bluuebunny/crossref_metadata_2025 huggingface dataset:
Controllable broadband multicolour single-mode polarized laser in a dye-assembled homoepitaxial MOF microcrystal
Authors: He Huajun , Cui Yuanjing , Li Hongjun , Shao Kai , Chen Banglin , Qian Guodong
Published: August 2020

Multicolour single-mode polarized microlasers with visible to near-infrared output have very important applications in photonic integration and multimodal biochemical sensing/imaging but are very difficult to realize. Here, we demonstrate a single crystal with multiple segments based on the host-guest metal-organic framework ZJU-68 hierarchically hybridized with different dye molecules generating controllable single-mode green, red, and near-infrared lasing, with the lasing mode mechanism revealed by computational simulation. The segmented and oriented assembly of different dye molecules within the ZJU-68 microcrystal causes it to act as a shortened resonator, enabling us to achieve dynamically controllable multicolour single-mode lasing with a low three-colour-lasing threshold of ~1.72 mJ/cm2 (approximately seven times lower than that of state-of-the-art designed heterostructure alloys, as reported by Fan F et al. (Nat. Nanotechnol. 10:796–803, 2015) considering the single pulse energy density) and degree of polarization >99.9%. Furthermore, the resulting three-colour single-mode lasing possesses the largest wavelength coverage of ~186 nm (ranging from ~534 to ~720 nm) ever reported. These findings may open a new route to the exploitation of multicolour single-mode micro/nanolasers constructed by MOF engineering for photonic and biochemical applications.
Targeting PD-L1 in non-small cell lung cancer using CAR T cells
Authors: Liu Ming , Wang Xu , Li Wei , Yu Xinfang , Flores-Villanueva Pedro , Xu-Monette Zijun Y. , Li Ling , Zhang Mingzhi , Young Ken H. , Ma Xiaodong , Li Yong
Published: August 2020

Antibodies against programmed cell death protein 1 (PD-1) and its ligand (PD-L1) have dramatically changed the landscape of therapies for non-small cell lung carcinoma (NSCLC); however, the majority of patients do not respond to these agents. In addition, hyperprogressive disease (HPD) develops in a larger portion of NSCLC patients treated with PD-1/PD-L1 inhibitors than in patients treated with standard chemotherapy. The use of chimeric antigen receptor (CAR) T cells has been successful to treat blood cancers but not for solid tumors like NSCLC. In this work, we constructed CAR T cells that target PD-L1 and evaluated their efficacy in NSCLC with either high or low PD-L1 expression. PD-L1-CAR T cells exhibited antigen-specific activation, cytokine production, and cytotoxic activity against PD-L1high NSCLC cells and xenograft tumors. Furthermore, the addition of a subtherapeutic dose of local radiotherapy improved the efficacy of PD-L1-CAR T cells against PD-L1low NSCLC cells and tumors. Our findings indicate that PD-L1-CAR T cells represent a novel therapeutic strategy for patients with PD-L1-positive NSCLC, particularly for those who are susceptible to HPD.
Understanding the diversity of the metal-organic framework ecosystem
Authors: Moosavi Seyed Mohamad , Nandy Aditya , Jablonka Kevin Maik , Ongari Daniele , Janet Jon Paul , Boyd Peter G. , Lee Yongjin , Smit Berend , Kulik Heather J.
Published: August 2020

Millions of distinct metal-organic frameworks (MOFs) can be made by combining metal nodes and organic linkers. At present, over 90,000 MOFs have been synthesized and over 500,000 predicted. This raises the question whether a new experimental or predicted structure adds new information. For MOF chemists, the chemical design space is a combination of pore geometry, metal nodes, organic linkers, and functional groups, but at present we do not have a formalism to quantify optimal coverage of chemical design space. In this work, we develop a machine learning method to quantify similarities of MOFs to analyse their chemical diversity. This diversity analysis identifies biases in the databases, and we show that such bias can lead to incorrect conclusions. The developed formalism in this study provides a simple and practical guideline to see whether new structures will have the potential for new insights, or constitute a relatively small variation of existing structures.
Development of light-responsive protein binding in the monobody non-immunoglobulin scaffold
Authors: Carrasco-López César , Zhao Evan M. , Gil Agnieszka A. , Alam Nathan , Toettcher Jared E. , Avalos José L.
Published: August 2020

Monobodies are synthetic non-immunoglobulin customizable protein binders invaluable to basic and applied research, and of considerable potential as future therapeutics and diagnostic tools. The ability to reversibly control their binding activity to their targets on demand would significantly expand their applications in biotechnology, medicine, and research. Here we present, as proof-of-principle, the development of a light-controlled monobody (OptoMB) that works in vitro and in cells and whose affinity for its SH2-domain target exhibits a 330-fold shift in binding affinity upon illumination. We demonstrate that our αSH2-OptoMB can be used to purify SH2-tagged proteins directly from crude E. coli extract, achieving 99.8% purity and over 40% yield in a single purification step. By virtue of their ability to be designed to bind any protein of interest, OptoMBs have the potential to find new powerful applications as light-switchable binders of untagged proteins with the temporal and spatial precision afforded by light.
Ybx1 fine-tunes PRC2 activities to control embryonic brain development
Authors: Evans Myron K. , Matsui Yurika , Xu Beisi , Willis Catherine , Loome Jennifer , Milburn Luis , Fan Yiping , Pagala Vishwajeeth , Peng Jamy C.
Published: August 2020

Chromatin modifiers affect spatiotemporal gene expression programs that underlie organismal development. The Polycomb repressive complex 2 (PRC2) is a crucial chromatin modifier in executing neurodevelopmental programs. Here, we find that PRC2 interacts with the nucleic acid–binding protein Ybx1. In the mouse embryo in vivo, Ybx1 is required for forebrain specification and restricting mid-hindbrain growth. In neural progenitor cells (NPCs), Ybx1 controls self-renewal and neuronal differentiation. Mechanistically, Ybx1 highly overlaps PRC2 binding genome-wide, controls PRC2 distribution, and inhibits H3K27me3 levels. These functions are consistent with Ybx1-mediated promotion of genes involved in forebrain specification, cell proliferation, or neuronal differentiation. In Ybx1-knockout NPCs, H3K27me3 reduction by PRC2 enzymatic inhibitor or genetic depletion partially rescues gene expression and NPC functions. Our findings suggest that Ybx1 fine-tunes PRC2 activities to regulate spatiotemporal gene expression in embryonic neural development and uncover a crucial epigenetic mechanism balancing forebrain–hindbrain lineages and self-renewal–differentiation choices in NPCs.
Elucidating the fundamental fibrotic processes driving abdominal adhesion formation
Authors: Foster Deshka S. , Marshall Clement D. , Gulati Gunsagar S. , Chinta Malini S. , Nguyen Alan , Salhotra Ankit , Jones R. Ellen , Burcham Austin , Lerbs Tristan , Cui Lu , King Megan E. , Titan Ashley L. , Ransom R. Chase , Manjunath Anoop , Hu Michael S. , Blackshear Charles P. , Mascharak Shamik , Moore Alessandra L. , Norton Jeffrey A. , Kin Cindy J. , Shelton Andrew A. , Januszyk Michael , Gurtner Geoffrey C. , Wernig Gerlinde , Longaker Michael T.
Published: August 2020

Adhesions are fibrotic scars that form between abdominal organs following surgery or infection, and may cause bowel obstruction, chronic pain, or infertility. Our understanding of adhesion biology is limited, which explains the paucity of anti-adhesion treatments. Here we present a systematic analysis of mouse and human adhesion tissues. First, we show that adhesions derive primarily from the visceral peritoneum, consistent with our clinical experience that adhesions form primarily following laparotomy rather than laparoscopy. Second, adhesions are formed by poly-clonal proliferating tissue-resident fibroblasts. Third, using single cell RNA-sequencing, we identify heterogeneity among adhesion fibroblasts, which is more pronounced at early timepoints. Fourth, JUN promotes adhesion formation and results in upregulation of PDGFRA expression. With JUN suppression, adhesion formation is diminished. Our findings support JUN as a therapeutic target to prevent adhesions. An anti-JUN therapy that could be applied intra-operatively to prevent adhesion formation could dramatically improve the lives of surgical patients.
A high-throughput neutralizing antibody assay for COVID-19 diagnosis and vaccine evaluation
Authors: Muruato Antonio E. , Fontes-Garfias Camila R. , Ren Ping , Garcia-Blanco Mariano A. , Menachery Vineet D. , Xie Xuping , Shi Pei-Yong
Published: August 2020

Virus neutralization remains the gold standard for determining antibody efficacy. Therefore, a high-throughput assay to measure SARS-CoV-2 neutralizing antibodies is urgently needed for COVID-19 serodiagnosis, convalescent plasma therapy, and vaccine development. Here, we report on a fluorescence-based SARS-CoV-2 neutralization assay that detects SARS-CoV-2 neutralizing antibodies in COVID-19 patient specimens and yields comparable results to plaque reduction neutralizing assay, the gold standard of serological testing. The fluorescence-based neutralization assay is specific to measure COVID-19 neutralizing antibodies without cross reacting with patient specimens with other viral, bacterial, or parasitic infections. Collectively, our approach offers a rapid platform that can be scaled to screen people for antibody protection from COVID-19, a key parameter necessary to safely reopen local communities.
Graphitic phosphorus coordinated single Fe atoms for hydrogenative transformations
Authors: Long Xiangdong , Li Zelong , Gao Guang , Sun Peng , Wang Jia , Zhang Bingsen , Zhong Jun , Jiang Zheng , Li Fuwei
Published: August 2020

Single-atom metal-nitrogen-carbon (M-N-C) catalysts have sparked intensive interests, however, the development of an atomically dispersed metal-phosphorus-carbon (M-P-C) catalyst has not been achieved, although molecular metal-phosphine complexes have found tremendous applications in homogeneous catalysis. Herein, we successfully construct graphitic phosphorus species coordinated single-atom Fe on P-doped carbon, which display outstanding catalytic performance and reaction generality in the heterogeneous hydrogenation of N-heterocycles, functionalized nitroarenes, and reductive amination reactions, while the corresponding atomically dispersed Fe atoms embedded on N-doped carbon are almost inactive under the same reaction conditions. Furthermore, we find that the catalytic activity of graphitic phosphorus coordinated single-atom Fe sharply decreased when Fe atoms were transformed to Fe clusters/nanoparticles by post-impregnation Fe species. This work can be of fundamental interest for the design of single-atom catalysts by utilizing P atoms as coordination sites as well as of practical use for the application of M-P-C catalysts in heterogeneous catalysis.
Broadband slow-wave modulation in posterior and anterior cortex tracks distinct states of propofol-induced unconsciousness
Authors: Stephen Emily P. , Hotan Gladia C. , Pierce Eric T. , Harrell P. Grace , Walsh John L. , Brown Emery N. , Purdon Patrick L.
Published: August 2020

A controversy has developed in recent years over the roles of frontal and posterior cortices in mediating consciousness and unconsciousness. Disruption of posterior cortex during sleep appears to suppress the contents of dreaming, yet activation of frontal cortex appears necessary for perception and can reverse unconsciousness under anesthesia. We used anesthesia to study how regional cortical disruption, mediated by slow wave modulation of broadband activity, changes during unconsciousness in humans. We found that broadband slow-wave modulation enveloped posterior cortex when subjects initially became unconscious, but later encompassed both frontal and posterior cortex when subjects were more deeply anesthetized and likely unarousable. Our results suggest that unconsciousness under anesthesia comprises several distinct shifts in brain state that disrupt the contents of consciousness distinct from arousal and awareness of those contents.
Native American ancestry significantly contributes to neuromyelitis optica susceptibility in the admixed Mexican population
Authors: Romero-Hidalgo Sandra , Flores-Rivera José , Rivas-Alonso Verónica , Barquera Rodrigo , Villarreal-Molina María Teresa , Antuna-Puente Bárbara , Macias-Kauffer Luis Rodrigo , Villalobos-Comparán Marisela , Ortiz-Maldonado Jair , Yu Neng , Lebedeva Tatiana V. , Alosco Sharon M. , García-Rodríguez Juan Daniel , González-Torres Carolina , Rosas-Madrigal Sandra , Ordoñez Graciela , Guerrero-Camacho Jorge Luis , Treviño-Frenk Irene , Escamilla-Tilch Monica , García-Lechuga Maricela , Tovar-Méndez Víctor Hugo , Pacheco-Ubaldo Hanna , Acuña-Alonzo Victor , Bortolini Maria-Cátira , Gallo Carla , Bedoya Gabriel , Rothhammer Francisco , González-Jose Rolando , Ruiz-Linares Andrés , Canizales-Quinteros Samuel , Yunis Edmond , Granados Julio , Corona Teresa
Published: August 2020

Neuromyelitis Optica (NMO) is an autoimmune disease with a higher prevalence in non-European populations. Because the Mexican population resulted from the admixture between mainly Native American and European populations, we used genome-wide microarray, HLA high-resolution typing and AQP4 gene sequencing data to analyze genetic ancestry and to seek genetic variants conferring NMO susceptibility in admixed Mexican patients. A total of 164 Mexican NMO patients and 1,208 controls were included. On average, NMO patients had a higher proportion of Native American ancestry than controls (68.1% vs 58.6%; p = 5 × 10–6). GWAS identified a HLA region associated with NMO, led by rs9272219 (OR = 2.48, P = 8 × 10–10). Class II HLA alleles HLA-DQB1*03:01, -DRB1*08:02, -DRB1*16:02, -DRB1*14:06 and -DQB1*04:02 showed the most significant associations with NMO risk. Local ancestry estimates suggest that all the NMO-associated alleles within the HLA region are of Native American origin. No novel or missense variants in the AQP4 gene were found in Mexican patients with NMO or multiple sclerosis. To our knowledge, this is the first study supporting the notion that Native American ancestry significantly contributes to NMO susceptibility in an admixed population, and is consistent with differences in NMO epidemiology in Mexico and Latin America.
Variability and reproducibility in deep learning for medical image segmentation
Authors: Renard Félix , Guedria Soulaimane , Palma Noel De , Vuillerme Nicolas
Published: August 2020

Medical image segmentation is an important tool for current clinical applications. It is the backbone of numerous clinical diagnosis methods, oncological treatments and computer-integrated surgeries. A new class of machine learning algorithm, deep learning algorithms, outperforms the results of classical segmentation in terms of accuracy. However, these techniques are complex and can have a high range of variability, calling the reproducibility of the results into question. In this article, through a literature review, we propose an original overview of the sources of variability to better understand the challenges and issues of reproducibility related to deep learning for medical image segmentation. Finally, we propose 3 main recommendations to address these potential issues: (1) an adequate description of the framework of deep learning, (2) a suitable analysis of the different sources of variability in the framework of deep learning, and (3) an efficient system for evaluating the segmentation results.
Deep versus shallow sources of CO2 and Rn from a multi-parametric approach: the case of the Nisyros caldera (Aegean Arc, Greece)
Authors: Bini Giulio , Chiodini Giovanni , Lucchetti Carlo , Moschini Piergiorgio , Caliro Stefano , Mollo Silvio , Selva Jacopo , Tuccimei Paola , Galli Gianfranco , Bachmann Olivier
Published: August 2020

Estimating the quantity of CO2 diffusively emitted from the Earth’s surface has important implications for volcanic surveillance and global atmospheric CO2 budgets. However, the identification and quantification of non-hydrothermal contributions to CO2 release can be ambiguous. Here, we describe a multi-parametric approach employed at the Nisyros caldera, Aegean Arc, Greece, to assess the relative influence of deep and shallow gases released from the soil. In April 2019, we measured diffuse soil surface CO2 fluxes, together with their carbon isotope compositions, and at a depth of 80 cm, the CO2 concentration, soil temperature, and the activities of radon and thoron. The contributions of deep CO2 and biogenic CO2 fluxes were distinguished on the basis of their carbon isotope compositions. A Principal Component Analysis (PCA), performed on the measured parameters, effectively discriminates between a deep- and a shallow degassing component. The total CO2 output estimated from a relatively small testing area was two times higher with respect to that observed in a previous survey (October 2018). The difference is ascribed to variation in the soil biogenic CO2 production, that was high in April 2019 (a wet period) and low or absent in October 2018 (a dry period). Accounting for seasonal biogenic activity is therefore critical in monitoring and quantifying CO2 emissions in volcanic areas, because they can partially- or completely overwhelm the volcanic-hydrothermal signal.
Magnetic resonance imaging of umbilical cord stem cells labeled with superparamagnetic iron oxide nanoparticles: effects of labelling and transplantation parameters
Authors: Ohki Akiko , Saito Shigeyoshi , Fukuchi Kazuki
Published: August 2020

Cell tracking with magnetic resonance imaging (MRI) is important for evaluating the biodistribution of transplanted cells. Umbilical cord-derived mesenchymal stem cells (UC-MSCs) have emerged as a promising therapeutic tool in regenerative medicine. We examined the UC-MSCs labeled with superparamagnetic (SPIO) and ultrasmall superparamagnetic iron oxide (USPIO) in terms of cell functioning and imaging efficiency in vitro and in vivo. The UC-MSCs were co-incubated with SPIO or USPIO at a concentration of 50 or 100 µg/mL of label. Viability and proliferation were assessed by Trypan blue dye exclusion and MTT assay, respectively. Differentiation (chondrogenesis, osteogenesis, and adipogenesis) was induced to examine the impact of labelling on stemness. For in vitro experiments, we used 7-T MRI to assess the T2 values of phantoms containing various concentrations of cell suspensions. For in vivo experiments, nine neonatal rats were divided into the control, SPIO, and USPIO groups. The UC-MSCs were injected directly into the rat brains. MRI images were obtained immediately and at 7 and 14 days post injection. The UC-MSCs were successfully labeled with SPIO and USPIO after 24 h of incubation. Cell viability was not changed by labelling. Nevertheless, labelling with 100 µg/mL USPIO led to a significant decrease in proliferation. The capacity for differentiation into cartilage was influenced by 100 µg/mL of SPIO. MRI showed that labeled cells exhibited clear hypointense signals, unlike unlabeled control cells. In the USPIO-labeled cells, a significant (P < 0.05) decrease in T2 values (= improved contrast) was observed when compared with the controls and between phantoms containing the fewest and the most cells (0.5 × 106 versus 2.0 × 106 cells/mL). In vivo, the labeled cells were discernible on T2-weighted images at days 0, 7, and 14. The presence of SPIO and USPIO particles at day 14 was confirmed by Prussian blue staining. Microscopy also suggested that the regions occupied by the particles were not as large as the corresponding hypointense areas observed on MRI. Both labels were readily taken up by the UC-MSCs and identified well on MRI. While SPIO and USPIO provide improved results in MRI studies, care must be taken while labelling cells with high concentrations of these agents.
Zoledronate and SPIO dual-targeting nanoparticles loaded with ICG for photothermal therapy of breast cancer tibial metastasis
Authors: Jiang Zichao , Li Jingyi , Chen Sijie , Guo Qi , Jing Zhaocheng , Huang Biying , Pan Yixiao , Wang Long , Hu Yihe
Published: August 2020

Currently, nanoparticles (NPs) for cancer photothermal therapy (PTT) have limited in vivo clearance, lack targeting ability and have unsatisfactory therapeutic efficiency. Herein, we report a dual-targeting and photothermally triggered nanotherapeutic system based on superparamagnetic iron oxide (Fe3O4) and indocyanine green (ICG)-entrapped poly-lactide-co-glycolide modified by ZOL (PLGA-ZOL) NPs (ICG/Fe3O4@PLGA-ZOL) for PTT of breast cancer tibial metastasis, which occurs frequently in the clinic and causes challenging complications in breast cancer. In this system, both ICG and Fe3O4 can convert light into heat, while NPs with Fe3O4 and ZOL can be attracted to a specific location in bone under an external magnetic field. Specifically, the dual-targeting and double photothermal agents guaranteed high accumulation in the tibia and perfect PTT efficiency. Furthermore, the in vivo studies showed that ICG/Fe3O4@PLGA-ZOL NPs have extraordinary antitumor therapeutic effects and that these NPs can be accurately located in the medullary cavity of the tibia to solve problems with deep lesions, such as breast cancer tibial metastasis, showing great potential for cancer theranostics.
Classification of femur fracture in pelvic X-ray images using meta-learned deep neural network
Authors: Lee Changhwan , Jang Jongseong , Lee Seunghun , Kim Young Soo , Jo Hang Joon , Kim Yeesuk
Published: August 2020

In the medical field, various studies using artificial intelligence (AI) techniques have been attempted. Numerous attempts have been made to diagnose and classify diseases using image data. However, different forms of fracture exist, and inaccurate results have been confirmed depending on condition at the time of imaging, which is problematic. To overcome this limitation, we present an encoder-decoder structured neural network that utilizes radiology reports as ancillary information at training. This is a type of meta-learning method used to generate sufficiently adequate features for classification. The proposed model learns representation for classification from X-ray images and radiology reports simultaneously. When using a dataset of only 459 cases for algorithm training, the model achieved a favorable performance in a test dataset containing 227 cases (classification accuracy of 86.78% and classification F1 score of 0.867 for fracture or normal classification). This finding demonstrates the potential for deep learning to improve performance and accelerate application of AI in clinical practice.
Damage severity of wood-destroying insects according to the Bevan damage classification system in log depots of Northwest Turkey
Authors: Yalcin Mesut , Akcay Caglar , Tascioglu Cihat , Yuksel Besir , Ozbayram Ali Kemal
Published: August 2020

The aim of the study was to determine damage severity of wood-destroying insects on logs stored in forest depots. The Bevan damage classification (BDC) system, developed in 1987, was utilized to determine damage severity in log depots in 21 locations throughout seven provinces in Turkey. Pheromone traps were placed in those locations at the beginning of April in 2015 and 2016. Furthermore some stored wood within the log depots were checked and split into small pieces to collect insects that damage wood. The BDC system was used for the first time to measure the severity of insect damage in log depots. Twenty-eight families, 104 genera and 123 species were identified in this study. Based on the BDC system, the highest damage was found from the Cerambycidae and Buprestidae families.Arhopalus rusticuswas determined as the insect responsible for the highest amount of damage with 8.8% severity rating in the pheromone-trapped insects group. When the stored wood material was considered,Hylotrupes bajuluswas found to be the cause of the highest damage. The lowest damage values were among the predator insects (Cleridae, Trogossitidae, Cantharidae) and those feeding on fungi colonized on the wood (Mordellidae, Cerylonidae, Nitidulidae). Some other predator insects of the Tenebrionidae family (Uloma cypraea, Uloma culinaris, Menephilus cylindricus) and Elateridae family (Lacon punctatus,Ampedussp.) exhibited relatively higher damage severity values since they had built tunnels and made holes in the stored wood material. When the environmental factors were considered, the Buprestidae family exhibited a very strong positive relationship (p < 0.005) with insect frequency distribution (r = 0.922), number of species (r = 0.879) and insect density (r = 0.942). Both families showed the highest number and frequency during July and August, highlighting the importance of insect control and management during these months.
Revising the mechanism of p75NTR activation: intrinsically monomeric state of death domains invokes the "helper" hypothesis
Authors: Goncharuk Sergey A. , Artemieva Lilya E. , Nadezhdin Kirill D. , Arseniev Alexander S. , Mineev Konstantin S.
Published: August 2020

The neurotrophin receptor p75NTR plays crucial roles in neuron development and regulates important neuronal processes like degeneration, apoptosis and cell survival. At the same time the detailed mechanism of signal transduction is unclear. One of the main hypotheses known as the snail-tong mechanism assumes that in the inactive state, the death domains interact with each other and in response to ligand binding there is a conformational change leading to their exposure. Here, we show that neither rat nor human p75NTR death domains homodimerize in solution. Moreover, there is no interaction between the death domains in a more native context: the dimerization of transmembrane domains in liposomes and the presence of activating mutation in extracellular juxtamembrane region do not lead to intracellular domain interaction. These findings suggest that the activation mechanism of p75NTR should be revised. Thus, we propose a novel model of p75NTR functioning based on interaction with “helper” protein.
Sex and race influence objective and self-report sleep and circadian measures in emerging adults independently of risk for bipolar spectrum disorder
Authors: Titone Madison K. , McArthur Brae Anne , Ng Tommy H. , Burke Taylor A. , McLaughlin Laura E. , MacMullen Laura E. , Goel Namni , Alloy Lauren B.
Published: August 2020

There is a need to better understand key factors that impact sleep and circadian function for young adults of differing races and sexes. Sex and race are common factors contributing to disparities in health outcomes; however, the influence of these variables on sleep and circadian patterns for young adults are not well known. Multiple objective and self-report facets of sleep and circadian function were assessed (melatonin onset, actigraphy, and sleep diaries) in an ecological momentary assessment study of 150 emerging adults (Mage = 21.8 years; 58.7% female; 56% White, 22.7% Black, 21.3% Other ethnicity) at high or low risk for bipolar spectrum disorder (BSD). Controlling for BSD risk status, sex and race were significant predictors of objective and self-reported sleep and circadian rhythm measures. Males self-reported better sleep efficiency and exhibited later dim light melatonin onset phase than females, whereas females exhibited more actigraphy-measured sleep periods. White participants exhibited more actigraphy-measured total sleep time (TST), better sleep efficiency, and fewer sleep periods, and more self-reported TST and better sleep efficiency than Black participants. Our findings enhance the literature by utilizing robust measurement of sleep and circadian parameters to extend previous findings to a young adult sample at high or low risk for BSD.
π phase shifter based on NbN-based ferromagnetic Josephson junction on a silicon substrate
Authors: Yamashita Taro , Kim Sunmi , Kato Haruki , Qiu Wei , Semba Kouichi , Fujimaki Akira , Terai Hirotaka
Published: August 2020

In the field of superconducting electronics, a π phase shifter based on a ferromagnetic Josephson junction is expected to provide various advantages to classical and quantum superconducting devices. Here we report niobium nitride (NbN)-based ferromagnetic π junctions on a silicon (Si) substrate with a titanium nitride (TiN) buffer layer, which have applications to flux-bias-free flux quantum bits (qubits) and classical digital logic elements. We fabricated and characterized NbN/aluminum nitride (AlN)/NbN Josephson junctions, NbN/copper nickel (CuNi)/NbN ferromagnetic Josephson junctions, and superconducting quantum interference devices (SQUIDs) consisting of these junctions on the Si substrate. The fabricated NbN/AlN/NbN junctions showed a high junction quality suitable for qubit applications. Furthermore, the magnetic field dependence of the SQUID’s critical current indicated that the NbN/CuNi/NbN junction worked as a π phase shifter on the Si substrate.
Robust half-metallicity and magnetic phase transition in Sr2CrReO6 via strain engineering
Authors: Ain Qurat-Ul , Naseem Shahnila , Nazir Safdar
Published: August 2020

Using ab-initio calculations, the electronic and magnetic properties of double perovskite oxide $${\text{Sr}}_2 {\text{CrReO}}_6$$

Sr
2

CrReO
6

with two type of strains: biaxial (along the [110]-direction) and hydrostatic (along [111]-direction) are investigated. The ground state of the unstrained system is half-metallic ferrimagnetic, due to a strong antiferromagnetic (AFM) coupling between Cr and Re atoms within both (GGA and GGA+U) exchange-correlation potentials. It is demonstrated that the robustness of half-metallicity can be preserved under the influence of both biaxial and hydrostatic strains. Interestingly, a transition from ferri-to-ferromagnetic is established due to Re spin flipping to that of the Cr ion (i.e. Cr and Re spin becomes parallel) within the GGA+U method for both biaxial and hydrostatic tensile strains of $$\ge +2\%$$

≥
+
2
%

. The strong confinement of orbitals due to tensile strain results in the decrease of electron hopping which further reduced the AFM coupling strength between Cr and Re atoms, this leads to a ferri-to-ferromagnetic transition. However, the GGA scheme holds the ferrimagnetic state with both kinds of strains. This work shows that tensile strain is a feasible way to optimize the magnetic properties of perovskite oxides, which are presumed to be beneficial for spintronic technology.
Attachment styles modulate neural markers of threat and imagery when engaging in self-criticism
Authors: Kim Jeffrey J. , Kent Kirsty M. , Cunnington Ross , Gilbert Paul , Kirby James N.
Published: August 2020

Attachment styles hold important downstream consequences for mental health through their contribution to the emergence of self-criticism. To date, no work has extended our understanding of the influence of attachment styles on self-criticism at a neurobiological level. Herein we investigate the relationship between self-reported attachment styles and neural markers of self-criticism using fMRI. A correlation network analysis revealed lingual gyrus activation during self-criticism, a marker of visual mental imagery, correlated with amygdala activity (threat response). It also identified that secure attachment positively correlated with lingual gyrus activation, whilst avoidant attachment was negatively correlated with lingual gyrus activation. Further, at greater levels of amygdala response, more securely attached individuals showed greater lingual gyrus activation, and more avoidantly attached individuals showed less lingual gyrus activation. Our data provide the first evidence that attachment mechanisms may modulate threat responses and mental imagery when engaging in self-criticism, which have important clinical and broader social implications.
Diverse species-specific phenotypic consequences of loss of function sorting nexin 14 mutations
Authors: Bryant Dale , Seda Marian , Peskett Emma , Maurer Constance , Pomeranz Gideon , Ghosh Marcus , Hawkins Thomas A. , Cleak James , Datta Sanchari , Hariri Hanaa , Eckert Kaitlyn M. , Jafree Daniyal J. , Walsh Claire , Demetriou Charalambos , Ishida Miho , Alemán-Charlet Cristina , Vestito Letizia , Seselgyte Rimante , McDonald Jeffrey G. , Bitner-Glindzicz Maria , Hemberger Myriam , Rihel Jason , Teboul Lydia , Henne W. Mike , Jenkins Dagan , Moore Gudrun E. , Stanier Philip
Published: August 2020

Mutations in the SNX14 gene cause spinocerebellar ataxia, autosomal recessive 20 (SCAR20) in both humans and dogs. Studies implicating the phenotypic consequences of SNX14 mutations to be consequences of subcellular disruption to autophagy and lipid metabolism have been limited to in vitro investigation of patient-derived dermal fibroblasts, laboratory engineered cell lines and developmental analysis of zebrafish morphants. SNX14 homologues Snz (Drosophila) and Mdm1 (yeast) have also been conducted, demonstrated an important biochemical role during lipid biogenesis. In this study we report the effect of loss of SNX14 in mice, which resulted in embryonic lethality around mid-gestation due to placental pathology that involves severe disruption to syncytiotrophoblast cell differentiation. In contrast to other vertebrates, zebrafish carrying a homozygous, maternal zygotic snx14 genetic loss-of-function mutation were both viable and anatomically normal. Whilst no obvious behavioural effects were observed, elevated levels of neutral lipids and phospholipids resemble previously reported effects on lipid homeostasis in other species. The biochemical role of SNX14 therefore appears largely conserved through evolution while the consequences of loss of function varies between species. Mouse and zebrafish models therefore provide valuable insights into the functional importance of SNX14 with distinct opportunities for investigating its cellular and metabolic function in vivo.
Molecular fluorescence spectroscopy with multi-way analysis techniques detects spectral variations distinguishing uninfected serum versus dengue or chikungunya viral infected samples
Authors: Santos Marfran C. D. , Monteiro Joelma D. , Araújo Josélio M. G. , Lima Kássio M. G.
Published: August 2020

Significant attempts are being made worldwide in an attempt to develop a tool that, with a simple analysis, is capable of distinguishing between different arboviruses. Herein, we employ molecular fluorescence spectroscopy as a sensitive and specific rapid tool, with simple methodology response, capable of identifying spectral variations between serum samples with or without the dengue or chikungunya viruses. Towards this, excitation emission matrices (EEM) of clinical samples from patients with dengue or chikungunya, in addition to uninfected controls, were separated into a training or test set and analysed using multi-way classification models such as n-PLSDA, PARAFAC-LDA and PARAFAC-QDA. Results were evaluated based on calculations of accuracy, sensitivity, specificity and F score; the most efficient model was identified to be PARAFAC-QDA, whereby 100% was obtained for all figures of merit. QDA was able to predict all samples in the test set based on the scores present in the factors selected by PARAFAC. The loadings obtained by PARAFAC can be used in future studies to prove the direct or indirect relationship of spectral changes caused by the presence of these viruses. This study demonstrates that molecular fluorescence spectroscopy has a greater capacity to detect spectral variations related to the presence of such viruses when compared to more conventional techniques.
Non-invasive in-vivo 3-D imaging of small animals using spatially filtered enhanced truncated-correlation photothermal coherence tomography
Authors: Tavakolian Pantea , Roointan Sohrab , Mandelis Andreas
Published: August 2020

We present enhanced truncated-correlation phototothermal coherence tomography (eTC-PCT) for non-invasive three-dimensional imaging of small animals. Tumor detection is reported in a mouse thigh by injecting cancerous cells in the thigh followed by eTC-PCT imaging. Detection of the tumor 3 days after injection may lead to potential for using the eTC-PCT method for cancer treatment studies. eTC-PCT was also applied successfully to non-invasive in-vivo mouse brain structural imaging. A unique spatial-gradient-gate adaptive filter was introduced in a scanned mode along the (x,y) coordinates of camera images from different sub-cranial depths, revealing absorber true spatial extent from diffusive photothermal images and restoring pre-diffusion lateral image resolution beyond the Rayleigh criterion limit in diffusion-wave imaging science. The spatial resolution and contrast enhancement demonstrated in photothermal in-vivo and ex-vivo images of the mouse brain revealed not only vascular structures but also other brain structures, such as the brain hemispheres, cerebellum, and olfactory lobes.
Flavagline synthetic derivative induces senescence in glioblastoma cancer cells without being toxic to healthy astrocytes
Authors: Harmouch Ezeddine , Seitlinger Joseph , Chaddad Hassan , Ubeaud-Sequier Geneviève , Barths Jochen , Saidu Sani , Désaubry Laurent , Grandemange Stéphanie , Massfelder Thierry , Fuhrmann Guy , Fioretti Florence , Dontenwill Monique , Benkirane-Jessel Nadia , Idoux-Gillet Ysia
Published: August 2020

Glioblastoma (GBM) is one of the most aggressive types of cancer, which begins within the brain. It is the most invasive type of glioma developed from astrocytes. Until today, Temozolomide (TMZ) is the only standard chemotherapy for patients with GBM. Even though chemotherapy extends the survival of patients, there are many undesirable side effects, and most cases show resistance to TMZ. FL3 is a synthetic flavagline which displays potent anticancer activities, and is known to inhibit cell proliferation, by provoking cell cycle arrest, and leads to apoptosis in a lot of cancer cell lines. However, the effect of FL3 in glioblastoma cancer cells has not yet been examined. Hypoxia is a major problem for patients with GBM, resulting in tumor resistance and aggressiveness. In this study, we explore the effect of FL3 in glioblastoma cells under normoxia and hypoxia conditions. Our results clearly indicate that this synthetic flavagline inhibits cell proliferation and induced senescence in glioblastoma cells cultured under both conditions. In addition, FL3 treatment had no effect on human brain astrocytes. These findings support the notion that the FL3 molecule could be used in combination with other chemotherapeutic agents or other therapies in glioblastoma treatments.
Author Correction: The growing importance of oceanic moisture sources for continental precipitation
Authors: Gimeno Luis , Nieto Raquel , Sorí Rogert
Published: August 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Trodusquemine displaces protein misfolded oligomers from cell membranes and abrogates their cytotoxicity through a generic mechanism
Authors: Limbocker Ryan , Mannini Benedetta , Ruggeri Francesco S. , Cascella Roberta , Xu Catherine K. , Perni Michele , Chia Sean , Chen Serene W. , Habchi Johnny , Bigi Alessandra , Kreiser Ryan P. , Wright Aidan K. , Albright J. Alex , Kartanas Tadas , Kumita Janet R. , Cremades Nunilo , Zasloff Michael , Cecchi Cristina , Knowles Tuomas P. J. , Chiti Fabrizio , Vendruscolo Michele , Dobson Christopher M.
Published: August 2020

The onset and progression of numerous protein misfolding diseases are associated with the presence of oligomers formed during the aberrant aggregation of several different proteins, including amyloid-β (Aβ) in Alzheimer’s disease and α-synuclein (αS) in Parkinson’s disease. These small, soluble aggregates are currently major targets for drug discovery. In this study, we show that trodusquemine, a naturally-occurring aminosterol, markedly reduces the cytotoxicity of αS, Aβ and HypF-N oligomers to human neuroblastoma cells by displacing the oligomers from cell membranes in the absence of any substantial morphological and structural changes to the oligomers. These results indicate that the reduced toxicity results from a mechanism that is common to oligomers from different proteins, shed light on the origin of the toxicity of the most deleterious species associated with protein aggregation and suggest that aminosterols have the therapeutically-relevant potential to protect cells from the oligomer-induced cytotoxicity associated with numerous protein misfolding diseases.
Lionheart LincRNA alleviates cardiac systolic dysfunction under pressure overload
Authors: Kuwabara Yasuhide , Tsuji Shuhei , Nishiga Masataka , Izuhara Masayasu , Ito Shinji , Nagao Kazuya , Horie Takahiro , Watanabe Shin , Koyama Satoshi , Kiryu Hisanori , Nakashima Yasuhiro , Baba Osamu , Nakao Tetsushi , Nishino Tomohiro , Sowa Naoya , Miyasaka Yui , Hatani Takeshi , Ide Yuya , Nakazeki Fumiko , Kimura Masahiro , Yoshida Yoshinori , Inada Tsukasa , Kimura Takeshi , Ono Koh
Published: August 2020

Recent high-throughput approaches have revealed a vast number of transcripts with unknown functions. Many of these transcripts are long noncoding RNAs (lncRNAs), and intergenic region-derived lncRNAs are classified as long intergenic noncoding RNAs (lincRNAs). Although Myosin heavy chain 6 (Myh6) encoding primary contractile protein is down-regulated in stressed hearts, the underlying mechanisms are not fully clarified especially in terms of lincRNAs. Here, we screen upregulated lincRNAs in pressure overloaded hearts and identify a muscle-abundant lincRNA termed Lionheart. Compared with controls, deletion of the Lionheart in mice leads to decreased systolic function and a reduction in MYH6 protein levels following pressure overload. We reveal decreased MYH6 results from an interaction between Lionheart and Purine-rich element-binding protein A after pressure overload. Furthermore, human LIONHEART levels in left ventricular biopsy specimens positively correlate with cardiac systolic function. Our results demonstrate Lionheart plays a pivotal role in cardiac remodeling via regulation of MYH6.
Oxytocin facilitates valence-dependent valuation of social evaluation of the self
Authors: Wang Danyang , Ma Yina
Published: August 2020

People are eager to know the self in other’s eyes even with personal costs. However, what drives people costly to know evaluations remains unknown. Here we tested the hypothesis of placing subjective value on knowing social evaluations. To quantify the subjective value, we developed apay-to-knowchoice task where individuals trade off profits against knowing social evaluations. Individuals computed independent unknown aversion towards positive and negative social evaluations and placed higher values on knowing social evaluation on positive than negative aspects. Such a valence-dependent valuation of social evaluation was facilitated by oxytocin, a neuropeptide linked to feedback learning and valuation processes, by decreasing values of negative social evaluation. Moreover, individuals scoring high in depression undervalued positive social evaluation, which was normalized by oxytocin. We reveal the psychological and computational processes underlying self-image formation/update and suggest a role of oxytocin in normalizing hypo-valuation of positive social evaluation in depression.
Engineering combinatorial and dynamic decoders using synthetic immediate-early genes
Authors: Ravindran Pavithran T. , Wilson Maxwell Z. , Jena Siddhartha G. , Toettcher Jared E.
Published: August 2020

Many cell- and tissue-level functions are coordinated by intracellular signaling pathways that trigger the expression of context-specific target genes. Yet the input–output relationships that link pathways to the genes they activate are incompletely understood. Mapping the pathway-decoding logic of natural target genes could also provide a basis for engineering novel signal-decoding circuits. Here we report the construction of synthetic immediate-early genes (SynIEGs), target genes of Erk signaling that implement complex, user-defined regulation and can be monitored by using live-cell biosensors to track their transcription and translation. We demonstrate the power of this approach by confirming Erk duration-sensing by FOS, elucidating how the BTG2 gene is differentially regulated by external stimuli, and designing a synthetic immediate-early gene that selectively responds to the combination of growth factor and DNA damage stimuli. SynIEGs pave the way toward engineering molecular circuits that decode signaling dynamics and combinations across a broad range of cellular contexts.
Comparative genomics of muskmelon reveals a potential role for retrotransposons in the modification of gene expression
Authors: Yano Ryoichi , Ariizumi Tohru , Nonaka Satoko , Kawazu Yoichi , Zhong Silin , Mueller Lukas , Giovannoni James J. , Rose Jocelyn K. C. , Ezura Hiroshi
Published: August 2020

Melon exhibits substantial natural variation especially in fruit ripening physiology, including both climacteric (ethylene-producing) and non-climacteric types. However, genomic mechanisms underlying such variation are not yet fully understood. Here, we report an Oxford Nanopore-based high-grade genome reference in the semi-climacteric cultivar Harukei-3 (378 Mb + 33,829 protein-coding genes), with an update of tissue-wide RNA-seq atlas in the Melonet-DB database. Comparison between Harukei-3 and DHL92, the first published melon genome, enabled identification of 24,758 one-to-one orthologue gene pairs, whereas others were candidates of copy number variation or presence/absence polymorphisms (PAPs). Further comparison based on 10 melon genome assemblies identified genome-wide PAPs of 415 retrotransposon Gag-like sequences. Of these, 160 showed fruit ripening-inducible expression, with 59.4% of the neighboring genes showing similar expression patterns (r > 0.8). Our results suggest that retrotransposons contributed to the modification of gene expression during diversification of melon genomes, and may affect fruit ripening-inducible gene expression.
Single-sulfur atom discrimination of polysulfides with a protein nanopore for improved batteries
Authors: Bétermier Fanny , Cressiot Benjamin , Di Muccio Giovanni , Jarroux Nathalie , Bacri Laurent , Morozzo della Rocca Blasco , Chinappi Mauro , Pelta Juan , Tarascon Jean-Marie
Published: August 2020

Research on batteries mostly focuses on electrodes and electrolytes while few activities regard separator membranes. However, they could be used as a toolbox for injecting chemical functionalities to capture unwanted species and enhance battery lifetime. Here, we report the use of biological membranes hosting a nanopore sensor for electrical single molecule detection and use aqueous sodium polysulfides encountered in sulfur-based batteries for proof of concept. By investigating the host-guest interaction between polysulfides of different chain-lengths and cyclodextrins, via combined chemical approaches and molecular docking simulations, and using a selective nanopore sensor inserted into a lipid membrane, we demonstrate that supramolecular polysulfide/cyclodextrin complexes only differing by one sulfur can be discriminated at the single molecule level. Our findings offer innovative perspectives to use nanopores as electrolyte sensors and chemically design membranes capable of selective speciation of parasitic molecules for battery applications and therefore pave the way towards smarter electrochemical storage systems.