bluuebunny/crossref_metadata_2025 huggingface dataset:
Drivers of Recent North Pacific Decadal Variability: The Role of Aerosol Forcing
Authors: Dittus Andrea J. , Hawkins Ed , Robson Jon I. , Smith Doug M. , Wilcox Laura J.
Published: November 2021

Climate variability in the Pacific has an important influence on climate around the globe. In the period from 1981 to 2012, there was an observed large‐scale cooling in the Pacific. This cooling projected onto the negative phase of the Pacific Decadal Oscillation (PDO) and contributed to a slowdown in the rate of near‐surface temperature warming. However, this cooling pattern is not simulated well by the majority of coupled climate models and its cause is uncertain. We use large multi‐model ensembles from the sixth Climate Model Intercomparison Project, and an ensemble of simulations with HadGEM3‐GC3.1‐LL that is specifically designed to sample the range of uncertainty in historical anthropogenic aerosol forcing, to revisit the role of external forcings. We show that anthropogenic aerosols can drive an atmospheric circulation response via an increase in North Pacific sea level pressure and contribute to a negative PDO during this period in several global climate models. In HadGEM3, this increase in North Pacific sea‐level pressure is associated with an anomalous Rossby Wave train across the North Pacific, which is also seen in observations. Our results provide further evidence that anthropogenic aerosols may have contributed to observed cooling in the Pacific in this period. However, the simulated cooling in response to aerosol forcing is substantially weaker than the warming induced by greenhouse gases, resulting in simulations that are warming faster than observations, and further highlighting the need to understand whether models correctly simulate atmospheric circulation responses.
Fluid Flow Concentration on Preferential Paths in Heterogeneous Porous Media: Application of Graph Theory
Authors: Tang Y. B. , Zhao J. Z. , Bernabé Y. , Li M.
Published: November 2021

Fluid flow through geological formations is often concentrated on distinct preferential flow paths owing to the presence of fractures or large‐scale permeability structures. However, the existence of such structures is not a mandatory condition of preferential paths formation. Pore‐scale spatial fluctuations of pore size and/or pore connectivity in statistically stationary porous media, if sufficiently large, can also lead to the concentration of fluid flow on distinct pathways. In this paper, we attempted to establish the conditions of formation of preferential flow paths in heterogeneous porous media in terms of pore‐size heterogeneity and pore connectivity. We simulated steady‐state flow through stochastically constructed two‐ and three‐dimensional pore networks, in which the width of the pore radius distribution and the pore coordination number (a measure of pore connectivity) were varied. We developed new techniques based on graph theory to identify potential preferential flow paths and characterize them. We observed a gradual transition from approximately uniform flow fields in low heterogeneity/high connectivity networks to flow localization on preferential paths with increasing pore‐size heterogeneity and decreasing connectivity. The transition occurred at lower heterogeneity levels in three‐dimensional than in two‐dimensional simulations and was less influenced by pore connectivity variations. These results were summarized in a phase diagram in pore‐size heterogeneity/pore connectivity parameter space, which we found consistent with relevant real rocks data.
Distribution and Dimethylsulfoniopropionate Degradation of Dimethylsulfoniopropionate‐Consuming Bacteria in the Yellow Sea and East China Sea
Authors: Yu Juan , Zhang Sheng‐Hui , Tian Ji‐Yuan , Zhang Zheng‐Yu , Zhao Li‐Jun , Xu Rui , Yang Gui‐Peng , Lai Jing‐Guang , Wang Xue‐Dan
Published: November 2021

The fate of dimethylsulfoniopropionate (DMSP), the precursor of the climatologically important gas dimethylsulfide (DMS), depends on the structure of marine communities. DMSP degradation by DMSP‐consuming bacteria (DCB) is an important sink of dissolved DMSP (DMSPd) in seawater. DMSP cleavage and demethylation are two DMSPd consumption pathways, and the DMSPd cleavage pathway involves DMSP lyase activity (DLA). Here, we studied the distribution of DMS, DMSP, DCB, and DLA in the seawater of the Yellow Sea and East China Sea in the summer of 2013 and the degradation of DMSPd by DCB. High DCB abundances, as well as DMS and dissolved, particulate, total DMSP (DMSPd,p,t) concentrations were observed near the Hongzhou Bay, which may be due to the high productivity of dinoflagellates. The spatial distribution of DCB abundance was most likely the result of the regional hydrography including upwelling near Hangzhou Bay and the discharge of Yangtze Diluted Water (YDW). The DLA along the YDW decreased from coastal water to open sea. The DMSPd consumption by DCB Bacillus sp. YES023 isolated from the seawater was accompanied by DMS production (≤8.2% of DMSPd consumption). Bacillus sp. YES023 could also grow using glycine betaine, acrylic acid, dimethylsulfoxide, monomethylamine, or dimethylamine as a sole carbon source. Glycine betaine and acrylic acid were the most favorable substrates for overall growth. These results help our understanding of bacterial catabolism and the degradation pathways of methyl sulfur compounds in the ocean.
Characterising 18F-fluciclovine uptake in breast cancer through the use of dynamic PET/CT imaging
Authors: Scott N. P. , Teoh E. J. , Flight H. , Jones B. E. , Niederer J. , Mustata L. , MacLean G. M. , Roy P. G. , Remoundos D. D. , Snell C. , Liu C. , Gleeson F. V. , Harris A. L. , Lord S. R. , McGowan D. R.
Published: November 2021

Background

18F-fluciclovine is a synthetic amino acid positron emission tomography (PET) radiotracer that is approved for use in prostate cancer. In this clinical study, we characterised the kinetic model best describing the uptake of 18F-fluciclovine in breast cancer and assessed differences in tracer kinetics and static parameters for different breast cancer receptor subtypes and tumour grades.

Methods

Thirty-nine patients with pathologically proven breast cancer underwent 20-min dynamic PET/computed tomography imaging following the administration of 18F-fluciclovine. Uptake into primary breast tumours was evaluated using one- and two-tissue reversible compartmental kinetic models and static parameters.

Results

A reversible one-tissue compartment model was shown to best describe tracer uptake in breast cancer. No significant differences were seen in kinetic or static parameters for different tumour receptor subtypes or grades. Kinetic and static parameters showed a good correlation.

Conclusions

18F-fluciclovine has potential in the imaging of primary breast cancer, but kinetic analysis may not have additional value over static measures of tracer uptake.

Clinical Trial Registration

NCT03036943.
Long range and highly tunable interaction between local spins coupled to a superconducting condensate
Authors: Küster Felix , Brinker Sascha , Lounis Samir , Parkin Stuart S. P. , Sessi Paolo
Published: November 2021

Interfacing magnetism with superconducting condensates is rapidly emerging as a viable route for the development of innovative quantum technologies. In this context, the development of rational design strategies to controllably tune the interaction between magnetic moments is crucial. Here we address this problem demonstrating the possibility of tuning the interaction between local spins coupled through a superconducting condensate with atomic scale precision. By using Cr atoms coupled to superconducting Nb, we use atomic manipulation techniques to precisely control the relative distance between local spins along distinct crystallographic directions while simultaneously sensing their coupling by scanning tunneling spectroscopy. Our results reveal the existence of highly anisotropic interactions, lasting up to very long distances, demonstrating the possibility of crossing a quantum phase transition by acting on the direction and interatomic distance between spins. The high tunability provides novel opportunities for the realization of topological superconductivity and the rational design of magneto-superconducting interfaces.
Identification of proximal SUMO-dependent interactors using SUMO-ID
Authors: Barroso-Gomila Orhi , Trulsson Fredrik , Muratore Veronica , Canosa Iñigo , Merino-Cacho Laura , Cortazar Ana Rosa , Pérez Coralia , Azkargorta Mikel , Iloro Ibon , Carracedo Arkaitz , Aransay Ana M. , Elortza Felix , Mayor Ugo , Vertegaal Alfred C. O. , Barrio Rosa , Sutherland James D.
Published: November 2021

The fast dynamics and reversibility of posttranslational modifications by the ubiquitin family pose significant challenges for research. Here we present SUMO-ID, a technology that merges proximity biotinylation by TurboID and protein-fragment complementation to find SUMO-dependent interactors of proteins of interest. We develop an optimized split-TurboID version and show SUMO interaction-dependent labelling of proteins proximal to PML and RANGAP1. SUMO-dependent interactors of PML are involved in transcription, DNA damage, stress response and SUMO modification and are highly enriched in SUMO Interacting Motifs, but may only represent a subset of the total PML proximal proteome. Likewise, SUMO-ID also allow us to identify interactors of SUMOylated SALL1, a less characterized SUMO substrate. Furthermore, using TP53 as a substrate, we identify SUMO1, SUMO2 and Ubiquitin preferential interactors. Thus, SUMO-ID is a powerful tool that allows to study the consequences of SUMO-dependent interactions, and may further unravel the complexity of the ubiquitin code.
Epromoters function as a hub to recruit key transcription factors required for the inflammatory response
Authors: Santiago-Algarra David , Souaid Charbel , Singh Himanshu , Dao Lan T. M. , Hussain Saadat , Medina-Rivera Alejandra , Ramirez-Navarro Lucia , Castro-Mondragon Jaime A. , Sadouni Nori , Charbonnier Guillaume , Spicuglia Salvatore
Published: November 2021

Gene expression is controlled by the involvement of gene-proximal (promoters) and distal (enhancers) regulatory elements. Our previous results demonstrated that a subset of gene promoters, termed Epromoters, work as bona fide enhancers and regulate distal gene expression. Here, we hypothesized that Epromoters play a key role in the coordination of rapid gene induction during the inflammatory response. Using a high-throughput reporter assay we explored the function of Epromoters in response to type I interferon. We find that clusters of IFNa-induced genes are frequently associated with Epromoters and that these regulatory elements preferentially recruit the STAT1/2 and IRF transcription factors and distally regulate the activation of interferon-response genes. Consistently, we identified and validated the involvement of Epromoter-containing clusters in the regulation of LPS-stimulated macrophages. Our findings suggest that Epromoters function as a local hub recruiting the key TFs required for coordinated regulation of gene clusters during the inflammatory response.
A mechanistic investigation of the Li10GeP2S12|LiNi1-x-yCoxMnyO2 interface stability in all-solid-state lithium batteries
Authors: Zuo Tong-Tong , Rueß Raffael , Pan Ruijun , Walther Felix , Rohnke Marcus , Hori Satoshi , Kanno Ryoji , Schröder Daniel , Janek Jürgen
Published: November 2021

All-solid-state batteries are intensively investigated, although their performance is not yet satisfactory for large-scale applications. In this context, the combination of Li10GeP2S12 solid electrolyte and LiNi1-x-yCoxMnyO2 positive electrode active materials is considered promising despite the yet unsatisfactory battery performance induced by the thermodynamically unstable electrode|electrolyte interface. Here, we report electrochemical and spectrometric studies to monitor the interface evolution during cycling and understand the reactivity and degradation kinetics. We found that the Wagner-type model for diffusion-controlled reactions describes the degradation kinetics very well, suggesting that electronic transport limits the growth of the degradation layer formed at the electrode|electrolyte interface. Furthermore, we demonstrate that the rate of interfacial degradation increases with the state of charge and the presence of two oxidation mechanisms at medium (3.7 V vs. Li+/Li < E < 4.2 V vs. Li+/Li) and high (E ≥ 4.2 V vs. Li+/Li) potentials. A high state of charge (>80%) triggers the structural instability and oxygen release at the positive electrode and leads to more severe degradation.
Jumper enables discontinuous transcript assembly in coronaviruses
Authors: Sashittal Palash , Zhang Chuanyi , Peng Jian , El-Kebir Mohammed
Published: November 2021

Genes in SARS-CoV-2 and other viruses in the order of Nidovirales are expressed by a process of discontinuous transcription which is distinct from alternative splicing in eukaryotes and is mediated by the viral RNA-dependent RNA polymerase. Here, we introduce the DISCONTINUOUS TRANSCRIPT ASSEMBLYproblem of finding transcripts and their abundances given an alignment of paired-end short reads under a maximum likelihood model that accounts for varying transcript lengths. We show, using simulations, that our method, JUMPER, outperforms existing methods for classical transcript assembly. On short-read data of SARS-CoV-1, SARS-CoV-2 and MERS-CoV samples, we find that JUMPER not only identifies canonical transcripts that are part of the reference transcriptome, but also predicts expression of non-canonical transcripts that are supported by subsequent orthogonal analyses. Moreover, application of JUMPER on samples with and without treatment reveals viral drug response at the transcript level. As such, JUMPER enables detailed analyses of Nidovirales transcriptomes under varying conditions.
30-year record of Himalaya mass-wasting reveals landscape perturbations by extreme events
Authors: Jones Joshua N. , Boulton Sarah J. , Stokes Martin , Bennett Georgina L. , Whitworth Michael R. Z.
Published: November 2021

In mountainous environments, quantifying the drivers of mass-wasting is fundamental for understanding landscape evolution and improving hazard management. Here, we quantify the magnitudes of mass-wasting caused by the Asia Summer Monsoon, extreme rainfall, and earthquakes in the Nepal Himalaya. Using a newly compiled 30-year mass-wasting inventory, we establish empirical relationships between monsoon-triggered mass-wasting and monsoon precipitation, before quantifying how other mass-wasting drivers perturb this relationship. We find that perturbations up to 5 times greater than that expected from the monsoon alone are caused by rainfall events with 5-to-30-year return periods and short-term (< 2 year) earthquake-induced landscape preconditioning. In 2015, the landscape preconditioning is strongly controlled by the topographic signature of the Gorkha earthquake, whereby high Peak Ground Accelerations coincident with high excess topography (rock volume above a landscape threshold angle) amplifies landscape damage. Furthermore, earlier earthquakes in 1934, 1988 and 2011 are not found to influence 2015 mass-wasting.
DeepPhospho accelerates DIA phosphoproteome profiling through in silico library generation
Authors: Lou Ronghui , Liu Weizhen , Li Rongjie , Li Shanshan , He Xuming , Shui Wenqing
Published: November 2021

Phosphoproteomics integrating data-independent acquisition (DIA) enables deep phosphoproteome profiling with improved quantification reproducibility and accuracy compared to data-dependent acquisition (DDA)-based phosphoproteomics. DIA data mining heavily relies on a spectral library that in most cases is built on DDA analysis of the same sample. Construction of this project-specific DDA library impairs the analytical throughput, limits the proteome coverage, and increases the sample size for DIA phosphoproteomics. Herein we introduce a deep neural network, DeepPhospho, which conceptually differs from previous deep learning models to achieve accurate predictions of LC-MS/MS data for phosphopeptides. By leveraging in silico libraries generated by DeepPhospho, we establish a DIA workflow for phosphoproteome profiling which involves DIA data acquisition and data mining with DeepPhospho predicted libraries, thus circumventing the need of DDA library construction. Our DeepPhospho-empowered workflow substantially expands the phosphoproteome coverage while maintaining high quantification performance, which leads to the discovery of more signaling pathways and regulated kinases in an EGF signaling study than the DDA library-based approach. DeepPhospho is provided as a web server as well as an offline app to facilitate user access to model training, predictions and library generation.
Mapping protein carboxymethylation sites provides insights into their role in proteostasis and cell proliferation
Authors: Di Sanzo Simone , Spengler Katrin , Leheis Anja , Kirkpatrick Joanna M. , Rändler Theresa L. , Baldensperger Tim , Dau Therese , Henning Christian , Parca Luca , Marx Christian , Wang Zhao-Qi , Glomb Marcus A. , Ori Alessandro , Heller Regine
Published: November 2021

Posttranslational mechanisms play a key role in modifying the abundance and function of cellular proteins. Among these, modification by advanced glycation end products has been shown to accumulate during aging and age-associated diseases but specific protein targets and functional consequences remain largely unexplored. Here, we devise a proteomic strategy to identify sites of carboxymethyllysine modification, one of the most abundant advanced glycation end products. We identify over 1000 sites of protein carboxymethylation in mouse and primary human cells treated with the glycating agent glyoxal. By using quantitative proteomics, we find that protein glycation triggers a proteotoxic response and indirectly affects the protein degradation machinery. In primary endothelial cells, we show that glyoxal induces cell cycle perturbation and that carboxymethyllysine modification reduces acetylation of tubulins and impairs microtubule dynamics. Our data demonstrate the relevance of carboxymethyllysine modification for cellular function and pinpoint specific protein networks that might become compromised during aging.
A cerebellar internal model calibrates a feedback controller involved in sensorimotor control
Authors: Markov Daniil A. , Petrucco Luigi , Kist Andreas M. , Portugues Ruben
Published: November 2021

Animals must adapt their behavior to survive in a changing environment. Behavioral adaptations can be evoked by two mechanisms: feedback control and internal-model-based control. Feedback controllers can maintain the sensory state of the animal at a desired level under different environmental conditions. In contrast, internal models learn the relationship between the motor output and its sensory consequences and can be used to recalibrate behaviors. Here, we present multiple unpredictable perturbations in visual feedback to larval zebrafish performing the optomotor response and show that they react to these perturbations through a feedback control mechanism. In contrast, if a perturbation is long-lasting, fish adapt their behavior by updating a cerebellum-dependent internal model. We use modelling and functional imaging to show that the neuronal requirements for these mechanisms are met in the larval zebrafish brain. Our results illustrate the role of the cerebellum in encoding internal models and how these can calibrate neuronal circuits involved in reactive behaviors depending on the interactions between animal and environment.
Soft elasticity optimises dissipation in 3D-printed liquid crystal elastomers
Authors: Mistry D. , Traugutt N. A. , Sanborn B. , Volpe R. H. , Chatham L. S. , Zhou R. , Song B. , Yu K. , Long K. N. , Yakacki C. M.
Published: November 2021

Soft-elasticity in monodomain liquid crystal elastomers (LCEs) is promising for impact-absorbing applications where strain energy is ideally absorbed at constant stress. Conventionally, compressive and impact studies on LCEs have not been performed given the notorious difficulty synthesizing sufficiently large monodomain devices. Here, we use direct-ink writing 3D printing to fabricate bulk (>cm3) monodomain LCE devices and study their compressive soft-elasticity over 8 decades of strain rate. At quasi-static rates, the monodomain soft-elastic LCE dissipated 45% of strain energy while comparator materials dissipated less than 20%. At strain rates up to 3000 s−1, our soft-elastic monodomain LCE consistently performed closest to an ideal-impact absorber. Drop testing reveals soft-elasticity as a likely mechanism for effectively reducing the severity of impacts – with soft elastic LCEs offering a Gadd Severity Index 40% lower than a comparable isotropic elastomer. Lastly, we demonstrate tailoring deformation and buckling behavior in monodomain LCEs via the printed director orientation.
Follicular T cells are clonally and transcriptionally distinct in B cell-driven mouse autoimmune disease
Authors: Akama-Garren Elliot H. , van den Broek Theo , Simoni Lea , Castrillon Carlos , van der Poel Cees E. , Carroll Michael C.
Published: November 2021

Pathogenic autoantibodies contribute to tissue damage and clinical decline in autoimmune disease. Follicular T cells are central regulators of germinal centers, although their contribution to autoantibody-mediated disease remains unclear. Here we perform single cell RNA and T cell receptor (TCR) sequencing of follicular T cells in a mouse model of autoantibody-mediated disease, allowing for analyses of paired transcriptomes and unbiased TCRαβ repertoires at single cell resolution. A minority of clonotypes are preferentially shared amongst autoimmune follicular T cells and clonotypic expansion is associated with differential gene signatures in autoimmune disease. Antigen prediction using algorithmic and machine learning approaches indicates convergence towards shared specificities between non-autoimmune and autoimmune follicular T cells. However, differential autoimmune transcriptional signatures are preserved even amongst follicular T cells with shared predicted specificities. These results demonstrate that follicular T cells are phenotypically distinct in B cell-driven autoimmune disease, providing potential therapeutic targets to modulate autoantibody development.
Multifactorial seroprofiling dissects the contribution of pre-existing human coronaviruses responses to SARS-CoV-2 immunity
Authors: Abela Irene A. , Pasin Chloé , Schwarzmüller Magdalena , Epp Selina , Sickmann Michèle E. , Schanz Merle M. , Rusert Peter , Weber Jacqueline , Schmutz Stefan , Audigé Annette , Maliqi Liridona , Hunziker Annika , Hesselman Maria C. , Niklaus Cyrille R. , Gottschalk Jochen , Schindler Eméry , Wepf Alexander , Karrer Urs , Wolfensberger Aline , Rampini Silvana K. , Meyer Sauteur Patrick M. , Berger Christoph , Huber Michael , Böni Jürg , Braun Dominique L. , Marconato Maddalena , Manz Markus G. , Frey Beat M. , Günthard Huldrych F. , Kouyos Roger D. , Trkola Alexandra
Published: November 2021

Determination of SARS-CoV-2 antibody responses in the context of pre-existing immunity to circulating human coronavirus (HCoV) is critical for understanding protective immunity. Here we perform a multifactorial analysis of SARS-CoV-2 and HCoV antibody responses in pre-pandemic (N = 825) and SARS-CoV-2-infected donors (N = 389) using a custom-designed multiplex ABCORA assay. ABCORA seroprofiling, when combined with computational modeling, enables accurate definition of SARS-CoV-2 seroconversion and prediction of neutralization activity, and reveals intriguing interrelations with HCoV immunity. Specifically, higher HCoV antibody levels in SARS-CoV-2-negative donors suggest that pre-existing HCoV immunity may provide protection against SARS-CoV-2 acquisition. In those infected, higher HCoV activity is associated with elevated SARS-CoV-2 responses, indicating cross-stimulation. Most importantly, HCoV immunity may impact disease severity, as patients with high HCoV reactivity are less likely to require hospitalization. Collectively, our results suggest that HCoV immunity may promote rapid development of SARS-CoV-2-specific immunity, thereby underscoring the importance of exploring cross-protective responses for comprehensive coronavirus prevention.
Decadal-scale onset and termination of Antarctic ice-mass loss during the last deglaciation
Authors: Weber Michael E. , Golledge Nicholas R. , Fogwill Chris J. , Turney Chris S. M. , Thomas Zoë A.
Published: November 2021

Emerging ice-sheet modeling suggests once initiated, retreat of the Antarctic Ice Sheet (AIS) can continue for centuries. Unfortunately, the short observational record cannot resolve the tipping points, rate of change, and timescale of responses. Iceberg-rafted debris data from Iceberg Alley identify eight retreat phases after the Last Glacial Maximum that each destabilized the AIS within a decade, contributing to global sea-level rise for centuries to a millennium, which subsequently re-stabilized equally rapidly. This dynamic response of the AIS is supported by (i) a West Antarctic blue ice record of ice-elevation drawdown >600 m during three such retreat events related to globally recognized deglacial meltwater pulses, (ii) step-wise retreat up to 400 km across the Ross Sea shelf, (iii) independent ice sheet modeling, and (iv) tipping point analysis. Our findings are consistent with a growing body of evidence suggesting the recent acceleration of AIS mass loss may mark the beginning of a prolonged period of ice sheet retreat and substantial global sea level rise.
Sand spikes pinpoint powerful palaeoseismicity
Authors: Buchner Elmar , Sach Volker J. , Schmieder Martin
Published: November 2021

Sand spikes, pin-shaped, carbonate-cemented sandstone bodies of variable size widely interpreted as sedimentary concretions, have been enigmatic for nearly two centuries. We here present a high-energy mechanism for their formation. Two classic sand spike occurrences are found in the North Alpine Foreland Basin of Central Europe and at Mount Signal in southern California, USA. A distinct seismite horizon in Mid-Miocene Molasse sediments of southern Germany, genetically linked with the Ries impact event, exhibits dewatering structures and contains numerous sand spikes with tails systematically orientated away from the Ries crater. Sand spikes at Mount Signal, strikingly similar in shape to those found in Germany, have tails that point away from the nearby San Andreas Fault. Based on their structural and stratigraphic context, we interpret sand spikes as a new type of seismite and a promising tool to identify strong impact-induced or tectonic palaeo-earthquakes and their source regions in the geologic record.
MDA5 disease variant M854K prevents ATP-dependent structural discrimination of viral and cellular RNA
Authors: Yu Qin , Herrero del Valle Alba , Singh Rahul , Modis Yorgo
Published: November 2021

Our innate immune responses to viral RNA are vital defenses. Long cytosolic double-stranded RNA (dsRNA) is recognized by MDA5. The ATPase activity of MDA5 contributes to its dsRNA binding selectivity. Mutations that reduce RNA selectivity can cause autoinflammatory disease. Here, we show how the disease-associated MDA5 variant M854K perturbs MDA5-dsRNA recognition. M854K MDA5 constitutively activates interferon signaling in the absence of exogenous RNA. M854K MDA5 lacks ATPase activity and binds more stably to synthetic Alu:Alu dsRNA. CryoEM structures of MDA5-dsRNA filaments at different stages of ATP hydrolysis show that the K854 sidechain forms polar bonds that constrain the conformation of MDA5 subdomains, disrupting key steps in the ATPase cycle- RNA footprint expansion and helical twist modulation. The M854K mutation inhibits ATP-dependent RNA proofreading via an allosteric mechanism, allowing MDA5 to form signaling complexes on endogenous RNAs. This work provides insights on how MDA5 recognizes dsRNA in health and disease.
Distinct conformations of the HIV-1 V3 loop crown are targetable for broad neutralization
Authors: Friedrich Nikolas , Stiegeler Emanuel , Glögl Matthias , Lemmin Thomas , Hansen Simon , Kadelka Claus , Wu Yufan , Ernst Patrick , Maliqi Liridona , Foulkes Caio , Morin Mylène , Eroglu Mustafa , Liechti Thomas , Ivan Branislav , Reinberg Thomas , Schaefer Jonas V. , Karakus Umut , Ursprung Stephan , Mann Axel , Rusert Peter , Kouyos Roger D. , Robinson John A. , Günthard Huldrych F. , Plückthun Andreas , Trkola Alexandra
Published: November 2021

The V3 loop of the HIV-1 envelope (Env) protein elicits a vigorous, but largely non-neutralizing antibody response directed to the V3-crown, whereas rare broadly neutralizing antibodies (bnAbs) target the V3-base. Challenging this view, we present V3-crown directed broadly neutralizing Designed Ankyrin Repeat Proteins (bnDs) matching the breadth of V3-base bnAbs. While most bnAbs target prefusion Env, V3-crown bnDs bind open Env conformations triggered by CD4 engagement. BnDs achieve breadth by focusing on highly conserved residues that are accessible in two distinct V3 conformations, one of which resembles CCR5-bound V3. We further show that these V3-crown conformations can, in principle, be attacked by antibodies. Supporting this conclusion, analysis of antibody binding activity in the Swiss 4.5 K HIV-1 cohort (n = 4,281) revealed a co-evolution of V3-crown reactivities and neutralization breadth. Our results indicate a role of V3-crown responses and its conformational preferences in bnAb development to be considered in preventive and therapeutic approaches.
Acyl carrier protein promotes MukBEF action in Escherichia coli chromosome organization-segregation
Authors: Prince Josh P. , Bolla Jani R. , Fisher Gemma L. M. , Mäkelä Jarno , Fournier Marjorie , Robinson Carol V. , Arciszewska Lidia K. , Sherratt David J.
Published: November 2021

Structural Maintenance of Chromosomes (SMC) complexes act ubiquitously to compact DNA linearly, thereby facilitating chromosome organization-segregation. SMC proteins have a conserved architecture, with a dimerization hinge and an ATPase head domain separated by a long antiparallel intramolecular coiled-coil. Dimeric SMC proteins interact with essential accessory proteins, kleisins that bridge the two subunits of an SMC dimer, and HAWK/KITE proteins that interact with kleisins. The ATPase activity of the Escherichia coli SMC protein, MukB, which is essential for its in vivo function, requires its interaction with the dimeric kleisin, MukF that in turn interacts with the KITE protein, MukE. Here we demonstrate that, in addition, MukB interacts specifically with Acyl Carrier Protein (AcpP) that has essential functions in fatty acid synthesis. We characterize the AcpP interaction at the joint of the MukB coiled-coil and show that the interaction is necessary for MukB ATPase and for MukBEF function in vivo.
The role of cyclonic activity in tropical temperature-rainfall scaling
Authors: Traxl Dominik , Boers Niklas , Rheinwalt Aljoscha , Bookhagen Bodo
Published: November 2021

The attribution of changing intensity of rainfall extremes to global warming is a key challenge of climate research. From a thermodynamic perspective, via the Clausius-Clapeyron relationship, rainfall events are expected to become stronger due to the increased water-holding capacity of a warmer atmosphere. Here, we employ global, 1-hourly temperature and 3-hourly rainfall data to investigate the scaling between temperature and extreme rainfall. Although the Clausius-Clapeyron scaling of +7% rainfall intensity increase per degree warming roughly holds on a global average, we find very heterogeneous spatial patterns. Over tropical oceans, we reveal areas with consistently strong negative scaling (below −40%∘C−1). We show that the negative scaling is due to a robust linear correlation between pre-rainfall cooling of near-surface air temperature and extreme rainfall intensity. We explain this correlation by atmospheric and oceanic dynamics associated with cyclonic activity. Our results emphasize that thermodynamic arguments alone are not enough to attribute changing rainfall extremes to global warming. Circulation dynamics must also be thoroughly considered.
Assessing saliva microbiome collection and processing methods
Authors: Armstrong Abigail J. S. , Parmar Veenat , Blaser Martin J.
Published: November 2021

The oral microbiome has been connected with lung health and may be of significance in the progression of SARS-CoV-2 infection. Saliva-based SARS-CoV-2 tests provide the opportunity to leverage stored samples for assessing the oral microbiome. However, these collection kits have not been tested for their accuracy in measuring the oral microbiome. Saliva is highly enriched with human DNA and reducing it prior to shotgun sequencing may increase the depth of bacterial reads. We examined both the effect of saliva collection method and sequence processing on measurement of microbiome depth and diversity by 16S rRNA gene amplicon and shotgun metagenomics. We collected 56 samples from 22 subjects. Each subject provided saliva samples with and without preservative, and a subset provided a second set of samples the following day. 16S rRNA gene (V4) sequencing was performed on all samples, and shotgun metagenomics was performed on a subset of samples collected with preservative with and without human DNA depletion before sequencing. We observed that the beta diversity distances within subjects over time was smaller than between unrelated subjects, and distances within subjects were smaller in samples collected with preservative. Samples collected with preservative had higher alpha diversity measuring both richness and evenness. Human DNA depletion before extraction and shotgun sequencing yielded higher total and relative reads mapping to bacterial sequences. We conclude that collecting saliva with preservative may provide more consistent measures of the oral microbiome and depleting human DNA increases yield of bacterial sequences.
Penultimate deglaciation Asian monsoon response to North Atlantic circulation collapse
Authors: Wassenburg Jasper A. , Vonhof Hubert B. , Cheng Hai , Martínez-García Alfredo , Ebner Pia-Rebecca , Li Xianglei , Zhang Haiwei , Sha Lijuan , Tian Ye , Edwards R. Lawrence , Fiebig Jens , Haug Gerald H.
Published: November 2021

During glacial terminations, massive iceberg discharges and meltwater pulses in the North Atlantic triggered a shutdown of the Atlantic Meridional Overturning Circulation (AMOC). Speleothem calcium carbonate oxygen isotope records (δ18OCc) indicate that the collapse of the AMOC caused dramatic changes in the distribution and variability of the East Asian and Indian monsoon rainfall. However, the mechanisms linking changes in the intensity of the AMOC and Asian monsoon δ18OCc are not fully understood. Part of the challenge arises from the fact that speleothem δ18OCc depends on not only the δ18O of precipitation but also temperature and kinetic isotope effects. Here we quantitatively deconvolve these parameters affecting δ18OCc by applying three geochemical techniques in speleothems covering the penultimate glacial termination. Our data suggest that the weakening of the AMOC during meltwater pulse 2A caused substantial cooling in East Asia and a shortening of the summer monsoon season, whereas the collapse of the AMOC during meltwater pulse 2B (133,000 years ago) also caused a dramatic decrease in the intensity of the Indian summer monsoon. These results reveal that the different modes of the AMOC produced distinct impacts on the monsoon system.
Optimization of non-coding regions for a non-modified mRNA COVID-19 vaccine
Authors: Gebre Makda S. , Rauch Susanne , Roth Nicole , Yu Jingyou , Chandrashekar Abishek , Mercado Noe B. , He Xuan , Liu Jinyan , McMahan Katherine , Martinot Amanda , Martinez David R. , Giffin Victoria , Hope David , Patel Shivani , Sellers Daniel , Sanborn Owen , Barrett Julia , Liu Xiaowen , Cole Andrew C. , Pessaint Laurent , Valentin Daniel , Flinchbaugh Zack , Yalley-Ogunro Jake , Muench Jeanne , Brown Renita , Cook Anthony , Teow Elyse , Andersen Hanne , Lewis Mark G. , Boon Adrianus C. M. , Baric Ralph S. , Mueller Stefan O. , Petsch Benjamin , Barouch Dan H.
Published: November 2021

The CVnCoV (CureVac) mRNA vaccine for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was recently evaluated in a phase 2b/3 efficacy trial in humans1. CV2CoV is a second-generation mRNA vaccine containing non-modified nucleosides but with optimized non-coding regions and enhanced antigen expression. Here we report the results of a head-to-head comparison of the immunogenicity and protective efficacy of CVnCoV and CV2CoV in non-human primates. We immunized 18 cynomolgus macaques with two doses of 12 μg lipid nanoparticle-formulated CVnCoV or CV2CoV or with sham (n = 6 per group). Compared with CVnCoV, CV2CoV induced substantially higher titres of binding and neutralizing antibodies, memory B cell responses and T cell responses as well as more potent neutralizing antibody responses against SARS-CoV-2 variants, including the Delta variant. Moreover, CV2CoV was found to be comparably immunogenic to the BNT162b2 (Pfizer) vaccine in macaques. Although CVnCoV provided partial protection against SARS-CoV-2 challenge, CV2CoV afforded more robust protection with markedly lower viral loads in the upper and lower respiratory tracts. Binding and neutralizing antibody titres were correlated with protective efficacy. These data demonstrate that optimization of non-coding regions can greatly improve the immunogenicity and protective efficacy of a non-modified mRNA SARS-CoV-2 vaccine in non-human primates.
Community psychological and behavioural responses to coronavirus disease 2019 over one year of the pandemic in 2020 in Hong Kong
Authors: Liao Qiuyan , Xiao Jingyi , Cheung Justin , Ng Tiffany W. Y. , Lam Wendy W. T. , Ni Michael Y. , Cowling Benjamin J.
Published: November 2021

Monitoring community psychological and behavioural responses to coronavirus disease 2019 (COVID-19) is important for informing policy making and risk communication to sustain public compliance with challenging precautionary behaviours and mitigating the psychological impacts. Monthly telephone-based cross-sectional surveys in January–April 2020 and then weekly surveys from May through December 2020 were conducted to monitor changes in public risk perception of COVID-19, personal efficacy in self-protection, confidence in government’s ability to control the pandemic, precautionary behaviours, perceived impact of precautionary behaviours, psychological fatigue and distress in Hong Kong, and examine their inter-relationships. While worry about contracting COVID-19 increased, personal efficacy and confidence in government declined as the community incidence of COVID-19 increased. The public maintained high compliance with most precautionary behaviours throughout but relaxed behaviours that were more challenging when disease incidence declined. Public confidence in government was persistently low throughout, of which, a lower level was associated with more psychological fatigue, lower compliance with precautionary behaviours and greater psychological distress. Perceived greater negative impact of precautionary behaviours was also associated with more psychological fatigue which in turn was associated with relaxation of precautionary behaviours. Female, younger and unemployed individuals reported greater psychological distress throughout different stages of the pandemic. Risk communication should focus on promoting confidence in self-protection and pandemic control to avoid helplessness to act when the pandemic resurges. Policy making should prioritize building public trust, enhancing support for sustaining precautionary behaviours, and helping vulnerable groups to adapt to the stress during the pandemic.
Thermal and optical properties of PMMA films reinforced with Nb2O5 nanoparticles
Authors: Hajduk B. , Bednarski H. , Jarka P. , Janeczek H. , Godzierz M. , Tański T.
Published: November 2021

The article presents the thermal and physical properties of PMMA composite films with the addition of Nb2O5 nanoparticles. The addition of nanoparticles to PMMA mainly influenced the optical transmission and glass transition temperature of composite films compared to pure PMMA. It is clearly visible in the results of the conducted ellipsometric and differential scanning calorimetry tests. X-ray studies showed that the heat treatment of the samples resulted in the ordering of the polymer structure (flattening of the polymer chains). Examining the surface of the samples with scanning electron microscopy, it can be seen that Nb2O5 nanoparticles formed unusual, branched formations resembling "snowflakes".
Social stress drives the multi-wave dynamics of COVID-19 outbreaks
Authors: Kastalskiy Innokentiy A. , Pankratova Evgeniya V. , Mirkes Evgeny M. , Kazantsev Victor B. , Gorban Alexander N.
Published: November 2021

The dynamics of epidemics depend on how people's behavior changes during an outbreak. At the beginning of the epidemic, people do not know about the virus, then, after the outbreak of epidemics and alarm, they begin to comply with the restrictions and the spreading of epidemics may decline. Over time, some people get tired/frustrated by the restrictions and stop following them (exhaustion), especially if the number of new cases drops down. After resting for a while, they can follow the restrictions again. But during this pause the second wave can come and become even stronger then the first one. Studies based on SIR models do not predict the observed quick exit from the first wave of epidemics. Social dynamics should be considered. The appearance of the second wave also depends on social factors. Many generalizations of the SIR model have been developed that take into account the weakening of immunity over time, the evolution of the virus, vaccination and other medical and biological details. However, these more sophisticated models do not explain the apparent differences in outbreak profiles between countries with different intrinsic socio-cultural features. In our work, a system of models of the COVID-19 pandemic is proposed, combining the dynamics of social stress with classical epidemic models. Social stress is described by the tools of sociophysics. The combination of a dynamic SIR-type model with the classical triad of stages of the general adaptation syndrome, alarm-resistance-exhaustion, makes it possible to describe with high accuracy the available statistical data for 13 countries. The sets of kinetic constants corresponding to optimal fit of model to data were found. These constants characterize the ability of society to mobilize efforts against epidemics and maintain this concentration over time and can further help in the development of management strategies specific to a particular society.
Requirement of direct contact between chondrocytes and macrophages for the maturation of regenerative cartilage
Authors: Kanda Kengo , Asawa Yukiyo , Inaki Ryoko , Fujihara Yuko , Hoshi Kazuto , Hikita Atsuhiko
Published: November 2021

Regenerative cartilage prepared from cultured chondrocytes is generally immature in vitro and matures after transplantation. Although many factors, including host cells and humoral factors, have been shown to affect cartilage maturation in vivo, the requirement of direct cell–cell contact between host and donor cells remains to be verified. In this study, we examined the host cells that promote cartilage maturation via cell–cell contact. Based on analysis of the transplanted chondrocytes, we examined the contribution of endothelial cells and macrophages. Using a semiclosed device that is permeable to tissue fluids while blocking host cells, we selectively transplanted chondrocytes and HUVECs or untreated/M1-polarized/M2-polarized RAW264.7 cells. As a result, untreated RAW264.7 cells induced cartilage regeneration. Furthermore, an in vitro coculture assay indicated communication between chondrocytes and RAW264.7 cells mediated by RNA, suggesting the involvement of extracellular vesicles in this process. These findings provide insights for establishing a method of in vitro cartilage regeneration.
Interploidy gene flow involving the sexual-asexual cycle facilitates the diversification of gynogenetic triploid Carassius fish
Authors: Mishina Tappei , Takeshima Hirohiko , Takada Mikumi , Iguchi Kei’ichiro , Zhang Chunguang , Zhao Yahui , Kawahara-Miki Ryouka , Hashiguchi Yasuyuki , Tabata Ryoichi , Sasaki Takeshi , Nishida Mutsumi , Watanabe Katsutoshi
Published: November 2021

Asexual vertebrates are rare and at risk of extinction due to their restricted adaptability through the loss of genetic recombination. We explore the mechanisms behind the generation and maintenance of genetic diversity in triploid asexual (gynogenetic) Carassius auratus fish, which is widespread in East Asian fresh waters and exhibits one of the most extensive distribution among asexual vertebrates despite its dependence on host sperm. Our analyses of genetic composition using dozens of genetic markers and genome-wide transcriptome sequencing uncover admixed genetic composition of Japanese asexual triploid Carassius consisting of both the diverged Japanese and Eurasian alleles, suggesting the involvement of Eurasian lineages in its origin. However, coexisting sexual diploid relatives and asexual triploids in Japan show regional genetic similarity in both mitochondrial and nuclear markers. These results are attributed to a unique unidirectional gene flow from diploids to sympatric triploids, with the involvement of occasional sexual reproduction. Additionally, the asexual triploid shows a weaker population structure than the sexual diploid, and multiple triploid lineages coexist in most Japanese rivers. The generated diversity via repeated interploidy gene flow as well as an increased establishment of immigrants is assumed to offset the cost of asexual reproduction and might contribute to the successful broad distribution of this asexual vertebrate.
Spatial and temporal patterns of genetic diversity in Bombus terrestris populations of the Iberian Peninsula and their conservation implications
Authors: Cejas Diego , De la Rúa Pilar , Ornosa Concepción , Michez Denis , Muñoz Irene
Published: November 2021

The bumblebee Bombus terrestris is used worldwide for crop pollination. Despite its positive impact on crop yield, it has become a widespread threat to biodiversity due to its interactions with local bumblebee populations. Commercial subspecies introduced to the Iberian Peninsula since the 1990s without any regulation have colonized the environment, with evidence of naturalization and introgression with the endemic subspecies Bombus terrestris lusitanicus. We have used mitochondrial and nuclear genetic data to describe the current genetic diversity of the Iberian population and to estimate the expansion of commercial bumblebees. Samples from the natural distribution range of the commercial subspecies, the natural intergradation area between the two subspecies and from a period prior to the use of commercial colonies (i.e., before the 1990s) have been used for comparison. Our results show that the mitochondrial haplotype of the commercial breeds has spread throughout the territory, which, together with subtle changes observed in the nuclear genetic diversity of the populations, indicates that hybridization and consequent introgression are occurring in most of the peninsula. It is, therefore, necessary to improve the existing legislation concerning the management and exportation of commercial bumblebees to conserve locally adapted populations.