bluuebunny/crossref_metadata_2025 huggingface dataset:
Intermittent fasting enhances long-term memory consolidation, adult hippocampal neurogenesis, and expression of longevity gene Klotho
Authors: Dias Gisele Pereira , Murphy Tytus , Stangl Doris , Ahmet Selda , Morisse Benjamin , Nix Alina , Aimone Lindsey J. , Aimone James B. , Kuro-O Makoto , Gage Fred H. , Thuret Sandrine
Published: May 2021

Daily calorie restriction (CR) and intermittent fasting (IF) enhance longevity and cognition but the effects and mechanisms that differentiate these two paradigms are unknown. We examined whether IF in the form of every-other-day feeding enhances cognition and adult hippocampal neurogenesis (AHN) when compared to a matched 10% daily CR intake and ad libitum conditions. After 3 months under IF, female C57BL6 mice exhibited improved long-term memory retention. IF increased the number of BrdU-labeled cells and neuroblasts in the hippocampus, and microarray analysis revealed that the longevity gene Klotho (Kl) was upregulated in the hippocampus by IF only. Furthermore, we found that downregulating Kl in human hippocampal progenitor cells led to decreased neurogenesis, whereas Kl overexpression increased neurogenesis. Finally, histological analysis of Kl knockout mice brains revealed that Kl is required for AHN, particularly in the dorsal hippocampus. These data suggest that IF is superior to 10% CR in enhancing memory and identifies Kl as a novel candidate molecule that regulates the effects of IF on cognition likely via AHN enhancement.
The chosen few—variations in common and rare soil bacteria across biomes
Authors: Bickel Samuel , Or Dani
Published: May 2021

Soil bacterial communities are dominated by a few abundant species, while their richness is associated with rare species with largely unknown ecological roles and biogeography. Analyses of previously published soil bacterial community data using a novel classification of common and rare bacteria indicate that only 0.4% of bacterial species can be considered common and are prevalent across biomes. The remaining bacterial species designated as rare are endemic with low relative abundances. Observations coupled with mechanistic models highlight the central role of soil wetness in shaping bacterial rarity. An individual-based model reveals systematic shifts in community composition induced by low carbon inputs in drier soils that deprive common species of exhibiting physiological advantages relative to other species. We find that only a “chosen few” common species shape bacterial communities across biomes; however, their contributions are curtailed in resource-limited environments where a larger number of rare species constitutes the soil microbiome.
Novel strain-level resolution of Crohn’s disease mucosa-associated microbiota via an ex vivo combination of microbe culture and metagenomic sequencing
Authors: Teh J J , Berendsen E M , Hoedt E C , Kang S , Zhang J , Zhang F , Liu Q , Hamilton A L , Wilson-O’Brien A , Ching J , Sung J J Y , Yu J , Ng S C , Kamm M A , Morrison M
Published: May 2021

The mucosa-associated microbiota is widely recognized as a potential trigger for Crohn’s disease pathophysiology but remains largely uncharacterised beyond its taxonomic composition. Unlike stool microbiota, the functional characterisation of these communities using current DNA/RNA sequencing approaches remains constrained by the relatively small microbial density on tissue, and the overwhelming amount of human DNA recovered during sample preparation. Here, we have used a novel ex vivo approach that combines microbe culture from anaerobically preserved tissue with metagenome sequencing (MC-MGS) to reveal patient-specific and strain-level differences among these communities in post-operative Crohn’s disease patients. The 16 S rRNA gene amplicon profiles showed these cultures provide a representative and holistic representation of the mucosa-associated microbiota, and MC-MGS produced both high quality metagenome-assembled genomes of recovered novel bacterial lineages. The MC-MGS approach also produced a strain-level resolution of key Enterobacteriacea and their associated virulence factors and revealed that urease activity underpins a key and diverse metabolic guild in these communities, which was confirmed by culture-based studies with axenic cultures. Collectively, these findings using MC-MGS show that the Crohn’s disease mucosa-associated microbiota possesses taxonomic and functional attributes that are highly individualistic, borne at least in part by novel bacterial lineages not readily isolated or characterised from stool samples using current sequencing approaches.
In-depth analysis of N2O fluxes in tropical forest soils of the Congo Basin combining isotope and functional gene analysis
Authors: Gallarotti Nora , Barthel Matti , Verhoeven Elizabeth , Pereira Engil Isadora Pujol , Bauters Marijn , Baumgartner Simon , Drake Travis W , Boeckx Pascal , Mohn Joachim , Longepierre Manon , Mugula John Kalume , Makelele Isaac Ahanamungu , Ntaboba Landry Cizungu , Six Johan
Published: May 2021

Primary tropical forests generally exhibit large gaseous nitrogen (N) losses, occurring as nitric oxide (NO), nitrous oxide (N2O) or elemental nitrogen (N2). The release of N2O is of particular concern due to its high global warming potential and destruction of stratospheric ozone. Tropical forest soils are predicted to be among the largest natural sources of N2O; however, despite being the world’s second-largest rainforest, measurements of gaseous N-losses from forest soils of the Congo Basin are scarce. In addition, long-term studies investigating N2O fluxes from different forest ecosystem types (lowland and montane forests) are scarce. In this study we show that fluxes measured in the Congo Basin were lower than fluxes measured in the Neotropics, and in the tropical forests of Australia and South East Asia. In addition, we show that despite different climatic conditions, average annual N2O fluxes in the Congo Basin’s lowland forests (0.97 ± 0.53 kg N ha−1 year−1) were comparable to those in its montane forest (0.88 ± 0.97 kg N ha−1 year−1). Measurements of soil pore air N2O isotope data at multiple depths suggests that a microbial reduction of N2O to N2 within the soil may account for the observed low surface N2O fluxes and low soil pore N2O concentrations. The potential for microbial reduction is corroborated by a significant abundance and expression of the gene nosZ in soil samples from both study sites. Although isotopic and functional gene analyses indicate an enzymatic potential for complete denitrification, combined gaseous N-losses (N2O, N2) are unlikely to account for the missing N-sink in these forests. Other N-losses such as NO, N2 via Feammox or hydrological particulate organic nitrogen export could play an important role in soils of the Congo Basin and should be the focus of future research.
OTUD7B stabilizes estrogen receptor α and promotes breast cancer cell proliferation
Authors: Tang Jianing , Wu Zeyu , Tian Zelin , Chen Wei , Wu Gaosong
Published: May 2021

Breast cancer is the most common malignancy in women worldwide. Estrogen receptor α (ERα) is expressed in ∼70% of breast cancer cases and promotes estrogen-dependent cancer progression. In the present study, we identified OTU domain-containing 7B (OTUD7B), a deubiquitylase belonging to A20 subgroup of ovarian tumor protein superfamily, as a bona fide deubiquitylase of ERα in breast cancer. OTUD7B expression was found to be positively correlated with ERα in breast cancer and associated with poor prognosis. OTUD7B could interact with, deubiquitylate, and stabilize ERα in a deubiquitylation activity-dependent manner. Depletion of OTUD7B decreased ERα protein level, the expression of ERα target genes, and the activity of estrogen response element in breast cancer cells. In addition, OTUD7B depletion significantly decreased ERα-positive breast cancer cell proliferation and migration. Finally, overexpression of ERα could rescue the suppressive effect induced by OTUD7B depletion, suggesting that the ERα status was essential to the function of OTUD7B in breast carcinogenesis. In conclusion, our study revealed an interesting post-translational mechanism between ERα and OTUD7B in ERα-positive breast cancer. Targeting the OTUD7B–ERα complex may prove to be a potential approach to treat patients with ERα-positive breast cancer.
Colorectal cancer cell intrinsic fibroblast activation protein alpha binds to Enolase1 and activates NF-κB pathway to promote metastasis
Authors: Yuan Ziming , Hu Hanqing , Zhu Yihao , Zhang Weiyuan , Fang Qingxiao , Qiao Tianyu , Ma Tianyi , Wang Meng , Huang Rui , Tang Qingchao , Gao Feng , Zou Chaoxia , Gao Xu , Wang Guiyu , Wang Xishan
Published: May 2021

Fibroblast activation protein alpha (FAP) is a marker of cancer-associated fibroblast, which is also expressed in cancer epithelial cells. However, the role of FAP in colorectal cancer (CRC) cells remains to be elucidated. Here we investigate the expression pattern of FAP in CRC tissues and cells to prove that FAP is upregulated in CRC cells. Loss- of and gain-of-function assays identified FAP promotes migration and invasion instead of an effect on cell proliferation. Microarray assays are adopted to identify the different expressed genes after FAP knockdown and gene set enrichment analysis (GSEA) is used to exploit the involved signaling pathway. Our works reveal FAP exerts a function dependent on NF-κB signaling pathway and FAP expression is associated with NF-κB signaling pathway in clinical samples. Our work shows FAP is secreted by CRC cells and soluble FAP could promote metastasis. To investigate the mechanism of FAP influencing the NF-κB signaling pathway, LC/MS is performed to identify the proteins interacting with FAP. We find that FAP binds to ENO1 and activates NF-κB signaling pathway dependent on ENO1. Blocking ENO1 could partially reverse the pro-metastatic effect mediated by FAP. We also provide evidences that both FAP and ENO1 are associated with CRC stages, and high levels of FAP and ENO1 predict a poor survival in CRC patients. In summary, our work could provide a novel mechanism of FAP in CRC cells and a potential strategy for treatment of metastatic CRC.
Circ_0001367 inhibits glioma proliferation, migration and invasion by sponging miR-431 and thus regulating NRXN3
Authors: Liu Liang , Zhang Peng , Dong Xuchen , Li Haoran , Li Suwen , Cheng Shan , Yuan Jiaqi , Yang Xuejun , Qian Zhiyuan , Dong Jun
Published: May 2021

Many studies have reported that circular RNAs play a vital role in the malignant progression of human cancers. However, the role and underlying mechanism of circRNAs in the development of gliomas have not been fully clarified. In this study, we found that circ_0001367 was downregulated in glioma tissues and showed a close correlation with glioma patient survival. Functional assays demonstrated that upregulation of circ_0001367 could suppress the proliferation, migration and invasion of glioma cells in vitro and inhibit glioma growth in vivo. Furthermore, bioinformatics analysis, luciferase reporter assay and RNA immunoprecipitation assay indicated that circ_0001367 can serve as a sponge for miR-431 and that miR-431 acts as an oncogene by regulating neurexin 3 (NRXN3). In addition, rescue experiments verified that circ_0001367 could regulate both the expression and function of NRXN3 in a miR-431-dependent manner. In conclusion, circ_0001367 functions as an suppressor in glioma by targeting the miR-431/NRXN3 axis and may be a promising therapeutic target against gliomas.
A Japanese hereditary spastic paraplegia family with a rare nonsynonymous variant in the SPAST gene
Authors: Morikawa Takuya , Miura Shiroh , Tateishi Takahisa , Noda Kazuhito , Shibata Hiroki
Published: May 2021

Spastic paraplegia (SPG) type 4 is an autosomal dominant SPG caused by functional variants in the SPAST gene. We examined a Japanese family with three autosomal dominant SPG patients. These patients presented with typical symptoms of SPG, such as spasticity of the lower limbs. We identified a rare nonsynonymous variant, NM_014946.4:c.1252G>A [p.Glu418Lys], in all three family members. This variant has previously been reported in a Russian SPG family as a “likely pathogenic” variant.5 Ascertainment of additional patients carrying this variant in an unrelated Japanese SPG family further supports its pathogenicity. Molecular diagnosis of SPG4 in this family with hereditary spastic paraplegia is confirmed.
Decreased GLUT2 and glucose uptake contribute to insulin secretion defects in MODY3/HNF1A hiPSC-derived mutant β cells
Authors: Low Blaise Su Jun , Lim Chang Siang , Ding Shirley Suet Lee , Tan Yaw Sing , Ng Natasha Hui Jin , Krishnan Vidhya Gomathi , Ang Su Fen , Neo Claire Wen Ying , Verma Chandra S. , Hoon Shawn , Lim Su Chi , Tai E. Shyong , Teo Adrian Kee Keong
Published: May 2021

Heterozygous HNF1A gene mutations can cause maturity onset diabetes of the young 3 (MODY3), characterized by insulin secretion defects. However, specific mechanisms of MODY3 in humans remain unclear due to lack of access to diseased human pancreatic cells. Here, we utilize MODY3 patient-derived human induced pluripotent stem cells (hiPSCs) to study the effect(s) of a causal HNF1A+/H126D mutation on pancreatic function. Molecular dynamics simulations predict that the H126D mutation could compromise DNA binding and gene target transcription. Genome-wide RNA-Seq and ChIP-Seq analyses on MODY3 hiPSC-derived endocrine progenitors reveal numerous HNF1A gene targets affected by the mutation. We find decreased glucose transporter GLUT2 expression, which is associated with reduced glucose uptake and ATP production in the MODY3 hiPSC-derived β-like cells. Overall, our findings reveal the importance of HNF1A in regulating GLUT2 and several genes involved in insulin secretion that can account for the insulin secretory defect clinically observed in MODY3 patients.
Longitudinal analysis of blood markers reveals progressive loss of resilience and predicts human lifespan limit
Authors: Pyrkov Timothy V. , Avchaciov Konstantin , Tarkhov Andrei E. , Menshikov Leonid I. , Gudkov Andrei V. , Fedichev Peter O.
Published: May 2021

We investigated the dynamic properties of the organism state fluctuations along individual aging trajectories in a large longitudinal database of CBC measurements from a consumer diagnostics laboratory. To simplify the analysis, we used a log-linear mortality estimate from the CBC variables as a single quantitative measure of the aging process, henceforth referred to as dynamic organism state indicator (DOSI). We observed, that the age-dependent population DOSI distribution broadening could be explained by a progressive loss of physiological resilience measured by the DOSI auto-correlation time. Extrapolation of this trend suggested that DOSI recovery time and variance would simultaneously diverge at a critical point of 120 − 150 years of age corresponding to a complete loss of resilience. The observation was immediately confirmed by the independent analysis of correlation properties of intraday physical activity levels fluctuations collected by wearable devices. We conclude that the criticality resulting in the end of life is an intrinsic biological property of an organism that is independent of stress factors and signifies a fundamental or absolute limit of human lifespan.
Motion of water monomers reveals a kinetic barrier to ice nucleation on graphene
Authors: Tamtögl Anton , Bahn Emanuel , Sacchi Marco , Zhu Jianding , Ward David J. , Jardine Andrew P. , Jenkins Stephen J. , Fouquet Peter , Ellis John , Allison William
Published: May 2021

The interfacial behaviour of water remains a central question to fields as diverse as protein folding, friction and ice formation. While the properties of water at interfaces differ from those in the bulk, major gaps in our knowledge limit our understanding at the molecular level. Information concerning the microscopic motion of water comes mostly from computation and, on an atomic scale, is largely unexplored by experiment. Here, we provide a detailed insight into the behaviour of water monomers on a graphene surface. The motion displays remarkably strong signatures of cooperative behaviour due to repulsive forces between the monomers, enhancing the monomer lifetime ( ≈ 3 s at 125 K) in a free-gas phase that precedes the nucleation of ice islands and, in turn, provides the opportunity for our experiments to be performed. Our results give a molecular perspective on a kinetic barrier to ice nucleation, providing routes to understand and control the processes involved in ice formation.
Network isolators inhibit failure spreading in complex networks
Authors: Kaiser Franz , Latora Vito , Witthaut Dirk
Published: May 2021

In our daily lives, we rely on the proper functioning of supply networks, from power grids to water transmission systems. A single failure in these critical infrastructures can lead to a complete collapse through a cascading failure mechanism. Counteracting strategies are thus heavily sought after. In this article, we introduce a general framework to analyse the spreading of failures in complex networks and demostrate that not only decreasing but also increasing the connectivity of the network can be an effective method to contain damages. We rigorously prove the existence of certain subgraphs, called network isolators, that can completely inhibit any failure spreading, and we show how to create such isolators in synthetic and real-world networks. The addition of selected links can thus prevent large scale outages as demonstrated for power transmission grids.
A 3D system to model human pancreas development and its reference single-cell transcriptome atlas identify signaling pathways required for progenitor expansion
Authors: Gonçalves Carla A. , Larsen Michael , Jung Sascha , Stratmann Johannes , Nakamura Akiko , Leuschner Marit , Hersemann Lena , Keshara Rashmiparvathi , Perlman Signe , Lundvall Lene , Thuesen Lea Langhoff , Hare Kristine Juul , Amit Ido , Jørgensen Anne , Kim Yung Hae , del Sol Antonio , Grapin-Botton Anne
Published: May 2021

Human organogenesis remains relatively unexplored for ethical and practical reasons. Here, we report the establishment of a single-cell transcriptome atlas of the human fetal pancreas between 7 and 10 post-conceptional weeks of development. To interrogate cell–cell interactions, we describe InterCom, an R-Package we developed for identifying receptor–ligand pairs and their downstream effects. We further report the establishment of a human pancreas culture system starting from fetal tissue or human pluripotent stem cells, enabling the long-term maintenance of pancreas progenitors in a minimal, defined medium in three-dimensions. Benchmarking the cells produced in 2-dimensions and those expanded in 3-dimensions to fetal tissue identifies that progenitors expanded in 3-dimensions are transcriptionally closer to the fetal pancreas. We further demonstrate the potential of this system as a screening platform and identify the importance of the EGF and FGF pathways controlling human pancreas progenitor expansion.
mRNA therapy restores euglycemia and prevents liver tumors in murine model of glycogen storage disease
Authors: Cao Jingsong , Choi Minjung , Guadagnin Eleonora , Soty Maud , Silva Marine , Verzieux Vincent , Weisser Edward , Markel Arianna , Zhuo Jenny , Liang Shi , Yin Ling , Frassetto Andrea , Graham Anne-Renee , Burke Kristine , Ketova Tatiana , Mihai Cosmin , Zalinger Zach , Levy Becca , Besin Gilles , Wolfrom Meredith , Tran Barbara , Tunkey Christopher , Owen Erik , Sarkis Joe , Dousis Athanasios , Presnyak Vladimir , Pepin Christopher , Zheng Wei , Ci Lei , Hard Marjie , Miracco Edward , Rice Lisa , Nguyen Vi , Zimmer Mike , Rajarajacholan Uma , Finn Patrick F. , Mithieux Gilles , Rajas Fabienne , Martini Paolo G. V. , Giangrande Paloma H.
Published: May 2021

Glycogen Storage Disease 1a (GSD1a) is a rare, inherited metabolic disorder caused by deficiency of glucose 6-phosphatase (G6Pase-α). G6Pase-α is critical for maintaining interprandial euglycemia. GSD1a patients exhibit life-threatening hypoglycemia and long-term liver complications including hepatocellular adenomas (HCAs) and carcinomas (HCCs). There is no treatment for GSD1a and the current standard-of-care for managing hypoglycemia (Glycosade®/modified cornstarch) fails to prevent HCA/HCC risk. Therapeutic modalities such as enzyme replacement therapy and gene therapy are not ideal options for patients due to challenges in drug-delivery, efficacy, and safety. To develop a new treatment for GSD1a capable of addressing both the life-threatening hypoglycemia and HCA/HCC risk, we encapsulated engineered mRNAs encoding human G6Pase-α in lipid nanoparticles. We demonstrate the efficacy and safety of our approach in a preclinical murine model that phenotypically resembles the human condition, thus presenting a potential therapy that could have a significant therapeutic impact on the treatment of GSD1a.
Novel symmetrical bifacial flexible CZTSSe thin film solar cells for indoor photovoltaic applications
Authors: Deng Hui , Sun Quanzhen , Yang Zhiyuan , Li Wangyang , Yan Qiong , Zhang Caixia , Zheng Qiao , Wang Xinghui , Lai Yunfeng , Cheng Shuying
Published: May 2021

Environment-friendly flexible Cu2ZnSn(S,Se)4 (CZTSSe) solar cells show great potentials for indoor photovoltaic market. Indoor lighting is weak and multi-directional, thus the researches of photovoltaic device structures, techniques and performances face new challenges. Here, we design symmetrical bifacial CZTSSe solar cells on flexible Mo-foil substrate to efficiently harvest the indoor energy. Such devices are fabricated by double-sided deposition techniques to ensure bifacial consistency and save cost. We report 9.3% and 9% efficiencies for the front and back sides of the flexible CZTSSe solar cell under the standard sun light. Considering the indoor environment, we verify weak-light response performance of the devices under LED illumination and flexibility properties after thousands of bending. Bifacial CZTSSe solar cells in parallel achieve the superposition of double-sided output current from multi-directional light, significantly enhancing the area utilization rate. The present results and methods are expected to expand indoor photovoltaic applications.
Amorphization-induced surface electronic states modulation of cobaltous oxide nanosheets for lithium-sulfur batteries
Authors: Li Ruilong , Rao Dewei , Zhou Jianbin , Wu Geng , Wang Guanzhong , Zhu Zixuan , Han Xiao , Sun Rongbo , Li Hai , Wang Chao , Yan Wensheng , Zheng Xusheng , Cui Peixin , Wu Yuen , Wang Gongming , Hong Xun
Published: May 2021

Lithium-sulfur batteries show great potential to achieve high-energy-density storage, but their long-term stability is still limited due to the shuttle effect caused by the dissolution of polysulfides into electrolyte. Herein, we report a strategy of significantly improving the polysulfides adsorption capability of cobaltous oxide by amorphization-induced surface electronic states modulation. The amorphous cobaltous oxide nanosheets as the cathode additives for lithium-sulfur batteries demonstrates the rate capability and cycling stability with an initial capacity of 1248.2 mAh g-1 at 1 C and a substantial capacity retention of 1037.3 mAh g-1 after 500 cycles. X-ray absorption spectroscopy analysis reveal that the coordination structures and symmetry of ligand field around Co atoms of cobaltous oxide nanosheets are notably changed after amorphization. Moreover, DFT studies further indicate that amorphization-induced re-distribution of d orbital makes more electrons occupy high energy level, thereby resulting in a high binding energy with polysulfides for favorable adsorption.
Molecular motion and tridimensional nanoscale localization of kindlin control integrin activation in focal adhesions
Authors: Orré Thomas , Joly Adrien , Karatas Zeynep , Kastberger Birgit , Cabriel Clément , Böttcher Ralph T. , Lévêque-Fort Sandrine , Sibarita Jean-Baptiste , Fässler Reinhard , Wehrle-Haller Bernhard , Rossier Olivier , Giannone Grégory
Published: May 2021

Focal adhesions (FAs) initiate chemical and mechanical signals involved in cell polarity, migration, proliferation and differentiation. Super-resolution microscopy revealed that FAs are organized at the nanoscale into functional layers from the lower plasma membrane to the upper actin cytoskeleton. Yet, how FAs proteins are guided into specific nano-layers to promote interaction with given targets is unknown. Using single protein tracking, super-resolution microscopy and functional assays, we link the molecular behavior and 3D nanoscale localization of kindlin with its function in integrin activation inside FAs. We show that immobilization of integrins in FAs depends on interaction with kindlin. Unlike talin, kindlin displays free diffusion along the plasma membrane outside and inside FAs. We demonstrate that the kindlin Pleckstrin Homology domain promotes membrane diffusion and localization to the membrane-proximal integrin nano-layer, necessary for kindlin enrichment and function in FAs. Using kindlin-deficient cells, we show that kindlin membrane localization and diffusion are crucial for integrin activation, cell spreading and FAs formation. Thus, kindlin uses a different route than talin to reach and activate integrins, providing a possible molecular basis for their complementarity during integrin activation.
The P-type ATPase transporter ATP7A promotes angiogenesis by limiting autophagic degradation of VEGFR2
Authors: Ash Dipankar , Sudhahar Varadarajan , Youn Seock-Won , Okur Mustafa Nazir , Das Archita , O’Bryan John P. , McMenamin Maggie , Hou Yali , Kaplan Jack H. , Fukai Tohru , Ushio-Fukai Masuko
Published: May 2021

VEGFR2 (KDR/Flk1) signaling in endothelial cells (ECs) plays a central role in angiogenesis. The P-type ATPase transporter ATP7A regulates copper homeostasis, and its role in VEGFR2 signaling and angiogenesis is entirely unknown. Here, we describe the unexpected crosstalk between the Copper transporter ATP7A, autophagy, and VEGFR2 degradation. The functional significance of this Copper transporter was demonstrated by the finding that inducible EC-specific ATP7A deficient mice or ATP7A-dysfunctional ATP7Amut mice showed impaired post-ischemic neovascularization. In ECs, loss of ATP7A inhibited VEGF-induced VEGFR2 signaling and angiogenic responses, in part by promoting ligand-induced VEGFR2 protein degradation. Mechanistically, VEGF stimulated ATP7A translocation from the trans-Golgi network to the plasma membrane where it bound to VEGFR2, which prevented autophagy-mediated lysosomal VEGFR2 degradation by inhibiting autophagic cargo/adapter p62/SQSTM1 binding to ubiquitinated VEGFR2. Enhanced autophagy flux due to ATP7A dysfunction in vivo was confirmed by autophagy reporter CAG-ATP7Amut -RFP-EGFP-LC3 transgenic mice. In summary, our study uncovers a novel function of ATP7A to limit autophagy-mediated degradation of VEGFR2, thereby promoting VEGFR2 signaling and angiogenesis, which restores perfusion recovery and neovascularization. Thus, endothelial ATP7A is identified as a potential therapeutic target for treatment of ischemic cardiovascular diseases.
Spurious North Tropical Atlantic precursors to El Niño
Authors: Zhang Wenjun , Jiang Feng , Stuecker Malte F. , Jin Fei-Fei , Timmermann Axel
Published: May 2021

The El Niño-Southern Oscillation (ENSO), the primary driver of year-to-year global climate variability, is known to influence the North Tropical Atlantic (NTA) sea surface temperature (SST), especially during boreal spring season. Focusing on statistical lead-lag relationships, previous studies have proposed that interannual NTA SST variability can also feed back on ENSO in a predictable manner. However, these studies did not properly account for ENSO’s autocorrelation and the fact that the SST in the Atlantic and Pacific, as well as their interaction are seasonally modulated. This can lead to misinterpretations of causality and the spurious identification of Atlantic precursors for ENSO. Revisiting this issue under consideration of seasonality, time-varying ENSO frequency, and greenhouse warming, we demonstrate that the cross-correlation characteristics between NTA SST and ENSO, are consistent with a one-way Pacific to Atlantic forcing, even though the interpretation of lead-lag relationships may suggest otherwise.
Deterministic transfer of optical-quality carbon nanotubes for atomically defined technology
Authors: Otsuka Keigo , Fang Nan , Yamashita Daiki , Taniguchi Takashi , Watanabe Kenji , Kato Yuichiro K.
Published: May 2021

When continued device scaling reaches the ultimate limit imposed by atoms, technology based on atomically precise structures is expected to emerge. Device fabrication will then require building blocks with identified atomic arrangements and assembly of the components without contamination. Here we report on a versatile dry transfer technique for deterministic placement of optical-quality carbon nanotubes. Single-crystalline anthracene is used as a medium which readily sublimes by mild heating, leaving behind clean nanotubes and thus enabling bright photoluminescence. We are able to position nanotubes of a desired chirality with a sub-micron accuracy under in-situ optical monitoring, thereby demonstrating deterministic coupling of a nanotube to a photonic crystal nanobeam cavity. A cross junction structure is also designed and constructed by repeating the nanotube transfer, where intertube exciton transfer is observed. Our results represent an important step towards development of devices consisting of atomically precise components and interfaces.
Reducing Dzyaloshinskii-Moriya interaction and field-free spin-orbit torque switching in synthetic antiferromagnets
Authors: Chen Ruyi , Cui Qirui , Liao Liyang , Zhu Yingmei , Zhang Ruiqi , Bai Hua , Zhou Yongjian , Xing Guozhong , Pan Feng , Yang Hongxin , Song Cheng
Published: May 2021

Perpendicularly magnetized synthetic antiferromagnets (SAF), possessing low net magnetization and high thermal stability as well as easy reading and writing characteristics, have been intensively explored to replace the ferromagnetic free layers of magnetic tunnel junctions as the kernel of spintronic devices. So far, utilizing spin-orbit torque (SOT) to realize deterministic switching of perpendicular SAF have been reported while a large external magnetic field is typically needed to break the symmetry, making it impractical for applications. Here, combining theoretic analysis and experimental results, we report that the effective modulation of Dzyaloshinskii-Moriya interaction by the interfacial crystallinity between ferromagnets and adjacent heavy metals plays an important role in domain wall configurations. By adjusting the domain wall configuration between Bloch type and Néel type, we successfully demonstrate the field-free SOT-induced magnetization switching in [Co/Pd]/Ru/[Co/Pd] SAF devices constructed with a simple wedged structure. Our work provides a practical route for utilization of perpendicularly SAF in SOT devices and paves the way for magnetic memory devices with high density, low stray field, and low power consumption.
Cellular lensing and near infrared fluorescent nanosensor arrays to enable chemical efflux cytometry
Authors: Cho Soo-Yeon , Gong Xun , Koman Volodymyr B. , Kuehne Matthias , Moon Sun Jin , Son Manki , Lew Tedrick Thomas Salim , Gordiichuk Pavlo , Jin Xiaojia , Sikes Hadley D. , Strano Michael S.
Published: May 2021

Nanosensors have proven to be powerful tools to monitor single cells, achieving spatiotemporal precision even at molecular level. However, there has not been way of extending this approach to statistically relevant numbers of living cells. Herein, we design and fabricate nanosensor array in microfluidics that addresses this limitation, creating a Nanosensor Chemical Cytometry (NCC). nIR fluorescent carbon nanotube array is integrated along microfluidic channel through which flowing cells is guided. We can utilize the flowing cell itself as highly informative Gaussian lenses projecting nIR profiles and extract rich information. This unique biophotonic waveguide allows for quantified cross-correlation of biomolecular information with various physical properties and creates label-free chemical cytometer for cellular heterogeneity measurement. As an example, the NCC can profile the immune heterogeneities of human monocyte populations at attomolar sensitivity in completely non-destructive and real-time manner with rate of ~600 cells/hr, highest range demonstrated to date for state-of-the-art chemical cytometry.
Sulfur stabilizing metal nanoclusters on carbon at high temperatures
Authors: Yin Peng , Luo Xiao , Ma Yanfu , Chu Sheng-Qi , Chen Si , Zheng Xusheng , Lu Junling , Wu Xiao-Jun , Liang Hai-Wei
Published: May 2021

Supported metal nanoclusters consisting of several dozen atoms are highly attractive for heterogeneous catalysis with unique catalytic properties. However, the metal nanocluster catalysts face the challenges of thermal sintering and consequent deactivation owing to the loss of metal surface areas particularly in the applications of high-temperature reactions. Here, we report that sulfur—a documented poison reagent for metal catalysts—when doped in a carbon matrix can stabilize ~1 nanometer metal nanoclusters (Pt, Ru, Rh, Os, and Ir) at high temperatures up to 700 °C. We find that the enhanced adhesion strength between metal nanoclusters and the sulfur-doped carbon support, which arises from the interfacial metal-sulfur bonding, greatly retards both metal atom diffusion and nanocluster migration. In catalyzing propane dehydrogenation at 550 °C, the sulfur-doped carbon supported Pt nanocluster catalyst with interfacial electronic effects exhibits higher selectivity to propene as well as more stable durability than sulfur-free carbon supported catalysts.
Boosting oxygen reduction activity and enhancing stability through structural transformation of layered lithium manganese oxide
Authors: Zhong Xuepeng , Oubla M’hamed , Wang Xiao , Huang Yangyang , Zeng Huiyan , Wang Shaofei , Liu Kun , Zhou Jian , He Lunhua , Zhong Haihong , Alonso-Vante Nicolas , Wang Chin-Wei , Wu Wen-Bin , Lin Hong-Ji , Chen Chien-Te , Hu Zhiwei , Huang Yunhui , Ma Jiwei
Published: May 2021

Structural degradation in manganese oxides leads to unstable electrocatalytic activity during long-term cycles. Herein, we overcome this obstacle by using proton exchange on well-defined layered Li2MnO3 with an O3-type structure to construct protonated Li2-xHxMnO3-n with a P3-type structure. The protonated catalyst exhibits high oxygen reduction reaction activity and excellent stability compared to previously reported cost-effective Mn-based oxides. Configuration interaction and density functional theory calculations indicate that Li2-xHxMnO3-n has fewer unstable O 2p holes with a Mn3.7+ valence state and a reduced interlayer distance, originating from the replacement of Li by H. The former is responsible for the structural stability, while the latter is responsible for the high transport property favorable for boosting activity. The optimization of both charge states to reduce unstable O 2p holes and crystalline structure to reduce the reaction pathway is an effective strategy for the rational design of electrocatalysts, with a likely extension to a broad variety of layered alkali-containing metal oxides.
Hydroarylation of olefins catalysed by a dimeric ytterbium(II) alkyl
Authors: Richardson Georgia M. , Douair Iskander , Cameron Scott A. , Bracegirdle Joe , Keyzers Robert A. , Hill Michael S. , Maron Laurent , Anker Mathew D.
Published: May 2021

Although the nucleophilic alkylation of aromatics has recently been achieved with a variety of potent main group reagents, all of this reactivity is limited to a stoichiometric regime. We now report that the ytterbium(II) hydride, [BDIDippYbH]2 (BDIDipp = CH[C(CH3)NDipp]2, Dipp = 2,6-diisopropylphenyl), reacts with ethene and propene to provide the ytterbium(II) n-alkyls, [BDIDippYbR]2 (R = Et or Pr), both of which alkylate benzene at room temperature. Density functional theory (DFT) calculations indicate that this latter process operates through the nucleophilic (SN2) displacement of hydride, while the resultant regeneration of [BDIDippYbH]2 facilitates further reaction with ethene or propene and enables the direct catalytic (anti-Markovnikov) hydroarylation of both alkenes with a benzene C-H bond.
Probing of the internal damage morphology in multilayered high-temperature superconducting wires
Authors: Zhou You-He , Liu Cong , Shen Lei , Zhang Xingyi
Published: May 2021

The second generation HTS wires have been used in many superconducting components of electrical engineering after they were fabricated. New challenge what we face to is how the damages occur in such wires with multi-layer structure under both mechanical and extreme environment, which also dominates their quality. In this work, a macroscale technique combined a real-time magneto-optical imaging with a cryogenic uniaxial-tensile loading system was established to investigate the damage behavior accompanied with magnetic flux evolution. Under a low speed of tensile strain, it was found that the local magnetic flux moves gradually to form intermittent multi-stack spindle penetrations, which corresponds to the cracks initiated from substrate and extend along both tape thickness and width directions, where the amorphous phases at the tip of cracks were also observed. The obtained results reveal the mechanism of damage formation and provide a potential orientation for improving mechanical quality of these wires.
Endogenous memory reactivation during sleep in humans is clocked by slow oscillation-spindle complexes
Authors: Schreiner Thomas , Petzka Marit , Staudigl Tobias , Staresina Bernhard P.
Published: May 2021

Sleep is thought to support memory consolidation via reactivation of prior experiences, with particular electrophysiological sleep signatures (slow oscillations (SOs) and sleep spindles) gating the information flow between relevant brain areas. However, empirical evidence for a role of endogenous memory reactivation (i.e., without experimentally delivered memory cues) for consolidation in humans is lacking. Here, we devised a paradigm in which participants acquired associative memories before taking a nap. Multivariate decoding was then used to capture endogenous memory reactivation during non-rapid eye movement (NREM) sleep in surface EEG recordings. Our results reveal reactivation of learning material during SO-spindle complexes, with the precision of SO-spindle coupling predicting reactivation strength. Critically, reactivation strength (i.e. classifier evidence in favor of the previously studied stimulus category) in turn predicts the level of consolidation across participants. These results elucidate the memory function of sleep in humans and emphasize the importance of SOs and spindles in clocking endogenous consolidation processes.
Modulation of the immune microenvironment of high-risk ductal carcinoma in situ by intralesional pembrolizumab injection
Authors: Glencer Alexa C. , Wong Jasmine M. , Hylton Nola M. , Krings Gregor , McCune Emma , Rothschild Harriet T. , Loveday Tristan A. , Alvarado Michael D. , Esserman Laura J. , Campbell Michael J.
Published: May 2021

Ductal carcinoma in situ (DCIS) is a risk factor for the subsequent development of invasive breast cancer. High-risk features include age <45 years, size >5 cm, high-grade, palpable mass, hormone receptor negativity, and HER2 positivity. We have previously shown that immune infiltrates are positively associated with these high-risk features, suggesting that manipulating the immune microenvironment in high-risk DCIS could potentially alter disease progression. Patients with high-risk DCIS were enrolled in this 3 × 3 phase 1 dose-escalation pilot study of 2, 4, and 8 mg intralesional injections of the PD-1 immune checkpoint inhibitor, pembrolizumab. Study participants received two intralesional injections, three weeks apart, prior to surgery. Tissue from pre-treatment biopsies and post-treatment surgical resections was analyzed using multiplex immunofluorescence (mIF) staining for various immune cell populations. The intralesional injections were easily administered and well-tolerated. mIF analyses demonstrated significant increases in total T cell and CD8+ T cell percentages in most patients after receiving pembrolizumab, even at the 2 mg dose. T cell expansion was confined primarily to the stroma rather than within DCIS-containing ducts. Neither cleaved caspase 3 (CC3) staining, a marker for apoptosis, nor DCIS volume (as measured by MRI) changed significantly following treatment. Intralesional injection of pembrolizumab is safe and feasible in patients with DCIS. Nearly all patients experienced robust total and CD8+ T cell responses. However, we did not observe evidence of cell death or tumor volume decrease by MRI, suggesting that additional strategies may be needed to elicit stronger anti-tumor immunity.
Reference SVA insertion polymorphisms are associated with Parkinson’s Disease progression and differential gene expression
Authors: Pfaff Abigail L. , Bubb Vivien J. , Quinn John P. , Koks Sulev
Published: May 2021

The development of Parkinson’s disease (PD) involves a complex interaction of genetic and environmental factors. Genome-wide association studies using extensive single nucleotide polymorphism datasets have identified many loci involved in disease. However much of the heritability of Parkinson’s disease is still to be identified and the functional elements associated with the risk to be determined and understood. To investigate the component of PD that may involve complex genetic variants we characterised the hominid specific retrotransposon SINE-VNTR-Alus (SVAs) in the Parkinson’s Progression Markers Initiative cohort utilising whole genome sequencing. We identified 81 reference SVAs polymorphic for their presence/absence, seven of which were associated with the progression of the disease and with differential gene expression in whole blood RNA sequencing data. This study highlights the importance of addressing SVA variants and potentially other types of retrotransposons in PD genetics, furthermore, these SVA elements should be considered as regulatory domains that could play a role in disease progression.
Parallel quantum simulation of large systems on small NISQ computers
Authors: Barratt F. , Dborin James , Bal Matthias , Stojevic Vid , Pollmann Frank , Green A. G.
Published: May 2021

Tensor networks permit computational and entanglement resources to be concentrated in interesting regions of Hilbert space. Implemented on NISQ machines they allow simulation of quantum systems that are much larger than the computational machine itself. This is achieved by parallelising the quantum simulation. Here, we demonstrate this in the simplest case; an infinite, translationally invariant quantum spin chain. We provide Cirq and Qiskit code that translates infinite, translationally invariant matrix product state (iMPS) algorithms to finite-depth quantum circuit machines, allowing the representation, optimisation and evolution of arbitrary one-dimensional systems. The illustrative simulated output of these codes for achievable circuit sizes is given.
Efficacy and tolerability of aripiprazole versus D2 antagonists in the early course of schizophrenia: a systematic review and meta-analysis
Authors: Kim David D. , Barr Alasdair M. , Lian Lulu , Yuen Jessica W. Y. , Fredrikson Diane , Honer William G. , Thornton Allen E. , Procyshyn Ric M.
Published: May 2021

Early intervention is essential for favorable long-term outcomes in schizophrenia. However, there is limited guidance in the scientific literature on how best to choose between dopamine D2 receptor (D2R) partial agonists and D2R antagonists in early stages of schizophrenia. The aim of this meta-analysis was to directly compare D2R partial agonists with D2R antagonists for efficacy and tolerability, using randomized controlled trials (RCTs) that involved participants diagnosed with first-episode psychosis, schizophrenia, or related psychotic disorders with a duration of illness ≤5 years. Fourteen RCTs, involving 2494 patients, were included in the meta-analysis. Aripiprazole was the only identified D2R partial agonist, and was not significantly different from pooled D2R antagonists for overall symptom reduction or all-cause discontinuation. However, aripiprazole was more favorable than pooled D2R antagonists for depressive symptoms, prolactin levels, and triglyceride levels. Specifically, aripiprazole was more favorable than paliperidone for triglyceride levels and more favorable than risperidone and olanzapine, but less favorable than ziprasidone, for weight gain. In addition, aripiprazole was less favorable for akathisia compared with second-generation D2R antagonists, in particular olanzapine and quetiapine, and less favorable for discontinuation due to inefficacy than risperidone. Lastly, aripiprazole was more favorable than haloperidol for various efficacy and tolerability outcomes. In conclusion, aripiprazole’s efficacy did not differ substantially from D2R antagonists in the early course of schizophrenia, whereas differential tolerability profiles were noted. More double-blind RCTs are required comparing the efficacy and tolerability of aripiprazole as well as other D2R partial agonists with D2R antagonists in early stages of schizophrenia.
Regional zircon U-Pb geochronology for the Maniitsoq region, southwest Greenland
Authors: Olierook Hugo K. H. , Kirkland Christopher L. , Hollis Julie A. , Gardiner Nicholas J. , Yakymchuk Chris , Szilas Kristoffer , Hartnady Michael I. H. , Barham Milo , McDonald Bradley J. , Evans Noreen J. , Steenfelt Agnete , Waterton Pedro
Published: May 2021

Zircon U-Pb geochronology places high-temperature geological events into temporal context. Here, we present a comprehensive zircon U-Pb geochronology dataset for the Meso- to Neoarchean Maniitsoq region in southwest Greenland, which includes the Akia Terrane, Tuno Terrane, and the intervening Alanngua Complex. The magmatic and metamorphic processes recorded in these terranes straddle a key change-point in early Earth geodynamics. This dataset comprises zircon U-Pb ages for 121 samples, including 46 that are newly dated. A principal crystallization peak occurs across all three terranes at ca. 3000 Ma, with subordinate crystallization age peaks at 3200 Ma (Akia Terrane and Alanngua Complex only), 2720 Ma and 2540 Ma. Metamorphic age peaks occur at 2990 Ma, 2820–2700 Ma, 2670–2600 Ma and 2540 Ma. Except for one sample, all dated metamorphic zircon growth after the Neoarchean occurred in the Alanngua Complex or within 20 km of its boundaries. This U-Pb dataset provides an important resource for addressing Earth Science topics as diverse as crustal evolution, fluid–rock interaction and mineral deposit genesis.
Comprehensive ultrahigh resolution whole brain in vivo MRI dataset as a human phantom
Authors: Lüsebrink Falk , Mattern Hendrik , Yakupov Renat , Acosta-Cabronero Julio , Ashtarayeh Mohammad , Oeltze-Jafra Steffen , Speck Oliver
Published: May 2021

Here, we present an extension to our previously published structural ultrahigh resolution T1-weighted magnetic resonance imaging (MRI) dataset with an isotropic resolution of 250 µm, consisting of multiple additional ultrahigh resolution contrasts. Included are up to 150 µm Time-of-Flight angiography, an updated 250 µm structural T1-weighted reconstruction, 330 µm quantitative susceptibility mapping, up to 450 µm structural T2-weighted imaging, 700 µm T1-weighted back-to-back scans, 800 µm diffusion tensor imaging, one hour continuous resting-state functional MRI with an isotropic spatial resolution of 1.8 mm as well as more than 120 other structural T1-weighted volumes together with multiple corresponding proton density weighted acquisitions collected over ten years. All data are from the same participant and were acquired on the same 7 T scanner. The repository contains the unprocessed data as well as (pre-)processing results. The data were acquired in multiple studies with individual goals. This is a unique and comprehensive collection comprising a “human phantom” dataset. Therefore, we compiled, processed, and structured the data, making them publicly available for further investigation.