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Muchen Pan, Ana L. Alvarez-Cabrera, Joon S. Kang, Lihua Wang, ,
Published: 7 July 2021
Nature Communications, Volume 12, pp 1-16; doi:10.1038/s41467-021-24455-4

Abstract:
Mammalian reovirus (MRV) is the prototypical member of genus Orthoreovirus of family Reoviridae. However, lacking high-resolution structures of its RNA polymerase cofactor μ2 and infectious particle, limits understanding of molecular interactions among proteins and RNA, and their contributions to virion assembly and RNA transcription. Here, we report the 3.3 Å-resolution asymmetric reconstruction of transcribing MRV and in situ atomic models of its capsid proteins, the asymmetrically attached RNA-dependent RNA polymerase (RdRp) λ3, and RdRp-bound nucleoside triphosphatase μ2 with a unique RNA-binding domain. We reveal molecular interactions among virion proteins and genomic and messenger RNA. Polymerase complexes in three Spinoreovirinae subfamily members are organized with different pseudo-D 3d symmetries to engage their highly diversified genomes. The above interactions and those between symmetry-mismatched receptor-binding σ1 trimers and RNA-capping λ2 pentamers balance competing needs of capsid assembly, external protein removal, and allosteric triggering of endogenous RNA transcription, before, during and after infection, respectively.
Cassandra Willyard
Published: 7 July 2021
Nature, Volume 595, pp 164-167; doi:10.1038/d41586-021-01826-x

Abstract:
After a school term filled with anxiety and vitriol, researchers assess the spread of coronavirus and the prospects for a return to normal. After a school term filled with anxiety and vitriol, researchers assess the spread of coronavirus and the prospects for a return to normal.
Correction
P. St-Jean, V. Goblot, E. Galopin, , T. Ozawa, L. Le Gratiet, I. Sagnes, J. Bloch, A. Amo
Published: 7 July 2021
Nature Photonics pp 1-1; doi:10.1038/s41566-021-00846-3

Retraction
Mengyang Zhao, Ping Xu, Zhen Liu, Yan Zhen, Yiyu Chen, Yiyi Liu, Qiaofen Fu, Xiaojie Deng, Zixi Liang, Yonghao Li, et al.
Published: 7 July 2021
Cell Death & Disease, Volume 12, pp 1-1; doi:10.1038/s41419-021-03974-4

Xu Xiao, Canqiang Xu, ,
Published: 7 July 2021
Nature Communications, Volume 12, pp 1-3; doi:10.1038/s41467-021-24303-5

Sabrina Ehnert, Tina Histing, Andreas K. Nüssler
Signal Transduction and Targeted Therapy, Volume 6, pp 1-2; doi:10.1038/s41392-021-00680-7

Ho-Seok Lee, Ilyeong Choi, Young Jeon, , Huikyong Cho, Jiwoo Kim, Jae-Hee Kim, Jung-Min Lee, Sunghee Lee, Julian Bünting, et al.
Published: 7 July 2021
Nature Communications, Volume 12, pp 1-13; doi:10.1038/s41467-021-24446-5

Abstract:
Photomorphogenesis, light-mediated development, is an essential feature of all terrestrial plants. While chloroplast development and brassinosteroid (BR) signaling are known players in photomorphogenesis, proteins that regulate both pathways have yet to be identified. Here we report that D E-ETIOLATION IN THE DARK A ND Y ELLOWING IN THE LIGHT (DAY), a membrane protein containing DnaJ-like domain, plays a dual-role in photomorphogenesis by stabilizing the BR receptor, BRI1, as well as a key enzyme in chlorophyll biosynthesis, POR. DAY localizes to both the endomembrane and chloroplasts via its first transmembrane domain and chloroplast transit peptide, respectively, and interacts with BRI1 and POR in their respective subcellular compartments. Using genetic analysis, we show that DAY acts independently on BR signaling and chlorophyll biogenesis. Collectively, this work uncovers DAY as a factor that simultaneously regulates BR signaling and chloroplast development, revealing a key regulator of photomorphogenesis that acts across cell compartments.
, , Stefania Venturi, Nic Pacini, Eusebi Vazquez, Lydia A. Olaka, Franco Tassi, Simona Crognale, Peter Herzsprung, , et al.
Published: 7 July 2021
Communications Biology, Volume 4, pp 1-12; doi:10.1038/s42003-021-02365-x

Abstract:
The contribution of oxic methane production to greenhouse gas emissions from lakes is globally relevant, yet uncertainties remain about the levels up to which methanogenesis can counterbalance methanotrophy by leading to CH4 oversaturation in productive surface waters. Here, we explored the biogeochemical and microbial community variation patterns in a meromictic soda lake, in the East African Rift Valley (Kenya), showing an extraordinarily high concentration of methane in oxic waters (up to 156 µmol L−1). Vertical profiles of dissolved gases and their isotopic signature indicated a biogenic origin of CH4. A bloom of Oxyphotobacteria co-occurred with abundant hydrogenotrophic and acetoclastic methanogens, mostly found within suspended aggregates promoting the interactions between Bacteria, Cyanobacteria, and Archaea. Moreover, aggregate sedimentation appeared critical in connecting the lake compartments through biomass and organic matter transfer. Our findings provide insights into understanding how hydrogeochemical features of a meromictic soda lake, the origin of carbon sources, and the microbial community profiles, could promote methane oversaturation and production up to exceptionally high rates.
, Quique Bassat, Javier Crespo, Gonzalo Fanjul, , Marcos López Hoyos, Carlos Mateos, José Muñoz Gutierrez, Denise Naniche, Miquel Oliu-Barton, et al.
Published: 7 July 2021
Communications Medicine, Volume 1, pp 1-4; doi:10.1038/s43856-021-00014-2

Abstract:
During the first five months of 2021, Spain’s COVID-19 vaccination campaign progressed slowly and failed to reach marginalised populations. Here, we discuss how, despite recent improvements, it remains important to further engage key stakeholders to ensure nobody is left behind. Lazarus et al. outline the barriers slowing down the COVID-19 vaccination campaign in Spain. They issue a call to action for all stakeholders to improve access to vaccines, with a particular emphasis on reaching marginalised populations.
Elizabeth Krieger, , Armand Keating,
Bone Marrow Transplantation pp 1-9; doi:10.1038/s41409-021-01393-9

Abstract:
Killer immunoglobulin-like receptor (KIR) and KIR-ligand (KIRL) interactions play an important role in natural killer cell-mediated graft versus leukemia effect (GVL) after hematopoietic cell transplant (HCT) for AML. Accounting for known KIR-KIRL interactions may identify donors with optimal NK cell-mediated alloreactivity and GVL. A retrospective study of 2359 donor-recipient pairs (DRP) who underwent unrelated donor (URD) HCT for AML was performed. KIR-KIRL combinations were determined and associations with clinical outcomes examined. Relapse risk was reduced in DRP with both higher inhibitory KIR-KIRL (iKIR) and missing KIRL (mKIR) scores, with HR 0.86 (P = 0.01) & HR 0.84 (P = 0.02) respectively. The iKIR and mKIR score components were summed to give a maximal inhibitory KIR ligand (IM-KIR) score for each donor, which if it was 5, as opposed to <5, was also associated with a lower relapse risk, SHR 0.8 (P = 0.004). All IM = 5 donors possess KIR Haplotype B/x. Transplant-related mortality was increased among those with IM-KIR = 5, HR, 1.32 (P = 0.01). In a subset analysis of those transplanted with 8/8 HLA-matched DRP, anti-thymocyte globulin recipients with IM-KIR = 5, had a lower relapse rate HR, 0.61 (p = 0.001). This study demonstrates that HLA-matched unrelated donors with the highest inhibitory KIR content confer relapse protection, albeit with increased TRM. These donors all have KIR haplotype B. Clinical trials utilizing donors with a higher iKIR content in conjunction with novel strategies to reduce TRM should be considered for URD HCT in recipients with AML to optimize clinical outcomes.
Botao Fa, Ting Wei, Yuan Zhou, Luke Johnston, Xin Yuan, Yanran Ma, Yue Zhang, Zhangsheng Yu
Published: 7 July 2021
Nature Communications, Volume 12, pp 1-11; doi:10.1038/s41467-021-24489-8

Abstract:
Single cell RNA sequencing (scRNA-seq) is a powerful tool in detailing the cellular landscape within complex tissues. Large-scale single cell transcriptomics provide both opportunities and challenges for identifying rare cells playing crucial roles in development and disease. Here, we develop GapClust, a light-weight algorithm to detect rare cell types from ultra-large scRNA-seq datasets with state-of-the-art speed and memory efficiency. Benchmarking on diverse experimental datasets demonstrates the superior performance of GapClust compared to other recently proposed methods. When applying our algorithm to an intestine and 68 k PBMC datasets, GapClust identifies the tuft cells and a previously unrecognised subtype of monocyte, respectively.
, , T. Bilgeri, X. Zhang, , F. Donati, , T. Choi
Published: 7 July 2021
Nature Communications, Volume 12, pp 1-6; doi:10.1038/s41467-021-24465-2

Abstract:
Atomic scale engineering of magnetic fields is a key ingredient for miniaturizing quantum devices and precision control of quantum systems. This requires a unique combination of magnetic stability and spin-manipulation capabilities. Surface-supported single atom magnets offer such possibilities, where long temporal and thermal stability of the magnetic states can be achieved by maximizing the magnet/ic anisotropy energy (MAE) and by minimizing quantum tunnelling of the magnetization. Here, we show that dysprosium (Dy) atoms on magnesium oxide (MgO) have a giant MAE of 250 meV, currently the highest among all surface spins. Using a variety of scanning tunnelling microscopy (STM) techniques including single atom electron spin resonance (ESR), we confirm no spontaneous spin-switching in Dy over days at ≈ 1 K under low and even vanishing magnetic field. We utilize these robust Dy single atom magnets to engineer magnetic nanostructures, demonstrating unique control of magnetic fields with atomic scale tunability.
, Tyler N. Starr, Christopher O. Barnes, Yiska Weisblum, Fabian Schmidt, Marina Caskey, Christian Gaebler, Alice Cho, Marianna Agudelo, Shlomo Finkin, et al.
Published: 7 July 2021
Nature Communications, Volume 12, pp 1-14; doi:10.1038/s41467-021-24435-8

Abstract:
Monoclonal antibodies targeting a variety of epitopes have been isolated from individuals previously infected with SARS-CoV-2, but the relative contributions of these different antibody classes to the polyclonal response remains unclear. Here we use a yeast-display system to map all mutations to the viral spike receptor-binding domain (RBD) that escape binding by representatives of three potently neutralizing classes of anti-RBD antibodies with high-resolution structures. We compare the antibody-escape maps to similar maps for convalescent polyclonal plasmas, including plasmas from individuals from whom some of the antibodies were isolated. While the binding of polyclonal plasma antibodies are affected by mutations across multiple RBD epitopes, the plasma-escape maps most resemble those of a single class of antibodies that target an epitope on the RBD that includes site E484. Therefore, although the human immune system can produce antibodies that target diverse RBD epitopes, in practice the polyclonal response to infection is skewed towards a single class of antibodies targeting an epitope that is already undergoing rapid evolution.
Megan C. Bakeberg, Anastazja M. Gorecki, , Madison E. Hoes, , P. Anthony Akkari, Frank L. Mastaglia,
Published: 7 July 2021
npj Parkinson's Disease, Volume 7, pp 1-9; doi:10.1038/s41531-021-00200-y

Abstract:
The translocase of outer mitochondrial membrane 40 (TOMM40) ‘523’ polymorphism has previously been associated with age of Alzheimer’s disease onset and cognitive functioning in non-pathological ageing, but has not been explored as a candidate risk marker for cognitive decline in Parkinson’s disease (PD). Therefore, this longitudinal study investigated the role of the ‘523’ variant in cognitive decline in a patient cohort from the Parkinson’s Progression Markers Initiative. As such, a group of 368 people with PD were assessed annually for cognitive performance using multiple neuropsychological protocols, and were genotyped for the TOMM40 ‘523’ variant using whole-genome sequencing data. Covariate-adjusted generalised linear mixed models were utilised to examine the relationship between TOMM40 ‘523’ allele lengths and cognitive scores, while taking into account the APOE ε genotype. Cognitive scores declined over the 5-year study period and were lower in males than in females. When accounting for APOE ε4, the TOMM40 ‘523’ variant was not robustly associated with overall cognitive performance. However, in APOE ε3/ε3 carriers, who accounted for ~60% of the whole cohort, carriage of shorter ‘523’ alleles was associated with more severe cognitive decline in both sexes, while carriage of the longer alleles in females were associated with better preservation of global cognition and a number of cognitive sub-domains, and with a delay in progression to dementia. The findings indicate that when taken in conjunction with the APOE genotype, TOMM40 ‘523’ allele length is a significant independent determinant and marker for the trajectory of cognitive decline and risk of dementia in PD.
Soon Wei Daniel Lim, Joon-Suh Park, , Ahmed H. Dorrah,
Published: 7 July 2021
Nature Communications, Volume 12, pp 1-10; doi:10.1038/s41467-021-24493-y

Abstract:
Optical phase singularities are zeros of a scalar light field. The most systematically studied class of singular fields is vortices: beams with helical wavefronts and a linear (1D) singularity along the optical axis. Beyond these common and stable 1D topologies, we show that a broader family of zero-dimensional (point) and two-dimensional (sheet) singularities can be engineered. We realize sheet singularities by maximizing the field phase gradient at the desired positions. These sheets, owning to their precise alignment requirements, would otherwise only be observed in rare scenarios with high symmetry. Furthermore, by applying an analogous procedure to the full vectorial electric field, we can engineer paraxial transverse polarization singularity sheets. As validation, we experimentally realize phase and polarization singularity sheets with heart-shaped cross-sections using metasurfaces. Singularity engineering of the dark enables new degrees of freedom for light-matter interaction and can inspire similar field topologies beyond optics, from electron beams to acoustics.
Yu Liu, Wu Xiong, Chu-Wang Wang, Jian-Ping Shi, Zhi-Qiang Shi, Jian-Da Zhou
Published: 7 July 2021
Laboratory Investigation pp 1-8; doi:10.1038/s41374-021-00621-6

Abstract:
The wound-healing process is a natural response to burn injury. Resveratrol (RES) may have potential as a therapy for wound healing, but how and whether RES regulates skin repair remains poorly understood. Human epidermal keratinocyte (HaCaT) cells were treated with lipopolysaccharide (LPS), and a mouse skin wound-healing model was established. Cell viability and apoptosis were analyzed by 3-(4,5-dimethyl-2-thiazolyl)−2,5-diphenyl-2-H-tetrazolium bromide or flow cytometry. Cell proliferation was assessed by cell viability and colony-formation analyses. Cell migration was tested by wound-healing analysis. The microRNA-212 (miR-212) and caspase-8 (CASP8) levels were determined by quantitative reverse transcription polymerase chain reaction and western blotting. The correlation between miR-212 and CASP8 was analyzed by dual-luciferase reporter analysis. Skin wound healing in mice was assessed by measuring the wound area and gap after hematoxylin–eosin (HE) staining. RES reduced the LPS-induced reduction in viability and apoptosis in HaCaT cells. miR-212 expression was reduced by LPS and increased by exposure to RES. RES promoted cell proliferation and migration after LPS treatment by increasing miR-212 levels. CASP8 was a target of miR-212. CASP8 silencing promoted cell proliferation and migration, which was reversed by miR-212 knockdown in LPS-treated HaCaT cells. RES promoted skin wound healing in mice, which was reduced by miR-212 knockdown. Thus, RES facilitates cell proliferation and migration in LPS-treated HaCaT cells and promotes skin wound-healing in a mouse model by regulating the miR-212/CASP8 axis. The authors aimed to provide new insights into the pathogenesis and treatment of cutaneous burns. They show that the plant polyphenol resveratrol contributes to cell proliferation and migration in lipopolysaccharide-stimulated human epidermal keratinocyte cells. Resveratrol promotes wound healing in a mouse skin wound model via regulation of the miR-212/CASP8 axis.
Katsuyuki Sakai, Risa Takao, , , ,
Published: 7 July 2021
The Journal of Antibiotics pp 1-3; doi:10.1038/s41429-021-00442-1

Abstract:
A novel angucyclinone, 6,9-dihydroxytetrangulol, was isolated from Streptomyces lividans TK23 transformed with a kinanthraquinone biosynthetic gene cluster in which the kiqO gene was disrupted. The chemical structure was elucidated by spectroscopic analyses. It showed significant antibacterial activities with an IC50 value of 1.9 μM against Staphylococcus aureus and moderate anticancer activities against HL-60 cells.
Zengyuan Zhang, Yanfang Zhang, Kefang Liu, Yan Li, Qiong Lu, Qingling Wang, Yuqin Zhang, , Hanyi Liao, Anqi Zheng, et al.
Published: 7 July 2021
Nature Communications, Volume 12, pp 1-10; doi:10.1038/s41467-021-24326-y

Abstract:
SARS-CoV-2 can infect many domestic animals, including dogs. Herein, we show that dog angiotensin-converting enzyme 2 (dACE2) can bind to the SARS-CoV-2 spike (S) protein receptor binding domain (RBD), and that both pseudotyped and authentic SARS-CoV-2 can infect dACE2-expressing cells. We solved the crystal structure of RBD in complex with dACE2 and found that the total number of contact residues, contact atoms, hydrogen bonds and salt bridges at the binding interface in this complex are slightly fewer than those in the complex of the RBD and human ACE2 (hACE2). This result is consistent with the fact that the binding affinity of RBD to dACE2 is lower than that of hACE2. We further show that a few important mutations in the RBD binding interface play a pivotal role in the binding affinity of RBD to both dACE2 and hACE2. Our work reveals a molecular basis for cross-species transmission and potential animal spread of SARS-CoV-2, and provides new clues to block the potential transmission chains of this virus.
, , Stephen C. Watts, Louise T. Cerdeira, ,
Published: 7 July 2021
Nature Communications, Volume 12, pp 1-16; doi:10.1038/s41467-021-24448-3

Abstract:
Klebsiella pneumoniae is a leading cause of antimicrobial-resistant (AMR) healthcare-associated infections, neonatal sepsis and community-acquired liver abscess, and is associated with chronic intestinal diseases. Its diversity and complex population structure pose challenges for analysis and interpretation of K. pneumoniae genome data. Here we introduce Kleborate, a tool for analysing genomes of K. pneumoniae and its associated species complex, which consolidates interrogation of key features of proven clinical importance. Kleborate provides a framework to support genomic surveillance and epidemiology in research, clinical and public health settings. To demonstrate its utility we apply Kleborate to analyse publicly available Klebsiella genomes, including clinical isolates from a pan-European study of carbapenemase-producing Klebsiella, highlighting global trends in AMR and virulence as examples of what could be achieved by applying this genomic framework within more systematic genomic surveillance efforts. We also demonstrate the application of Kleborate to detect and type K. pneumoniae from gut metagenomes.
Correction
Manivannan Subramanian, Seung Jae Hyeon, Tanuza Das, Yoon Seok Suh, , Jeong-Soo Lee, , Hoon Ryu,
Published: 7 July 2021
Nature Communications, Volume 12, pp 1-1; doi:10.1038/s41467-021-24572-0

Donghai Xiong, Yian Wang, Ming You
Published: 7 July 2021
Nature Communications, Volume 12, pp 1-4; doi:10.1038/s41467-021-24304-4

Connor S. Murray, Yingnan Gao,
Published: 7 July 2021
Nature Communications, Volume 12, pp 1-5; doi:10.1038/s41467-021-24128-2

Zhaofa Xu, Annabel Ma,
Signal Transduction and Targeted Therapy, Volume 6, pp 1-2; doi:10.1038/s41392-021-00683-4

Dan Meyerstein
Published: 7 July 2021
Nature Reviews Chemistry pp 1-3; doi:10.1038/s41570-021-00310-4

Abstract:
The Fenton and Fenton-like reactions are important in biology because they are a major source of oxidative stress. The reactions also feature in advanced oxidation technologies to remediate organic pollutants. Unfortunately, these reactions are often simplistically viewed as affording only OH˙ radicals as the active species. Indeed, a variety of additional oxidizing intermediates form, including OR˙, Mn+2Lm, MnLm−1(O2H−), MnLm−1(O2R−) and CO3˙−, depending on the system. Under physiological conditions, CO3˙− is probably the major oxidizing intermediate. The Fenton and Fenton-like reactions feature in oxidative stress and are central to advanced oxidation technologies to remediate organic pollutants. The reactions are often simplistically taught to afford only hydroxyl radical as the active oxidant. Yet, this is just one of many possible oxidants and is probably not the major oxidant formed under biological conditions.
, M. Cade Lawson, Camila Z. Apablaza
Published: 7 July 2021
Scientific Data, Volume 8, pp 1-7; doi:10.1038/s41597-021-00956-1

Abstract:
Problems of poor network interoperability in electric vehicle (EV) infrastructure, where data about real-time usage or consumption is not easily shared across service providers, has plagued the widespread analysis of energy used for transportation. In this article, we present a high-resolution dataset of real-time EV charging transactions resolved to the nearest second over a one-year period at a multi-site corporate campus. This includes 105 charging stations across 25 different facilities operated by a single firm in the U.S. Department of Energy Workplace Charging Challenge. The high-resolution data has 3,395 real-time transactions and 85 users with both paid and free sessions. The data has been expanded for re-use such as identifying charging behaviour and segmenting user groups by frequency of usage, stage of adoption, and employee type. Potential applications include but are not limited to simulating and parameterizing energy demand models; investigating flexible charge scheduling and optimal power flow problems; characterizing transportation emissions and electric mobility patterns at high temporal resolution; and evaluating characteristics of early adopters and lead user innovation.
Nikhil Tilak, Xinyuan Lai, Shuang Wu, Zhenyuan Zhang, Mingyu Xu, , Paul C. Canfield,
Published: 7 July 2021
Nature Communications, Volume 12, pp 1-7; doi:10.1038/s41467-021-24480-3

Abstract:
Magic-angle twisted bilayer graphene has emerged as a powerful platform for studying strongly correlated electron physics, owing to its almost dispersionless low-energy bands and the ability to tune the band filling by electrostatic gating. Techniques to control the twist angle between graphene layers have led to rapid experimental progress but improving sample quality is essential for separating the delicate correlated electron physics from disorder effects. Owing to the 2D nature of the system and the relatively low carrier density, the samples are highly susceptible to small doping inhomogeneity which can drastically modify the local potential landscape. This potential disorder is distinct from the twist angle variation which has been studied elsewhere. Here, by using low temperature scanning tunneling spectroscopy and planar tunneling junction measurements, we demonstrate that flat bands in twisted bilayer graphene can amplify small doping inhomogeneity that surprisingly leads to carrier confinement, which in graphene could previously only be realized in the presence of a strong magnetic field.
Wilhelm Eschen, Sici Wang, Chang Liu, Robert Klas, Michael Steinert, Sergiy Yulin, Heide Meißner, Michael Bussmann, , Jens Limpert, et al.
Published: 7 July 2021
Communications Physics, Volume 4, pp 1-7; doi:10.1038/s42005-021-00658-5

Abstract:
Nanoscale coherent imaging has emerged as an indispensable modality, allowing to surpass the resolution limit given by classical imaging optics. At the same time, attosecond science has experienced enormous progress and has revealed the ultrafast dynamics in complex materials. Combining attosecond temporal resolution of pump-probe experiments with nanometer spatial resolution would allow studying ultrafast dynamics on the smallest spatio-temporal scales but has not been demonstrated yet. To date, the large bandwidth of attosecond pulses poses a major challenge to high-resolution coherent imaging. Here, we present broadband holography-enhanced coherent imaging, which enables the combination of high-resolution coherent imaging with a large spectral bandwidth. By implementing our method at a high harmonic source, we demonstrate a spatial resolution of 34 nm in combination with a spectral bandwidth of 5.5 eV at a central photon energy of 92 eV. The method is single-shot capable and retrieves the spectrum from the measured diffraction pattern.
Nicholas F. Brazeau, Cedar L. Mitchell, Andrew P. Morgan, Molly Deutsch-Feldman, , Kyaw L. Thwai, Pere Gelabert, , , Andreea Waltmann, et al.
Published: 7 July 2021
Nature Communications, Volume 12, pp 1-10; doi:10.1038/s41467-021-24216-3

Abstract:
Reports of P. vivax infections among Duffy-negative hosts have accumulated throughout sub-Saharan Africa. Despite this growing body of evidence, no nationally representative epidemiological surveys of P. vivax in sub-Saharan Africa have been performed. To overcome this gap in knowledge, we screened over 17,000 adults in the Democratic Republic of the Congo (DRC) for P. vivax using samples from the 2013-2014 Demographic Health Survey. Overall, we found a 2.97% (95% CI: 2.28%, 3.65%) prevalence of P. vivax infections across the DRC. Infections were associated with few risk-factors and demonstrated a relatively flat distribution of prevalence across space with focal regions of relatively higher prevalence in the north and northeast. Mitochondrial genomes suggested that DRC P. vivax were distinct from circulating non-human ape strains and an ancestral European P. vivax strain, and instead may be part of a separate contemporary clade. Our findings suggest P. vivax is diffusely spread across the DRC at a low prevalence, which may be associated with long-term carriage of low parasitemia, frequent relapses, or a general pool of infections with limited forward propagation.
M. Preißinger, K. Karube, D. Ehlers, B. Szigeti, H.-A. Krug von Nidda, , V. Ukleev, , Y. Tokunaga, A. Kikkawa, et al.
Published: 7 July 2021
npj Quantum Materials, Volume 6, pp 1-9; doi:10.1038/s41535-021-00365-y

Abstract:
Magnetic anisotropy is anticipated to govern the formation of exotic spin textures reported recently in cubic chiral magnets, like low-temperature tilted conical and skyrmion lattice (SkL) states and metastable SkLs with various lattice geometry. Motivated by these findings, we quantified the cubic anisotropy in a series of CoZnMn-type cubic chiral magnets. We found that the strength of anisotropy is highly enhanced towards low temperatures. Moreover, not only the magnitude but also the character of cubic anisotropy drastically varies upon changing the Co/Mn ratio. We correlate these changes with temperature- and composition-induced variations of the helical modulation vectors, deformations of skyrmions, structural rearrangements of the metastable SkLs and the large enhancement of Gilbert damping. Similar studies on magnetic anisotropy are required for the quantitative, unified description of the known stable and metastable modulated spin textures and for the systematic exploration of novel ones in this large class of skyrmion hosts.
Babatunde Adedokun, Zhaohui Du, Guimin Gao, , , Gary Zirpoli, , Esther M. John, , , et al.
Published: 7 July 2021
Nature Communications, Volume 12, pp 1-8; doi:10.1038/s41467-021-24327-x

Abstract:
Our study describes breast cancer risk loci using a cross-ancestry GWAS approach. We first identify variants that are associated with breast cancer at P < 0.05 from African ancestry GWAS meta-analysis (9241 cases and 10193 controls), then meta-analyze with European ancestry GWAS data (122977 cases and 105974 controls) from the Breast Cancer Association Consortium. The approach identifies four loci for overall breast cancer risk [1p13.3, 5q31.1, 15q24 (two independent signals), and 15q26.3] and two loci for estrogen receptor-negative disease (1q41 and 7q11.23) at genome-wide significance. Four of the index single nucleotide polymorphisms (SNPs) lie within introns of genes (KCNK2, C5orf56, SCAMP2, and SIN3A) and the other index SNPs are located close to GSTM4, AMPD2, CASTOR2, and RP11-168G16.2. Here we present risk loci with consistent direction of associations in African and European descendants. The study suggests that replication across multiple ancestry populations can help improve the understanding of breast cancer genetics and identify causal variants.
Magaly Tribet, Caroline Marques, Sarah Mougnaud, Véronique Broudic, Christophe Jegou, Sylvain Peuget
Published: 7 July 2021
npj Materials Degradation, Volume 5, pp 1-11; doi:10.1038/s41529-021-00183-4

Abstract:
In the prospect of deep geological disposal, the long-term behavior of high-level nuclear glasses has to be investigated regarding alpha radiation induced by long-life minor actinides. The present study focuses on the effects of alpha radiation on the long-term chemical reactivity of R7T7-type glasses, by separately considering the alpha dose rate and the alpha decay dose. Old SON68 glasses doped with 238/239PuO2 or 244CmO2 were studied to simulate high alpha dose rates corresponding to an early water ingress and a high level of alpha decay doses corresponding to long-term disposal conditions. A part of the 238/239Pu-doped glass block was annealed to fully recover the irradiation-induced damage accumulated since the glass was fabricated and to dissociate the effect of the alpha dose rate from that of the alpha decay dose. The glasses were then leached under static conditions at 90 °C for several years. The results showed that the residual alteration rate is not affected by the alpha dose rate over a wide range of dose rate values expected under disposal conditions: this glass remained relatively insensitive to the alpha radiolysis phenomena at the glass–water interface. However, over the duration of the experiments, the residual alteration rate of the damaged 238/239Pu-doped glass was enhanced compared to that of the annealed glass. This result is in agreement with those obtained on the 244Cm-doped glass and with reported values in the literature on simplified externally irradiated glasses, indicating that the ballistic effects of the recoil nuclei are responsible for this increase in the residual alteration rate.
Published: 7 July 2021
Nature Communications, Volume 12, pp 1-9; doi:10.1038/s41467-021-23978-0

Abstract:
Speckle is maybe the most fundamental interference effect of light in disordered media, giving rise to fascinating physical phenomena and cutting edge applications. While speckle formed outside a sample is easily measured and analysed, true bulk speckle, as formed inside random media, is difficult to investigate directly due to the obvious issue of physical access. Furthermore, its proper theoretical description poses enormous challenges. Here we report on the first direct measurements of spatially resolved intensity correlations of light inside a disordered medium, using embedded DNA strings decorated with emitters separated by a controlled nanometric distance. Our method provides in situ access to fundamental properties of bulk speckles as their size and polarization degrees of freedom, both of which are found to deviate significantly from theoretical predictions. The deviations are explained, by comparison with rigorous numerical calculations, in terms of correlations among polarization components and non-universal near-field contributions at the nanoscale.
, Gor Oganesyan, Marica Branchesi, Stefano Ascenzi, , Francesco Brighenti, Simone Dall’Osso, Paolo D’Avanzo, , Gabriele Ghisellini, et al.
Published: 7 July 2021
Nature Communications, Volume 12, pp 1-9; doi:10.1038/s41467-021-24246-x

Abstract:
γ-ray bursts (GRBs) are short-lived transients releasing a large amount of energy (1051 − 1053 erg) in the keV-MeV energy range. GRBs are thought to originate from internal dissipation of the energy carried by ultra-relativistic jets launched by the remnant of a massive star’s death or a compact binary coalescence. While thousands of GRBs have been observed over the last thirty years, we still have an incomplete understanding of where and how the radiation is generated in the jet. Here we show a relation between the spectral index and the flux found by investigating the X-ray tails of bright GRB pulses via time-resolved spectral analysis. This relation is incompatible with the long standing scenario which invokes the delayed arrival of photons from high-latitude parts of the jet. While the alternative scenarios cannot be firmly excluded, the adiabatic cooling of the emitting particles is the most plausible explanation for the discovered relation, suggesting a proton-synchrotron origin of the GRB emission.
Karol Nienałtowski, Rachel E. Rigby, Jarosław Walczak, Karolina E. Zakrzewska, Edyta Głów, ,
Published: 7 July 2021
Nature Communications, Volume 12, pp 1-10; doi:10.1038/s41467-021-24449-2

Abstract:
Although we can now measure single-cell signaling responses with multivariate, high-throughput techniques our ability to interpret such measurements is still limited. Even interpretation of dose–response based on single-cell data is not straightforward: signaling responses can differ significantly between cells, encompass multiple signaling effectors, and have dynamic character. Here, we use probabilistic modeling and information-theory to introduce fractional response analysis (FRA), which quantifies changes in fractions of cells with given response levels. FRA can be universally performed for heterogeneous, multivariate, and dynamic measurements and, as we demonstrate, quantifies otherwise hidden patterns in single-cell data. In particular, we show that fractional responses to type I interferon in human peripheral blood mononuclear cells are very similar across different cell types, despite significant differences in mean or median responses and degrees of cell-to-cell heterogeneity. Further, we demonstrate that fractional responses to cytokines scale linearly with the log of the cytokine dose, which uncovers that heterogeneous cellular populations are sensitive to fold-changes in the dose, as opposed to additive changes.
Xianhui Liu, Ivana Blaženović, Adam J. Contreras, Thu M. Pham, Christine A. Tabuloc, Ying H. Li, Jian Ji, ,
Published: 7 July 2021
Nature Communications, Volume 12, pp 1-16; doi:10.1038/s41467-021-24301-7

Abstract:
The integration of circadian and metabolic signals is essential for maintaining robust circadian rhythms and ensuring efficient metabolism and energy use. Using Drosophila as an animal model, we show that cellular protein O-GlcNAcylation exhibits robust 24-hour rhythm and represents a key post-translational mechanism that regulates circadian physiology. We observe strong correlation between protein O-GlcNAcylation rhythms and clock-controlled feeding-fasting cycles, suggesting that O-GlcNAcylation rhythms are primarily driven by nutrient input. Interestingly, daily O-GlcNAcylation rhythms are severely dampened when we subject flies to time-restricted feeding at unnatural feeding time. This suggests the presence of clock-regulated buffering mechanisms that prevent excessive O-GlcNAcylation at non-optimal times of the day-night cycle. We show that this buffering mechanism is mediated by the expression and activity of GFAT, OGT, and OGA, which are regulated through integration of circadian and metabolic signals. Finally, we generate a mathematical model to describe the key factors that regulate daily O-GlcNAcylation rhythm.
, , Sazlina Shariff Ghazali, Hani Salim, Jasmine Wong, Norita Hussein, Rizawati Ramli, , Su May Liew, Nik Sherina Hanafi, et al.
npj Primary Care Respiratory Medicine, Volume 31, pp 1-8; doi:10.1038/s41533-021-00250-y

Abstract:
Asthma self-management is a crucial component of asthma management. We sought to explore healthcare professionals’ (HCPs’) perceptions on barriers to asthma self-management implementation in primary care. We recruited 26 HCPs from six public primary care clinics in a semi-urban district of Malaysia in 2019. The analysis was done inductively. HCPs described barriers that resonated with the “COM-B” behaviour change framework. Capability-related issues stemmed from a need for specific self-management skills training. Opportunity-related barriers included the need to balance competing tasks and limited, poorly tailored resources. Motivation-related barriers included lack of awareness about self-management benefits, which was not prioritised in consultations with perceived lack of receptiveness from patients. These were compounded by contextual barriers of the healthcare organisation and multilingual society. The approach to implementation of asthma self-management needs to be comprehensive, addressing systemic, professional, and patient barriers and tailored to the local language, health literacy, and societal context.
Leilei Huang, Hongyi Zhou, Kai Feng, Chongjin Xie
Published: 7 July 2021
npj Quantum Information, Volume 7, pp 1-7; doi:10.1038/s41534-021-00442-x

Abstract:
Randomness lays the foundation for information security. Quantum random number generation based on various quantum principles has been proposed to provide true randomness in the last two decades. We integrate four different types of quantum random number generators on the Alibaba Cloud servers to enhance cybersecurity. Post-processing modules are integrated into the quantum platform to extract true random numbers. We employ improved authentication protocols where original pseudo-random numbers are replaced with quantum ones. Users from the Alibaba Cloud, such as Ant Financial and Smart Access Gateway, request random numbers from the quantum platform for various cryptographic tasks. For cloud services demanding the highest security, such as Alipay at Ant Financial, we combine the random numbers from four quantum devices by XOR the outputs to enhance practical security. The quantum platform has been continuously run for more than a year.
Jian Min, Zuo-Lei Wang, Yun-Peng Li, Wen-Ze Tao, , Jun-Gang Lei, Dong-Xue Xi, Da Fan, Jun-Biao Wang
Published: 7 July 2021
npj Microgravity, Volume 7, pp 1-10; doi:10.1038/s41526-021-00154-8

Abstract:
Taiji-1, which is the first technical verification satellite of China’s Space Gravitational Wave Detection Program, was successfully launched on August 31, 2019. The mission aimed to investigate the key technologies used in space gravitational wave detection. The inertial sensor, which was one of the main payloads, measured the residual acceleration of the satellite, and verified the drag-free control technology. Its performance was crucial to the success of the Taiji-1 mission. To ensure its performance in orbit, the inertial sensor was fully evaluated prior to launch. Owing to the gravitational acceleration on the ground, it is impossible to verify all the properties of the inertial sensor in a routine laboratory. A feasible method to conduct such tests is to use a drop tower. To guarantee the safety of the inertial sensor, a substitute was used with similar structure and circuit design. A total of 20 falls in three groups were completed, a set of research methods was established, and the importance of conducting simulations before the drop tests was verified. For the first time, the switch of different circuit gains in a drop tower test has been achieved and the National Microgravity Laboratory of China (NMLC) drop tower’s residual accelerations in three dimensions were measured. The results demonstrated that the microgravity level of the drop tower can reach about 58 μg0 in the fall direction and 13 μg0 along the horizontal axes.
, Mikael C. F. Karlsson, Anurak Sawatdee, Mohammad Yusuf Mulla, Naveed Ul Hassan Alvi, Valerio Beni, David Nilsson
Published: 7 July 2021
npj Flexible Electronics, Volume 5, pp 1-8; doi:10.1038/s41528-021-00111-1

Abstract:
This study illustrates an innovative way to fabricate inkjet-printed tracks by sequential printing of Zn nanoparticle ink and curing ink for low temperature in situ chemical sintering. Employing chemical curing in place of standard sintering methods leads to the advantages of using flexible substrates that may not withstand the high thermal budgets of the standard methods. A general formulation engineering method is adopted to produce highly concentrated Zn ink which is cured by inkjet printing an over-layer of aqueous acetic acid which is the curing agent. The experimental results reveal that a narrow window of acid concentration of curing ink plays a crucial role in determining the electrical properties of the printed Zn nanoparticles. Highly conductive (~105 S m−1) and mechanically flexible printed Zn features are achieved. In addition, from systematic material characterization, we obtain an understanding of the curing mechanism. Finally, a touch sensor circuit is demonstrated involving all-Zn printed conductive tracks.
Meiron Zollmann, Boris Rubinsky, , Alexander Golberg
Published: 7 July 2021
Communications Biology, Volume 4, pp 1-11; doi:10.1038/s42003-021-02371-z

Abstract:
Multi-scale macroalgae growth models are required for the efficient design of sustainable, economically viable, and environmentally safe farms. Here, we develop a multi-scale model for Ulva sp. macroalgae growth and nitrogen sequestration in an intensive cultivation farm, regulated by temperature, light, and nutrients. The model incorporates a range of scales by incorporating spatial effects in two steps: light extinction at the reactor scale (1 m) and nutrient absorption at the farm scale (1 km). The model was validated on real data from an experimental reactor installed in the sea. Biomass production rates, chemical compositions, and nitrogen removal were simulated under different seasons, levels of dilution in the environment and water-exchange rate in the reactor. This multi-scale model provides an important tool for environmental authorities and seaweed farmers who desire to upscale to large bioremediation and/or macroalgae biomass production farms, thus promoting the marine sustainable development and the macroalgae-based bioeconomy.
Indira Bag, Shue Chen, , , Chen-Yu Liu, Guo-Yun Yu, Elissa P. Lei
Published: 7 July 2021
Nature Communications, Volume 12, pp 1-18; doi:10.1038/s41467-021-24407-y

Abstract:
Genome organization is driven by forces affecting transcriptional state, but the relationship between transcription and genome architecture remains unclear. Here, we identified the Drosophila transcription factor Motif 1 Binding Protein (M1BP) in physical association with the gypsy chromatin insulator core complex, including the universal insulator protein CP190. M1BP is required for enhancer-blocking and barrier activities of the gypsy insulator as well as its proper nuclear localization. Genome-wide, M1BP specifically colocalizes with CP190 at Motif 1-containing promoters, which are enriched at topologically associating domain (TAD) borders. M1BP facilitates CP190 chromatin binding at many shared sites and vice versa. Both factors promote Motif 1-dependent gene expression and transcription near TAD borders genome-wide. Finally, loss of M1BP reduces chromatin accessibility and increases both inter- and intra-TAD local genome compaction. Our results reveal physical and functional interaction between CP190 and M1BP to activate transcription at TAD borders and mediate chromatin insulator-dependent genome organization.
Pan Xiong, Fan Zhang, Xiuyun Zhang, Yifan Liu, Yunyan Wu, Shijian Wang, Javad Safaei, , Renzhi Ma, , et al.
Published: 7 July 2021
Nature Communications, Volume 12, pp 1-15; doi:10.1038/s41467-021-24399-9

Abstract:
The regulation of anions and cations at the atomic scale is of great significance in membrane-based separation technologies. Ionic transport regulation techniques could also play a crucial role in developing high-performance alkali metal batteries such as alkali metal-sulfur and alkali metal-selenium batteries, which suffer from the non-uniform transport of alkali metal ions (e.g., Li+ or Na+) and detrimental shuttling effect of polysulfide/polyselenide anions. These drawbacks could cause unfavourable growth of alkali metal depositions at the metal electrode and irreversible consumption of cathode active materials, leading to capacity decay and short cycling life. Herein, we propose the use of a polypropylene separator coated with negatively charged Ti0.87O2 nanosheets with Ti atomic vacancies to tackle these issues. In particular, we demonstrate that the electrostatic interactions between the negatively charged Ti0.87O2 nanosheets and polysulfide/polyselenide anions reduce the shuttling effect. Moreover, the Ti0.87O2-coated separator regulates the migration of alkali ions ensuring a homogeneous ion flux and the Ti vacancies, acting as sub-nanometric pores, promote fast alkali-ion diffusion.
Kyung-Ran Kim, Hyeon-Ju Jeong, Yoonsub Kim, Seung Yeon Lee, Yujin Kim, Hyun-Ji Kim, , Hana Cho, Jong-Sun Kang, Won-Kyung Ho
Experimental & Molecular Medicine pp 1-14; doi:10.1038/s12276-021-00645-4

Abstract:
Calbindin, a major Ca2+ buffer in dentate granule cells (GCs), plays a critical role in shaping Ca2+ signals, yet how it regulates neuronal function remains largely unknown. Here, we found that calbindin knockout (CBKO) mice exhibited dentate GC hyperexcitability and impaired pattern separation, which co-occurred with reduced K+ current due to downregulated surface expression of Kv4.1. Relatedly, manipulation of calbindin expression in HT22 cells led to changes in CaMKII activation and the level of surface localization of Kv4.1 through phosphorylation at serine 555, confirming the mechanism underlying neuronal hyperexcitability in CBKO mice. We also discovered that Ca2+ buffering capacity was significantly reduced in the GCs of Tg2576 mice to the level of CBKO GCs, and this reduction was restored to normal levels by antioxidants, suggesting that calbindin is a target of oxidative stress. Our data suggest that the regulation of CaMKII signaling by Ca2+ buffering is crucial for neuronal excitability regulation.
Rina Nishii, Takanori Mizuno, Daniel Rehling, , Brandi L. Clark, Xujie Zhao, Scott A. Brown, Brandon Smart, Takaya Moriyama, Yuji Yamada, et al.
Published: 7 July 2021
Nature Communications, Volume 12, pp 1-9; doi:10.1038/s41467-021-24509-7

Abstract:
Nucleobase and nucleoside analogs (NNA) are widely used as anti-viral and anti-cancer agents, and NNA phosphorylation is essential for the activity of this class of drugs. Recently, diphosphatase NUDT15 was linked to thiopurine metabolism with NUDT15 polymorphism associated with drug toxicity in patients. Profiling NNA drugs, we identify acyclovir (ACV) and ganciclovir (GCV) as two new NNAs metabolized by NUDT15. NUDT15 hydrolyzes ACV and GCV triphosphate metabolites, reducing their effects against cytomegalovirus (CMV) in vitro. Loss of NUDT15 potentiates cytotoxicity of ACV and GCV in host cells. In hematopoietic stem cell transplant patients, the risk of CMV viremia following ACV prophylaxis is associated with NUDT15 genotype (P = 0.015). Donor NUDT15 deficiency is linked to graft failure in patients receiving CMV-seropositive stem cells (P = 0.047). In conclusion, NUDT15 is an important metabolizing enzyme for ACV and GCV, and NUDT15 variation contributes to inter-patient variability in their therapeutic effects.
, , Grant M. Cox, Adam R. Nordsvan, , Chuang Xuan, , Xu Liu, Xiaofang He
Published: 7 July 2021
Nature Communications, Volume 12, pp 1-9; doi:10.1038/s41467-021-24439-4

Abstract:
The snowball Earth hypothesis—that a runaway ice-albedo feedback can cause global glaciation—seeks to explain low-latitude glacial deposits, as well as geological anomalies including the re-emergence of banded iron formation and “cap” carbonates. One of the most significant challenges to snowball Earth has been sedimentological cyclicity that has been taken to imply more climate dynamics than expected when the ocean is completely covered in ice. However, recent climate models suggest that as atmospheric CO2 accumulates, the snowball climate system becomes sensitive to orbital forcing. Here we show the presence of nearly all Milankovitch (orbital) cycles preserved in stratified banded iron formation deposited during the Sturtian snowball Earth. These results provide evidence for orbitally forced cyclicity of global ice sheets that resulted in periodic oxidation of ferrous iron. Orbital glacial advance and retreat cycles provide a simple mechanism to reconcile both the sedimentary dynamics and the enigmatic survival of multicellular life during snowball Earth.
, Erick M. G. Cordeiro, Bartlomiej J. Troczka, Adam Pym, Joanna Mackisack, Thomas C. Mathers, Ana Duarte, Fabrice Legeai, Stéphanie Robin, Pablo Bielza, et al.
Published: 7 July 2021
Communications Biology, Volume 4, pp 1-16; doi:10.1038/s42003-021-02373-x

Abstract:
The aphid Myzus persicae is a destructive agricultural pest that displays an exceptional ability to develop resistance to both natural and synthetic insecticides. To investigate the evolution of resistance in this species we generated a chromosome-scale genome assembly and living panel of >110 fully sequenced globally sampled clonal lines. Our analyses reveal a remarkable diversity of resistance mutations segregating in global populations of M. persicae. We show that the emergence and spread of these mechanisms is influenced by host–plant associations, uncovering the widespread co‐option of a host-plant adaptation that also offers resistance against synthetic insecticides. We identify both the repeated evolution of independent resistance mutations at the same locus, and multiple instances of the evolution of novel resistance mechanisms against key insecticides. Our findings provide fundamental insights into the genomic responses of global insect populations to strong selective forces, and hold practical relevance for the control of pests and parasites.
Fu Sun, Jingshan Qin, , Mengzhou Yu, Xianhong Wu, XiaoMing Sun,
Published: 7 July 2021
Nature Communications, Volume 12, pp 1-11; doi:10.1038/s41467-021-24529-3

Abstract:
Seawater electrolysis represents a potential solution to grid-scale production of carbon-neutral hydrogen energy without reliance on freshwater. However, it is challenged by high energy costs and detrimental chlorine chemistry in complex chemical environments. Here we demonstrate chlorine-free hydrogen production by hybrid seawater splitting coupling hydrazine degradation. It yields hydrogen at a rate of 9.2 mol h–1 gcat –1 on NiCo/MXene-based electrodes with a low electricity expense of 2.75 kWh per m3 H2 at 500 mA cm–2 and 48% lower energy equivalent input relative to commercial alkaline water electrolysis. Chlorine electrochemistry is avoided by low cell voltages without anode protection regardless Cl– crossover. This electrolyzer meanwhile enables fast hydrazine degradation to ~3 ppb residual. Self-powered hybrid seawater electrolysis is realized by integrating low-voltage direct hydrazine fuel cells or solar cells. These findings enable further opportunities for efficient conversion of ocean resources to hydrogen fuel while removing harmful pollutants.
Published: 7 July 2021
Nature, Volume 595, pp 155-155; doi:10.1038/d41586-021-01825-y

Abstract:
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, Merycarla Pichardo, Edwin Rijo, Gustavo Espino, Ramon Rodriguez Lay, Rafael Estrella
Prostate Cancer and Prostatic Diseases pp 1-1; doi:10.1038/s41391-021-00414-4

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