance is barely affected by TrxR inhibition or knockout. Therefore, results of cellular imaging or inhibitor screening using 1,2-dithiolanes should not be interpreted as reflecting TrxR activity, and previous studies may need re-evaluation. To understand 1,2-dithiolanes’ complex behaviour, probe localisation, environment-dependent fluorescence, reduction-independent ring-opening polymerisation, and thiol-dependent cellular uptake must all be considered; particular caution is needed when co-applying thiophilic inhibitors. We present a general approach controlling against assay misinterpretation with reducible probes, to ensure future TrxR-targeted designs are robustly evaluated for selectivity, and to better orient future research.
The promotion effect of π-π interactions in Pd NPs catalysed selective hydrogenation
Authors: Guo Miao , Jayakumar Sanjeevi , Luo Mengfei , Kong Xiangtao , Li Chunzhi , Li He , Chen Jian , Yang Qihua 
Published: April 2022

AbstractThe utilization of weak interactions to improve the catalytic performance of supported metal catalysts is an important strategy for catalysts design, but still remains a big challenge. In this work, the weak interactions nearby the Pd nanoparticles (NPs) are finely tuned by using a series of imine-linked covalent organic frameworks (COFs) with different conjugation skeletons. The Pd NPs embedded in pyrene-COF are ca. 3 to 10-fold more active than those in COFs without pyrene in the hydrogenation of aromatic ketones/aldehydes, quinolines and nitrobenzene, though Pd have similar size and surface structure. With acetophenone (AP) hydrogenation as a model reaction, systematic studies imply that the π-π interaction of AP and pyrene rings in the vicinity of Pd NPs could significantly reduce the activation barrier in the rate-determining step. This work highlights the important role of non-covalent interactions beyond the active sites in modulating the catalytic performance of supported metal NPs.
Imaging vesicle formation dynamics supports the flexible model of clathrin-mediated endocytosis
Authors: Nawara Tomasz J. , Williams Yancey D. , Rao Tejeshwar C. , Hu Yuesong , Sztul Elizabeth , Salaita Khalid , Mattheyses Alexa L. 
Published: April 2022

AbstractClathrin polymerization and changes in plasma membrane architecture are necessary steps in forming vesicles to internalize cargo during clathrin-mediated endocytosis (CME). Simultaneous analysis of clathrin dynamics and membrane structure is challenging due to the limited axial resolution of fluorescence microscopes and the heterogeneity of CME. This has fueled conflicting models of vesicle assembly and obscured the roles of flat clathrin assemblies. Here, using Simultaneous Two-wavelength Axial Ratiometry (STAR) microscopy, we bridge this critical knowledge gap by quantifying the nanoscale dynamics of clathrin-coat shape change during vesicle assembly. We find that de novo clathrin accumulations generate both flat and curved structures. High-throughput analysis reveals that the initiation of vesicle curvature does not directly correlate with clathrin accumulation. We show clathrin accumulation is preferentially simultaneous with curvature formation at shorter-lived clathrin-coated vesicles (CCVs), but favors a flat-to-curved transition at longer-lived CCVs. The broad spectrum of curvature initiation dynamics revealed by STAR microscopy supports multiple productive mechanisms of vesicle formation and advocates for the flexible model of CME.
Long-chain ceramides are cell non-autonomous signals linking lipotoxicity to endoplasmic reticulum stress in skeletal muscle
Authors: McNally Ben D. , Ashley Dean F. , Hänschke Lea , Daou Hélène N. , Watt Nicole T. , Murfitt Steven A. , MacCannell Amanda D. V. , Whitehead Anna , Bowen T. Scott , Sanders Francis W. B. , Vacca Michele , Witte Klaus K. , Davies Graeme R. , Bauer Reinhard , Griffin Julian L. , Roberts Lee D. 
Published: April 2022

AbstractThe endoplasmic reticulum (ER) regulates cellular protein and lipid biosynthesis. ER dysfunction leads to protein misfolding and the unfolded protein response (UPR), which limits protein synthesis to prevent cytotoxicity. Chronic ER stress in skeletal muscle is a unifying mechanism linking lipotoxicity to metabolic disease. Unidentified signals from cells undergoing ER stress propagate paracrine and systemic UPR activation. Here, we induce ER stress and lipotoxicity in myotubes. We observe ER stress-inducing lipid cell non-autonomous signal(s). Lipidomics identifies that palmitate-induced cell stress induces long-chain ceramide 40:1 and 42:1 secretion. Ceramide synthesis through the ceramide synthase 2 de novo pathway is regulated by UPR kinase Perk. Inactivation of CerS2 in mice reduces systemic and muscle ceramide signals and muscle UPR activation. The ceramides are packaged into extracellular vesicles, secreted and induce UPR activation in naïve myotubes through dihydroceramide accumulation. This study furthers our understanding of ER stress by identifying UPR-inducing cell non-autonomous signals.
Kerr reversal in Josephson meta-material and traveling wave parametric amplification
Authors: Ranadive Arpit , Esposito Martina , Planat Luca , Bonet Edgar , Naud Cécile , Buisson Olivier , Guichard Wiebke , Roch Nicolas 
Published: April 2022

AbstractJosephson meta-materials have recently emerged as very promising platform for superconducting quantum science and technologies. Their distinguishing potential resides in ability to engineer them at sub-wavelength scales, which allows complete control over wave dispersion and nonlinear interaction. In this article we report a versatile Josephson transmission line with strong third order nonlinearity which can be tuned from positive to negative values, and suppressed second order non linearity. As an initial implementation of this multipurpose meta-material, we operate it to demonstrate reversed Kerr phase-matching mechanism in traveling wave parametric amplification. Compared to previous state of the art phase matching approaches, this reversed Kerr phase matching avoids the presence of gaps in transmission, can reduce gain ripples, and allows in situ tunability of the amplification band over an unprecedented wide range. Besides such notable advancements in the amplification performance with direct applications to superconducting quantum computing and generation of broadband squeezing, the in-situ tunability with sign reversal of the nonlinearity in traveling wave structures, with no counterpart in optics to the best of our knowledge, opens exciting experimental possibilities in the general framework of microwave quantum optics, single-photon detection and quantum limited amplification.
The future poleward shift of Southern Hemisphere summer mid-latitude storm tracks stems from ocean coupling
Authors: Chemke Rei 
Published: April 2022

AbstractThe latitudinal position of mid-latitude storm tracks has large climate impacts affecting the distribution of precipitation, temperature, humidity, and winds over the extratropics. By the end of this century, climate models project a poleward shift of summer mid-latitude storm tracks in the Southern Hemisphere. Most previous mechanisms for the poleward shift of the storm tracks focused on the role of atmospheric temperature changes. However, the relative roles of other climate system components in the projected storm tracks’ shift have not been examined to date. Here it is shown that thermodynamic ocean coupling is responsible for the future poleward shift of the storm tracks as it overcomes the effect of dynamic ocean coupling to shift the storm tracks equatorward. These results stress the importance of using full-physics ocean models to investigate the future shift of the storm tracks, and of better monitoring ocean coupling processes to improve our preparedness for future climate changes.
High failure rate of ChAdOx1-nCoV19 immunization against asymptomatic infection in healthcare workers during a Delta variant surge
Authors: Ujjainiya Rajat , Tyagi Akansha , Sardana Viren , Naushin Salwa , Bhatheja Nitin , Kumar Kartik , Barman Joydeb , Prakash Satyartha , Kutum Rintu , Bhaskar Akash Kumar , Singh Prateek , Chaudhary Kumardeep , Loomba Menka , Khanna Yukti , Walecha Chestha , Ahmed Rizwan , Yadav Ashutosh , Bajaj Archana , Malik Gaurav , Qureshi Sahar , Waghdhare Swati , Siddiqui Samreen , Trehan Kamal Krishan , Mani Manju , Dang Rajiv , Das Poonam , Dougall Pankaj , Mahajan Monica , Sonar Sudipta , Jakhar Kamini , Kumar Reema , Tiwari Mahima , Mani Shailendra , Bhattacharyya Sankar , Budhiraja Sandeep , Agrawal Anurag , Dash Debasis , Jha Sujeet , Sengupta Shantanu 
Published: April 2022

AbstractImmunization is expected to confer protection against infection and severe disease for vaccines while reducing risks to unimmunized populations by inhibiting transmission. Here, based on serial serological studies of an observational cohort of healthcare workers, we show that during a Severe Acute Respiratory Syndrome -Coronavirus 2 Delta-variant outbreak in Delhi, 25.3% (95% Confidence Interval 16.9-35.2) of previously uninfected, ChAdOx1-nCoV19 double vaccinated, healthcare workers were infected within less than two months, based on serology. Induction of anti-spike response was similar between groups with breakthrough infection (541 U/ml, Inter Quartile Range 374) and without (342 U/ml, Inter Quartile Range 497), as was the induction of neutralization activity to wildtype. This was not vaccine failure since vaccine effectiveness estimate based on infection rates in an unvaccinated cohort were about 70% and most infections were asymptomatic. We find that while ChAdOx1-nCoV19 vaccination remains effective in preventing severe infections, it is unlikely to be completely able to block transmission and provide herd immunity.
Temporal and spatial characterisation of protein liquid-liquid phase separation using NMR spectroscopy
Authors: Bramham Jack E. , Golovanov Alexander P. 
Published: April 2022

AbstractLiquid-liquid phase separation (LLPS) of protein solutions is increasingly recognised as an important phenomenon in cell biology and biotechnology. However, opalescence and concentration fluctuations render LLPS difficult to study, particularly when characterising the kinetics of the phase transition and layer separation. Here, we demonstrate the use of a probe molecule trifluoroethanol (TFE) to characterise the kinetics of protein LLPS by NMR spectroscopy. The chemical shift and linewidth of the probe molecule are sensitive to local protein concentration, with this sensitivity resulting in different characteristic signals arising from the dense and lean phases. Monitoring of these probe signals by conventional bulk-detection19F NMR reports on the formation and evolution of both phases throughout the sample, including their concentrations and volumes. Meanwhile, spatially-selective19F NMR, in which spectra are recorded from smaller slices of the sample, was used to track the distribution of the different phases during layer separation. This experimental strategy enables comprehensive characterisation of the process and kinetics of LLPS, and may be useful to study phase separation in protein systems as a function of their environment.
Platicon microcomb generation using laser self-injection locking
Authors: Lihachev Grigory , Weng Wenle , Liu Junqiu , Chang Lin , Guo Joel , He Jijun , Wang Rui Ning , Anderson Miles H. , Liu Yang , Bowers John E. , Kippenberg Tobias J. 
Published: April 2022

AbstractThe past decade has witnessed major advances in the development and system-level applications of photonic integrated microcombs, that are coherent, broadband optical frequency combs with repetition rates in the millimeter-wave to terahertz domain. Most of these advances are based on harnessing of dissipative Kerr solitons (DKS) in microresonators with anomalous group velocity dispersion (GVD). However, microcombs can also be generated with normal GVD using localized structures that are referred to as dark pulses, switching waves or platicons. Compared with DKS microcombs that require specific designs and fabrication techniques for dispersion engineering, platicon microcombs can be readily built using CMOS-compatible platforms such as thin-film (i.e., thickness below 300 nm) silicon nitride with normal GVD. Here, we use laser self-injection locking to demonstrate a fully integrated platicon microcomb operating at a microwave K-band repetition rate. A distributed feedback (DFB) laser edge-coupled to a Si3N4 chip is self-injection-locked to a high-Q ( > 107) microresonator with high confinement waveguides, and directly excites platicons without sophisticated active control. We demonstrate multi-platicon states and switching, perform optical feedback phase study and characterize the phase noise of the K-band platicon repetition rate and the pump laser. Laser self-injection-locked platicons could facilitate the wide adoption of microcombs as a building block in photonic integrated circuits via commercial foundry service.
Dual-wavelength switchable single-mode lasing from a lanthanide-doped resonator
Authors: Jin Limin , Chen Xian , Wu Yunkai , Ai Xiangzhe , Yang Xiaoli , Xiao Shumin , Song Qinghai 
Published: April 2022

AbstractThe development of multi-wavelength lasing, particularly with the wavelength tuning in a wide spectral range, is challenging but highly desirable for integrated photonic devices due to its dynamic switching functionality, high spectral purity and contrast. Here, we propose a general strategy, that relies on the simultaneous design on the electronic states and the optical states, to demonstrate dynamically switchable single-mode lasing spanning beyond the record range (300 nm). This is achieved through integrating the reversely designed nanocrystals with two size-mismatched coupled microcavities. We show an experimental validation of a crosstalk-free violet-to-red single-mode behavior through collective control of asymmetric excitation and excitation wavelength. The single-mode action persists for a wide power range, and presents significant enhancement when compared with that in the microdisk laser. These findings enlighten the reverse design of luminescent materials. Given the remarkable doping flexibility, our results may create new opportunities in a variety of frontier applications.
Stereoselective intermolecular radical cascade reactions of tryptophans or ɤ-alkenyl-α-amino acids with acrylamides via photoredox catalysis
Authors: Li Jiang-Tao , Luo Jian-Nan , Wang Jia-Le , Wang De-Ku , Yu Yi-Zhe , Zhuo Chun-Xiang 
Published: April 2022

AbstractThe radical cascade reaction is considered as one of the most powerful methods to build molecular complexity. However, highly stereoselective intermolecular radical cascade reactions that can produce complex cyclic compounds bearing multiple stereocenters via visible-light-induced photocatalysis have been challenging yet desirable. Herein we report a facile and efficient synthesis of multi-substituted trans-fused hexahydrocarbazoles via a stereoselective intermolecular radical cascade reaction of readily available tryptophans and acrylamides enabled by visible-light-induced photoredox catalysis. The trans-fused hexahydrocarbazoles with up to five stereocenters including two quaternary ones can be accessed in up to 82% yield, >20/1 diastereoselectivity, and 96% ee. Interestingly, the tetrahydrocarbazoles are favorably formed when the reaction is performed under air. Moreover, by simply switching the starting material from tryptophans to ɤ-alkenyl substituted α-amino acids, this protocol can be further applied to the stereoselective syntheses of 1,3,5-trisubstituted cyclohexanes which are otherwise challenging to access. Preliminary mechanistic studies suggest that the reaction goes through radical addition cascade and radical-polar crossover processes.
Therapeutic and immunomodulatory potential of pazopanib in malignant phyllodes tumor
Authors: Ng Dave Yong Xiang , Li Zhimei , Lee Elizabeth , Kok Jessica Sook Ting , Lee Jing Yi , Koh Joanna , Ng Cedric Chuan-Young , Lim Abner Herbert , Liu Wei , Ng Sheng Rong , Lim Kah Suan , Huang Xi Xiao , Hong Jing Han , Guan Peiyong , Sim Yirong , Thike Aye Aye , Nasir Nur Diyana Md , Li Shang , Tan Puay Hoon , Teh Bin Tean , Chan Jason Yongsheng 
Published: April 2022

AbstractMalignant phyllodes tumors (PT) are rare aggressive fibroepithelial neoplasms with high metastatic potential and lack effective therapy. We established a patient-derived xenograft (PDX) and cell line model (designated MPT-S1) of malignant PT which demonstrated clinical response to pazopanib. Whole exome sequencing identified somatic mutations in TP53, RB1, MED12, and KMT2D. Immunohistochemistry and genomic profiles of the tumor, PDX and cell line were concordant. In keeping with clinical observation, pazopanib reduced cell viability in a dose-dependent manner and evoked apoptosis, and led to significant abrogation of in vivo tumor growth. Whole transcriptomic analysis revealed that pazopanib decreased expression of genes involved in oncogenic and apoptosis signaling. We also observed decreased expression of ENPP1, with known roles in cancer invasion and metastasis, as well as STING pathway upregulation. Accordingly, pazopanib induced micronuclei formation, and evoked phospho-TBK1 and PD-L1 expression. In an additional cohort of malignant PT (n = 14), six (42.9%) showed comparable or higher levels of ENPP1 relative to MPT-S1, highlighting its potential role as a therapeutic target. In conclusion, we established MPT-S1, a new PDX and cell line model, and provided evidence for the clinical efficacy of pazopanib in malignant PT.
Cryogenic spray quenching of simulated propellant tank wall using coating and flow pulsing in microgravity
Authors: Chung J. N. , Dong Jun , Wang Hao , Darr S. R. , Hartwig J. W. 
Published: April 2022

AbstractIn-space cryogenic propulsion will play a vital role in NASA’s return to the Moon mission and future mission to Mars. The enabling of in-space cryogenic engines and cryogenic fuel depots for these future manned and robotic space exploration missions begins with the technology development of advanced cryogenic thermal-fluid management systems for the propellant transfer lines and storage system. Before single-phase liquid can flow to the engine or spacecraft receiver tank, the connecting transfer line and storage tank must first be chilled down to cryogenic temperatures. The most direct and simplest method to quench the line and the tank is to use the cold propellant itself that results in the requirement of minimizing propellant consumption during chilldown. In view of the needs stated above, a highly efficient thermal-fluid management technology must be developed to consume the minimum amount of cryogen during chilldown of a transfer line and a storage tank. In this paper, we suggest the use of the cryogenic spray for storage tank chilldown. We have successfully demonstrated its feasibility and high efficiency in a simulated space microgravity condition. In order to maximize the storage tank chilldown efficiency for the least amount of cryogen consumption, the technology adopted included cryogenic spray cooling, Teflon thin-film coating of the simulated tank surface, and spray flow pulsing. The completed flight experiments successfully demonstrated that spray cooling is the most efficient cooling method for the tank chilldown in microgravity. In microgravity, Teflon coating alone can improve the efficiency up to 72% and the efficiency can be improved up to 59% by flow pulsing alone. However, Teflon coating together with flow pulsing was found to substantially enhance the chilldown efficiency in microgravity for up to 113%.