bluuebunny/crossref_metadata_2025 huggingface dataset:
Contribution of tree community structure to forest productivity across a thermal gradient in eastern Asia
Authors: Kohyama Tetsuo I. , Sheil Douglas , Sun I-Fang , Niiyama Kaoru , Suzuki Eizi , Hiura Tsutom , Nishimura Naoyuki , Hoshizaki Kazuhiko , Wu Shu-Hui , Chao Wei-Chun , Nur Hajar Zamah S. , Rahajoe Joeni S. , Kohyama Takashi S.
Published: March 2023

Despite their fundamental importance the links between forest productivity, diversity and climate remain contentious. We consider whether variation in productivity across climates reflects adjustment among tree species and individuals, or changes in tree community structure. We analysed data from 60 plots of humid old-growth forests spanning mean annual temperatures (MAT) from 2.0 to 26.6 °C. Comparing forests at equivalent aboveground biomass (160 Mg C ha–1), tropical forests ≥24 °C MAT averaged more than double the aboveground woody productivity of forests <12 °C (3.7 ± 0.3 versus 1.6 ± 0.1 Mg C ha–1 yr–1). Nonetheless, species with similar standing biomass and maximum stature had similar productivity across plots regardless of temperature. We find that differences in the relative contribution of smaller- and larger-biomass species explained 86% of the observed productivity differences. Species-rich tropical forests are more productive than other forests due to the high relative productivity of many short-stature, small-biomass species.
Snapshots of the second-step self-splicing of Tetrahymena ribozyme revealed by cryo-EM
Authors: Li Shanshan , Palo Michael Z. , Zhang Xiaojing , Pintilie Grigore , Zhang Kaiming
Published: March 2023

Group I introns are catalytic RNAs that coordinate two consecutive transesterification reactions for self-splicing. To understand how the group I intron promotes catalysis and coordinates self-splicing reactions, we determine the structures of L-16 Tetrahymena ribozyme in complex with a 5′-splice site analog product and a 3′-splice site analog substrate using cryo-EM. We solve six conformations from a single specimen, corresponding to different splicing intermediates after the first ester-transfer reaction. The structures reveal dynamics during self-splicing, including large conformational changes of the internal guide sequence and the J5/4 junction as well as subtle rearrangements of active-site metals and the hydrogen bond formed between the 2′-OH group of A261 and the N2 group of guanosine substrate. These results help complete a detailed structural and mechanistic view of this paradigmatic group I intron undergoing the second step of self-splicing.
MicroRNA156 conditions auxin sensitivity to enable growth plasticity in response to environmental changes in Arabidopsis
Authors: Sang Qing , Fan Lusheng , Liu Tianxiang , Qiu Yongjian , Du Juan , Mo Beixin , Chen Meng , Chen Xuemei
Published: March 2023

MicroRNAs (miRNAs) play diverse roles in plant development, but whether and how miRNAs participate in thermomorphogenesis remain ambiguous. Here we show that HYPONASTIC LEAVES 1 (HYL1)—a key component of miRNA biogenesis—acts downstream of the thermal regulator PHYTOCHROME INTERACTING FACTOR 4 in the temperature-dependent plasticity of hypocotyl growth inArabidopsis. Ahyl1-2suppressor screen identified a dominantdicer-like1allele that rescueshyl1-2’s defects in miRNA biogenesis and thermoresponsive hypocotyl elongation. Genome-wide miRNA and transcriptome analysis revealed microRNA156 (miR156) and its targetSQUAMOSA PROMOTER-BINDING-PROTEIN-LIKE 9(SPL9) to be critical regulators of thermomorphogenesis. Surprisingly, perturbation of the miR156/SPL9module disengages seedling responsiveness to warm temperatures by impeding auxin sensitivity. Moreover, miR156-dependent auxin sensitivity also operates in the shade avoidance response at lower temperatures. Thus, these results unveil the miR156/SPL9module as a previously uncharacterized genetic circuit that enables plant growth plasticity in response to environmental temperature and light changes.
SAPS3 subunit of protein phosphatase 6 is an AMPK inhibitor and controls metabolic homeostasis upon dietary challenge in male mice
Authors: Yang Ying , Reid Michael A. , Hanse Eric A. , Li Haiqing , Li Yuanding , Ruiz Bryan I. , Fan Qi , Kong Mei
Published: March 2023

Inhibition of AMPK is tightly associated with metabolic perturbations upon over nutrition, yet the molecular mechanisms underlying are not clear. Here, we demonstrate the serine/threonine-protein phosphatase 6 regulatory subunit 3, SAPS3, is a negative regulator of AMPK. SAPS3 is induced under high fat diet (HFD) and recruits the PP6 catalytic subunit to deactivate phosphorylated-AMPK, thereby inhibiting AMPK-controlled metabolic pathways. Either whole-body or liver-specific deletion of SAPS3 protects male mice against HFD-induced detrimental consequences and reverses HFD-induced metabolic and transcriptional alterations while loss of SAPS3 has no effects on mice under balanced diets. Furthermore, genetic inhibition of AMPK is sufficient to block the protective phenotype in SAPS3 knockout mice under HFD. Together, our results reveal that SAPS3 is a negative regulator of AMPK and suppression of SAPS3 functions as a guardian when metabolism is perturbed and represents a potential therapeutic strategy to treat metabolic syndromes.
2019 M7.1 Ridgecrest earthquake slip distribution controlled by fault geometry inherited from Independence dike swarm
Authors: Nevitt Johanna M. , Brooks Benjamin A. , Hardebeck Jeanne L. , Aagaard Brad T.
Published: March 2023

Faults often form through reactivation of pre-existing structures, developing geometries and mechanical properties specific to the system’s geologic inheritance. Competition between fault geometry and other factors (e.g., lithology) to control slip at Earth’s surface is an open question that is central to our knowledge of fault processes and seismic hazards. Here we use remote sensing data and field observations to investigate the origin of the 2019 M7.1 Ridgecrest, California, earthquake rupture geometry and test its impact on the slip distribution observed at Earth’s surface. Common geometries suggest the fault system evolved through reactivation of structures within the surrounding Independence dike swarm (IDS). Mechanical models testing a range of fault geometries and stress fields indicate that the inherited rupture geometry strongly controlled the M7.1 earthquake slip distribution. These results motivate revisiting the development of other large-magnitude earthquake ruptures (1992 M7.3 Landers, 1999 M7.1 Hector Mine) and tectonic provinces within the IDS.
Creating complex protocells and prototissues using simple DNA building blocks
Authors: Arulkumaran Nishkantha , Singer Mervyn , Howorka Stefan , Burns Jonathan R.
Published: March 2023

Building synthetic protocells and prototissues hinges on the formation of biomimetic skeletal frameworks. Recreating the complexity of cytoskeletal and exoskeletal fibers, with their widely varying dimensions, cellular locations and functions, represents a major material hurdle and intellectual challenge which is compounded by the additional demand of using simple building blocks to ease fabrication and control. Here we harness simplicity to create complexity by assembling structural frameworks from subunits that can support membrane-based protocells and prototissues. We show that five oligonucleotides can anneal into nanotubes or fibers whose tunable thicknesses and lengths spans four orders of magnitude. We demonstrate that the assemblies’ location inside protocells is controllable to enhance their mechanical, functional and osmolar stability. Furthermore, the macrostructures can coat the outside of protocells to mimic exoskeletons and support the formation of millimeter-scale prototissues. Our strategy could be exploited in the bottom-up design of synthetic cells and tissues, to the generation of smart material devices in medicine.
Real-time single-molecule 3D tracking in E. coli based on cross-entropy minimization
Authors: Amselem Elias , Broadwater Bo , Hävermark Tora , Johansson Magnus , Elf Johan
Published: March 2023

Reaching sub-millisecond 3D tracking of individual molecules in living cells would enable direct measurements of diffusion-limited macromolecular interactions under physiological conditions. Here, we present a 3D tracking principle that approaches the relevant regime. The method is based on the true excitation point spread function and cross-entropy minimization for position localization of moving fluorescent reporters. Tests on beads moving on a stage reaches 67 nm lateral and 109 nm axial precision with a time resolution of 0.84 ms at a photon count rate of 60 kHz; the measurements agree with the theoretical and simulated predictions. Our implementation also features a method for microsecond 3D PSF positioning and an estimator for diffusion analysis of tracking data. Finally, we successfully apply these methods to track the Trigger Factor protein in living bacterial cells. Overall, our results show that while it is possible to reach sub-millisecond live-cell single-molecule tracking, it is still hard to resolve state transitions based on diffusivity at this time scale.
Higher productivity in forests with mixed mycorrhizal strategies
Authors: Luo Shan , Phillips Richard P. , Jo Insu , Fei Songlin , Liang Jingjing , Schmid Bernhard , Eisenhauer Nico
Published: March 2023

Decades of theory and empirical studies have demonstrated links between biodiversity and ecosystem functioning, yet the putative processes that underlie these patterns remain elusive. This is especially true for forest ecosystems, where the functional traits of plant species are challenging to quantify. We analyzed 74,563 forest inventory plots that span 35 ecoregions in the contiguous USA and found that in ~77% of the ecoregions mixed mycorrhizal plots were more productive than plots where either arbuscular or ectomycorrhizal fungal-associated tree species were dominant. Moreover, the positive effects of mixing mycorrhizal strategies on forest productivity were more pronounced at low than high tree species richness. We conclude that at low richness different mycorrhizal strategies may allow tree species to partition nutrient uptake and thus can increase community productivity, whereas at high richness other dimensions of functional diversity can enhance resource partitioning and community productivity. Our findings highlight the importance of mixed mycorrhizal strategies, in addition to that of taxonomic diversity in general, for maintaining ecosystem functioning in forests.
Biased IL-2 signals induce Foxp3-rich pulmonary lymphoid structures and facilitate long-term lung allograft acceptance in mice
Authors: Yamada Yoshito , Nguyen Tuan Thanh , Impellizzieri Daniela , Mineura Katsutaka , Shibuya Rintaro , Gomariz Alvaro , Haberecker Martina , Nilsson Jakob , Nombela-Arrieta César , Jungraithmayr Wolfgang , Boyman Onur
Published: March 2023

Transplantation of solid organs can be life-saving in patients with end-stage organ failure, however, graft rejection remains a major challenge. In this study, by pre-conditioning with interleukin-2 (IL-2)/anti-IL-2 antibody complex treatment biased toward IL-2 receptor α, we achieved acceptance of fully mismatched orthotopic lung allografts that remained morphologically and functionally intact for more than 90 days in immunocompetent mice. These allografts are tolerated by the actions of forkhead box p3 (Foxp3)+ regulatory T (Treg) cells that home to the lung allografts. Although counts of circulating Treg cells rapidly return to baseline following cessation of IL-2 treatment, Foxp3+ Treg cells persist in peribronchial and peribronchiolar areas of the grafted lungs, forming organized clusters reminiscent of inducible tertiary lymphoid structures (iTLS). These iTLS in lung allografts are made of Foxp3+ Treg cells, conventional T cells, and B cells, as evidenced by using microscopy-based distribution and neighborhood analyses. Foxp3-transgenic mice with inducible and selective deletion of Foxp3+ cells are unable to form iTLS in lung allografts, and these mice acutely reject lung allografts. Collectively, we report that short-term, high-intensity and biased IL-2 pre-conditioning facilitates acceptance of vascularized and ventilated lung allografts without the need of immunosuppression, by inducing Foxp3-controlled iTLS formation within allografts.
A phase I open-label clinical trial to study drug-drug interactions of Dorzagliatin and Sitagliptin in patients with type 2 diabetes and obesity
Authors: Chen Li , Zhang Jiayi , Sun Yu , Zhao Yu , Liu Xiang , Fang Zhiyin , Feng Lingge , He Bin , Zou Quanfei , Tracey Gregory J.
Published: March 2023

This is a phase 1, open-label, single-sequence, multiple-dose, single-center trial conducted in the US (NCT03790839), to evaluate the clinical pharmacokinetics, safety and pharmacodynamics of dorzagliatin co-administered with sitagliptin in patients with T2D and obesity. The trial has completed. 15 patients with T2D and obesity were recruited and treated with sitagliptin 100 mg QD on Day 1-5, followed by a combination of sitagliptin 100 mg QD with dorzagliatin 75 mg BID at second stage on Day 6-10 and the third stage of dorzagliatin 75 mg BID alone on Day 11-15. Primary outcomes include pharmacokinetic geometric mean ratio (GMR), safety and tolerability. Secondary outcomes include the incremental area under the curve for 4 hours post oral glucose tolerance test (iAUC) of pharmacodynamic biomarkers and glucose sensitivity. GMR for AUC0-24h and Cmax were 92.63 (90% CI, 85.61, 100.22) and 98.14 (90% CI, 83.73, 115.03) in combination/sitagliptin, and 100.34 (90% CI, 96.08, 104.79) and 102.34 (90% CI, 86.92, 120.50) in combination/dorzagliatin, respectively. Combination treatment did not increase the adverse events and well-tolerated in T2D patients. Lack of clinically meaningful pharmacokinetic interactions between dorzagliatin and sitagliptin, and an improvement of glycemic control under combination potentially support their co-administration for diabetes management.
Perovskite quantum dot one-dimensional topological laser
Authors: Tian Jingyi , Tan Qi Ying , Wang Yutao , Yang Yihao , Yuan Guanghui , Adamo Giorgio , Soci Cesare
Published: March 2023

Various topological laser concepts have recently enabled the demonstration of robust light-emitting devices that are immune to structural deformations and tolerant to fabrication imperfections. Current realizations of photonic cavities with topological boundaries are often limited by outcoupling issues or poor directionality and require complex design and fabrication that hinder operation at small wavelengths. Here we propose a topological cavity design based on interface states between two one-dimensional photonic crystals with distinct Zak phases. Using a few monolayers of solution-processed all-inorganic cesium lead halide perovskite quantum dots as the ultrathin gain medium, we demonstrate a lithography-free, vertical-emitting, low-threshold, and single-mode laser emitting in the green. We show that the topological laser, akin to vertical-cavity surface-emitting lasers (VCSELs), is robust against local perturbations of the multilayer structure. We argue that the design simplicity and reduction of the gain medium thickness enabled by the topological cavity make this architecture suitable for low-cost and efficient quantum dot vertical emitting lasers operating across the visible spectral region.
Evidence-based guidance on reflective pavement for urban heat mitigation in Arizona
Authors: Schneider Florian A. , Ortiz Johny Cordova , Vanos Jennifer K. , Sailor David J. , Middel Ariane
Published: March 2023

Urban overheating is an increasing threat to people, infrastructure, and the environment. Common heat mitigation strategies, such as green infrastructure, confront space limitations in current car-centric cities. In 2020, the City of Phoenix, Arizona, piloted a “cool pavement” program using a solar reflective pavement seal on 58 km of residential streets. Comprehensive micrometeorological observations are used to evaluate the cooling potential of the reflective pavement based on three heat exposure metrics—surface, air, and mean radiant temperatures—across three residential reflective pavement-treated and untreated neighborhoods. In addition, the solar reflectivity of reflective pavement is observed over 7 months across eight residential neighborhoods. Results are synthesized with the literature to provide context-based reflective pavement implementation guidelines to mitigate urban overheating where common strategies cannot be applied. The three most important contextual factors to consider for effective implementation include urban location, background climate type, and heat exposure metric of interest.
Indoor air surveillance and factors associated with respiratory pathogen detection in community settings in Belgium
Authors: Raymenants Joren , Geenen Caspar , Budts Lore , Thibaut Jonathan , Thijssen Marijn , De Mulder Hannelore , Gorissen Sarah , Craessaerts Bastiaan , Laenen Lies , Beuselinck Kurt , Ombelet Sien , Keyaerts Els , André Emmanuel
Published: March 2023

Currently, the real-life impact of indoor climate, human behaviour, ventilation and air filtration on respiratory pathogen detection and concentration are poorly understood. This hinders the interpretability of bioaerosol quantification in indoor air to surveil respiratory pathogens and transmission risk. We tested 341 indoor air samples from 21 community settings in Belgium for 29 respiratory pathogens using qPCR. On average, 3.9 pathogens were positive per sample and 85.3% of samples tested positive for at least one. Pathogen detection and concentration varied significantly by pathogen, month, and age group in generalised linear (mixed) models and generalised estimating equations. High CO2 and low natural ventilation were independent risk factors for detection. The odds ratio for detection was 1.09 (95% CI 1.03–1.15) per 100 parts per million (ppm) increase in CO2, and 0.88 (95% CI 0.80–0.97) per stepwise increase in natural ventilation (on a Likert scale). CO2 concentration and portable air filtration were independently associated with pathogen concentration. Each 100ppm increase in CO2 was associated with a qPCR Ct value decrease of 0.08 (95% CI −0.12 to −0.04), and portable air filtration with a 0.58 (95% CI 0.25–0.91) increase. The effects of occupancy, sampling duration, mask wearing, vocalisation, temperature, humidity and mechanical ventilation were not significant. Our results support the importance of ventilation and air filtration to reduce transmission.
Pan-genome inversion index reveals evolutionary insights into the subpopulation structure of Asian rice
Authors: Zhou Yong , Yu Zhichao , Chebotarov Dmytro , Chougule Kapeel , Lu Zhenyuan , Rivera Luis F. , Kathiresan Nagarajan , Al-Bader Noor , Mohammed Nahed , Alsantely Aseel , Mussurova Saule , Santos João , Thimma Manjula , Troukhan Maxim , Fornasiero Alice , Green Carl D. , Copetti Dario , Kudrna David , Llaca Victor , Lorieux Mathias , Zuccolo Andrea , Ware Doreen , McNally Kenneth , Zhang Jianwei , Wing Rod A.
Published: March 2023

Understanding and exploiting genetic diversity is a key factor for the productive and stable production of rice. Here, we utilize 73 high-quality genomes that encompass the subpopulation structure of Asian rice (Oryza sativa), plus the genomes of two wild relatives (O. rufipogonandO. punctata), to build a pan-genome inversion index of 1769 non-redundant inversions that span an average of ~29% of theO. sativacv. Nipponbare reference genome sequence. Using this index, we estimate an inversion rate of ~700 inversions per million years in Asian rice, which is 16 to 50 times higher than previously estimated for plants. Detailed analyses of these inversions show evidence of their effects on gene expression, recombination rate, and linkage disequilibrium. Our study uncovers the prevalence and scale of large inversions (≥100 bp) across the pan-genome of Asian rice and hints at their largely unexplored role in functional biology and crop performance.
Hybrid spin Hall nano-oscillators based on ferromagnetic metal/ferrimagnetic insulator heterostructures
Authors: Ren Haowen , Zheng Xin Yu , Channa Sanyum , Wu Guanzhong , O’Mahoney Daisy A. , Suzuki Yuri , Kent Andrew D.
Published: March 2023

Spin-Hall nano-oscillators (SHNOs) are promising spintronic devices to realize current controlled GHz frequency signals in nanoscale devices for neuromorphic computing and creating Ising systems. However, traditional SHNOs devices based on transition metals have high auto-oscillation threshold currents as well as low quality factors and output powers. Here we demonstrate a new type of hybrid SHNO based on a permalloy (Py) ferromagnetic-metal nanowire and low-damping ferrimagnetic insulator, in the form of epitaxial lithium aluminum ferrite (LAFO) thin films. The superior characteristics of such SHNOs are associated with the excitation of larger spin-precession angles and volumes. We further find that the presence of the ferrimagnetic insulator enhances the auto-oscillation amplitude of spin-wave edge modes, consistent with our micromagnetic modeling. This hybrid SHNO expands spintronic applications, including providing new means of coupling multiple SHNOs for neuromorphic computing and advancing magnonics.
An in-solution snapshot of SARS-COV-2 main protease maturation process and inhibition
Authors: Noske Gabriela Dias , Song Yun , Fernandes Rafaela Sachetto , Chalk Rod , Elmassoudi Haitem , Koekemoer Lizbé , Owen C. David , El-Baba Tarick J. , Robinson Carol V. ,   The COVID Moonshot Consortium, Oliva Glaucius , Godoy Andre Schutzer
Published: March 2023

The main protease from SARS-CoV-2 (Mpro) is responsible for cleavage of the viral polyprotein. Mpro self-processing is called maturation, and it is crucial for enzyme dimerization and activity. Here we use C145S Mpro to study the structure and dynamics of N-terminal cleavage in solution. Native mass spectroscopy analysis shows that mixed oligomeric states are composed of cleaved and uncleaved particles, indicating that N-terminal processing is not critical for dimerization. A 3.5 Å cryo-EM structure provides details of Mpro N-terminal cleavage outside the constrains of crystal environment. We show that different classes of inhibitors shift the balance between oligomeric states. While non-covalent inhibitor MAT-POS-e194df51-1 prevents dimerization, the covalent inhibitor nirmatrelvir induces the conversion of monomers into dimers, even with intact N-termini. Our data indicates that the Mpro dimerization is triggered by induced fit due to covalent linkage during substrate processing rather than the N-terminal processing.
The Torreya grandis genome illuminates the origin and evolution of gymnosperm-specific sciadonic acid biosynthesis
Authors: Lou Heqiang , Song Lili , Li Xiaolong , Zi Hailing , Chen Weijie , Gao Yadi , Zheng Shan , Fei Zhangjun , Sun Xuepeng , Wu Jiasheng
Published: March 2023

Torreya plants produce dry fruits with assorted functions. Here, we report the 19-Gb chromosome-level genome assembly of T. grandis. The genome is shaped by ancient whole-genome duplications and recurrent LTR retrotransposon bursts. Comparative genomic analyses reveal key genes involved in reproductive organ development, cell wall biosynthesis and seed storage. Two genes encoding a C18 Δ9-elongase and a C20 Δ5-desaturase are identified to be responsible for sciadonic acid biosynthesis and both are present in diverse plant lineages except angiosperms. We demonstrate that the histidine-rich boxes of the Δ5-desaturase are crucial for its catalytic activity. Methylome analysis reveals that methylation valleys of the T. grandis seed genome harbor genes associated with important seed activities, including cell wall and lipid biosynthesis. Moreover, seed development is accompanied by DNA methylation changes that possibly fuel energy production. This study provides important genomic resources and elucidates the evolutionary mechanism of sciadonic acid biosynthesis in land plants.
Association of SARS-CoV-2 BA.4/BA.5 Omicron lineages with immune escape and clinical outcome
Authors: Lewnard Joseph A. , Hong Vennis , Kim Jeniffer S. , Shaw Sally F. , Lewin Bruno , Takhar Harpreet , Tartof Sara Y.
Published: March 2023

Expansion of the SARS-CoV-2 BA.4 and BA.5 Omicron subvariants in populations with prevalent immunity from prior infection and vaccination, and associated burden of severe COVID-19, has raised concerns about epidemiologic characteristics of these lineages including their association with immune escape or severe clinical outcomes. Here we show that BA.4/BA.5 cases in a large US healthcare system had at least 55% (95% confidence interval: 43–69%) higher adjusted odds of prior documented infection than time-matched BA.2 cases, as well as 15% (9–21%) and 38% (27–49%) higher adjusted odds of having received 3 and ≥4 COVID-19 vaccine doses, respectively. However, after adjusting for differences in epidemiologic characteristics among cases with each lineage, BA.4/BA.5 infection was not associated with differential risk of emergency department presentation, hospital admission, or intensive care unit admission following an initial outpatient diagnosis. This finding held in sensitivity analyses correcting for potential exposure misclassification resulting from unascertained prior infections. Our results demonstrate that the reduced severity associated with prior (BA.1 and BA.2) Omicron lineages, relative to the Delta variant, has persisted with BA.4/BA.5, despite the association of BA.4/BA.5 with increased risk of breakthrough infection among previously vaccinated or infected individuals.
PIP4K2B is mechanoresponsive and controls heterochromatin-driven nuclear softening through UHRF1
Authors: Poli Alessandro , Pennacchio Fabrizio A. , Ghisleni Andrea , di Gennaro Mariagrazia , Lecacheur Margaux , Nastały Paulina , Crestani Michele , Pramotton Francesca M. , Iannelli Fabio , Beznusenko Galina , Mironov Alexander A. , Panzetta Valeria , Fusco Sabato , Sheth Bhavwanti , Poulikakos Dimos , Ferrari Aldo , Gauthier Nils , Netti Paolo A. , Divecha Nullin , Maiuri Paolo
Published: March 2023

Phosphatidylinositol-5-phosphate (PtdIns5P)−4-kinases (PIP4Ks) are stress-regulated phosphoinositide kinases able to phosphorylate PtdIns5P to PtdIns(4,5)P2. In cancer patients their expression is typically associated with bad prognosis. Among the three PIP4K isoforms expressed in mammalian cells, PIP4K2B is the one with more prominent nuclear localisation. Here, we unveil the role of PIP4K2B as a mechanoresponsive enzyme. PIP4K2B protein level strongly decreases in cells growing on soft substrates. Its direct silencing or pharmacological inhibition, mimicking cell response to softness, triggers a concomitant reduction of the epigenetic regulator UHRF1 and induces changes in nuclear polarity, nuclear envelope tension and chromatin compaction. This substantial rewiring of the nucleus mechanical state drives YAP cytoplasmic retention and impairment of its activity as transcriptional regulator, finally leading to defects in cell spreading and motility. Since YAP signalling is essential for initiation and growth of human malignancies, our data suggest that potential therapeutic approaches targeting PIP4K2B could be beneficial in the control of the altered mechanical properties of cancer cells.
Genesis of Hawaiian lavas by crystallization of picritic magma in the deep mantle
Authors: Yang Junlong , Wang Chao , Zhang Junfeng , Jin Zhenmin
Published: March 2023

Olivine is the dominant phenocryst or xenocryst of Hawaiian tholeiitic basalts, and the general consensus is that lavas with MgO concentrations from 7.5 to about 15 weight percent were derived from their primary magmas, which contain ~18–20 weight percent MgO, by only olivine crystallization. However, the major element composition of estimated primary magmas through olivine crystallization correction is inconsistent with direct partial melting of either mantle peridotite or its hybrid with subducted oceanic crust. Our melting experiments on peridotite-derived melt composition show that this discrepancy can be resolved if the primary magmas experienced two other processes before abundant olivine fractionation. First, the primary magmas experienced crystallization of clinopyroxene and garnet in the chamber at the base of the lithosphere (approximately the depths of 90–100 km). Second, the evolved magmas re-equilibrated with harzburgite when passing through the lithospheric mantle (approximately the depths of 60–10 km). Different from the isotopic evidence, the major and rare earth element compositions of Hawaiian post-shield alkali basalts and shield tholeiites suggest that they form from the same source by assimilating different amounts of orthopyroxene.
RETRACTED ARTICLE: Polymerase θ inhibition activates the cGAS-STING pathway and cooperates with immune checkpoint blockade in models of BRCA-deficient cancer
Authors: Patterson-Fortin Jeffrey , Jadhav Heta , Pantelidou Constantia , Phan Tin , Grochala Carter , Mehta Anita K. , Guerriero Jennifer L. , Wulf Gerburg M. , Wolpin Brian M. , Stanger Ben Z. , Aguirre Andrew J. , Cleary James M. , D’Andrea Alan D. , Shapiro Geoffrey I.
Published: March 2023

Recently developed inhibitors of polymerase theta (POLθ) have demonstrated synthetic lethality in BRCA-deficient tumor models. To examine the contribution of the immune microenvironment to antitumor efficacy, we characterized the effects of POLθ inhibition in immunocompetent models of BRCA1-deficient triple-negative breast cancer (TNBC) or BRCA2-deficient pancreatic ductal adenocarcinoma (PDAC). We demonstrate that genetic POLQ depletion or pharmacological POLθ inhibition induces both innate and adaptive immune responses in these models. POLθ inhibition resulted in increased micronuclei, cGAS/STING pathway activation, type I interferon gene expression, CD8+ T cell infiltration and activation, local paracrine activation of dendritic cells and upregulation of PD-L1 expression. Depletion of CD8+ T cells compromised the efficacy of POLθ inhibition, whereas antitumor effects were augmented in combination with anti-PD-1 immunotherapy. Collectively, our findings demonstrate that POLθ inhibition induces immune responses in a cGAS/STING-dependent manner and provide a rationale for combining POLθ inhibition with immune checkpoint blockade for the treatment of HR-deficient cancers.
Conformational transitions and allosteric modulation in a heteromeric glycine receptor
Authors: Gibbs Eric , Klemm Emily , Seiferth David , Kumar Arvind , Ilca Serban L. , Biggin Philip C. , Chakrapani Sudha
Published: March 2023

Glycine Receptors (GlyRs) provide inhibitory neuronal input in the spinal cord and brainstem, which is critical for muscle coordination and sensory perception. Synaptic GlyRs are a heteromeric assembly of α and β subunits. Here we present cryo-EM structures of full-length zebrafish α1βBGlyR in the presence of an antagonist (strychnine), agonist (glycine), or agonist with a positive allosteric modulator (glycine/ivermectin). Each structure shows a distinct pore conformation with varying degrees of asymmetry. Molecular dynamic simulations found the structures were in a closed (strychnine) and desensitized states (glycine and glycine/ivermectin). Ivermectin binds at all five interfaces, but in a distinct binding pose at the β-α interface. Subunit-specific features were sufficient to solve structures without a fiduciary marker and to confirm the 4α:1β stoichiometry recently observed. We also report features of the extracellular and intracellular domains. Together, our results show distinct compositional and conformational properties of α1βGlyR and provide a framework for further study of this physiologically important channel.
High thermoelectric efficiency realized in SnSe crystals via structural modulation
Authors: Qin Bingchao , Wang Dongyang , Hong Tao , Wang Yuping , Liu Dongrui , Wang Ziyuan , Gao Xiang , Ge Zhen-Hua , Zhao Li-Dong
Published: March 2023

Crystalline thermoelectrics have been developed to be potential candidates for power generation and electronic cooling, among which SnSe crystals are becoming the most representative. Herein, we realize high-performance SnSe crystals with promising efficiency through a structural modulation strategy. By alloying strontium at Sn sites, we modify the crystal structure and facilitate the multiband synglisis in p-type SnSe, favoring the optimization of interactive parameters μ and m*. Resultantly, we obtain a significantly enhanced PF ~85 μW cm−1 K−2, with an ultrahigh ZT ~1.4 at 300 K and ZTave ~2.0 among 300–673 K. Moreover, the excellent properties lead to single-leg device efficiency of ~8.9% under a temperature difference ΔT ~300 K, showing superiority among the current low- to mid-temperature thermoelectrics, with an enhanced cooling ΔTmax of ~50.4 K in the 7-pair thermoelectric device. Our study further advances p-type SnSe crystals for practical waste heat recovery and electronic cooling.
1,2,4,5-Tetrazine-tethered probes for fluorogenically imaging superoxide in live cells with ultrahigh specificity
Authors: Jiang Xuefeng , Li Min , Wang Yule , Wang Chao , Wang Yingchao , Shen Tianruo , Shen Lili , Liu Xiaogang , Wang Yi , Li Xin
Published: March 2023

Superoxide (O2·−) is the primary reactive oxygen species in mammal cells. Detecting superoxide is crucial for understanding redox signaling but remains challenging. Herein, we introduce a class of activity-based sensing probes. The probes utilize 1,2,4,5-tetrazine as a superoxide-responsive trigger, which can be modularly tethered to various fluorophores to tune probe sensitivity and emission color. These probes afford ultra-specific and ultra-fluorogenic responses towards superoxide, and enable multiplexed imaging of various cellular superoxide levels in an organelle-resolved way. Notably, the probes reveal the aberrant superoxide generation in the pathology of myocardial ischemia/reperfusion injury, and facilitate the establishment of a high-content screening pipeline for mediators of superoxide homeostasis. One such identified mediator, coprostanone, is shown to effectively ameliorating oxidative stress-induced injury in mice with myocardial ischemia/reperfusion injury. Collectively, these results showcase the potential of 1,2,4,5-tetrazine-tethered probes as versatile tools to monitor superoxide in a range of pathophysiological settings.
A male-killing gene encoded by a symbiotic virus of Drosophila
Authors: Kageyama Daisuke , Harumoto Toshiyuki , Nagamine Keisuke , Fujiwara Akiko , Sugimoto Takafumi N. , Jouraku Akiya , Tamura Masaru , Katoh Takehiro K. , Watada Masayoshi
Published: March 2023

In most eukaryotes, biparentally inherited nuclear genomes and maternally inherited cytoplasmic genomes have different evolutionary interests. Strongly female-biased sex ratios that are repeatedly observed in various arthropods often result from the male-specific lethality (male-killing) induced by maternally inherited symbiotic bacteria such as Spiroplasma and Wolbachia. However, despite some plausible case reports wherein viruses are raised as male-killers, it is not well understood how viruses, having much smaller genomes than bacteria, are capable of inducing male-killing. Here we show that a maternally inherited double-stranded RNA (dsRNA) virus belonging to the family Partitiviridae (designated DbMKPV1) induces male-killing in Drosophila. DbMKPV1 localizes in the cytoplasm and possesses only four genes, i.e., one gene in each of the four genomic segments (dsRNA1−dsRNA4), in contrast to ca. 1000 or more genes possessed by Spiroplasma or Wolbachia. We also show that a protein (designated PVMKp1; 330 amino acids in size), encoded by a gene on the dsRNA4 segment, is necessary and sufficient for inducing male-killing. Our results imply that male-killing genes can be easily acquired by symbiotic viruses through reassortment and that symbiotic viruses are hidden players in arthropod evolution. We anticipate that host-manipulating genes possessed by symbiotic viruses can be utilized for controlling arthropods.
A co-anchoring strategy for the synthesis of polar bimodal polyethylene
Authors: Zou Chen , Wang Quan , Si Guifu , Chen Changle
Published: March 2023

Since polar groups can poison the metal centers in catalysts, the incorporation of polar comonomers usually comes at the expense of catalytic activity and polymer molecular weight. In this contribution, we demonstrate polar bimodal polyethylene as a potential solution to this trade-off. The more-polar/more-branched low-molecular-weight fraction provides polarity and processability, while the less-polar/less-branched high-molecular-weight fraction provides mechanical and melt properties. To achieve high miscibility between these two fractions, three synthetic routes are investigated: mixtures of homogeneous catalysts, separately supported heterogeneous catalysts, and a co-anchoring strategy (CAS) to heterogenize different homogeneous catalysts on one solid support. The CAS route is the only viable strategy for the synthesis of polar bimodal polyethylene with good molecular level entanglement and minimal phase separation. This produces polyolefin materials with excellent mechanical properties, surface/dyeing properties, gas barrier properties, as well as extrudability and 3D-printability.
Acute liver steatosis translationally controls the epigenetic regulator MIER1 to promote liver regeneration in a study with male mice
Authors: Chen Yanhao , Chen Lanlan , Wu Xiaoshan , Zhao Yongxu , Wang Yuchen , Jiang Dacheng , Liu Xiaojian , Zhou Tingting , Li Shuang , Wei Yuda , Liu Yan , Hu Cheng , Zhou Ben , Qin Jun , Ying Hao , Ding Qiurong
Published: March 2023

The early phase lipid accumulation is essential for liver regeneration. However, whether this acute lipid accumulation can serve as signals to direct liver regeneration rather than simply providing building blocks for cell proliferation remains unclear. Through in vivo CRISPR screening, we identify MIER1 (mesoderm induction early response 1) as a key epigenetic regulator that bridges the acute lipid accumulation and cell cycle gene expression during liver regeneration in male animals. Physiologically, liver acute lipid accumulation induces the phosphorylation of EIF2S1(eukaryotic translation initiation factor 2), which consequently attenuated Mier1 translation. MIER1 downregulation in turn promotes cell cycle gene expression and regeneration through chromatin remodeling. Importantly, the lipids-EIF2S1-MIER1 pathway is impaired in animals with chronic liver steatosis; whereas MIER1 depletion significantly improves regeneration in these animals. Taken together, our studies identify an epigenetic mechanism by which the early phase lipid redistribution from adipose tissue to liver during regeneration impacts hepatocyte proliferation, and suggest a potential strategy to boost liver regeneration.
High-resolution separation of bioisomers using ion cloud profiling
Authors: Zhou Xiaoyu , Wang Zhuofan , Fan Jingjin , Ouyang Zheng
Published: March 2023

Elucidation of complex structures of biomolecules plays a key role in the field of chemistry and life sciences. In the past decade, ion mobility, by coupling with mass spectrometry, has become a unique tool for distinguishing isomers and isoforms of biomolecules. In this study, we develop a concept for performing ion mobility analysis using an ion trap, which enables isomer separation under ultra-high fields to achieve super high resolutions over 10,000. The potential of this technology has been demonstrated for analysis of isomers for biomolecules including disaccharides, phospholipids, and peptides with post-translational modifications.
Signatures of hot carriers and hot phonons in the re-entrant metallic and semiconducting states of Moiré-gapped graphene
Authors: Nathawat Jubin , Mansaray Ishiaka , Sakanashi Kohei , Wada Naoto , Randle Michael D. , Yin Shenchu , He Keke , Arabchigavkani Nargess , Dixit Ripudaman , Barut Bilal , Zhao Miao , Ramamoorthy Harihara , Somphonsane Ratchanok , Kim Gil-Ho , Watanabe Kenji , Taniguchi Takashi , Aoki Nobuyuki , Han Jong E. , Bird Jonathan P.
Published: March 2023

Stacking of graphene with hexagonal boron nitride (h-BN) can dramatically modify its bands from their usual linear form, opening a series of narrow minigaps that are separated by wider minibands. While the resulting spectrum offers strong potential for use in functional (opto)electronic devices, a proper understanding of the dynamics of hot carriers in these bands is a prerequisite for such applications. In this work, we therefore apply a strategy of rapid electrical pulsing to drive carriers in graphene/h-BN heterostructures deep into the dissipative limit of strong electron-phonon coupling. By using electrical gating to move the chemical potential through the “Moiré bands”, we demonstrate a cyclical evolution between metallic and semiconducting states. This behavior is captured in a self-consistent model of non-equilibrium transport that considers the competition of electrically driven inter-band tunneling and hot-carrier scattering by strongly non-equilibrium phonons. Overall, our results demonstrate how a treatment of the dynamics of both hot carriers and hot phonons is essential to understanding the properties of functional graphene superlattices.
Anisotropy oxidation behavior and mechanism of textured Ti3(SiAl)C2 ceramic
Authors: He Guangqi , Zhang Xintao , Wang Wenting , Ma Ke , Zuo Jun , Li Meishuan , Liu Changsheng , Xu Jingjun
Published: March 2023

Adjusting the grain growth orientation may be a feasible way to improve the oxidation resistance. In this work, textured Ti3(SiAl)C2 ceramic was successfully fabricated via the spark plasma sintering technique. The crystal orientation and microstructure were investigated by XRD combined with EBSD. The oxidation behavior of textured Ti3(SiAl)C2 was investigated at 1000–1300 °C for 10 h. The results showed that the oxidation was significantly anisotropic and the surface parallel to the compression direction exhibited better oxidation resistance below 1200 °C. The improved oxidation resistance was primarily attributed to the formation of passivated Al2O3 scale by rapid out-diffusion of Al elements on the orientated (hko) planes in textured Ti3(SiAl)C2. The formation of oxide scales was strongly dependent on the crystallographic orientation of Ti3(SiAl)C2.
DBS-evoked cortical responses index optimal contact orientations and motor outcomes in Parkinson’s disease
Authors: Spooner Rachel K. , Bahners Bahne H. , Schnitzler Alfons , Florin Esther
Published: March 2023

Although subthalamic deep brain stimulation (DBS) is a highly-effective treatment for alleviating motor dysfunction in patients with Parkinson’s disease (PD), clinicians currently lack reliable neurophysiological correlates of clinical outcomes for optimizing DBS parameter settings, which may contribute to treatment inefficacies. One parameter that could aid DBS efficacy is the orientation of current administered, albeit the precise mechanisms underlying optimal contact orientations and associated clinical benefits are not well understood. Herein, 24 PD patients received monopolar stimulation of the left STN during magnetoencephalography and standardized movement protocols to interrogate the directional specificity of STN-DBS current administration on accelerometer metrics of fine hand movements. Our findings demonstrate that optimal contact orientations elicit larger DBS-evoked cortical responses in the ipsilateral sensorimotor cortex, and importantly, are differentially predictive of smoother movement profiles in a contact-dependent manner. Moreover, we summarize traditional evaluations of clinical efficacy (e.g., therapeutic windows, side effects) for a comprehensive review of optimal/non-optimal STN-DBS contact settings. Together, these data suggest that DBS-evoked cortical responses and quantitative movement outcomes may provide clinical insight for characterizing the optimal DBS parameters necessary for alleviating motor symptoms in patients with PD in the future.
Predictive and prognostic value of leptin status in asthma
Authors: Wang Juan , Zhu Ruochen , Shi Wenjing , Mao Song
Published: March 2023

Asthma is closely associated with inflammation. We evaluated the predictive and prognostic value of leptin status in asthma. We searched the electronic databases for articles that determined the leptin level in asthma cases through May 2020. We compared the differences of leptin level between asthma and non-asthma controls, as well as between severe and mild asthma cases. We also investigated the impact of age and gender on these differences by using meta-regression analysis. 59 studies were included in our pooled analysis. Asthma cases demonstrated significantly higher leptin level than that in non-asthma controls among overall populations (SMD:1.061, 95% CI: 0.784–1.338, p < 10−4), Caucasians (SMD:0.287, 95% CI: 0.125–0.448, p = 0.001), Asians (SMD:1.500, 95% CI: 1.064–1.936, p < 10−4) and Africans (SMD: 8.386, 95% CI: 6.519–10.253, p < 10−4). Severe asthma cases showed markedly higher leptin level than that in mild asthma cases among overall populations (SMD:1.638, 95% CI: 0.952–2.323, p < 10–4) and Asians (SMD:2.600, 95% CI: 1.854–3.345, p < 10–4). No significant difference of leptin level between severe and mild asthma was observed in Caucasians (SMD:−0.819, 95% CI: −1.998–0.360, p = 0.173). Cumulative analyses yielded similar results regarding the difference of leptin status between asthma and non-asthma controls, as well as between severe and mild asthma cases among overall populations. Age and male/ female ratio were not associated with the difference of leptin status between asthma and non-asthma controls (coefficient:−0.031, 95% CI: −0.123–0.061, p = 0.495; coefficient:0.172, 95% CI: −2.445–2.789, p = 0.895), as well as between severe and mild asthma cases among overall populations (coefficient:−0.072, 95% CI: −0.208–0.063, p = 0.279; coefficient: 2.373, 95% CI: −0.414–5.161, p = 0.090). Asthma demonstrated significantly higher level of leptin than that in non-asthma controls among overall populations, Caucasians, Asians and Africans. Severe asthma cases showed markedly higher leptin level than that in mild cases among overall populations and Asians. Leptin may be a risk predictor and prognostic marker of asthma. Early monitoring and intervention of leptin may be needed for asthma.
Flexomagnetic noncollinear state with a plumb line shape spin configuration in edged two-dimensional magnetic CrI3
Authors: Qiu Guotao , Li Zongjin , Zhou Kun , Cai Yongqing
Published: March 2023

The flexomagnetic effect involves the coupling of inhomogeneous mechanical and magnetic excitations to generate exotic spin orders. The intrinsic edge stress associated with lifting of periodic degeneracy at surfaces or edges in nanostructures facilitates the flexocoupling effects. Here, we combine first-principles calculation and Maximum Information Coefficient (MIC) statistics to quantitatively reveal the impact of bending on the geometries, spin ordering state, and exchange interactions in chromium triiodide (CrI3) nanoribbons. Our results reveal a divergent magnetic ground state at small curvature but a plumb line shape noncollinear state at large curvatures. More importantly, our work establishes a gradient dependence of the exchange coupling on the locally asymmetric bending angles of the Cr-I-Cr hinge, governed by the coupling of the t2g and eg states of Cr. The superexchange gradient accompanied with the bending-induced inhomogeneous deformation sheds light on the evolution of magnetic ordering associated with asymmetric coordinating systems for sensors and spintronics.