bluuebunny/crossref_metadata_2025 huggingface dataset:
Reconciling the Carbon Balance of Northern Sweden Through Integration of Observations and Modelling
Authors: Sathyanadh Anusha , Monteil Guillaume , Scholze Marko , Klosterhalfen Anne , Laudon Hjalmar , Wu Zhendong , Gerbig Christoph , Peters Wouter , Bastrikov Vladislav , Nilsson Mats B. , Peichl Matthias
Published: November 2021

The boreal biome plays an important role in the global carbon cycle. However, current estimates of its sink‐source strength and responses to changes in climate are primarily derived from models and thus remain uncertain. A major challenge is the validation of these models at a regional scale since empirical flux estimates are typically confined to ecosystem or continental scales. The Integrated Carbon Observation System (ICOS)‐Svartberget atmospheric station (SVB) provides observations including tall tower eddy covariance (EC) and atmospheric concentration measurements that can contribute to such validation in Northern Sweden. Thus, the overall aim of this study was to quantify the carbon balance in Northern Sweden region by integrating land‐atmosphere fluxes and atmospheric carbon dioxide (CO2) concentrations. There were three specific objectives. First, to compare flux estimates from four models (VPRM, LPJ‐GUESS, ORCHIDEE, and SiBCASA) to tall tower EC measurements at SVB during the years 2016–2018. Second to assess the fluxes' impact on atmospheric CO2concentrations using a regional transport model. Third, to assess the impact of the drought in 2018. The comparison of estimated concentrations with ICOS observations helped the evaluation of the models' regional scale performance. Both the simulations and observations indicate there were similar reductions in the net CO2uptake during drought. All the models (except for SiBCASA) and observations indicated the region was a net carbon sink during the 3‐year study period. Our study highlights a need to improve vegetation models through comparisons with empirical data and demonstrate the ICOS network's potential utility for constraining CO2fluxes in the region.
Summer Season Precipitation Biases in 4 km WRF Forecasts Over Southern China: Diagnoses of the Causes of Biases
Authors: Zhu Kefeng , Yu Biyu , Xue Ming , Zhou Bowen , Hu Xiao‐Ming
Published: November 2021

In a recent study, we evaluated the performance of real‐time convection‐permitting WRF model forecasting over China. Although the overall rainfall distribution and diurnal cycle are well simulated, the model greatly overestimates the rainfall intensity in southern China and the predicted rainfall shows a southeast location bias. In this study, possible factors contributing to the precipitation forecast bias are discussed. The precipitation over southern China is found to be greatly influenced by land‐sea circulations. While the model captures diurnal variations of winds well, the predicted amplitude and onset timing of the land/sea breezes differ from observations. Cold bias of land‐surface temperature is shown to partially cause wind bias. In the afternoon, the cold bias results in a weakened inland penetration of sea breeze, which in turn leads to more rain on the eastern south‐China coastline. During nighttime, excessive cooling over land results in a stronger land breeze, leading to location bias of early morning precipitation. While the observed coastal rain belt is mostly located over land during early morning, the predicted coastal rain belt is mostly located over ocean. In addition, the model overestimates moisture at low levels, especially over the southern slope of the coastal mountains and over ocean, which explains the excessive rainfall over southern China. This study emphasizes the importance of accurately simulating land‐surface‐related variables for precipitation forecast in coastal regions where land‐sea contrast plays an important role.
Cloud and Aerosol Distributions From SAGE III/ISS Observations
Authors: Schoeberl Mark , Jensen Eric , Wang Tao , Taha Ghassan , Ueyama Rei , Wang Yi , DeLand Matthew , Dessler Andrew
Published: November 2021

We describe our Solar Aerosol and Gas Experiment (SAGE) III/ISS cloud detection algorithm and observations. We identify three types of clouds: visible cirrus (extinction coefficient > 3 x 10−2 km−1), subvisible cirrus (extinction coefficient between 3 x 10−2 km−1 and 10−3 km−1), and very low extinction cloud‐aerosol mixtures (extinction coefficient between 10−3 km−1and 10−4 km−1). Visible cirrus cannot be quantitatively measured by SAGE because of its high extinction, but we infer the presence of cirrus through the termination of the SAGE vertical scan. We then assume that cirrus layers extend 0.5 km below the scan termination height. SAGE cirrus cloud fraction estimated in this way is in qualitative agreement with Cloud‐Aerosol Lidar with Orthogonal Polarization (CALIOP) measurements. Analyzing 2018–2020 SAGE III/ISS data, we find that visible cirrus and subvisible cirrus have nearly equal abundance in the tropical upper troposphere and the average cloud fraction is about 25%. At 16 km, the highest concentration of visible cirrus and subvisible cirrus is over the Tropical West Pacific, central Africa, and central South America during boreal winter. Latitudinal gaps in zonal mean cloud fraction are aligned with descending branch of the residual mean circulation. Using tropopause relative coordinates, we show that maximum cloud‐top heights are consistently restricted to a narrow region near the tropopause. The aerosol extinction fields also show the latitudinal gaps coincident with the descending residual circulation. We identify four anomalous aerosol extinction periods that can be tentatively assigned to significant volcanic or fire events.
The Limpopo Magma‐Rich Transform Margin, South Mozambique: 1. Insights From Deep‐Structure Seismic Imaging
Authors: Watremez L. , Leroy S. , d’Acremont E. , Roche V. , Evain M. , Leprêtre A. , Verrier F. , Aslanian D. , Dias N. , Afilhado A. , Schnürle P. , Castilla R. , Despinois F. , Moulin M.
Published: November 2021

A variety of structures results from the interplay of evolving far‐field forces, plate kinematics, and magmatic activity during continental break‐up. The east Limpopo transform margin, offshore northern Mozambique, formed as Africa and Antarctica separated during the mid‐Jurassic period break‐up of the Gondwana supercontinent. The nature of the crust onshore has been discussed for decades in an effort to resolve issues with plate kinematic models. Two seismic refraction profiles with coincident multichannel seismic reflection profiles allow us to interpret the seismic velocity structures across the margin, both onshore and offshore. These seismic profiles allow us to (a) delineate the major regional crustal domains; (b) identify widespread indications of magmatic activity; and (c) map crustal structure and geometry of this magma‐rich transform margin. Careful examination of the profiles allows us to make the following observations and interpretations: (a) on land, continental crust is overlain by a >10‐km thick volcano‐sedimentary wedge related to an early rifting stage, (b) offshore, thick oceanic crust formed due to intense magmatic activity, and between the two (c) a 50–60‐km wide transform zone where the crustal structures are affected by intense magmatic activity and faulting. The prominent presence of intrusive and extrusive igneous units may be attributed to the combination of a deep‐seated melting anomaly and a trans‐tensional fault zone running through thinned lithosphere that allowed melt to reach the surface. A comparison of the crustal thinning along other transform margins shows a probable dependence with the thermal and/or tectonic history of the lithosphere.
Roughness‐Based Method for Simulating Hydraulic Consequences of Both Woody Debris Clogging and Breakage at Bridges in Basin‐Scale Flood Modeling
Authors: Macchione Francesco , Lombardo Margherita
Published: November 2021

Obstructions at bridge can exacerbate flood hazard: when woody debris occlude a bridge, backwater increases, and sometimes a temporary reservoir can form. If the condition for the collapse of the jam exists, the phenomenon can evolve into a dam break flow resulting in an increase in downstream discharge or a steepening in the flow hydrograph. A rigorous description of backwater formed by debris at the bridge, and more generally of the interaction between flood and structure, is still a challenge and only few studies focus on the breakage phase and its consequence on flood dynamic. Unfortunately, analyzing the hydraulics of so many localized situations within a large area in detail would involve considerable modeling and calculation costs. Therefore, treatment methods are desirable that provide correct results in terms of the reference hydraulic variables for assessing the hazard without the need to model extremely local phenomena. The purpose of this study is to evaluate the possibility to reproduce an observed or estimated backwater by the use of an equivalent roughness at the place of the bridge and simulate the breakage phase by a sudden variation of its value. The method, applied to the numerical reconstruction of the experimental tests of dam break performed by the Waterways Experiment Station in 1961, has provided results that overlap well with the experimental values. Furthermore, it was applied to the reconstruction of the historical flood occurred in the Soverato river (Calabria, Italy). It did not require local grid refinement and provided results faithful to flood marks.
Thermal Experiments for Fractured Rock Characterization: Theoretical Analysis and Inverse Modeling
Authors: Zhou Zitong , Roubinet Delphine , Tartakovsky Daniel M.
Published: November 2021

Field‐scale properties of fractured rocks play a crucial role in many subsurface applications, yet methodologies for identification of the statistical parameters of a discrete fracture network (DFN) are scarce. We present an inversion technique to infer two such parameters, fracture density and fractal dimension, from cross‐borehole thermal experiments data. It is based on a particle‐based heat‐transfer model, whose evaluation is accelerated with a deep neural network (DNN) surrogate that is integrated into a grid search. The DNN is trained on a small number of the heat‐transfer model runs and predicts the cumulative density function of the thermal field. The latter is used to compute fine posterior distributions of the (to be estimated) parameters. Our synthetic experiments reveal that fracture density is well constrained by data, while fractal dimension is harder to determine. Adding nonuniform prior information related to the DFN connectivity improves the inference of this parameter.
Association of pre-pregnancy body mass index and rate of weight gain during pregnancy with maternal indicators of cardiometabolic risk
Authors: Omaña-Guzmán Luz Isabel , Ortiz-Hernández Luis , Ancira-Moreno Mónica , Morales-Hernández Vanesa , O’Neill Marie S. , Vadillo-Ortega Felipe
Published: November 2021

Background/objective

Changes in metabolism and extensive hemodynamic adjustments occur during normal pregnancy. The presence of maternal obesity imposes an overload to these physiological adaptations that may result in increased risk for the development of cardiometabolic complications during and after pregnancy. The aim of this study is to describe total cholesterol (TC), triglycerides (TG), glucose, and arterial blood pressure (BP) trajectories and to analyze the association of these cardiometabolic risk indicators during pregnancy with pre-pregnancy body mass index (pBMI) and monthly gestational weight gain (MGWG).

Subjects/methods

A prospective cohort study of pregnant women was conducted in Mexico City. Monthly samples of blood were taken during clinical follow-up and biochemical and blood pressure were measured during each visit. Adjusted linear mixed-effect regression models were fit to describe the trajectories of these biomarkers during pregnancy and to analyze the association with pBMI and MGWG.

Results

Seven hundred and twenty women were included of which 16.6% had pre-gestational obesity, 33.2% had pre-gestational overweight, 45.8% had normal pBMI and 4.4% had pre-gestational underweight. Women with pre-gestational obesity had higher lipids concentrations in the beginning of pregnancy (TC: $$\hat \beta$$

β

̂

= 33.08, p = 0.010; TG: $$\hat \beta$$

β

̂

= 31.29, p = <0.001) but the concentrations increased less than in women with normal pBMI (TC: $$\hat \beta$$

β

̂

= −14.18, p = 0.001; TG: $$\hat \beta$$

β

̂

= −5.42, p < 0.001). By the end of pregnancy, women with pre-gestational obesity had lower concentrations of lipids than women with normal pBMI. By contrast, women with pre-gestational obesity had higher glucose concentrations and higher BP levels than women with normal pBMI over pregnancy.

Conclusions

pBMI is differentially associated with longitudinal trajectories of maternal biochemical markers of cardiometabolic risk. MGWG did not significantly affect the biochemical indicators or BP trajectories. Our results suggest that pBMI is more relevant to predicting adverse cardiometabolic markers trajectories during pregnancy than MGWG.
High-temperature superconductivity on the verge of a structural instability in lanthanum superhydride
Authors: Sun Dan , Minkov Vasily S. , Mozaffari Shirin , Sun Ying , Ma Yanming , Chariton Stella , Prakapenka Vitali B. , Eremets Mikhail I. , Balicas Luis , Balakirev Fedor F.
Published: November 2021

The possibility of high, room-temperature superconductivity was predicted for metallic hydrogen in the 1960s. However, metallization and superconductivity of hydrogen are yet to be unambiguously demonstrated and may require pressures as high as 5 million atmospheres. Rare earth based “superhydrides”, such as LaH10, can be considered as a close approximation of metallic hydrogen even though they form at moderately lower pressures. In superhydrides the predominance of H-H metallic bonds and high superconducting transition temperatures bear the hallmarks of metallic hydrogen. Still, experimental studies revealing the key factors controlling their superconductivity are scarce. Here, we report the pressure and magnetic field dependence of the superconducting order observed in LaH10. We determine that the high-symmetry high-temperature superconducting Fm-3m phase of LaH10 can be stabilized at substantially lower pressures than previously thought. We find a remarkable correlation between superconductivity and a structural instability indicating that lattice vibrations, responsible for the monoclinic structural distortions in LaH10, strongly affect the superconducting coupling.
Gut microbiome drives individual memory variation in bumblebees
Authors: Li Li , Solvi Cwyn , Zhang Feng , Qi Zhaoyang , Chittka Lars , Zhao Wei
Published: November 2021

The potential of the gut microbiome as a driver of individual cognitive differences in natural populations of animals remains unexplored. Here, using metagenomic sequencing of individual bumblebee hindguts, we find a positive correlation between the abundance of Lactobacillus Firm-5 cluster and memory retention on a visual discrimination task. Supplementation with the Firm-5 species Lactobacillus apis, but not other non-Firm-5 bacterial species, enhances bees’ memory. Untargeted metabolomics after L. apis supplementation show increased LPA (14:0) glycerophospholipid in the haemolymph. Oral administration of the LPA increases long-term memory significantly. Based on our findings and metagenomic/metabolomic analyses, we propose a molecular pathway for this gut-brain interaction. Our results provide insights into proximate and ultimate causes of cognitive differences in natural bumblebee populations.
Carbon response of tundra ecosystems to advancing greenup and snowmelt in Alaska
Authors: Kim JiHyun , Kim Yeonjoo , Zona Donatella , Oechel Walter , Park Sang-Jong , Lee Bang-Yong , Yi Yonghong , Erb Angela , Schaaf Crystal L.
Published: November 2021

The ongoing disproportionate increases in temperature and precipitation over the Arctic region may greatly alter the latitudinal gradients in greenup and snowmelt timings as well as associated carbon dynamics of tundra ecosystems. Here we use remotely-sensed and ground-based datasets and model results embedding snowmelt timing in phenology at seven tundra flux tower sites in Alaska during 2001–2018, showing that the carbon response to early greenup or delayed snowmelt varies greatly depending upon local climatic limits. Increases in net ecosystem productivity (NEP) due to early greenup were amplified at the higher latitudes where temperature and water strongly colimit vegetation growth, while NEP decreases due to delayed snowmelt were alleviated by a relief of water stress. Given the high likelihood of more frequent delayed snowmelt at higher latitudes, this study highlights the importance of understanding the role of snowmelt timing in vegetation growth and terrestrial carbon cycles across warming Arctic ecosystems.
Heterogeneous recruitment abilities to RNA polymerases generate nonlinear scaling of gene expression with cell volume
Authors: Wang Qirun , Lin Jie
Published: November 2021

While most genes’ expression levels are proportional to cell volumes, some genes exhibit nonlinear scaling between their expression levels and cell volume. Therefore, their mRNA and protein concentrations change as the cell volume increases, which often have crucial biological functions such as cell-cycle regulation. However, the biophysical mechanism underlying the nonlinear scaling between gene expression and cell volume is still unclear. In this work, we show that the nonlinear scaling is a direct consequence of the heterogeneous recruitment abilities of promoters to RNA polymerases based on a gene expression model at the whole-cell level. Those genes with weaker (stronger) recruitment abilities than the average ability spontaneously exhibit superlinear (sublinear) scaling with cell volume. Analysis of the promoter sequences and the nonlinear scaling of Saccharomyces cerevisiae’s mRNA levels shows that motifs associated with transcription regulation are indeed enriched in genes exhibiting nonlinear scaling, in concert with our model.
Fluid-injection-induced earthquakes characterized by hybrid-frequency waveforms manifest the transition from aseismic to seismic slip
Authors: Yu Hongyu , Harrington Rebecca M. , Kao Honn , Liu Yajing , Wang Bei
Published: November 2021

Aseismic slip loading has recently been proposed as a complementary mechanism to induce moderate-sized earthquakes located within a few kilometers of the wellbore over the timescales of hydraulic stimulation. However, aseismic slip signals linked to injection-induced earthquakes remain largely undocumented to date. Here we report a new type of earthquake characterized by hybrid-frequency waveforms (EHWs). Distinguishing features from typical induced earthquakes include broader P and S-pulses and relatively lower-frequency coda content. Both features may be causally related to lower corner frequencies, implying longer source durations, thus, either slower rupture speeds, lower stress drop values, or a combination of both. The source characteristics of EHWs are identical to those of low-frequency earthquakes widely documented in plate boundary fault transition zones. The distribution of EHWs further suggests a possible role of aseismic slip in fault loading. EHWs could thus represent the manifestation of slow rupture transitioning from aseismic to seismic slip.
Plasma virome and the risk of blood-borne infection in persons with substance use disorder
Authors: Kandathil Abraham J. , Cox Andrea L. , Page Kimberly , Mohr David , Razaghi Roham , Ghanem Khalil G. , Tuddenham Susan A. , Hsieh Yu-Hsiang , Evans Jennifer L. , Coller Kelly E. , Timp Winston , Celentano David D. , Ray Stuart C. , Thomas David L.
Published: November 2021

There is an urgent need for innovative methods to reduce transmission of bloodborne pathogens like HIV and HCV among people who inject drugs (PWID). We investigate if PWID who acquire non-pathogenic bloodborne viruses like anelloviruses and pegiviruses might be at greater risk of acquiring a bloodborne pathogen. PWID who later acquire HCV accumulate more non-pathogenic viruses in plasma than matched controls who do not acquire HCV infection. Additionally, phylogenetic analysis of those non-pathogenic virus sequences reveals drug use networks. Here we find first in Baltimore and confirm in San Francisco that the accumulation of non-pathogenic viruses in PWID is a harbinger for subsequent acquisition of pathogenic viruses, knowledge that may guide the prioritization of the public health resources to combat HIV and HCV.
Revealing topology with transformation optics
Authors: Lu Lizhen , Ding Kun , Galiffi Emanuele , Ma Xikui , Dong Tianyu , Pendry J. B.
Published: November 2021

Symmetry deepens our insight into a physical system and its interplay with topology enables the discovery of topological phases. Symmetry analysis is conventionally performed either in the physical space of interest, or in the corresponding reciprocal space. Here we borrow the concept of virtual space from transformation optics to demonstrate how a certain class of symmetries can be visualised in a transformed, spectrally related coordinate space, illuminating the underlying topological transitions. By projecting a plasmonic system in a higher-dimensional virtual space onto a lower-dimensional system in real space, we show how transformation optics allows us to construct a topologically non-trivial system by inspecting its modes in the virtual space. Interestingly, we find that the topological invariant can be controlled via the singularities in the conformal mapping, enabling the intuitive engineering of edge states. The confluence of transformation optics and topology here can be generalized to other wave realms beyond photonics.
Structure of HIV-1 Vpr in complex with the human nucleotide excision repair protein hHR23A
Authors: Byeon In-Ja L. , Calero Guillermo , Wu Ying , Byeon Chang H. , Jung Jinwon , DeLucia Maria , Zhou Xiaohong , Weiss Simon , Ahn Jinwoo , Hao Caili , Skowronski Jacek , Gronenborn Angela M.
Published: November 2021

HIV-1 Vpr is a prototypic member of a large family of structurally related lentiviral virulence factors that antagonize various aspects of innate antiviral immunity. It subverts host cell DNA repair and protein degradation machineries by binding and inhibiting specific post-replication repair enzymes, linking them via the DCAF1 substrate adaptor to the Cullin 4 RING E3 ligase (CRL4DCAF1). HIV-1 Vpr also binds to the multi-domain protein hHR23A, which interacts with the nucleotide excision repair protein XPC and shuttles ubiquitinated proteins to the proteasome. Here, we report the atomic resolution structure of Vpr in complex with the C-terminal half of hHR23A, containing the XPC-binding (XPCB) and ubiquitin-associated (UBA2) domains. The XPCB and UBA2 domains bind to different sides of Vpr’s 3-helix-bundle structure, with UBA2 interacting with the α2 and α3 helices of Vpr, while the XPCB domain contacts the opposite side of Vpr’s α3 helix. The structure as well as biochemical results reveal that hHR23A and DCAF1 use overlapping binding surfaces on Vpr, even though the two proteins exhibit entirely different three-dimensional structures. Our findings show that Vpr independently targets hHR23A- and DCAF1- dependent pathways and highlight HIV-1 Vpr as a versatile module that interferes with DNA repair and protein degradation pathways.
Autumn destabilization of deep porewater CO2 store in a northern peatland driven by turbulent diffusion
Authors: Campeau A. , Vachon D. , Bishop K. , Nilsson M. B. , Wallin M. B.
Published: November 2021

The deep porewater of northern peatlands stores large amounts of carbon dioxide (CO2). This store is viewed as a stable feature in the peatland CO2cycle. Here, we report large and rapid fluctuations in deep porewater CO2concentration recurring every autumn over four consecutive years in a boreal peatland. Estimates of the vertical diffusion of heat indicate that CO2diffusion occurs at the turbulent rather than molecular rate. The weakening of porewater thermal stratification in autumn likely increases turbulent diffusion, thus fostering a rapid diffusion of deeper porewater CO2towards the surface where net losses occur. This phenomenon periodically decreases the peat porewater CO2store by between 29 and 90 g C m−2throughout autumn, which is comparable to the peatland’s annual C-sink. Our results establish the need to consider the role of turbulent diffusion in regularly destabilizing the CO2store in peat porewater.
Room-temperature dynamic nuclear polarization enhanced NMR spectroscopy of small biological molecules in water
Authors: Dai Danhua , Wang Xianwei , Liu Yiwei , Yang Xiao-Liang , Glaubitz Clemens , Denysenkov Vasyl , He Xiao , Prisner Thomas , Mao Jiafei
Published: November 2021

Nuclear magnetic resonance (NMR) spectroscopy is a powerful and popular technique for probing the molecular structures, dynamics and chemical properties. However the conventional NMR spectroscopy is bottlenecked by its low sensitivity. Dynamic nuclear polarization (DNP) boosts NMR sensitivity by orders of magnitude and resolves this limitation. In liquid-state this revolutionizing technique has been restricted to a few specific non-biological model molecules in organic solvents. Here we show that the carbon polarization in small biological molecules, including carbohydrates and amino acids, can be enhanced sizably by in situ Overhauser DNP (ODNP) in water at room temperature and at high magnetic field. An observed connection between ODNP13C enhancement factor and paramagnetic13C NMR shift has led to the exploration of biologically relevant heterocyclic compound indole. The QM/MM MD simulation underscores the dynamics of intermolecular hydrogen bonds as the driving force for the scalar ODNP in a long-living radical-substrate complex. Our work reconciles results obtained by DNP spectroscopy, paramagnetic NMR and computational chemistry and provides new mechanistic insights into the high-field scalar ODNP.
Visible-light-mediated catalyst-free synthesis of unnatural α-amino acids and peptide macrocycles
Authors: Wang Mengran , Wang Chao , Huo Yumei , Dang Xiaobo , Xue Hongxiang , Liu Liangyu , Chai Hongli , Xie Xiuling , Li Zhixuan , Lu Doudou , Xu Zhaoqing
Published: November 2021

The visible light induced, photocatalysts or photoabsorbing EDA complexes mediated cleavage of pyridinium C-N bond were reported in the past years. Here, we report an ionic compound promote homolytic cleavage of pyridinium C-N bond by exploiting the photonic energy from visible light. This finding is successfully applied in deaminative hydroalkylation of a series of alkenes including naturally occurring dehydroalanine, which provides an efficient way to prepare β-alkyl substituted unnatural amino acids under mild and photocatalyst-free conditions. Importantly, by using this protocol, the deaminative cyclization of peptide backbone N-terminals is realized. Furthermore, the use of Et3N or PPh3 as reductants and H2O as hydrogen atom source is a practical advantage. We anticipate that our protocol will be useful in peptide synthesis and modern peptide drug discovery.
Molecular mechanisms and topological consequences of drastic chromosomal rearrangements of muntjac deer
Authors: Yin Yuan , Fan Huizhong , Zhou Botong , Hu Yibo , Fan Guangyi , Wang Jinhuan , Zhou Fan , Nie Wenhui , Zhang Chenzhou , Liu Lin , Zhong Zhenyu , Zhu Wenbo , Liu Guichun , Lin Zeshan , Liu Chang , Zhou Jiong , Huang Guangping , Li Zihe , Yu Jianping , Zhang Yaolei , Yang Yue , Zhuo Bingzhao , Zhang Baowei , Chang Jiang , Qian Haiyuan , Peng Yingmei , Chen Xianqing , Chen Lei , Li Zhipeng , Zhou Qi , Wang Wen , Wei Fuwen
Published: November 2021

Muntjac deer have experienced drastic karyotype changes during their speciation, making it an ideal model for studying mechanisms and functional consequences of mammalian chromosome evolution. Here we generated chromosome-level genomes for Hydropotes inermis (2n = 70), Muntiacus reevesi (2n = 46), female and male M. crinifrons (2n = 8/9) and a contig-level genome for M. gongshanensis (2n = 8/9). These high-quality genomes combined with Hi-C data allowed us to reveal the evolution of 3D chromatin architectures during mammalian chromosome evolution. We find that the chromosome fusion events of muntjac species did not alter the A/B compartment structure and topologically associated domains near the fusion sites, but new chromatin interactions were gradually established across the fusion sites. The recently borne neo-Y chromosome of M. crinifrons, which underwent male-specific inversions, has dramatically restructured chromatin compartments, recapitulating the early evolution of canonical mammalian Y chromosomes. We also reveal that a complex structure containing unique centromeric satellite, truncated telomeric and palindrome repeats might have mediated muntjacs’ recurrent chromosome fusions. These results provide insights into the recurrent chromosome tandem fusion in muntjacs, early evolution of mammalian sex chromosomes, and reveal how chromosome rearrangements can reshape the 3D chromatin regulatory conformations during species evolution.
Pediatric COVID-19 patients in South Brazil show abundant viral mRNA and strong specific anti-viral responses
Authors: Fazolo Tiago , Lima Karina , Fontoura Julia C. , de Souza Priscila Oliveira , Hilario Gabriel , Zorzetto Renata , Júnior Luiz Rodrigues , Pscheidt Veridiane Maria , de Castilhos Ferreira Neto Jayme , Haubert Alisson F. , Gambin Izza , Oliveira Aline C. , Mello Raissa S. , de Bastos Balbe e Gutierres Matheus , Gassen Rodrigo Benedetti , Coimbra Lais Durço , Borin Alexandre , Marques Rafael Elias , Sartor Ivaine Tais Sauthier , Zavaglia Gabriela Oliveira , Fernandes Ingrid Rodrigues , Nakaya Helder I. , Varela Fernanda Hammes , Polese-Bonatto Márcia , Borges Thiago J. , Callegari-Jacques Sidia Maria , da Costa Marcela Santos Correa , de Araujo Schwartz Jaqueline , Scotta Marcelo Comerlato , Stein Renato T. , Bonorino Cristina
Published: November 2021

COVID-19 manifests as a milder disease in children than adults, but the underlying mechanisms are not fully characterized. Here we assess the difference in cellular or humoral immune responses of pediatric and adult COVID-19 patients to see if these factors contribute to the severity dichotomy. Children’s non-specific immune profile is dominated by naive lymphocytes and HLA-DRhighCX3CR1low dendritic cells; meanwhile, children show strong specific antibody and T cell responses for viral structural proteins, with their T cell responses differing from adults by having weaker CD8+TNF+ T cells responses to S peptide pool but stronger responses to N and M peptide pools. Finally, viral mRNA is more abundant in pediatric patients. Our data thus support a scenario in which SARS-CoV-2 infected children contribute to transmission yet are less susceptible to COVID-19 symptoms due to strong and differential responses to the virus.
Epigenetic interaction between UTX and DNMT1 regulates diet-induced myogenic remodeling in brown fat
Authors: Li Fenfen , Jing Jia , Movahed Miranda , Cui Xin , Cao Qiang , Wu Rui , Chen Ziyue , Yu Liqing , Pan Yi , Shi Huidong , Shi Hang , Xue Bingzhong
Published: November 2021

Brown adipocytes share the same developmental origin with skeletal muscle. Here we find that a brown adipocyte-to-myocyte remodeling also exists in mature brown adipocytes, and is induced by prolonged high fat diet (HFD) feeding, leading to brown fat dysfunction. This process is regulated by the interaction of epigenetic pathways involving histone and DNA methylation. In mature brown adipocytes, the histone demethylase UTX maintains persistent demethylation of the repressive mark H3K27me3 at Prdm16 promoter, leading to high Prdm16 expression. PRDM16 then recruits DNA methyltransferase DNMT1 to Myod1 promoter, causing Myod1 promoter hypermethylation and suppressing its expression. The interaction between PRDM16 and DNMT1 coordinately serves to maintain brown adipocyte identity while repressing myogenic remodeling in mature brown adipocytes, thus promoting their active brown adipocyte thermogenic function. Suppressing this interaction by HFD feeding induces brown adipocyte-to-myocyte remodeling, which limits brown adipocyte thermogenic capacity and compromises diet-induced thermogenesis, leading to the development of obesity.
Imprinted lncRNA Dio3os preprograms intergenerational brown fat development and obesity resistance
Authors: Chen Yan-Ting , Yang Qi-Yuan , Hu Yun , Liu Xiang-Dong , de Avila Jeanene M. , Zhu Mei-Jun , Nathanielsz Peter W. , Du Min
Published: November 2021

Maternal obesity (MO) predisposes offspring to obesity and metabolic disorders but little is known about the contribution of offspring brown adipose tissue (BAT). We find that MO impairs fetal BAT development, which persistently suppresses BAT thermogenesis and primes female offspring to metabolic dysfunction. In fetal BAT, MO enhances expression of Dio3, which encodes deiodinase 3 (D3) to catabolize triiodothyronine (T3), while a maternally imprinted long noncoding RNA, Dio3 antisense RNA (Dio3os), is inhibited, leading to intracellular T3 deficiency and suppression of BAT development. Gain and loss of function shows Dio3os reduces D3 content and enhances BAT thermogenesis, rendering female offspring resistant to high fat diet-induced obesity. Attributing to Dio3os inactivation, its promoter has higher DNA methylation in obese dam oocytes which persists in fetal and adult BAT, uncovering an oocyte origin of intergenerational obesity. Overall, our data uncover key features of Dio3os activation in BAT to prevent intergenerational obesity and metabolic dysfunctions.
Cryo-EM structures of intermediates suggest an alternative catalytic reaction cycle for cytochrome c oxidase
Authors: Kolbe F. , Safarian S. , Piórek Ż. , Welsch S. , Müller H. , Michel H.
Published: November 2021

Cytochrome c oxidases are among the most important and fundamental enzymes of life. Integrated into membranes they use four electrons from cytochrome c molecules to reduce molecular oxygen (dioxygen) to water. Their catalytic cycle has been considered to start with the oxidized form. Subsequent electron transfers lead to the E-state, the R-state (which binds oxygen), the P-state (with an already split dioxygen bond), the F-state and the O-state again. Here, we determined structures of up to 1.9 Å resolution of these intermediates by single particle cryo-EM. Our results suggest that in the O-state the active site contains a peroxide dianion and in the P-state possibly an intact dioxygen molecule, the F-state may contain a superoxide anion. Thus, the enzyme’s catalytic cycle may have to be turned by 180 degrees.
A structured RNA motif locks Argonaute2:miR-122 onto the 5’ end of the HCV genome
Authors: Gebert Luca F. R. , Law Mansun , MacRae Ian J.
Published: November 2021

microRNAs (miRNAs) form regulatory networks in metazoans. Viruses engage miRNA networks in numerous ways, with Flaviviridae members exploiting direct interactions of their RNA genomes with host miRNAs. For hepatitis C virus (HCV), binding of liver-abundant miR-122 stabilizes the viral RNA and regulates viral translation. Here, we investigate the structural basis for these activities, taking into consideration that miRNAs function in complex with Argonaute (Ago) proteins. The crystal structure of the Ago2:miR-122:HCV complex reveals a structured RNA motif that traps Ago2 on the viral RNA, masking its 5’ end from enzymatic attack. The trapped Ago2 can recruit host factor PCBP2, implicated in viral translation, while binding of a second Ago2:miR-122 competes with PCBP2, creating a potential molecular switch for translational control. Combined results reveal a viral RNA structure that modulates Ago2:miR-122 dynamics and repurposes host proteins to generate a functional analog of the mRNA cap-binding complex.
Spike residue 403 affects binding of coronavirus spikes to human ACE2
Authors: Zech Fabian , Schniertshauer Daniel , Jung Christoph , Herrmann Alexandra , Cordsmeier Arne , Xie Qinya , Nchioua Rayhane , Prelli Bozzo Caterina , Volcic Meta , Koepke Lennart , Müller Janis A. , Krüger Jana , Heller Sandra , Stenger Steffen , Hoffmann Markus , Pöhlmann Stefan , Kleger Alexander , Jacob Timo , Conzelmann Karl-Klaus , Ensser Armin , Sparrer Konstantin M. J. , Kirchhoff Frank
Published: November 2021

The bat sarbecovirus RaTG13 is a close relative of SARS-CoV-2, the cause of the COVID-19 pandemic. However, this bat virus was most likely unable to directly infect humans since its Spike (S) protein does not interact efficiently with the human ACE2 receptor. Here, we show that a single T403R mutation increases binding of RaTG13 S to human ACE2 and allows VSV pseudoparticle infection of human lung cells and intestinal organoids. Conversely, mutation of R403T in the SARS-CoV-2 S reduces pseudoparticle infection and viral replication. The T403R RaTG13 S is neutralized by sera from individuals vaccinated against COVID-19 indicating that vaccination might protect against future zoonoses. Our data suggest that a positively charged amino acid at position 403 in the S protein is critical for efficient utilization of human ACE2 by S proteins of bat coronaviruses. This finding could help to better predict the zoonotic potential of animal coronaviruses.
Cross-feeding between intestinal pathobionts promotes their overgrowth during undernutrition
Authors: Huus K. E. , Hoang T. T. , Creus-Cuadros A. , Cirstea M. , Vogt S. L. , Knuff-Janzen K. , Sansonetti P. J. , Vonaesch P. , Finlay B. B.
Published: November 2021

Child undernutrition is a global health issue associated with a high burden of infectious disease. Undernourished children display an overabundance of intestinal pathogens and pathobionts, and these bacteria induce enteric dysfunction in undernourished mice; however, the cause of their overgrowth remains poorly defined. Here, we show that disease-inducing human isolates of Enterobacteriaceae and Bacteroidales spp. are capable of multi-species symbiotic cross-feeding, resulting in synergistic growth of a mixed community in vitro. Growth synergy occurs uniquely under malnourished conditions limited in protein and iron: in this context, Bacteroidales spp. liberate diet- and mucin-derived sugars and Enterobacteriaceae spp. enhance the bioavailability of iron. Analysis of human microbiota datasets reveals that Bacteroidaceae and Enterobacteriaceae are strongly correlated in undernourished children, but not in adequately nourished children, consistent with a diet-dependent growth synergy in the human gut. Together these data suggest that dietary cross-feeding fuels the overgrowth of pathobionts in undernutrition.
Accelerated discovery of superoxide-dismutase nanozymes via high-throughput computational screening
Authors: Wang Zhenzhen , Wu Jiangjiexing , Zheng Jia-Jia , Shen Xiaomei , Yan Liang , Wei Hui , Gao Xingfa , Zhao Yuliang
Published: November 2021

The activity of nanomaterials (NMs) in catalytically scavenging superoxide anions mimics that of superoxide dismutase (SOD). Although dozens of NMs have been demonstrated to possess such activity, the underlying principles are unclear, hindering the discovery of NMs as the novel SOD mimics. In this work, we use density functional theory calculations to study the thermodynamics and kinetics of the catalytic processes, and we develop two principles, namely, an energy level principle and an adsorption energy principle, for the activity. The first principle quantitatively describes the role of the intermediate frontier molecular orbital in transferring electrons for catalysis. The second one quantitatively describes the competition between the desired catalytic reaction and undesired side reactions. The ability of the principles to predict the SOD-like activities of metal-organic frameworks were verified by experiments. Both principles can be easily implemented in computer programs to computationally screen NMs with the intrinsic SOD-like activity.
Functional convalescent plasma antibodies and pre-infusion titers shape the early severe COVID-19 immune response
Authors: Herman Jonathan D. , Wang Chuangqi , Loos Carolin , Yoon Hyunah , Rivera Johanna , Eugenia Dieterle M. , Haslwanter Denise , Jangra Rohit K. , Bortz Robert H. , Bar Katharine J. , Julg Boris , Chandran Kartik , Lauffenburger Douglas , Pirofski Liise-anne , Alter Galit
Published: November 2021

Transfer of convalescent plasma (CP) had been proposed early during the SARS-CoV-2 pandemic as an accessible therapy, yet trial results worldwide have been mixed, potentially due to the heterogeneous nature of CP. Here we perform deep profiling of SARS-CoV-2-specific antibody titer, Fc-receptor binding, and Fc-mediated functional assays in CP units, as well as in plasma from hospitalized COVID-19 patients before and after CP administration. The profiling results show that, although all recipients exhibit expanded SARS-CoV-2-specific humoral immune responses, CP units contain more functional antibodies than recipient plasma. Meanwhile, CP functional profiles influence the evolution of recipient humoral immunity in conjuncture with the recipient’s pre-existing SARS-CoV2-specific antibody titers: CP-derived SARS-CoV-2 nucleocapsid-specific antibody functions are associated with muted humoral immune evolution in patients with high titer anti-spike IgG. Our data thus provide insights into the unexpected impact of CP-derived functional anti-spike and anti-nucleocapsid antibodies on the evolution of SARS-CoV-2-specific response following severe infection.
Single-photon detection and cryogenic reconfigurability in lithium niobate nanophotonic circuits
Authors: Lomonte Emma , Wolff Martin A. , Beutel Fabian , Ferrari Simone , Schuck Carsten , Pernice Wolfram H. P. , Lenzini Francesco
Published: November 2021

Lithium-Niobate-On-Insulator (LNOI) is emerging as a promising platform for integrated quantum photonic technologies because of its high second-order nonlinearity and compact waveguide footprint. Importantly, LNOI allows for creating electro-optically reconfigurable circuits, which can be efficiently operated at cryogenic temperature. Their integration with superconducting nanowire single-photon detectors (SNSPDs) paves the way for realizing scalable photonic devices for active manipulation and detection of quantum states of light. Here we demonstrate integration of these two key components in a low loss (0.2 dB/cm) LNOI waveguide network. As an experimental showcase of our technology, we demonstrate the combined operation of an electrically tunable Mach-Zehnder interferometer and two waveguide-integrated SNSPDs at its outputs. We show static reconfigurability of our system with a bias-drift-free operation over a time of 12 hours, as well as high-speed modulation at a frequency up to 1 GHz. Our results provide blueprints for implementing complex quantum photonic devices on the LNOI platform.
Interlayer exciton mediated second harmonic generation in bilayer MoS2
Authors: Shree Shivangi , Lagarde Delphine , Lombez Laurent , Robert Cedric , Balocchi Andrea , Watanabe Kenji , Taniguchi Takashi , Marie Xavier , Gerber Iann C. , Glazov Mikhail M. , Golub Leonid E. , Urbaszek Bernhard , Paradisanos Ioannis
Published: November 2021

Second-harmonic generation (SHG) is a non-linear optical process, where two photons coherently combine into one photon of twice their energy. Efficient SHG occurs for crystals with broken inversion symmetry, such as transition metal dichalcogenide monolayers. Here we show tuning of non-linear optical processes in an inversion symmetric crystal. This tunability is based on the unique properties of bilayer MoS2, that shows strong optical oscillator strength for the intra- but also interlayer exciton resonances. As we tune the SHG signal onto these resonances by varying the laser energy, the SHG amplitude is enhanced by several orders of magnitude. In the resonant case the bilayer SHG signal reaches amplitudes comparable to the off-resonant signal from a monolayer. In applied electric fields the interlayer exciton energies can be tuned due to their in-built electric dipole via the Stark effect. As a result the interlayer exciton degeneracy is lifted and the bilayer SHG response is further enhanced by an additional two orders of magnitude, well reproduced by our model calculations. Since interlayer exciton transitions are highly tunable also by choosing twist angle and material combination our results open up new approaches for designing the SHG response of layered materials.
Risk-stratification of febrile African children at risk of sepsis using sTREM-1 as basis for a rapid triage test
Authors: Leligdowicz Aleksandra , Conroy Andrea L. , Hawkes Michael , Richard-Greenblatt Melissa , Zhong Kathleen , Opoka Robert O. , Namasopo Sophie , Bell David , Liles W. Conrad , da Costa Bruno R. , Jüni Peter , Kain Kevin C.
Published: November 2021

Identifying febrile children at risk of sepsis in low-resource settings can improve survival, but recognition triage tools are lacking. Here we test the hypothesis that measuring circulating markers of immune and endothelial activation may identify children with sepsis at risk of all-cause mortality. In a prospective cohort study of 2,502 children in Uganda, we show that Soluble Triggering Receptor Expressed on Myeloid cells-1 (sTREM-1) measured at first clinical presentation, had high predictive accuracy for subsequent in-hospital mortality. sTREM-1 had the best performance, versus 10 other markers, with an AUROC for discriminating children at risk of death of 0.893 in derivation (95% CI 0.843–0.944) and 0.901 in validation (95% CI 0.856–0.947) cohort. sTREM-1 cutoffs corresponding to a negative likelihood ratio (LR) of 0.10 and a positive LR of 10 classified children into low (1,306 children, 53.1%), intermediate (942, 38.3%) and high (212, 8.6%) risk zones. The estimated incidence of death was 0.5%, 3.9%, and 31.8%, respectively, suggesting sTREM-1 could be used to risk-stratify febrile children. These findings do not attempt to derive a risk prediction model, but rather define sTREM-1 cutoffs as the basis for rapid triage test for all cause fever syndromes in children in low-resource settings.
Axonal TDP-43 condensates drive neuromuscular junction disruption through inhibition of local synthesis of nuclear encoded mitochondrial proteins
Authors: Altman Topaz , Ionescu Ariel , Ibraheem Amjad , Priesmann Dominik , Gradus-Pery Tal , Farberov Luba , Alexandra Gayster , Shelestovich Natalia , Dafinca Ruxandra , Shomron Noam , Rage Florence , Talbot Kevin , Ward Michael E. , Dori Amir , Krüger Marcus , Perlson Eran
Published: November 2021

Mislocalization of the predominantly nuclear RNA/DNA binding protein, TDP-43, occurs in motor neurons of ~95% of amyotrophic lateral sclerosis (ALS) patients, but the contribution of axonal TDP-43 to this neurodegenerative disease is unclear. Here, we show TDP-43 accumulation in intra-muscular nerves from ALS patients and in axons of human iPSC-derived motor neurons of ALS patient, as well as in motor neurons and neuromuscular junctions (NMJs) of a TDP-43 mislocalization mouse model. In axons, TDP-43 is hyper-phosphorylated and promotes G3BP1-positive ribonucleoprotein (RNP) condensate assembly, consequently inhibiting local protein synthesis in distal axons and NMJs. Specifically, the axonal and synaptic levels of nuclear-encoded mitochondrial proteins are reduced. Clearance of axonal TDP-43 or dissociation of G3BP1 condensates restored local translation and resolved TDP-43-derived toxicity in both axons and NMJs. These findings support an axonal gain of function of TDP-43 in ALS, which can be targeted for therapeutic development.