bluuebunny/crossref_metadata_2025 huggingface dataset:
Carl Schmitt's Institutional Theory
Authors: Croce Mariano , Salvatore Andrea
Published: June 2022

In 1922, Carl Schmitt penned Political Theology, the celebrated essay in which he elaborated on the notorious theory that the heart of politics lies in the sovereign power to issue emergency measures that suspend the legal order. Ever since, Schmitt's thinking has largely been identified with this concept, despite him renouncing it over time. Offering a comprehensive analysis of Schmitt's writings, Carl Schmitt's Institutional Theory provides an ambitious, novel perspective on Carl Schmitt and his legal and political thinking. By delving into Schmitt's output over his decades-long career, Mariano Croce and Andrea Salvatore explore Schmitt's varied and developing thoughts on exceptionalism, societal pluralism and the law as the progenitor and enforcer of normality. Challenging dominant interpretations, Croce and Salvatore dethrone the false centrality of certain key texts, and instead provide a more unified, coherent account of his institutional theory from across his long and controversial career.
Revisiting Darwin's comparisons between human and non-human primate facial signals
Authors: Kavanagh Eithne , Kimock Clare , Whitehouse Jamie , Micheletta Jerome , Waller Bridget M.
Published: June 2022

Darwin and other pioneering scholars made comparisons between human facial signals and those of non-human primates, suggesting that they share evolutionary history. We now have tools available (the Facial Action Coding System) to make these comparisons anatomically based and standardised, as well as analytical methods to facilitate comparative studies. Here we review the evidence establishing a shared anatomical basis between the facial behaviour of human and non-human primate species, concluding which signals are probably related, and which are not. We then review the evidence for shared function and discuss the implications for understanding human communication. Where differences between humans and other species exist, we explore possible explanations and future directions for enquiry.
BROWNLIE IIAND THE SERVICE-OUT JURISDICTION UNDER ENGLISH LAW
Authors: Arzandeh Ardavan
Published: June 2022

FS Cairo (Nile Plaza) LLC v Brownlie(Brownlie II) is arguably the United Kingdom's highest appellate court's most significant decision this century on a private international law question. The judgment has ended nearly two decades of debate about the meaning of ‘damage’ sustained in England for the purpose of paragraph 3.1(9)(a) of Practice Direction 6B of the Civil Procedure Rules. In a four-to-one majority ruling, the Supreme Court decided that the provision was to be interpreted widely, such that, in a personal injury claim, any significant harm of any kind suffered by a claimant in England could provide a basis for the service of proceedings on a foreign-based defendant. The article is critical of the majority's decision, as it is liable to create both immediate and long-term problems in the context of the service-out jurisdiction in England. It also examines the court's pronouncements on the other question before it concerning proof of foreign law.
Parents’ talk about conceptual categories with infants: stability, variability, and implications for expressive language development
Authors: WEI Ran , KIRBY Anna , NAIGLES Letitia R. , ROWE Meredith L.
Published: June 2022

Children’s exposure to talk about conceptual categories plays a powerful role in shaping their conceptual development. However, it remains unclear when parents begin to talk about categories with young children and whether such talk relates to children’s language skills. This study examines relations between parents’ talk about conceptual categories and infants’ expressive language development. Forty-seven parent-infant dyads were videotaped playing together at child age 10, 12, 14, and 16 months. Transcripts of interactions were analyzed to identify parents’ talk about conceptual categories. Children’s expressive language development was assessed at 18 months. Findings indicate that parents indeed talked about conceptual categories with infants and that talk was stable across time, with college-educated parents producing more than non-college-educated parents. Further, parents’ talk about conceptual categories between 10 and 16 months predicted children’s 18-month expressive language. This study sheds new light on mechanisms through which early experiences may support children’s language development.
THE POLITICS OF FUNDING: THE ROCKEFELLER FOUNDATION AND FRENCH ECONOMICS, 1945–1955
Authors: Benest Serge
Published: June 2022

Following World War II, the director of the social sciences division at the Rockefeller Foundation, the industrial economist Joseph H. Willits, thought it important to extend its activities to Europe, especially France. His agenda was to strengthen institutional economics and to create modern research centers with a view to stabilizing the political situation. In the postwar decade, almost all economic research centers in France were funded by the Foundation, which helped provide greater autonomy to French economists within academia but failed to reshape French economic training and research.
Seismic Sources in Stress‐Induced Anisotropic Media
Authors: Li Wenqiang , Hu Hengshan
Published: June 2022

Rocks in the upper mantle are extensively subjected to initial stress. The rock exhibits elastic anisotropy under the deviatoric stress, which affects the seismic response of underground structures. This paper aims to study the effect of stress‐induced anisotropy on the seismic source. The seismic moment tensor generated by a shear faulting in a homogeneous isotropic medium with initial stress is derived by using the motion description in the intermediate configuration, the constitutive relation of third‐order elasticity, and the boundary condition considering the effect of initial stress. Then the seismic moment tensor is decomposed to investigate seismic source characters quantitatively. Our results show that shear faulting in a stress‐induced anisotropic medium can produce significant non‐double‐couple (non‐DC) mechanisms, including compensated linear vector dipole (CLVD) and isotropic (ISO) components. ISO and CLVD components vary linearly with the initial shear stress on faults. In addition, stress‐induced anisotropy causes the double‐couple (DC) to deviate from the plane defined by the fault normal and slip direction. The initial stress not only affects the source intensity but also affects the propagation of seismic waves. The radiation patterns of longitudinal waves have non‐uniform lobes, which shows the characteristic of anisotropy. Stress‐induced anisotropic parameters are smaller than intrinsic anisotropy at high‐stress levels and a nearly linear function of the increased initial stress. These results underscore the importance of considering stress‐induced anisotropy in the inversion of focal mechanisms and provide a new perspective for monitoring underground stress.
Ecosystems at Glacier Margins Can Serve as Climate‐Change Laboratories
Authors: Gaglioti B. V. , Mann D. H. , Wiles G. C.
Published: June 2022

Reconstructing how biota have responded to fast‐paced warming events in the past can help predict their responses to rapid climate changes in the future. Here we suggest that natural communities located near glaciers are useful laboratories for this purpose as they experienced climate changes accentuated by past ice‐margin fluctuations. By reconstructing an Alaskan glacier's position over a 166‐year period and measuring the periglacial air temperatures over the last 3 years, we estimate that the adjacent temperate rainforest episodically cooled and warmed by 0.5–0.7°C/decade. These rates of change exceed most historical warming trends measured elsewhere on Earth and are comparable to the rates of climate warming predicted for the next century. The ring‐width responses of yellow‐cedar trees growing at varying distances from the ice edge illustrate the potential for using periglacial ecosystems to predict how forests may respond to rapid warming in the future.
Periodontitis may induce gut microbiota dysbiosis via salivary microbiota
Authors: Bao Jun , Li Lili , Zhang Yangheng , Wang Min , Chen Faming , Ge Shaohua , Chen Bin , Yan Fuhua
Published: June 2022

The aim of this study was to identify whether periodontitis induces gut microbiota dysbiosis via invasion by salivary microbes. First, faecal and salivary samples were collected from periodontally healthy participants (PH group, n = 16) and patients with severe periodontitis (SP group, n = 21) and analysed by 16S ribosomal RNA sequencing. Significant differences were observed in both the faecal and salivary microbiota between the PH and SP groups. Notably, more saliva-sourced microbes were observed in the faecal samples of the SP group. Then, the remaining salivary microbes were transplanted into C57BL6/J mice (the C-PH group and the C-SP group), and it was found that the composition of the gut microbiota of the C-SP group was significantly different from that of the C-PH group, with Porphyromonadaceae and Fusobacterium being significantly enriched in the C-SP group. In the colon, the C-SP group showed significantly reduced crypt depth and zonula occludens-1 expression. The mRNA expression levels of pro-inflammatory cytokines, chemokines and tight junction proteins were significantly higher in the C-SP group. To further investigate whether salivary bacteria could persist in the intestine, the salivary microbiota was stained with carboxyfluorescein diacetate succinimidyl ester and transplanted into mice. We found that salivary microbes from both the PH group and the SP group could persist in the gut for at least 24 h. Thus, our data demonstrate that periodontitis may induce gut microbiota dysbiosis through the influx of salivary microbes.
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

Pharmacologically 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

Circular 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

The 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

In-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

Pluripotent 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

In 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

The 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

The 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

The 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

Few 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

Achieving 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

Mitochondrial 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

Cell 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

Naturally, 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

NVSI-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

Quasi-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.
Poor outcome of pediatric patients with acute myeloid leukemia harboring high FLT3/ITD allelic ratios
Authors: Qiu Kun-yin , Liao Xiong-yu , Liu Yong , Huang Ke , Li Yang , Fang Jian-pei , Zhou Dun-hua
Published: June 2022

Activating FLT3 mutations are the most common mutations in acute myeloid leukemia (AML), but the optimal threshold of FLT3/ITD allelic ratio (AR) among pediatric AML patients remains controversial. Here, we present the outcome and prognostic significance of FLT3/ITD AR analysis among pediatric patients with AML from the TARGET dataset. Applying fitting curve models and threshold effect analysis using the restrictive cubic spline function following Cox proportional hazards models identifies the cut-off value of 0.5 on FLT3/ITD AR. Moreover, we observe that high FLT3/ITD AR patients have an inferior outcome when compared to low AR patients. Our study also demonstrates that stem cell transplantation may improve the outcome in pediatric AML patients with high FLT3/ITD AR and may be further improved when combined with additional therapies such as Gemtuzumab Ozogamicin. These findings underline the importance of individualized treatment of pediatric AML.
Age-dependent impact of two exercise training regimens on genomic and metabolic remodeling in skeletal muscle and liver of male mice
Authors: Bernier Michel , Enamorado Ignacio Navas , Gómez-Cabrera Mari Carmen , Calvo-Rubio Miguel , González-Reyes Jose Antonio , Price Nathan L. , Cortés-Rodríguez Ana Belén , Rodríguez-Aguilera Juan Carlos , Rodríguez-López Sandra , Mitchell Sarah J. , Murt Kelsey N. , Kalafut Krystle , Williams Katrina M. , Ward Christopher W. , Stains Joseph P. , Brea-Calvo Gloria , Villalba Jose M. , Cortassa Sonia , Aon Miguel A. , de Cabo Rafael
Published: June 2022

Skeletal muscle adapts to different exercise training modalities with age; however, the impact of both variables at the systemic and tissue levels is not fully understood. Here, adult and old C57BL/6 male mice were assigned to one of three groups: sedentary, daily high-intensity intermittent training (HIIT), or moderate intensity continuous training (MICT) for 4 weeks, compatible with the older group’s exercise capacity. Improvements in body composition, fasting blood glucose, and muscle strength were mostly observed in the MICT old group, while effects of HIIT training in adult and old animals was less clear. Skeletal muscle exhibited structural and functional adaptations to exercise training, as revealed by electron microscopy, OXPHOS assays, respirometry, and muscle protein biomarkers. Transcriptomics analysis of gastrocnemius muscle combined with liver and serum metabolomics unveiled an age-dependent metabolic remodeling in response to exercise training. These results support a tailored exercise prescription approach aimed at improving health and ameliorating age-associated loss of muscle strength and function in the elderly.
Piezoelectric strain sensor with high sensitivity and high stretchability based on kirigami design cutting
Authors: Kim Young-Gyun , Song Ji-Hyeon , Hong Seongheon , Ahn Sung-Hoon
Published: June 2022

Wearable technology requires high-performance sensors with properties such as small size, flexibility, and wireless communication. Stretchability, sensitivity, and tunability are crucial sensor properties; stretchability and sensitivity ensure user comfort and accurate sensing performance, while tunability is essential for implementing sensors in diverse applications with different ranges of motion. In this study, we developed a high performance kirigami piezoelectric strain sensor. Using finite element analysis, the sensing performance was evaluated, and the kirigami patterns were optimized. The electromechanical properties of sensors with four different kirigami patterns were analyzed. A sensor voltage measurement circuit was also designed, amplifying the output voltage 86.5 times by improving measurement accuracy. A piezoelectric kirigami sensor was constructed with a sensitivity of 9.86 V/cm2 and a stretchability of 320.8%, higher than those of previously reported kirigami piezoelectric strain sensors. Finally, the fabricated sensor was successfully applied in a haptic glove for playing musical instruments.
An epitope-optimized human H3N2 influenza vaccine induces broadly protective immunity in mice and ferrets
Authors: Bullard Brianna L. , DeBeauchamp Jennifer , Pekarek Matthew J. , Petro-Turnquist Erika , Vogel Peter , Webby Richard J. , Weaver Eric A.
Published: June 2022

There is a crucial need for an improved H3N2 influenza virus vaccine due to low vaccine efficacy rates and increased morbidity and mortality associated with H3N2-dominated influenza seasons. Here, we utilize a computational design strategy to produce epitope-optimized, broadly cross-reactive H3 hemagglutinins in order to create a universal H3N2 influenza vaccine. The Epigraph immunogens are designed to maximize the viral population frequency of epitopes incorporated into the immunogen. We compared our Epigraph H3 vaccine to the traditional egg-based inactivated influenza vaccine from 2018–19, FluZone. Epigraph vaccination-induced stronger cross-reactive antibody responses than FluZone against 18 H3N2 viruses isolated from 1968 to 2019 in both mice and ferrets, with protective hemagglutination inhibition titers against 93–100% of the contemporary H3N2 strains compared to only 27% protection measured from FluZone. In addition, Epigraph vaccination-induced strong cross-reactive T-cell immunity which significantly contributes to protection against lethal influenza virus infection. Finally, Epigraph vaccination protected ferrets from influenza disease after challenge with two H3N2 viruses. The superior cross-reactive immunity induced by these Epigraph immunogens supports their development as a universal H3N2 influenza vaccine.
Tree-ring data set for dendroclimatic reconstructions and dendrochronological dating in European Russia
Authors: Solomina Olga , Matskovsky Vladimir , Dolgova Ekaterina , Kuznetsova Veronika , Semenyak Nadezhda , Bebchuk Tatiana , Mikhalenko Vladimir , Karpukhin Alexey , Khasanov Bulat
Published: June 2022

The data set presented represents 15 years of collection. It contains tree-ring width measurements from 64 sites of living trees and ten historical chronologies based on archaeological and construction wood up to year 572 CE, altogether 2909 tree-ring series and more than 450000 measured and cross-dated tree rings. It covers the vast territory of European Russia, including its forested northern and central parts, and the Northern Caucasus mountains. The potential use of these data include climatic reconstructions of regional and hemispheric scale, dendrochronological dating of historical and cultural wood, ecological and remote sensing studies.
CRISPR activation screen identifies TGFβ-associated PEG10 as a crucial tumor suppressor in Ewing sarcoma
Authors: Saratov Vadim , Ngo Quy A. , Pedot Gloria , Sidorov Semjon , Wachtel Marco , Niggli Felix K. , Schäfer Beat W.
Published: June 2022

As the second most common pediatric bone and soft tissue tumor, Ewing sarcoma (ES) is an aggressive disease with a pathognomonic chromosomal translocation t(11;22) resulting in expression of EWS-FLI1, an “undruggable” fusion protein acting as transcriptional modulator. EWS-FLI1 rewires the protein expression in cancer cells by activating and repressing a multitude of genes. The role and contribution of most repressed genes remains unknown to date. To address this, we established a CRISPR activation system in clonal SKNMC cell lines and interrogated a custom focused library covering 871 genes repressed by EWS-FLI1. Among the hits several members of the TGFβ pathway were identified, where PEG10 emerged as prime candidate due to its strong antiproliferative effect. Mechanistic investigations revealed that PEG10 overexpression caused cellular dropout via induction of cell death. Furthermore, non-canonical TGFβ pathways such as RAF/MEK/ERK, MKK/JNK, MKK/P38, known to lead to apoptosis or autophagy, were highly activated upon PEG10 overexpression. Our study sheds new light onto the contribution of TGFβ signalling pathway repression to ES tumorigenesis and suggest that its re-activation might constitute a novel therapeutic strategy.
Microbial production of toluene in oxygen minimum zone waters in the Humboldt Current System off Chile
Authors: Srain Benjamín M. , Pantoja-Gutiérrez Silvio
Published: June 2022

Expansion of oxygen minimum zones in the world's oceans is likely to enhance the production of anaerobic metabolites by marine microorganisms. Here we show that toluene is present throughout the year in shelf waters of the upwelling ecosystem off Concepción (36° S), Chile, and it is a product of microbial anaerobic metabolism. The intra-annual variability in toluene concentrations is consistent with seasonal variability in the strengths of suboxic equatorial and oxygenated subantarctic water masses. Laboratory incubations of oxygen minimum zone water showed microbial production of toluene in the absence of O2. Toluene concentrations were elevated (up to 96 nM) in deeper O2-depleted waters and followed a seasonal pattern in oceanographic conditions. There is evidence to hypothesize that microbial production of toluene could be a homeostatic biochemical mechanism to thrive in the more acidic oxygen minimum zone waters. On the other hand, evidence indicates that microbial anaerobic degradation of toluene may be a source of NO2− by partial denitrification, as shown for aquifer sediments. Since toluene production was not detected in incubations under aerobic conditions, we hypothesize that oxygen minimum zone waters export toluene to surrounding oxygenated waters. Expansion of hypoxia in the ocean will certainly enhance the production and export of anaerobic metabolites by marine microorganisms.
Phylogenetic relationships among Bradyrhizobium species nodulating groundnut (Arachis hypogea L.), jack bean (Canavalia ensiformis L.) and soybean (Glycine max Merr.) in Eswatini
Authors: Ngwenya Zanele D. , Mohammed Mustapha , Jaiswal Sanjay K. , Dakora Felix D.
Published: June 2022

This study assessed the genetic diversity and phylogenetic relationships of rhizobial isolates obtained from root nodules of groundnut, jack bean and soybean planted in different locations within Eswatini. Seventy-six rhizobial isolates were studied using ERIC-PCR (enterobacterial repetitive intergenic consensus) fingerprinting and PCR amplification of 16S rRNA, housekeeping genes (atpD, dnaK, glnllandrpoB) and symbiotic genes (nifHandnodC). The dendrogram generated from the ERIC-PCR banding patterns grouped the test rhizobial isolates into 16 major clusters (Cluster I–XVI), with three isolates, namely TUTAHeS60, TUTGMeS3 and TUTAHeS127, forming outgroups of Clusters IV, VI and IX, respectively. Furthermore, the 76 test isolates were grouped into 56 ERIC-PCR types at 70% similarity level. The phylogenetic analysis of the 16S rRNA gene and multilocus sequence analysis of four housekeeping (atpD, dnaK, glnIIandrpoB) and two symbiotic (nifHandnodC) genes showed that all three legumes (groundnut, jack bean and soybean) were nodulated by bacterial symbionts belonging to the genusBradyrhizobium, with some isolates exhibiting high divergence from the known reference type strains. The results also showed thatB. arachidis, B. iriomotenseandB. canariensewere the closest type strains to the groundnut isolates, whileB. pachyrhiziandB. elkaniiwere the closest relatives to the bacterial symbionts associated with the nodulation of both jack bean and soybean. This study is the first report to describe of the bacterial symbionts nodulating jack bean in African soils.
A new type of half-metallic fully compensated ferrimagnet
Authors: Semboshi S. , Umetsu R. Y. , Kawahito Y. , Akai H.
Published: June 2022

Half-metallic fully compensated ferrimagnets (HM-FCFMs) constitute a special class of half-metals exhibiting zero magnetization at zero temperature. While there have been a number of theoretical studies predicting the existence of such materials over the last 25 years, very few of those have been synthesized and observed that they exhibit expected properties. Herein, we demonstrate that a NiAs-type hexagonal-structured (CrFe)S compound could serve as an HM-FCFM material. It has a half-metallic nature of 100% spin-polarised Fermi surfaces and yet zero magnetisation at the ground state. The magnetisation shows linear behaviour as a function of the magnetic field at temperatures below the compensation temperature (~ 190 K). In addition, it shows a high magnetic coercivity of 3.8 T at 300 K. These magnetic features contribute to a significant development in the application of HM-FCFMs for spintronics devices.