bluuebunny/crossref_metadata_2025 huggingface dataset:
Laboratory Experiments on Tsunamigenic Discrete Subaqueous Volcanic Eruptions. Part 1: Free Surface Disturbances
Authors: Shen Yaxiong , Whittaker Colin N. , Lane Emily M. , White James D.L. , Power William , Nomikou Paraskevi
Published: May 2021

A submarine volcanic eruption has the potential to generate a dangerous local tsunami. To better understand the free surface disturbance generated by an underwater volcanic eruption, which will form the initial condition for any subsequent wave generation, we conducted a series of laboratory experiments. In these experiments, compressed air was injected into a tank filled with water to simulate an underwater eruption. The experiments were repeated over a range of different pressures and water depths. Each eruption can be divided into three phases: A momentum‐driven jet, a buoyancy‐driven plume, and a fountain‐generation regime. Our experiments exhibit two fountain regimes (a dome regime and a finger regime), with a transition between them. These fountain regimes have been observed in several real submarine volcanic eruptions. This paper proposes a Froude number criterion to combine the water depths and source conditions together with the aspect ratios of fountains to quantify different fountain regimes. This quantitative relationship holds for two real subaqueous volcanic eruption cases (Myojin‐Sho eruption in 1952 and 1996 eruption in Karymskoye Lake). The fountain of the Myojin‐Sho shallow submarine eruption on September 23,1952 appears to have been in the dome regime, which means it was a relatively weak eruption. Unlike other eruptions from this volcano, which did generate tsunamis, no tsunami waves were detected on September 23 . This study contributes to an enhanced understanding of the usually unseen mechanism of free surface disturbances by volcanic gas injection during submarine eruptions.
Uneven Warming Likely Contributed to Declining Near‐Surface Wind Speeds in Northern China Between 1961 and 2016
Authors: Zhang Gangfeng , Azorin‐Molina Cesar , Chen Deliang , McVicar Tim R. , Guijarro Jose A. , Kong Feng , Minola Lorenzo , Deng Kaiqiang , Shi Peijun
Published: May 2021

A decline in mean near‐surface (10 m) wind speed has been widely reported for many land regions over recent decades, yet the underlying cause(s) remains uncertain. This study investigates changes in near‐surface wind speed over northern China from 1961 to 2016, and analyzes the associated physical mechanisms using station observations, reanalysis products and model simulations from the Community Atmosphere Model version 5.1 (CAM5). The homogenized near‐surface wind speed shows a significantly (p < 0.05) decline trend of −0.103 m s−1 decade−1, which stabilized from the 1990s onwards. Similar negative trends are observed for all seasons, with the strongest trends occurring in the central and eastern parts of northern China. Fast warming has occurred at high‐latitudes (i.e., >50°N) in recent decades, which has weakened the annual and seasonal meridional air temperature gradient (−0.33°C to −0.12°C dec−1, p < 0.05, except autumn) between these regions (50°–60°N, 75°–135°E) and the northern China zone (35°–45°N, 75°–135°E). This caused a significant (p < 0.05) decrease in annual and seasonal pressure gradient (−0.43 to −0.20 hPa dec−1) between the two zones, which contributed to the slowdown of winds. CAM5 simulations demonstrate that spatially uneven air temperature increases and near‐surface wind speed decreases over northern China can be realistically reproduced using the so‐called “all forcing” simulation, while the “natural only forcing” simulation fails to realistically simulate the uneven warming patterns and declines in near‐surface wind speed over most of northern China, except for summer.
Influences on Discharge Partitioning on a Large River Delta: Case Study of the Mississippi‐Atchafalaya Diversion, 1926–1950
Authors: Shaw John B. , Mason Kashauna G. , Ma Hongbo , McCain Gordon W.
Published: May 2021

The modern Mississippi River (M.R.) Delta is plumbed by the Mississippi and Atchafalaya rivers, setting water and sediment dispersal pathways for Earth’s fifth‐largest river system. The Atchafalaya River’s (A.R.) partial annexation of discharge from the M.R., particularly between 1926 and 1950, prompted warnings of a rapid river avulsion and the construction of the Old River Control Structure to regulate flow. Natural and anthropogenic causes of this discharge annexation are difficult to disentangle. Here, we develop and validate a hydrodynamic model of flow partitioning through the historic channel network. We then isolate how several key changes to the system affected discharge partitioning and stage at the A.R.‐M.R. diversion. Simulations show that erosion of the upper A.R. can account for 73% of the water discharge increase. Dredging in the lower A.R. between 1932 and 1950 can account for 35% of the water discharge increase, and was also an important control on shear stress distribution. The lower M.R. was slightly erosional during this period, and therefore hindered the A.R. discharge increase. Significant lacustrine delta deposition in A.R. had little effect on partitioning. These findings highlight the importance of A.R. enlargement processes on avulsion dynamics at this site. Given the essential nature of this river junction to the society, transportation, and commerce of the United States, improved attribution of discharge increases may lead to future management strategies that are broadly impactful.
Convective Transport Explains “Missing” Ice near the Tropical Tropopause
Authors: Shultz David
Published: May 2021

Spaceborne lidar shows that more ice than expected is leaving the tropical tropopause layer in the atmosphere.
Neural integration underlying naturalistic prediction flexibly adapts to varying sensory input rate
Authors: Baumgarten Thomas J. , Maniscalco Brian , Lee Jennifer L. , Flounders Matthew W. , Abry Patrice , He Biyu J.
Published: May 2021

Prediction of future sensory input based on past sensory information is essential for organisms to effectively adapt their behavior in dynamic environments. Humans successfully predict future stimuli in various natural settings. Yet, it remains elusive how the brain achieves effective prediction despite enormous variations in sensory input rate, which directly affect how fast sensory information can accumulate. We presented participants with acoustic sequences capturing temporal statistical regularities prevalent in nature and investigated neural mechanisms underlying predictive computation using MEG. By parametrically manipulating sequence presentation speed, we tested two hypotheses: neural prediction relies on integrating past sensory information over fixed time periods or fixed amounts of information. We demonstrate that across halved and doubled presentation speeds, predictive information in neural activity stems from integration over fixed amounts of information. Our findings reveal the neural mechanisms enabling humans to robustly predict dynamic stimuli in natural environments despite large sensory input rate variations.
The genomic loci of specific human tRNA genes exhibit ageing-related DNA hypermethylation
Authors: Acton Richard J. , Yuan Wei , Gao Fei , Xia Yudong , Bourne Emma , Wozniak Eva , Bell Jordana , Lillycrop Karen , Wang Jun , Dennison Elaine , Harvey Nicholas C. , Mein Charles A. , Spector Tim D. , Hysi Pirro G. , Cooper Cyrus , Bell Christopher G.
Published: May 2021

The epigenome has been shown to deteriorate with age, potentially impacting on ageing-related disease. tRNA, while arising from only ˜46 kb (<0.002% genome), is the second most abundant cellular transcript. tRNAs also control metabolic processes known to affect ageing, through core translational and additional regulatory roles. Here, we interrogate the DNA methylation state of the genomic loci of human tRNA. We identify a genomic enrichment for age-related DNA hypermethylation at tRNA loci. Analysis in 4,350 MeDIP-seq peripheral-blood DNA methylomes (16–82 years), identifies 44 and 21 hypermethylating specific tRNAs at study-and genome-wide significance, respectively, contrasting with none hypomethylating. Validation and replication (450k array and independent targeted Bisuphite-sequencing) supported the hypermethylation of this functional unit. Tissue-specificity is a significant driver, although the strongest consistent signals, also independent of major cell-type change, occur in tRNA-iMet-CAT-1-4 and tRNA-Ser-AGA-2-6. This study presents a comprehensive evaluation of the genomic DNA methylation state of human tRNA genes and reveals a discreet hypermethylation with advancing age.
Probing subwavelength in-plane anisotropy with antenna-assisted infrared nano-spectroscopy
Authors: Yao Ziheng , Chen Xinzhong , Wehmeier Lukas , Xu Suheng , Shao Yinming , Zeng Zimeng , Liu Fanwei , Mcleod Alexander S. , Gilbert Corder Stephanie N. , Tsuneto Makoto , Shi Wu , Wang Zihang , Zheng Wenjun , Bechtel Hans A. , Carr G. L. , Martin Michael C. , Zettl Alex , Basov D. N. , Chen Xi , Eng Lukas M. , Kehr Susanne C. , Liu Mengkun
Published: May 2021

Infrared nano-spectroscopy based on scattering-type scanning near-field optical microscopy (s-SNOM) is commonly employed to probe the vibrational fingerprints of materials at the nanometer length scale. However, due to the elongated and axisymmetric tip shank, s-SNOM is less sensitive to the in-plane sample anisotropy in general. In this article, we report an easy-to-implement method to probe the in-plane dielectric responses of materials with the assistance of a metallic disk micro-antenna. As a proof-of-concept demonstration, we investigate here the in-plane phonon responses of two prototypical samples, i.e. in (100) sapphire and x-cut lithium niobate (LiNbO3). In particular, the sapphire in-plane vibrations between 350 cm−1 to 800 cm−1 that correspond to LO phonon modes along the crystal b- and c-axis are determined with a spatial resolution of < λ/10, without needing any fitting parameters. In LiNbO3, we identify the in-plane orientation of its optical axis via the phonon modes, demonstrating that our method can be applied without prior knowledge of the crystal orientation. Our method can be elegantly adapted to retrieve the in-plane anisotropic response of a broad range of materials, i.e. subwavelength microcrystals, van-der-Waals materials, or topological insulators.
Deriving the skyrmion Hall angle from skyrmion lattice dynamics
Authors: Brearton R. , Turnbull L. A. , Verezhak J. A. T. , Balakrishnan G. , Hatton P. D. , van der Laan G. , Hesjedal T.
Published: May 2021

Magnetic skyrmions are topologically non-trivial, swirling magnetization textures that form lattices in helimagnetic materials. These magnetic nanoparticles show promise as high efficiency next-generation information carriers, with dynamics that are governed by their topology. Among the many unusual properties of skyrmions is the tendency of their direction of motion to deviate from that of a driving force; the angle by which they diverge is a materials constant, known as the skyrmion Hall angle. In magnetic multilayer systems, where skyrmions often appear individually, not arranging themselves in a lattice, this deflection angle can be easily measured by tracing the real space motion of individual skyrmions. Here we describe a reciprocal space technique which can be used to determine the skyrmion Hall angle in the skyrmion lattice state, leveraging the properties of the skyrmion lattice under a shear drive. We demonstrate this procedure to yield a quantitative measurement of the skyrmion Hall angle in the room-temperature skyrmion system FeGe, shearing the skyrmion lattice with the magnetic field gradient generated by a single turn Oersted wire.
The tepary bean genome provides insight into evolution and domestication under heat stress
Authors: Moghaddam Samira Mafi , Oladzad Atena , Koh Chushin , Ramsay Larissa , Hart John P. , Mamidi Sujan , Hoopes Genevieve , Sreedasyam Avinash , Wiersma Andrew , Zhao Dongyan , Grimwood Jane , Hamilton John P. , Jenkins Jerry , Vaillancourt Brieanne , Wood Joshua C. , Schmutz Jeremy , Kagale Sateesh , Porch Timothy , Bett Kirstin E. , Buell C. Robin , McClean Phillip E.
Published: May 2021

Tepary bean (Phaseolus acutifolis A. Gray), native to the Sonoran Desert, is highly adapted to heat and drought. It is a sister species of common bean (Phaseolus vulgaris L.), the most important legume protein source for direct human consumption, and whose production is threatened by climate change. Here, we report on the tepary genome including exploration of possible mechanisms for resilience to moderate heat stress and a reduced disease resistance gene repertoire, consistent with adaptation to arid and hot environments. Extensive collinearity and shared gene content among these Phaseolus species will facilitate engineering climate adaptation in common bean, a key food security crop, and accelerate tepary bean improvement.
Nicotinamide riboside attenuates age-associated metabolic and functional changes in hematopoietic stem cells
Authors: Sun Xuan , Cao Benjamin , Naval-Sanchez Marina , Pham Tony , Sun Yu Bo Yang , Williams Brenda , Heazlewood Shen Y. , Deshpande Nikita , Li Jinhua , Kraus Felix , Rae James , Nguyen Quan , Yari Hamed , Schröder Jan , Heazlewood Chad K. , Fulton Madeline , Hatwell-Humble Jessica , Das Gupta Kaustav , Kapetanovic Ronan , Chen Xiaoli , Sweet Matthew J. , Parton Robert G. , Ryan Michael T. , Polo Jose M. , Nefzger Christian M. , Nilsson Susan K.
Published: May 2021

With age, hematopoietic stem cells (HSC) undergo changes in function, including reduced regenerative potential and loss of quiescence, which is accompanied by a significant expansion of the stem cell pool that can lead to haematological disorders. Elevated metabolic activity has been implicated in driving the HSC ageing phenotype. Here we show that nicotinamide riboside (NR), a form of vitamin B3, restores youthful metabolic capacity by modifying mitochondrial function in multiple ways including reduced expression of nuclear encoded metabolic pathway genes, damping of mitochondrial stress and a decrease in mitochondrial mass and network-size. Metabolic restoration is dependent on continuous NR supplementation and accompanied by a shift of the aged transcriptome towards the young HSC state, more youthful bone marrow cellular composition and an improved regenerative capacity in a transplant setting. Consequently, NR administration could support healthy ageing by re-establishing a more youthful hematopoietic system.
Single-component multilayered self-assembling nanoparticles presenting rationally designed glycoprotein trimers as Ebola virus vaccines
Authors: He Linling , Chaudhary Anshul , Lin Xiaohe , Sou Cindy , Alkutkar Tanwee , Kumar Sonu , Ngo Timothy , Kosviner Ezra , Ozorowski Gabriel , Stanfield Robyn L. , Ward Andrew B. , Wilson Ian A. , Zhu Jiang
Published: May 2021

Ebola virus (EBOV) glycoprotein (GP) can be recognized by neutralizing antibodies (NAbs) and is the main target for vaccine design. Here, we first investigate the contribution of the stalk and heptad repeat 1-C (HR1C) regions to GP metastability. Specific stalk and HR1Cmodifications in a mucin-deleted form (GPΔmuc) increase trimer yield, whereas alterations of HR1Cexert a more complex effect on thermostability. Crystal structures are determined to validate two rationally designed GPΔmuc trimers in their unliganded state. We then display a modified GPΔmuc trimer on reengineered protein nanoparticles that encapsulate a layer of locking domains (LD) and a cluster of helper T-cell epitopes. In mice and rabbits, GP trimers and nanoparticles elicit cross-ebolavirus NAbs, as well as non-NAbs that enhance pseudovirus infection. Repertoire sequencing reveals quantitative profiles of vaccine-induced B-cell responses. This study demonstrates a promising vaccine strategy for filoviruses, such as EBOV, based on GP stabilization and nanoparticle display.
A machine learning model for identifying patients at risk for wild-type transthyretin amyloid cardiomyopathy
Authors: Huda Ahsan , Castaño Adam , Niyogi Anindita , Schumacher Jennifer , Stewart Michelle , Bruno Marianna , Hu Mo , Ahmad Faraz S. , Deo Rahul C. , Shah Sanjiv J.
Published: May 2021

Transthyretin amyloid cardiomyopathy, an often unrecognized cause of heart failure, is now treatable with a transthyretin stabilizer. It is therefore important to identify at-risk patients who can undergo targeted testing for earlier diagnosis and treatment, prior to the development of irreversible heart failure. Here we show that a random forest machine learning model can identify potential wild-type transthyretin amyloid cardiomyopathy using medical claims data. We derive a machine learning model in 1071 cases and 1071 non-amyloid heart failure controls and validate the model in three nationally representative cohorts (9412 cases, 9412 matched controls), and a large, single-center electronic health record-based cohort (261 cases, 39393 controls). We show that the machine learning model performs well in identifying patients with cardiac amyloidosis in the derivation cohort and all four validation cohorts, thereby providing a systematic framework to increase the suspicion of transthyretin cardiac amyloidosis in patients with heart failure.
Inverse-design magnonic devices
Authors: Wang Qi , Chumak Andrii V. , Pirro Philipp
Published: May 2021

The field of magnonics offers a new type of low-power information processing, in which magnons, the quanta of spin waves, carry and process data instead of electrons. Many magnonic devices were demonstrated recently, but the development of each of them requires specialized investigations and, usually, one device design is suitable for one function only. Here, we introduce the method of inverse-design magnonics, in which any functionality can be specified first, and a feedback-based computational algorithm is used to obtain the device design. We validate this method using the means of micromagnetic simulations. Our proof-of-concept prototype is based on a rectangular ferromagnetic area that can be patterned using square-shaped voids. To demonstrate the universality of this approach, we explore linear, nonlinear and nonreciprocal magnonic functionalities and use the same algorithm to create a magnonic (de-)multiplexer, a nonlinear switch and a circulator. Thus, inverse-design magnonics can be used to develop highly efficient rf applications as well as Boolean and neuromorphic computing building blocks.
A seamlessly integrated device of micro-supercapacitor and wireless charging with ultrahigh energy density and capacitance
Authors: Gao Chang , Huang Jiancheng , Xiao Yukun , Zhang Guoqiang , Dai Chunlong , Li Zengling , Zhao Yang , Jiang Lan , Qu Liangti
Published: May 2021

Microdevice integrating energy storage with wireless charging could create opportunities for electronics design, such as moveable charging. Herein, we report seamlessly integrated wireless charging micro-supercapacitors by taking advantage of a designed highly consistent material system that both wireless coils and electrodes are of the graphite paper. The transferring power efficiency of the wireless charging is 52.8%. Benefitting from unique circuit structure, the intact device displays low resistance and excellent voltage tolerability with a capacitance of 454.1 mF cm−2, superior to state-of-the-art conventional planar micro-supercapacitors. Besides, a record high energy density of 463.1 μWh cm−2 exceeds the existing metal ion hybrid micro-supercapacitors and even commercial thin film battery (350 μWh cm−2). After charging for 6 min, the integrated device reaches up to a power output of 45.9 mW, which can drive an electrical toy car immediately. This work brings an insight for contactless micro-electronics and flexible micro-robotics.
The RNA binding protein FgRbp1 regulates specific pre-mRNA splicing via interacting with U2AF23 in Fusarium
Authors: Wang Minhui , Ma Tianling , Wang Haixia , Liu Jianzhao , Chen Yun , Shim Won Bo , Ma Zhonghua
Published: May 2021

Precursor messenger RNA (pre-mRNA) splicing is an essential and tightly regulated process in eukaryotic cells; however, the regulatory mechanisms for the splicing are not well understood. Here, we characterize a RNA binding protein named FgRbp1 in Fusarium graminearum, a fungal pathogen of cereal crops worldwide. Deletion of FgRbp1 leads to reduced splicing efficiency in 47% of the F. graminearum intron-containing gene transcripts that are involved in various cellular processes including vegetative growth, development, and virulence. The human ortholog RBM42 is able to fully rescue the growth defects of ΔFgRbp1. FgRbp1 binds to the motif CAAGR in its target mRNAs, and interacts with the splicing factor FgU2AF23, a highly conserved protein involved in 3’ splice site recognition, leading to enhanced recruitment of FgU2AF23 to the target mRNAs. This study demonstrates that FgRbp1 is a splicing regulator and regulates the pre-mRNA splicing in a sequence-dependent manner in F. graminearum.
Coherent vibrational dynamics reveals lattice anharmonicity in organic–inorganic halide perovskite nanocrystals
Authors: Debnath Tushar , Sarker Debalaya , Huang He , Han Zhong-Kang , Dey Amrita , Polavarapu Lakshminarayana , Levchenko Sergey V. , Feldmann Jochen
Published: May 2021

The halide ions of organic-inorganic hybrid perovskites can strongly influence the interaction between the central organic moiety and the inorganic metal halide octahedral units and thus their lattice vibrations. Here, we report the halide-ion-dependent vibrational coherences in formamidinium lead halide (FAPbX3, X = Br, I) perovskite nanocrystals (PNCs) via the combination of femtosecond pump–probe spectroscopy and density functional theory calculations. We find that the FAPbX3 PNCs generate halide-dependent coherent vibronic wave packets upon above-bandgap non-resonant excitation. More importantly, we observe several higher harmonics of the fundamental modes for FAPbI3 PNCs as compared to FAPbBr3 PNCs. This is likely due to the weaker interaction between the central FA moiety and the inorganic cage for FAPbI3 PNCs, and thus the PbI64− unit can vibrate more freely. This weakening reveals the intrinsic anharmonicity in the Pb-I framework, and thus facilitating the energy transfer into overtone and combination bands. These findings not only unveil the superior stability of Br–based PNCs over I–based PNCs but are also important for a better understanding of their electronic and polaronic properties.
Confinement effects and acid strength in zeolites
Authors: Grifoni Emanuele , Piccini GiovanniMaria , Lercher Johannes A. , Glezakou Vassiliki-Alexandra , Rousseau Roger , Parrinello Michele
Published: May 2021

Chemical reactivity and sorption in zeolites are coupled to confinement and—to a lesser extent—to the acid strength of Brønsted acid sites (BAS). In presence of water the zeolite Brønsted acid sites eventually convert into hydronium ions. The gradual transition from zeolite Brønsted acid sites to hydronium ions in zeolites of varying pore size is examined by ab initio molecular dynamics combined with enhanced sampling based on Well-Tempered Metadynamics and a recently developed set of collective variables. While at low water content (1–2 water/BAS) the acidic protons prefer to be shared between zeolites and water, higher water contents (n > 2) invariably lead to solvation of the protons within a localized water cluster adjacent to the BAS. At low water loadings the standard free energy of the formed complexes is dominated by enthalpy and is associated with the acid strength of the BAS and the space around the site. Conversely, the entropy increases linearly with the concentration of waters in the pores, favors proton solvation and is independent of the pore size/shape.
Following replicative DNA synthesis by time-resolved X-ray crystallography
Authors: Chim Nicholas , Meza Roman A. , Trinh Anh M. , Yang Kefan , Chaput John C.
Published: May 2021

The mechanism of DNA synthesis has been inferred from static structures, but the absence of temporal information raises longstanding questions about the order of events in one of life’s most central processes. Here we follow the reaction pathway of a replicative DNA polymerase using time-resolved X-ray crystallography to elucidate the order and transition between intermediates. In contrast to the canonical model, the structural changes observed in the time-lapsed images reveal a catalytic cycle in which translocation precedes catalysis. The translocation step appears to follow a push-pull mechanism where the O-O1 loop of the finger subdomain acts as a pawl to facilitate unidirectional movement along the template with conserved tyrosine residues 714 and 719 functioning as tandem gatekeepers of DNA synthesis. The structures capture the precise order of critical events that may be a general feature of enzymatic catalysis among replicative DNA polymerases.
Neutralizing antibody responses to SARS-CoV-2 in symptomatic COVID-19 is persistent and critical for survival
Authors: Dispinseri Stefania , Secchi Massimiliano , Pirillo Maria Franca , Tolazzi Monica , Borghi Martina , Brigatti Cristina , De Angelis Maria Laura , Baratella Marco , Bazzigaluppi Elena , Venturi Giulietta , Sironi Francesca , Canitano Andrea , Marzinotto Ilaria , Tresoldi Cristina , Ciceri Fabio , Piemonti Lorenzo , Negri Donatella , Cara Andrea , Lampasona Vito , Scarlatti Gabriella
Published: May 2021

Understanding how antibody responses to SARS-CoV-2 evolve during infection may provide important insight into therapeutic approaches and vaccination for COVID-19. Here we profile the antibody responses of 162 COVID-19 symptomatic patients in the COVID-BioB cohort followed longitudinally for up to eight months from symptom onset to find SARS-CoV-2 neutralization, as well as antibodies either recognizing SARS-CoV-2 spike antigens and nucleoprotein, or specific for S2 antigen of seasonal beta-coronaviruses and hemagglutinin of the H1N1 flu virus. The presence of neutralizing antibodies within the first weeks from symptoms onset correlates with time to a negative swab result (p = 0.002), while the lack of neutralizing capacity correlates with an increased risk of a fatal outcome (p = 0.008). Neutralizing antibody titers progressively drop after 5–8 weeks but are still detectable up to 8 months in the majority of recovered patients regardless of age or co-morbidities, with IgG to spike antigens providing the best correlate of neutralization. Antibody responses to seasonal coronaviruses are temporarily boosted, and parallel those to SARS-CoV-2 without dampening the specific response or worsening disease progression. Our results thus suggest compromised immune responses to the SARS-CoV-2 spike to be a major trait of COVID-19 patients with critical conditions, and thereby inform on the planning of COVID-19 patient care and therapy prioritization.
The ubiquitylation of IL-1β limits its cleavage by caspase-1 and targets it for proteasomal degradation
Authors: Vijayaraj Swarna L. , Feltham Rebecca , Rashidi Maryam , Frank Daniel , Liu Zhengyang , Simpson Daniel S. , Ebert Gregor , Vince Angelina , Herold Marco J. , Kueh Andrew , Pearson Jaclyn S. , Dagley Laura F. , Murphy James M. , Webb Andrew I. , Lawlor Kate E. , Vince James E.
Published: May 2021

Interleukin-1β (IL-1β) is activated by inflammasome-associated caspase-1 in rare autoinflammatory conditions and in a variety of other inflammatory diseases. Therefore, IL-1β activity must be fine-tuned to enable anti-microbial responses whilst limiting collateral damage. Here, we show that precursor IL-1β is rapidly turned over by the proteasome and this correlates with its decoration by K11-linked, K63-linked and K48-linked ubiquitin chains. The ubiquitylation of IL-1β is not just a degradation signal triggered by inflammasome priming and activating stimuli, but also limits IL-1β cleavage by caspase-1. IL-1β K133 is modified by ubiquitin and forms a salt bridge with IL-1β D129. Loss of IL-1β K133 ubiquitylation, or disruption of the K133:D129 electrostatic interaction, stabilizes IL-1β. Accordingly, Il1bK133R/K133R mice have increased levels of precursor IL-1β upon inflammasome priming and increased production of bioactive IL-1β, both in vitro and in response to LPS injection. These findings identify mechanisms that can limit IL-1β activity and safeguard against damaging inflammation.
Timescales of the permafrost carbon cycle and legacy effects of temperature overshoot scenarios
Authors: de Vrese Philipp , Brovkin Victor
Published: May 2021

Minimizing the risks and impacts of climate change requires limiting the global temperature increase to 1.5 °C above preindustrial levels, while the difficulty of reducing carbon emissions at the necessary rate increases the likelihood of temporarily overshooting this climate target. Using simulations with the land surface model JSBACH, we show that it takes high-latitude ecosystems and the state of permafrost-affected soils several centuries to adjust to the atmospheric conditions that arise at the 1.5 °C-target. Here, a temporary warming of the Arctic entails important legacy effects and we show that feedbacks between water-, energy- and carbon cycles allow for multiple steady-states in permafrost regions, which differ with respect to the physical state of the soil, the soil carbon concentrations and the terrestrial carbon uptake and -release. The steady-states depend on the soil organic matter content at the point of climate stabilization, which is significantly affected by an overshoot-induced soil carbon loss.
Conformational rearrangement of the NMDA receptor amino-terminal domain during activation and allosteric modulation
Authors: Vyklicky Vojtech , Stanley Cherise , Habrian Chris , Isacoff Ehud Y.
Published: May 2021

N-Methyl-D-aspartate receptors (NMDARs) are ionotropic glutamate receptors essential for synaptic plasticity and memory. Receptor activation involves glycine- and glutamate-stabilized closure of the GluN1 and GluN2 subunit ligand binding domains that is allosterically regulated by the amino-terminal domain (ATD). Using single molecule fluorescence resonance energy transfer (smFRET) to monitor subunit rearrangements in real-time, we observe a stable ATD inter-dimer distance in the Apo state and test the effects of agonists and antagonists. We find that GluN1 and GluN2 have distinct gating functions. Glutamate binding to GluN2 subunits elicits two identical, sequential steps of ATD dimer separation. Glycine binding to GluN1 has no detectable effect, but unlocks the receptor for activation so that glycine and glutamate together drive an altered activation trajectory that is consistent with ATD dimer separation and rotation. We find that protons exert allosteric inhibition by suppressing the glutamate-driven ATD separation steps, and that greater ATD separation translates into greater rotation and higher open probability.
Exotic plants accumulate and share herbivores yet dominate communities via rapid growth
Authors: Allen Warwick J. , Waller Lauren P. , Barratt Barbara I. P. , Dickie Ian A. , Tylianakis Jason M.
Published: May 2021

Herbivores may facilitate or impede exotic plant invasion, depending on their direct and indirect interactions with exotic plants relative to co-occurring natives. However, previous studies investigating direct effects have mostly used pairwise native-exotic comparisons with few enemies, reached conflicting conclusions, and largely overlooked indirect interactions such as apparent competition. Here, we ask whether native and exotic plants differ in their interactions with invertebrate herbivores. We manipulate and measure plant-herbivore and plant-soil biota interactions in 160 experimental mesocosm communities to test several invasion hypotheses. We find that compared with natives, exotic plants support higher herbivore diversity and biomass, and experience larger proportional biomass reductions from herbivory, regardless of whether specialist soil biota are present. Yet, exotics consistently dominate community biomass, likely due to their fast growth rates rather than strong potential to exert apparent competition on neighbors. We conclude that polyphagous invertebrate herbivores are unlikely to play significant direct or indirect roles in mediating plant invasions, especially for fast-growing exotic plants.
Disruption of FOXO3a-miRNA feedback inhibition of IGF2/IGF-1R/IRS1 signaling confers Herceptin resistance in HER2-positive breast cancer
Authors: Luo Liyun , Zhang Zhijie , Qiu Ni , Ling Li , Jia Xiaoting , Song Ying , Li Hongsheng , Li Jiansheng , Lyu Hui , Liu Hao , He Zhimin , Liu Bolin , Zheng Guopei
Published: May 2021

Resistance to Herceptin represents a significant challenge for successful treatment of HER2-positive breast cancer. Here, we show that in Herceptin-sensitive cells, FOXO3a regulates specific miRNAs to control IGF2 and IRS1 expression, retaining basic IGF2/IGF-1R/IRS1 signaling. The basic activity maintains expression of PPP3CB, a subunit of the serine/threonine-protein phosphatase 2B, to restrict FOXO3a phosphorylation (p-FOXO3a), inducing IGF2- and IRS1-targeting miRNAs. However, in Herceptin-resistant cells, p-FOXO3a levels are elevated due to transcriptional suppression of PPP3CB, disrupting the negative feedback inhibition loop formed by FOXO3a and the miRNAs, thereby upregulating IGF2 and IRS1. Moreover, we detect significantly increased IGF2 in blood and IRS1 in the tumors of breast cancer patients with poor response to Herceptin-containing regimens. Collectively, we demonstrate that the IGF2/IGF-1R/IRS1 signaling is aberrantly activated in Herceptin-resistant breast cancer via disruption of the FOXO3a-miRNA negative feedback inhibition. Such insights provide avenues to identify predictive biomarkers and effective strategies overcoming Herceptin resistance.
Protein-based antigen presentation platforms for nanoparticle vaccines
Authors: Nguyen Brian , Tolia Niraj H.
Published: May 2021

Modern vaccine design has sought a minimalization approach, moving to the isolation of antigens from pathogens that invoke a strong neutralizing immune response. This approach has created safer vaccines but may limit vaccine efficacy due to poor immunogenicity. To combat global diseases such as COVID-19, malaria, and AIDS there is a clear urgency for more effective next-generation vaccines. One approach to improve the immunogenicity of vaccines is the use of nanoparticle platforms that present a repetitive array of antigen on its surface. This technology has been shown to improve antigen presenting cell uptake, lymph node trafficking, and B-cell activation through increased avidity and particle size. With a focus on design, we summarize natural platforms, methods of antigen attachment, and advancements in generating self-assembly that have led to new engineered platforms. We further examine critical parameters that will direct the usage and development of more effective platforms.
Mangrove roots model suggest an optimal porosity to prevent erosion
Authors: Kazemi Amirkhosro , Castillo Luciano , Curet Oscar M.
Published: May 2021

Mangrove swamps are extremely productive ecosystems providing many ecological services in coastal regions. The hydrodynamic interactions of mangrove roots and water flow have been proposed as a key element to mitigate erosion. Several studies reveal that precise prediction of the morphological evolution of coastal areas, in the face of global warming and the consequent sea-level rise, requires an understanding of interactions between root porosity (the fraction of the volume of void space over the total volume), water flows, and sediment transport. Water flows around the mangrove prop roots create a complex energetic process that mixes up sediments and generates a depositional region posterior to the roots. In this work, we investigated the boundary layer behind permeable arrays of cylinders (patch) that represent the mangrove roots to explore the impact of patch porosity on the onset of sediment transport. The flow measurements were performed in a vertical plane along the water depth downstream of the mangrove root models. A high-resolution Particle Image Velocimetry (PIV) was used in a flume to observe the impact of porosity on the mean flow, velocity derivatives, skin friction coefficient, and production of turbulent kinetic energy for Reynolds number of 2500 (based on patch diameter length-scale). Here, we proposed a predictive model for critical velocity for incipient motion that takes into account the mangrove roots porosity and the near-bed turbulence effect. It is found that the patch with the $$\phi =47\%$$

ϕ
=
47
%

porosity, has the maximum critical velocity over which the sediment transport initiates. We found the optimum porosity has the minimum sediment erosion and creates negative vorticity sources near the bed that increases the critical velocity. This signifies an optimum porosity for the onset of sediment transport consistent with the porosity of mangroves in nature. The phenomenological model is elucidated based on an analysis of the vorticity evolution equation for viscous incompressible flows. For the optimum porous patch, a sink of vorticity was formed which yielded to lower the near-bed turbulence and vorticity. The minimum velocity fluctuations were sufficient to initiate the boundary layer transition, however, the viscous dissipation dominated the turbulence production to obstruct the sediment transport. This work identified the pivotal role of mangrove root porosity in sediment transport in terms of velocity and its derivatives in wall-bounded flows. Our work also provides insight into the sediment transport and erosion processes that govern the evolution of the shapes of shorelines.
IDH2 mutations in patients with normal karyotype AML predict favorable responses to daunorubicin, cytarabine and cladribine regimen
Authors: Libura Marta , Bialopiotrowicz Emilia , Giebel Sebastian , Wierzbowska Agnieszka , Roboz Gail J. , Piatkowska-Jakubas Beata , Pawelczyk Marta , Gorniak Patryk , Borg Katarzyna , Wojtas Magdalena , Florek Izabella , Matiakowska Karolina , Jazwiec Bozena , Solarska Iwona , Noyszewska-Kania Monika , Piechna Karolina , Zawada Magdalena , Czekalska Sylwia , Salamanczuk Zoriana , Karabin Karolina , Wasilewska Katarzyna , Paluszewska Monika , Urbanowska Elzbieta , Gajkowska-Kulik Justyna , Semenczuk Grazyna , Rybka Justyna , Wrobel Tomasz , Ejduk Anna , Kata Dariusz , Grosicki Sebastian , Robak Tadeusz , Pluta Agnieszka , Kominek Agata , Piwocka Katarzyna , Pyziak Karolina , Sroka-Porada Agnieszka , Wrobel Anna , Przybylowicz Agnieszka , Wojtaszewska Marzena , Lewandowski Krzysztof , Gil Lidia , Piekarska Agnieszka , Knopinska Wanda , Bolkun Lukasz , Warzocha Krzysztof , Kuliczkowski Kazimierz , Sacha Tomasz , Basak Grzegorz , Jedrzejczak Wieslaw Wiktor , Holowiecki Jerzy , Juszczynski Przemysław , Haus Olga
Published: May 2021

Mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) genes occur in about 20% patients with acute myeloid leukemia (AML), leading to DNA hypermethylation and epigenetic deregulation. We assessed the prognostic significance of IDH1/2 mutations (IDH1/2+) in 398 AML patients with normal karyotype (NK-AML), treated with daunorubicine + cytarabine (DA), DA + cladribine (DAC), or DA + fludarabine. IDH2 mutation was an independent favorable prognostic factor for 4-year overall survival (OS) in total NK-AML population (p = 0.03, censoring at allotransplant). We next evaluated the effect of addition of cladribine to induction regimen on the patients’ outcome according to IDH1/2 mutation status. In DAC group, 4-year OS was increased in IDH2+ patients, compared to IDH-wild type group (54% vs 33%; p = 0.0087, censoring at allotransplant), while no difference was observed for DA-treated subjects. In multivariate analysis, DAC independently improved the survival of IDH2+ patients (HR = 0.6 [0.37–0.93]; p = 0.024; censored at transplant), indicating that this group specifically benefits from cladribine-containing therapy. In AML cells with R140Q or R172K IDH2 mutations, cladribine restrained mutations-related DNA hypermethylation. Altogether, DAC regimen produces better outcomes in IDH2+ NK-AML patients than DA, and this likely results from the hypomethylating activity of cladribine. Our observations warrant further investigations of induction protocols combining cladribine with IDH1/2 inhibitors in IDH2-mutant.
Combining radiomic phenotypes of non-small cell lung cancer with liquid biopsy data may improve prediction of response to EGFR inhibitors
Authors: Yousefi Bardia , LaRiviere Michael J. , Cohen Eric A. , Buckingham Thomas H. , Yee Stephanie S. , Black Taylor A. , Chien Austin L. , Noël Peter , Hwang Wei-Ting , Katz Sharyn I. , Aggarwal Charu , Thompson Jeffrey C. , Carpenter Erica L. , Kontos Despina
Published: May 2021

Among non-small cell lung cancer (NSCLC) patients with therapeutically targetable tumor mutations in epidermal growth factor receptor (EGFR), not all patients respond to targeted therapy. Combining circulating-tumor DNA (ctDNA), clinical variables, and radiomic phenotypes may improve prediction of EGFR-targeted therapy outcomes for NSCLC. This single-center retrospective study included 40 EGFR-mutant advanced NSCLC patients treated with EGFR-targeted therapy. ctDNA data included number of mutations and detection of EGFR T790M. Clinical data included age, smoking status, and ECOG performance status. Baseline chest CT scans were analyzed to extract 429 radiomic features from each primary tumor. Unsupervised hierarchical clustering was used to group tumors into phenotypes. Kaplan–Meier (K–M) curves and Cox proportional hazards regression were modeled for progression-free survival (PFS) and overall survival (OS). Likelihood ratio test (LRT) was used to compare fit between models. Among 40 patients (73% women, median age 62 years), consensus clustering identified two radiomic phenotypes. For PFS, the model combining radiomic phenotypes with ctDNA and clinical variables had c-statistic of 0.77 and a better fit (LRT p = 0.01) than the model with clinical and ctDNA variables alone with a c-statistic of 0.73. For OS, adding radiomic phenotypes resulted in c-statistic of 0.83 versus 0.80 when using clinical and ctDNA variables (LRT p = 0.08). Both models showed separation of K–M curves dichotomized by median prognostic score (p < 0.005). Combining radiomic phenotypes, ctDNA, and clinical variables may enhance precision oncology approaches to managing advanced non-small cell lung cancer with EGFR mutations.
Hemiacetal-less rapamycin derivatives designed and produced by genetic engineering of a type I polyketide synthase
Authors: Kudo Kei , Nishimura Takehiro , Kozone Ikuko , Hashimoto Junko , Kagaya Noritaka , Suenaga Hikaru , Ikeda Haruo , Shin-ya Kazuo
Published: May 2021

Engineering polyketide synthases is one of the most promising ways of producing a variety of polyketide derivatives. Exploring the undiscovered chemical space of this medicinally important class of middle molecular weight natural products will aid in the development of improved drugs in the future. In previous work, we established methodology designated ‘module editing’ to precisely manipulate polyketide synthase genes cloned in a bacterial artificial chromosome. Here, in the course of investigating the engineering capacity of the rapamycin PKS, novel rapamycin derivatives 1–4, which lack the hemiacetal moiety, were produced through the heterologous expression of engineered variants of the rapamycin PKS. Three kinds of module deletions in the polyketide synthase RapC were designed, and the genetically engineered vectors were prepared by the in vitro module editing technique. Streptomyces avermitilis SUKA34 transformed with these edited PKSs produced new rapamycin derivatives. The planar structures of 1–4 established based on 1D and 2D NMR, ESI–TOF–MS and UV spectra revealed that 2 and 3 had skeletons well-matched to the designs, but 1 and 4 did not. The observations provide important insights into the mechanisms of the later steps of rapamycin skeletal formation as well as the ketone-forming oxygenase RapJ.
Delineating visual, auditory and motor regions in the human brain with functional neuroimaging: a BrainMap-based meta-analytic synthesis
Authors: Heckner Marisa K. , Cieslik Edna C. , Küppers Vincent , Fox Peter T. , Eickhoff Simon B. , Langner Robert
Published: May 2021

Most everyday behaviors and laboratory tasks rely on visual, auditory and/or motor-related processes. Yet, to date, there has been no large-scale quantitative synthesis of functional neuroimaging studies mapping the brain regions consistently recruited during such perceptuo-motor processing. We therefore performed three coordinate-based meta-analyses, sampling the results of neuroimaging experiments on visual (n = 114), auditory (n = 122), or motor-related (n = 251) processing, respectively, from the BrainMap database. Our analyses yielded both regions known to be recruited for basic perceptual or motor processes and additional regions in posterior frontal cortex. Comparing our results with data-driven network definitions based on resting-state functional connectivity revealed good overlap in expected regions but also showed that perceptual and motor task-related activations consistently involve additional frontal, cerebellar, and subcortical areas associated with “higher-order” cognitive functions, extending beyond what is captured when the brain is at “rest.” Our resulting sets of domain-typical brain regions can be used by the neuroimaging community as robust functional definitions or masks of regions of interest when investigating brain correlates of perceptual or motor processes and their interplay with other mental functions such as cognitive control or affective processing. The maps are made publicly available via the ANIMA database.
A new approach to radon temporal correction factor based on active environmental monitoring devices
Authors: Dicu T. , Burghele B. D. , Botoş M. , Cucoș A. , Dobrei G. , Florică Ș. , Grecu Ș. , Lupulescu A. , Pap I. , Szacsvai K. , Țenter A. , Sainz C.
Published: May 2021

The present study aims to identify novel means of increasing the accuracy of the estimated annual indoor radon concentration based on the application of temporal correction factors to short-term radon measurements. The necessity of accurate and more reliable temporal correction factors is in high demand, in the present age of speed. In this sense, radon measurements were continuously carried out, using a newly developed smart device accompanied by CR-39 detectors, for one full year, in 71 residential buildings located in 5 Romanian cities. The coefficient of variation for the temporal correction factors calculated for combinations between the start month and the duration of the measurement presented a low value (less than 10%) for measurements longer than 7 months, while a variability close to 20% can be reached by measurements of up to 4 months. Results obtained by generalized estimating equations indicate that average temporal correction factors are positively associated with CO2 ratio, as well as the interaction between this parameter and the month in which the measurement took place. The impact of the indoor-outdoor temperature differences was statistically insignificant. The obtained results could represent a reference point in the elaboration of new strategies for calculating the temporal correction factors and, consequently, the reduction of the uncertainties related to the estimation of the annual indoor radon concentration.