bluuebunny/crossref_metadata_2025_split huggingface dataset:
Over the Edge: Extending the duration of a reconsolidation intervention for spider fear
Authors: Filmer Anna I. , Peters Jacqueline , Bridge Lara A. , Visser Renée M. , Kindt Merel 
Published: June 2022

AbstractPharmacologically disrupting fear memory reconsolidation dramatically reduces fear behaviour. For example, 2–3 min of tarantula exposure followed by 40 mg of propranolol HCl (i.e., a reconsolidation intervention) abruptly decreased spider avoidance, an effect that persisted one year later. However, the success of reconsolidation interventions is not guaranteed: Pavlovian fear-conditioning research shows that the window to target memory reconsolidation is small and easy to miss. If exposure is too long to trigger reconsolidation, but too short for extinction learning, an inactive transitional limbo state occurs, rendering the fear memory unchanged and insensitive to amnesic agents. In this pre-registered study, we aimed to find this behaviourally-controlled boundary condition. Spider-fearful participants underwent a ~3 min (n = 23) or ~14 min (n = 20) exposure to a tarantula, intended to trigger reconsolidation or the limbo state respectively, followed by 40 mg of propranolol. We expected greater spider fear reduction after 3 than 14 min of exposure. Unexpectedly, there were no group differences on any outcome measures. In both groups, Bayesian analysis revealed a marked reduction in fear behaviour towards a generalisation stimulus (a house spider) accompanied by lower self-reported distress, with a sharp decline in spider fear scores two days after treatment that persisted one year later. Possible explanations include that the boundary conditions of reconsolidation are wider in older and stronger memories than experimentally-induced fears, or that alternative processes caused the treatment effects. Although the mechanism is unclear, these results carry a tentative promising message for the potential of brief reconsolidation-targeting interventions to mitigate irrational fears.
CircRNA circ_0006156 inhibits the metastasis of prostate cancer by blocking the ubiquitination of S100A9
Authors: Zhang Yuwei , Liu Fengping , Feng Yangkun , Xu Xinyu , Wang Yang , Zhu Sha , Dong Jian , Zhao Shanchao , Xu Bin , Feng Ninghan 
Published: June 2022

AbstractCircular RNAs (circRNAs) have been demonstrated to play vital roles in cancer development and progression. However, studies on the association between circRNAs and prostate cancer (PCa) are still lacking. CircRNA sequencing of two pairs of PCa tissues and adjacent normal tissues was conducted in the present study, and qRT–PCR was performed to verify the results. Functional experiments were performed to investigate cellular functions after specific changes. Mass spectrometry analysis after RNA pull-down experiments and Co-IP assays were further conducted. Downstream target proteins were predicted via online databases and detected in vitro by Western blot analysis and in vivo by immunohistochemistry. Hsa_circ_0006156 (subsequently named circ_0006156) expresses at low levels in both PCa tissues and cells, and it significantly inhibits the migration and invasion of PCa cells. Circ_0006156 binds to and blocks the ubiquitination of S100A9. Moreover, functional assays revealed that circ_0006156 represses the malignant progression of PCa by binding to S100A9. Finally, in vivo experiments showed that circ_0006156 suppresses PCa migration and invasion by increasing S100A9, revealing circ_0006156 as a potential novel effective target for PCa treatment.
Laboratory evolution of synthetic electron transport system variants reveals a larger metabolic respiratory system and its plasticity
Authors: Anand Amitesh , Patel Arjun , Chen Ke , Olson Connor A. , Phaneuf Patrick V. , Lamoureux Cameron , Hefner Ying , Szubin Richard , Feist Adam M. , Palsson Bernhard O. 
Published: June 2022

AbstractThe bacterial respiratory electron transport system (ETS) is branched to allow condition-specific modulation of energy metabolism. There is a detailed understanding of the structural and biochemical features of respiratory enzymes; however, a holistic examination of the system and its plasticity is lacking. Here we generate four strains of Escherichia coli harboring unbranched ETS that pump 1, 2, 3, or 4 proton(s) per electron and characterized them using a combination of synergistic methods (adaptive laboratory evolution, multi-omic analyses, and computation of proteome allocation). We report that: (a) all four ETS variants evolve to a similar optimized growth rate, and (b) the laboratory evolutions generate specific rewiring of major energy-generating pathways, coupled to the ETS, to optimize ATP production capability. We thus define an Aero-Type System (ATS), which is a generalization of the aerobic bioenergetics and is a metabolic systems biology description of respiration and its inherent plasticity.
In situ 3D bioprinting with bioconcrete bioink
Authors: Xie Mingjun , Shi Yang , Zhang Chun , Ge Mingjie , Zhang Jingbo , Chen Zichen , Fu Jianzhong , Xie Zhijian , He Yong 
Published: June 2022

AbstractIn-situ bioprinting is attractive for directly depositing the therapy bioink at the defective organs to repair them, especially for occupations such as soldiers, athletes, and drivers who can be injured in emergency. However, traditional bioink displays obvious limitations in its complex operation environments. Here, we design a bioconcrete bioink with electrosprayed cell-laden microgels as the aggregate and gelatin methacryloyl (GelMA) precursor solution as the cement. Promising printability is guaranteed with a wide temperature range benefiting from robust rheological properties of photocrosslinked microgel aggregate and fluidity of GelMA cement. Composite components simultaneously self-adapt to biocompatibility and different tissue mechanical microenvironment. Strong binding on tissue-hydrogel interface is achieved by hydrogen bonds and friction when the cement is photocrosslinked. This bioink owns good portability and can be easily prepared in urgent accidents. Meanwhile, microgels can be cultured to mini tissues and then mixed as bioink aggregates, indicating our bioconcrete can be functionalized faster than normal bioinks. The cranial defects repair results verify the superiority of this bioink and its potential in clinical settings required in in-situ treatment.
G1/S restriction point coordinates phasic gene expression and cell differentiation
Authors: DeVeale Brian , Liu Leqian , Boileau Ryan , Swindlehurst-Chan Jennifer , Marsh Bryan , Freimer Jacob W. , Abate Adam , Blelloch Robert 
Published: June 2022

AbstractPluripotent embryonic stem cells have a unique cell cycle structure with a suppressed G1/S restriction point and little differential expression across the cell cycle phases. Here, we evaluate the link between G1/S restriction point activation, phasic gene expression, and cellular differentiation. Expression analysis reveals a gain in phasic gene expression across lineages between embryonic days E7.5 and E9.5. Genetic manipulation of the G1/S restriction point regulators miR-302 and P27 respectively accelerates or delays the onset of phasic gene expression in mouse embryos. Loss of miR-302-mediated p21 or p27 suppression expedites embryonic stem cell differentiation, while a constitutive Cyclin E mutant blocks it. Together, these findings uncover a causal relationship between emergence of the G1/S restriction point with a gain in phasic gene expression and cellular differentiation.
All-in-one, bio-inspired, and low-power crypto engines for near-sensor security based on two-dimensional memtransistors
Authors: Dodda Akhil , Trainor Nicholas , Redwing Joan. M. , Das Saptarshi 
Published: June 2022

AbstractIn the emerging era of the internet of things (IoT), ubiquitous sensors continuously collect, consume, store, and communicate a huge volume of information which is becoming increasingly vulnerable to theft and misuse. Modern software cryptosystems require extensive computational infrastructure for implementing ciphering algorithms, making them difficult to be adopted by IoT edge sensors that operate with limited hardware resources and at low energy budgets. Here we propose and experimentally demonstrate an“all-in-one”8 × 8 array of robust, low-power, and bio-inspired crypto engines monolithically integrated with IoT edge sensors based on two-dimensional (2D) memtransistors. Each engine comprises five 2D memtransistors to accomplish sensing and encoding functionalities. The ciphered information is shown to be secure from an eavesdropper with finite resources and access to deep neural networks. Our hardware platform consists of a total of 320 fully integrated monolayer MoS2-based memtransistors and consumes energy in the range of hundreds of picojoules and offers near-sensor security.
HOX epimutations driven by maternal SMCHD1/LRIF1 haploinsufficiency trigger homeotic transformations in genetically wildtype offspring
Authors: Xue Shifeng , Ly Thanh Thao Nguyen , Vijayakar Raunak S. , Chen Jingyi , Ng Joel , Mathuru Ajay S. , Magdinier Frederique , Reversade Bruno 
Published: June 2022

AbstractThe body plan of animals is laid out by an evolutionary-conserved HOX code which is colinearly transcribed after zygotic genome activation (ZGA). Here we report that SMCHD1, a chromatin-modifying enzyme needed for X-inactivation in mammals, is maternally required for timely HOX expression. Using zebrafish and mouse Smchd1 knockout animals, we demonstrate that Smchd1 haplo-insufficiency brings about precocious and ectopic HOX transcription during oogenesis and embryogenesis. Unexpectedly, wild-type offspring born to heterozygous knockout zebrafish smchd1 mothers exhibited patent vertebrate patterning defects. The loss of maternal Smchd1 was accompanied by HOX epi-mutations driven by aberrant DNA methylation. We further show that this regulation is mediated by Lrif1, a direct interacting partner of Smchd1, whose knockout in zebrafish phenocopies that of Smchd1. Rather than being a short-lived maternal effect, HOX mis-regulation is stably inherited through cell divisions and persists in cultured fibroblasts derived from FSHD2 patients haploinsufficient for SMCHD1. We conclude that maternal SMCHD1/LRIF1 sets up an epigenetic state in the HOX loci that can only be reset in the germline. Such an unusual inter-generational inheritance, whereby a phenotype can be one generation removed from its genotype, casts a new light on how unresolved Mendelian diseases may be interpreted.
Targeting climate adaptation to safeguard and advance the Sustainable Development Goals
Authors: Fuldauer Lena I. , Thacker Scott , Haggis Robyn A. , Fuso-Nerini Francesco , Nicholls Robert J. , Hall Jim W. 
Published: June 2022

AbstractThe international community has committed to achieve 169 Sustainable Development Goal (SDG) targets by 2030 and to enhance climate adaptation under the Paris Agreement. Despite the potential for synergies, aligning SDG and climate adaptation efforts is inhibited by an inadequate understanding of the complex relationship between SDG targets and adaptation to impacts of climate change. Here we propose a framework to conceptualise how ecosystems and socio-economic sectors mediate this relationship, which provides a more nuanced understanding of the impacts of climate change on all 169 SDG targets. Global application of the framework reveals that adaptation of wetlands, rivers, cropland, construction, water, electricity, and housing in the most vulnerable countries is required to safeguard achievement of 68% of SDG targets from near-term climate risk by 2030. We discuss how our framework can help align National Adaptation Plans with SDG targets, thus ensuring that adaptation advances, rather than detracts from, sustainable development.
High-dimensional profiling reveals Tc17 cell enrichment in active Crohn’s disease and identifies a potentially targetable signature
Authors: Globig A.-M. , Hipp A. V. , Otto-Mora P. , Heeg M. , Mayer L. S. , Ehl S. , Schwacha H. , Bewtra M. , Tomov V. , Thimme R. , Hasselblatt P. , Bengsch B. 
Published: June 2022

AbstractThe immune-pathology in Crohn’s disease is linked to dysregulated CD4+ T cell responses biased towards pathogenic TH17 cells. However, the role of CD8+ T cells able to produce IL-17 (Tc17 cells) remains unclear. Here we characterize the peripheral blood and intestinal tissue of Crohn’s disease patients (n = 61) with flow and mass cytometry and reveal a strong increase of Tc17 cells in active disease, mainly due to induction of conventional T cells. Mass cytometry shows that Tc17 cells express a distinct immune signature (CD6high, CD39, CD69, PD-1, CD27low) which was validated in an independent patient cohort. This signature stratifies patients into groups with distinct flare-free survival associated with differential CD6 expression. Targeting of CD6 in vitro reduces IL-17, IFN-γ and TNF production. These results identify a distinct Tc17 cell population in Crohn’s disease with proinflammatory features linked to disease activity. The Tc17 signature informs clinical outcomes and may guide personalized treatment decisions.
Combinatorial immunotherapies overcome MYC-driven immune evasion in triple negative breast cancer
Authors: Lee Joyce V. , Housley Filomena , Yau Christina , Nakagawa Rachel , Winkler Juliane , Anttila Johanna M. , Munne Pauliina M. , Savelius Mariel , Houlahan Kathleen E. , Van de Mark Daniel , Hemmati Golzar , Hernandez Grace A. , Zhang Yibing , Samson Susan , Baas Carole , Kok Marleen , Esserman Laura J. , van ‘t Veer Laura J. , Rugo Hope S. , Curtis Christina , Klefström Juha , Matloubian Mehrdad , Goga Andrei 
Published: June 2022

AbstractFew patients with triple negative breast cancer (TNBC) benefit from immune checkpoint inhibitors with complete and durable remissions being quite rare. Oncogenes can regulate tumor immune infiltration, however whether oncogenes dictate diminished response to immunotherapy and whether these effects are reversible remains poorly understood. Here, we report that TNBCs with elevated MYC expression are resistant to immune checkpoint inhibitor therapy. Using mouse models and patient data, we show that MYC signaling is associated with low tumor cell PD-L1, low overall immune cell infiltration, and low tumor cell MHC-I expression. Restoring interferon signaling in the tumor increases MHC-I expression. By combining a TLR9 agonist and an agonistic antibody against OX40 with anti-PD-L1, mice experience tumor regression and are protected from new TNBC tumor outgrowth. Our findings demonstrate that MYC-dependent immune evasion is reversible and druggable, and when strategically targeted, may improve outcomes for patients treated with immune checkpoint inhibitors.
Breaking the nanoparticle’s dispersible limit via rotatable surface ligands
Authors: Liu Yue , Peng Na , Yao Yifeng , Zhang Xuan , Peng Xianqi , Zhao Liyan , Wang Jing , Peng Liang , Wang Zuankai , Mochizuki Kenji , Yue Min , Yang Shikuan 
Published: June 2022

AbstractAchieving versatile dispersion of nanoparticles in a broad range of solvents (e.g., water, oil, and biofluids) without repeatedly recourse to chemical modifications are desirable in optoelectronic devices, self-assembly, sensing, and biomedical fields. However, such a target is limited by the strategies used to decorate nanoparticle’s surface properties, leading to a narrow range of solvents for existing nanoparticles. Here we report a concept to break the nanoparticle’s dispersible limit via electrochemically anchoring surface ligands capable of sensing the surrounding liquid medium and rotating to adapt to it, immediately forming stable dispersions in a wide range of solvents (polar and nonpolar, biofluids, etc.). Moreover, the smart nanoparticles can be continuously electrodeposited in the electrolyte, overcoming the electrode surface-confined low throughput limitation of conventional electrodeposition methods. The anomalous dispersive property of the smart Ag nanoparticles enables them to resist bacteria secreted species-induced aggregation and the structural similarity of the surface ligands to that of the bacterial membrane assists them to enter the bacteria, leading to high antibacterial activity. The simple but massive fabrication process and the enhanced dispersion properties offer great application opportunities to the smart nanoparticles in diverse fields.
Substrate binding in the mitochondrial ADP/ATP carrier is a step-wise process guiding the structural changes in the transport cycle
Authors: Mavridou Vasiliki , King Martin S. , Tavoulari Sotiria , Ruprecht Jonathan J. , Palmer Shane M. , Kunji Edmund R. S. 
Published: June 2022

AbstractMitochondrial ADP/ATP carriers import ADP into the mitochondrial matrix and export ATP to the cytosol to fuel cellular processes. Structures of the inhibited cytoplasmic- and matrix-open states have confirmed an alternating access transport mechanism, but the molecular details of substrate binding remain unresolved. Here, we evaluate the role of the solvent-exposed residues of the translocation pathway in the process of substrate binding. We identify the main binding site, comprising three positively charged and a set of aliphatic and aromatic residues, which bind ADP and ATP in both states. Additionally, there are two pairs of asparagine/arginine residues on opposite sides of this site that are involved in substrate binding in a state-dependent manner. Thus, the substrates are directed through a series of binding poses, inducing the conformational changes of the carrier that lead to their translocation. The properties of this site explain the electrogenic and reversible nature of adenine nucleotide transport.
Context-aware deconvolution of cell–cell communication with Tensor-cell2cell
Authors: Armingol Erick , Baghdassarian Hratch M. , Martino Cameron , Perez-Lopez Araceli , Aamodt Caitlin , Knight Rob , Lewis Nathan E. 
Published: June 2022

AbstractCell interactions determine phenotypes, and intercellular communication is shaped by cellular contexts such as disease state, organismal life stage, and tissue microenvironment. Single-cell technologies measure the molecules mediating cell–cell communication, and emerging computational tools can exploit these data to decipher intercellular communication. However, current methods either disregard cellular context or rely on simple pairwise comparisons between samples, thus limiting the ability to decipher complex cell–cell communication across multiple time points, levels of disease severity, or spatial contexts. Here we present Tensor-cell2cell, an unsupervised method using tensor decomposition, which deciphers context-driven intercellular communication by simultaneously accounting for multiple stages, states, or locations of the cells. To do so, Tensor-cell2cell uncovers context-driven patterns of communication associated with different phenotypic states and determined by unique combinations of cell types and ligand-receptor pairs. As such, Tensor-cell2cell robustly improves upon and extends the analytical capabilities of existing tools. We show Tensor-cell2cell can identify multiple modules associated with distinct communication processes (e.g., participating cell–cell and ligand-receptor pairs) linked to severities of Coronavirus Disease 2019 and to Autism Spectrum Disorder. Thus, we introduce an effective and easy-to-use strategy for understanding complex communication patterns across diverse conditions.
Engineering substrate specificity of HAD phosphatases and multienzyme systems development for the thermodynamic-driven manufacturing sugars
Authors: Tian Chaoyu , Yang Jiangang , Liu Cui , Chen Peng , Zhang Tong , Men Yan , Ma Hongwu , Sun Yuanxia , Ma Yanhe 
Published: June 2022

AbstractNaturally, haloacid dehalogenase superfamily phosphatases have been evolved with broad substrate promiscuity; however, strong specificity to a particular substrate is required for developing thermodynamically driven routes for manufacturing sugars. How to alter the intrinsic substrate promiscuity of phosphatases and fit the “one enzyme-one substrate” model remains a challenge. Herein, we report the structure-guided engineering of a phosphatase, and successfully provide variants with tailor-made preference for three widespread phosphorylated sugars, namely, glucose 6-phosphate, fructose 6-phosphate, and mannose 6-phosphate, while simultaneously enhancement in catalytic efficiency. A 12000-fold switch from unfavorite substrate to dedicated one is generated. Molecular dynamics simulations reveal the origin of improved activity and substrate specificity. Furthermore, we develop four coordinated multienzyme systems and accomplish the conversion of inexpensive sucrose and starch to fructose and mannose in excellent yield of 94–96%. This innovative sugar-biosynthesis strategy overcomes the reaction equilibrium of isomerization and provides the promise of high-yield manufacturing of other monosaccharides and polyols.
Safety and immunogenicity of a hybrid-type vaccine booster in BBIBP-CorV recipients in a randomized phase 2 trial
Authors: Kaabi Nawal Al , Yang Yun Kai , Du Li Fang , Xu Ke , Shao Shuai , Liang Yu , Kang Yun , Su Ji Guo , Zhang Jing , Yang Tian , Hussein Salah , ElDein Mohamed Saif , Yang Sen Sen , Lei Wenwen , Gao Xue Jun , Jiang Zhiwei , Cong Xiangfeng , Tan Yao , Wang Hui , Li Meng , Mekki Hanadi Mekki , Zaher Walid , Mahmoud Sally , Zhang Xue , Qu Chang , Liu Dan Ying , Zhang Jing , Yang Mengjie , Eltantawy Islam , Hou Jun Wei , Lei Ze Hua , Xiao Peng , Wang Zhao Nian , Yin Jin Liang , Mao Xiao Yan , Zhang Jin , Qu Liang , Zhang Yun Tao , Yang Xiao Ming , Wu Guizhen , Li Qi Ming 
Published: June 2022

AbstractNVSI-06-08 is a potential broad-spectrum recombinant COVID-19 vaccine that integrates the antigens from multiple SARS-CoV-2 strains into a single immunogen. Here, we evaluate the safety and immunogenicity of NVSI-06-08 as a heterologous booster dose in BBIBP-CorV recipients in a randomized, double-blind, controlled, phase 2 trial conducted in the United Arab Emirates (NCT05069129). Three groups of healthy adults over 18 years of age (600 participants per group) who have administered two doses of BBIBP-CorV 4-6-month, 7-9-month and >9-month earlier, respectively, are randomized 1:1 to receive either a homologous booster of BBIBP-CorV or a heterologous booster of NVSI-06-08. The incidence of adverse reactions is low, and the overall safety profile is quite similar between two booster regimens. Both Neutralizing and IgG antibodies elicited by NVSI-06-08 booster are significantly higher than those by BBIBP-CorV booster against not only SARS-CoV-2 prototype strain but also multiple variants of concerns (VOCs). Especially, the neutralizing antibody GMT against Omicron variant induced by heterologous NVSI-06-08 booster reaches 367.67, which is substantially greater than that boosted by BBIBP-CorV (GMT: 45.03). In summary, NVSI-06-08 is safe and immunogenic as a booster dose following two doses of BBIBP-CorV, which is immunogenically superior to the homologous boost with another dose of BBIBP-CorV.
Quasi-solid-state Zn-air batteries with an atomically dispersed cobalt electrocatalyst and organohydrogel electrolyte
Authors: Wang Qichen , Feng Qingguo , Lei Yongpeng , Tang Shuaihao , Xu Liang , Xiong Yu , Fang Guozhao , Wang Yuchao , Yang Peiyao , Liu Jingjing , Liu Wei , Xiong Xiang 
Published: June 2022

AbstractQuasi-solid-state Zn-air batteries are usually limited to relatively low-rate ability (<10 mA cm−2), which is caused in part by sluggish oxygen electrocatalysis and unstable electrochemical interfaces. Here we present a high-rate and robust quasi-solid-state Zn-air battery enabled by atomically dispersed cobalt sites anchored on wrinkled nitrogen doped graphene as the air cathode and a polyacrylamide organohydrogel electrolyte with its hydrogen-bond network modified by the addition of dimethyl sulfoxide. This design enables a cycling current density of 100 mA cm−2 over 50 h at 25 °C. A low-temperature cycling stability of over 300 h (at 0.5 mA cm−2) with over 90% capacity retention at −60 °C and a broad temperature adaptability (−60 to 60 °C) are also demonstrated.