bluuebunny/crossref_metadata_2025 huggingface dataset:
Endosomal trafficking defects alter neural progenitor proliferation and cause microcephaly
Authors: Carpentieri Jacopo A. , Di Cicco Amandine , Lampic Marusa , Andreau David , Del Maestro Laurence , El Marjou Fatima , Coquand Laure , Bahi-Buisson Nadia , Brault Jean-Baptiste , Baffet Alexandre D.
Published: January 2022

Primary microcephaly and megalencephaly are severe brain malformations defined by reduced and increased brain size, respectively. Whether these two pathologies arise from related alterations at the molecular level is unclear. Microcephaly has been largely associated with centrosomal defects, leading to cell death. Here, we investigate the consequences of WDR81 loss of function, which causes severe microcephaly in patients. We show that WDR81 regulates endosomal trafficking of EGFR and that loss of function leads to reduced MAP kinase pathway activation. Mouse radial glial progenitor cells knocked-out for WDR81 exhibit reduced proliferation rate, subsequently leading to reduced brain size. These proliferation defects are rescued in vivo by expressing a megalencephaly-causing mutant form of Cyclin D2. Our results identify the endosomal machinery as an important regulator of proliferation rates and brain growth, demonstrating that microcephaly and megalencephaly can be caused by opposite effects on the proliferation rate of radial glial progenitors.
Temperature sensitivity of Notch signaling underlies species-specific developmental plasticity and robustness in amniote brains
Authors: Nomura Tadashi , Nagao Kohjiro , Shirai Ryo , Gotoh Hitoshi , Umeda Masato , Ono Katsuhiko
Published: January 2022

Ambient temperature significantly affects developmental timing in animals. The temperature sensitivity of embryogenesis is generally believed to be a consequence of the thermal dependency of cellular metabolism. However, the adaptive molecular mechanisms that respond to variations in temperature remain unclear. Here, we report species-specific thermal sensitivity of Notch signaling in the developing amniote brain. Transient hypothermic conditions increase canonical Notch activity and reduce neurogenesis in chick neural progenitors. Increased biosynthesis of phosphatidylethanolamine, a major glycerophospholipid components of the plasma membrane, mediates hypothermia-induced Notch activation. Furthermore, the species-specific thermal dependency of Notch signaling is associated with developmental robustness to altered Notch signaling. Our results reveal unique regulatory mechanisms for temperature-dependent neurogenic potentials that underlie developmental and evolutionary adaptations to a range of ambient temperatures in amniotes.
Age-dependent pathogenic characteristics of SARS-CoV-2 infection in ferrets
Authors: Kim Young-Il , Yu Kwang-Min , Koh June-Young , Kim Eun-Ha , Kim Se-Mi , Kim Eun Ji , Casel Mark Anthony B. , Rollon Rare , Jang Seung-Gyu , Song Min-Suk , Park Su-Jin , Jeong Hye Won , Kim Eung-Gook , Lee Ok-Jun , Kim Yong-Dae , Choi Younho , Lee Shin-Ae , Choi Youn Jung , Park Su-Hyung , Jung Jae U. , Choi Young Ki
Published: January 2022

While the seroprevalence of SARS-CoV-2 in healthy people does not differ significantly among age groups, those aged 65 years or older exhibit strikingly higher COVID-19 mortality compared to younger individuals. To further understand differing COVID-19 manifestations in patients of different ages, three age groups of ferrets are infected with SARS-CoV-2. Although SARS-CoV-2 is isolated from all ferrets regardless of age, aged ferrets (≥3 years old) show higher viral loads, longer nasal virus shedding, and more severe lung inflammatory cell infiltration, and clinical symptoms compared to juvenile (≤6 months) and young adult (1–2 years) groups. Furthermore, direct contact ferrets co-housed with the virus-infected aged group shed more virus than direct-contact ferrets co-housed with virus-infected juvenile or young adult ferrets. Transcriptome analysis of aged ferret lungs reveals strong enrichment of gene sets related to type I interferon, activated T cells, and M1 macrophage responses, mimicking the gene expression profile of severe COVID-19 patients. Thus, SARS-CoV-2-infected aged ferrets highly recapitulate COVID-19 patients with severe symptoms and are useful for understanding age-associated infection, transmission, and pathogenesis of SARS-CoV-2.
Achieving long cycle life for all-solid-state rechargeable Li-I2 battery by a confined dissolution strategy
Authors: Cheng Zhu , Pan Hui , Li Fan , Duan Chun , Liu Hang , Zhong Hanyun , Sheng Chuanchao , Hou Guangjin , He Ping , Zhou Haoshen
Published: January 2022

Rechargeable Li-I2 battery has attracted considerable attentions due to its high theoretical capacity, low cost and environment-friendliness. Dissolution of polyiodides are required to facilitate the electrochemical redox reaction of the I2 cathode, which would lead to a harmful shuttle effect. All-solid-state Li-I2 battery totally avoids the polyiodides shuttle in a liquid system. However, the insoluble discharge product at the conventional solid interface results in a sluggish electrochemical reaction and poor rechargeability. In this work, by adopting a well-designed hybrid electrolyte composed of a dispersion layer and a blocking layer, we successfully promote a new polyiodides chemistry and localize the polyiodides dissolution within a limited space near the cathode. Owing to this confined dissolution strategy, a rechargeable and highly reversible all-solid-state Li-I2 battery is demonstrated and shows a long-term life of over 9000 cycles at 1C with a capacity retention of 84.1%.
Unlocking surface octahedral tilt in two-dimensional Ruddlesden-Popper perovskites
Authors: Shao Yan , Gao Wei , Yan Hejin , Li Runlai , Abdelwahab Ibrahim , Chi Xiao , Rogée Lukas , Zhuang Lyuchao , Fu Wei , Lau Shu Ping , Yu Siu Fung , Cai Yongqing , Loh Kian Ping , Leng Kai
Published: January 2022

Molecularly soft organic-inorganic hybrid perovskites are susceptible to dynamic instabilities of the lattice called octahedral tilt, which directly impacts their carrier transport and exciton-phonon coupling. Although the structural phase transitions associated with octahedral tilt has been extensively studied in 3D hybrid halide perovskites, its impact in hybrid 2D perovskites is not well understood. Here, we used scanning tunneling microscopy (STM) to directly visualize surface octahedral tilt in freshly exfoliated 2D Ruddlesden-Popper perovskites (RPPs) across the homologous series, whereby the steric hindrance imposed by long organic cations is unlocked by exfoliation. The experimentally determined octahedral tilts from n = 1 to n = 4 RPPs from STM images are found to agree very well with out-of-plane surface octahedral tilts predicted by density functional theory calculations. The surface-enhanced octahedral tilt is correlated to excitonic redshift observed in photoluminescence (PL), and it enhances inversion asymmetry normal to the direction of quantum well and promotes Rashba spin splitting for n > 1.
The legacy of the extinct Neotropical megafauna on plants and biomes
Authors: Dantas Vinicius L. , Pausas Juli G.
Published: January 2022

Large mammal herbivores are important drivers of plant evolution and vegetation patterns, but the extent to which plant trait and ecosystem geography currently reflect the historical distribution of extinct megafauna is unknown. We address this question for South and Central America (Neotropical biogeographic realm) by compiling data on plant defence traits, climate, soil, and fire, as well as on the historical distribution of extinct megafauna and extant mammal herbivores. We show that historical mammal herbivory, especially by extinct megafauna, and soil fertility explain substantial variability in wood density, leaf size, spines and latex. We also identified three distinct regions (‘‘antiherbiomes’’), differing in plant defences, environmental conditions, and megafauna history. These patterns largely matched those observed in African ecosystems, where abundant megafauna still roams, and suggest that some ecoregions experienced savanna-to-forest shifts following megafauna extinctions. Here, we show that extinct megafauna left a significant imprint on current ecosystem biogeography.
Yeast-derived nanoparticles remodel the immunosuppressive microenvironment in tumor and tumor-draining lymph nodes to suppress tumor growth
Authors: Xu Jialu , Ma Qingle , Zhang Yue , Fei Ziying , Sun Yifei , Fan Qin , Liu Bo , Bai Jinyu , Yu Yue , Chu Jianhong , Chen Jingrun , Wang Chao
Published: January 2022

Microbe-based cancer immunotherapy has recently emerged as a hot topic for cancer treatment. However, serious limitations remain including infection associated side-effect and unsatisfactory outcomes in clinic trials. Here, we fabricate different sizes of nano-formulations derived from yeast cell wall (YCW NPs) by differential centrifugation. The induction of anticancer immunity of our formulations appears to inversely correlate with their size due to the ability to accumulate in tumor-draining lymph node (TDLN). Moreover, we use a percolation model to explain their distribution behavior toward TDLN. The abundance and functional orientation of each effector component are significantly improved not only in the microenvironment in tumor but also in the TDLN following small size YCW NPs treatment. In combination with programmed death-ligand 1 (PD-L1) blockade, we demonstrate anticancer efficiency in melanoma-challenged mice. We delineate potential strategy to target immunosuppressive microenvironment by microbe-based nanoparticles and highlight the role of size effect in microbe-based immune therapeutics.
Competition between crystal growth and intracrystalline chain diffusion determines the lamellar thickness in semicrystalline polymers
Authors: Schulz Martha , Schäfer Mareen , Saalwächter Kay , Thurn-Albrecht Thomas
Published: January 2022

The non-equilibrium thickness of lamellar crystals in semicrystalline polymers varies significantly between different polymer systems and depends on the crystallization temperature Tc. There is currently no consensus on the mechanism of thickness selection. Previous work has highlighted the decisive role of intracrystalline chain diffusion (ICD) in special cases, but a systematic dependence of lamellar thickness on relevant timescales such as that of ICD and stem attachment has not yet been established. Studying the morphology by small-angle X-ray scattering and the two timescales by NMR methods and polarization microscopy respectively, we here present data on poly(oxymethylene), a case with relatively slow ICD. It fills the gap between previously studied cases of absent and fast ICD, enabling us to establish a quantitative dependence of lamellar thickness on the competition between the noted timescales.
Microbial enzymes induce colitis by reactivating triclosan in the mouse gastrointestinal tract
Authors: Zhang Jianan , Walker Morgan E. , Sanidad Katherine Z. , Zhang Hongna , Liang Yanshan , Zhao Ermin , Chacon-Vargas Katherine , Yeliseyev Vladimir , Parsonnet Julie , Haggerty Thomas D. , Wang Guangqiang , Simpson Joshua B. , Jariwala Parth B. , Beaty Violet V. , Yang Jun , Yang Haixia , Panigrahy Anand , Minter Lisa M. , Kim Daeyoung , Gibbons John G. , Liu LinShu , Li Zhengze , Xiao Hang , Borlandelli Valentina , Overkleeft Hermen S. , Cloer Erica W. , Major Michael B. , Goldfarb Dennis , Cai Zongwei , Redinbo Matthew R. , Zhang Guodong
Published: January 2022

Emerging research supports that triclosan (TCS), an antimicrobial agent found in thousands of consumer products, exacerbates colitis and colitis-associated colorectal tumorigenesis in animal models. While the intestinal toxicities of TCS require the presence of gut microbiota, the molecular mechanisms involved have not been defined. Here we show that intestinal commensal microbes mediate metabolic activation of TCS in the colon and drive its gut toxicology. Using a range of in vitro, ex vivo, and in vivo approaches, we identify specific microbial β-glucuronidase (GUS) enzymes involved and pinpoint molecular motifs required to metabolically activate TCS in the gut. Finally, we show that targeted inhibition of bacterial GUS enzymes abolishes the colitis-promoting effects of TCS, supporting an essential role of specific microbial proteins in TCS toxicity. Together, our results define a mechanism by which intestinal microbes contribute to the metabolic activation and gut toxicity of TCS, and highlight the importance of considering the contributions of the gut microbiota in evaluating the toxic potential of environmental chemicals.
Enhanced hydrogen generation by reverse spillover effects over bicomponent catalysts
Authors: Gao Zhe , Wang Guofu , Lei Tingyu , Lv Zhengxing , Xiong Mi , Wang Liancheng , Xing Shuangfeng , Ma Jingyuan , Jiang Zheng , Qin Yong
Published: January 2022

The contribution of the reverse spillover effect to hydrogen generation reactions is still controversial. Herein, the promotion functions for reverse spillover in the ammonia borane hydrolysis reaction are proven by constructing a spatially separated NiO/Al2O3/Pt bicomponent catalyst via atomic layer deposition and performing in situ quick X-ray absorption near-edge structure (XANES) characterization. For the NiO/Al2O3/Pt catalyst, NiO and Pt nanoparticles are attached to the outer and inner surfaces of Al2O3nanotubes, respectively. In situ XANES results reveal that for ammonia borane hydrolysis, the H species generated at NiO sites spill across the support to the Pt sites reversely. The reverse spillover effects account for enhanced H2generation rates for NiO/Al2O3/Pt. For the CoOx/Al2O3/Pt and NiO/TiO2/Pt catalysts, reverse spillover effects are also confirmed. We believe that an in-depth understanding of the reverse effects will be helpful to clarify the catalytic mechanisms and provide a guide for designing highly efficient catalysts for hydrogen generation reactions.
Phenology is the dominant control of methane emissions in a tropical non-forested wetland
Authors: Helfter Carole , Gondwe Mangaliso , Murray-Hudson Michael , Makati Anastacia , Lunt Mark F. , Palmer Paul I. , Skiba Ute
Published: January 2022

Tropical wetlands are a significant source of atmospheric methane (CH4), but their importance to the global CH4 budget is uncertain due to a paucity of direct observations. Net wetland emissions result from complex interactions and co-variation between microbial production and oxidation in the soil, and transport to the atmosphere. Here we show that phenology is the overarching control of net CH4 emissions to the atmosphere from a permanent, vegetated tropical swamp in the Okavango Delta, Botswana, and we find that vegetative processes modulate net CH4 emissions at sub-daily to inter-annual timescales. Without considering the role played by papyrus on regulating the efflux of CH4 to the atmosphere, the annual budget for the entire Okavango Delta, would be under- or over-estimated by a factor of two. Our measurements demonstrate the importance of including vegetative processes such as phenological cycles into wetlands emission budgets of CH4.
3D atomic-scale imaging of mixed Co-Fe spinel oxide nanoparticles during oxygen evolution reaction
Authors: Xiang Weikai , Yang Nating , Li Xiaopeng , Linnemann Julia , Hagemann Ulrich , Ruediger Olaf , Heidelmann Markus , Falk Tobias , Aramini Matteo , DeBeer Serena , Muhler Martin , Tschulik Kristina , Li Tong
Published: January 2022

The three-dimensional (3D) distribution of individual atoms on the surface of catalyst nanoparticles plays a vital role in their activity and stability. Optimising the performance of electrocatalysts requires atomic-scale information, but it is difficult to obtain. Here, we use atom probe tomography to elucidate the 3D structure of 10 nm sized Co2FeO4and CoFe2O4nanoparticles during oxygen evolution reaction (OER). We reveal nanoscale spinodal decomposition in pristine Co2FeO4. The interfaces of Co-rich and Fe-rich nanodomains of Co2FeO4become trapping sites for hydroxyl groups, contributing to a higher OER activity compared to that of CoFe2O4. However, the activity of Co2FeO4drops considerably due to concurrent irreversible transformation towards CoIVO2and pronounced Fe dissolution. In contrast, there is negligible elemental redistribution for CoFe2O4after OER, except for surface structural transformation towards (FeIII, CoIII)2O3. Overall, our study provides a unique 3D compositional distribution of mixed Co-Fe spinel oxides, which gives atomic-scale insights into active sites and the deactivation of electrocatalysts during OER.
Coupling aqueous zinc batteries and perovskite solar cells for simultaneous energy harvest, conversion and storage
Authors: Chen Peng , Li Tian-Tian , Yang Yuan-Bo , Li Guo-Ran , Gao Xue-Ping
Published: January 2022

Simultaneously harvesting, converting and storing solar energy in a single device represents an ideal technological approach for the next generation of power sources. Herein, we propose a device consisting of an integrated carbon-based perovskite solar cell module capable of harvesting solar energy (and converting it into electricity) and a rechargeable aqueous zinc metal cell. The electrochemical energy storage cell utilizes heterostructural Co2P-CoP-NiCoO2 nanometric arrays and zinc metal as the cathode and anode, respectively, and shows a capacity retention of approximately 78% after 25000 cycles at 32 A/g. In particular, the battery cathode and perovskite material of the solar cell are combined in a sandwich joint electrode unit. As a result, the device delivers a specific power of 54 kW/kg and specific energy of 366 Wh/kg at 32 A/g and 2 A/g, respectively. Moreover, benefiting from its narrow voltage range (1.40–1.90 V), the device demonstrates an efficiency of approximately 6%, which is stable for 200 photocharge and discharge cycles.
Association of mutation signature effectuating processes with mutation hotspots in driver genes and non-coding regions
Authors: Wong John K. L. , Aichmüller Christian , Schulze Markus , Hlevnjak Mario , Elgaafary Shaymaa , Lichter Peter , Zapatka Marc
Published: January 2022

Cancer driving mutations are difficult to identify especially in the non-coding part of the genome. Here, we present sigDriver, an algorithm dedicated to call driver mutations. Using 3813 whole-genome sequenced tumors from International Cancer Genome Consortium, The Cancer Genome Atlas Program, and a childhood pan-cancer cohort, we employ mutational signatures based on single-base substitution in the context of tri- and penta-nucleotide motifs for hotspot discovery. Knowledge-based annotations on mutational hotspots reveal enrichment in coding regions and regulatory elements for 6 mutational signatures, including APOBEC and somatic hypermutation signatures. APOBEC activity is associated with 32 hotspots of which 11 are known and 11 are putative regulatory drivers. Somatic single nucleotide variants clusters detected at hypermutation-associated hotspots are distinct from translocation or gene amplifications. Patients carrying APOBEC induced PIK3CA driver mutations show lower occurrence of signature SBS39. In summary, sigDriver uncovers mutational processes associated with known and putative tumor drivers and hotspots particularly in the non-coding regions of the genome.
Genomic alterations and evolution of cell clusters in metastatic invasive micropapillary carcinoma of the breast
Authors: Shi Qianqian , Shao Kang , Jia Hongqin , Cao Boyang , Li Weidong , Dong Shichen , Liu Jian , Wu Kailiang , Liu Meng , Liu Fangfang , Zhou Hanlin , Lv Jianke , Gu Feng , Li Luyuan , Zhu Shida , Li Shuai , Li Guibo , Fu Li
Published: January 2022

Invasive micropapillary carcinoma (IMPC) has very high rates of lymphovascular invasion and lymph node metastasis and has been reported in several organs. However, the genomic mechanisms underlying its metastasis are unclear. Here, we perform whole-genome sequencing of tumor cell clusters from primary IMPC and paired axillary lymph node metastases. Cell clusters in multiple lymph node foci arise from a single subclone of the primary tumor. We find evidence that the monoclonal metastatic ancestor in primary IMPC shares high frequency copy-number loss of PRDM16 and IGSF9 and the copy number gain of ALDH2. Immunohistochemistry analysis further shows that low expression of IGSF9 and PRDM16 and high expression of ALDH2 are associated with lymph node metastasis and poor survival of patients with IMPC. We expect these genomic and evolutionary profiles to contribute to the accurate diagnosis of IMPC.
Spatial transcriptomics using combinatorial fluorescence spectral and lifetime encoding, imaging and analysis
Authors: Vu Tam , Vallmitjana Alexander , Gu Joshua , La Kieu , Xu Qi , Flores Jesus , Zimak Jan , Shiu Jessica , Hosohama Linzi , Wu Jie , Douglas Christopher , Waterman Marian L. , Ganesan Anand , Hedde Per Niklas , Gratton Enrico , Zhao Weian
Published: January 2022

Multiplexed mRNA profiling in the spatial context provides new information enabling basic research and clinical applications. Unfortunately, existing spatial transcriptomics methods are limited due to either low multiplexing or complexity. Here, we introduce a spatialomics technology, termed Multi Omic Single-scan Assay with Integrated Combinatorial Analysis (MOSAICA), that integrates in situ labeling of mRNA and protein markers in cells or tissues with combinatorial fluorescence spectral and lifetime encoded probes, spectral and time-resolved fluorescence imaging, and machine learning-based decoding. We demonstrate MOSAICA’s multiplexing scalability in detecting 10-plex targets in fixed colorectal cancer cells using combinatorial labeling of five fluorophores with facile error-detection and removal of autofluorescence. MOSAICA’s analysis is strongly correlated with sequencing data (Pearson’s r = 0.96) and was further benchmarked using RNAscopeTMand LGC StellarisTM. We further apply MOSAICA for multiplexed analysis of clinical melanoma Formalin-Fixed Paraffin-Embedded (FFPE) tissues. We finally demonstrate simultaneous co-detection of protein and mRNA in cancer cells.
Synthetic prodrug design enables biocatalytic activation in mice to elicit tumor growth suppression
Authors: Nasibullin Igor , Smirnov Ivan , Ahmadi Peni , Vong Kenward , Kurbangalieva Almira , Tanaka Katsunori
Published: January 2022

Considering the intrinsic toxicities of transition metals, their incorporation into drug therapies must operate at minimal amounts while ensuring adequate catalytic activity within complex biological systems. As a way to address this issue, this study investigates the design of synthetic prodrugs that are not only tuned to be harmless, but can be robustly transformed in vivo to reach therapeutically relevant levels. To accomplish this, retrosynthetic prodrug design highlights the potential of naphthylcombretastatin-based prodrugs, which form highly active cytostatic agents via sequential ring-closing metathesis and aromatization. Structural adjustments will also be done to improve aspects related to catalytic reactivity, intrinsic bioactivity, and hydrolytic stability. The developed prodrug therapy is found to possess excellent anticancer activities in cell-based assays. Furthermore, in vivo activation by intravenously administered glycosylated artificial metalloenzymes can also induce significant reduction of implanted tumor growth in mice.
Engineering immunomodulatory and osteoinductive implant surfaces via mussel adhesion-mediated ion coordination and molecular clicking
Authors: Wang Tao , Bai Jiaxiang , Lu Min , Huang Chenglong , Geng Dechun , Chen Gang , Wang Lei , Qi Jin , Cui Wenguo , Deng Lianfu
Published: January 2022

Immune response and new tissue formation are important aspects of tissue repair. However, only a single aspect is generally considered in previous biomedical interventions, and the synergistic effect is unclear. Here, a dual-effect coating with immobilized immunomodulatory metal ions (e.g., Zn2+) and osteoinductive growth factors (e.g., BMP-2 peptide) is designed via mussel adhesion-mediated ion coordination and molecular clicking strategy. Compared to the bare TiO2 group, Zn2+ can increase M2 macrophage recruitment by up to 92.5% in vivo and upregulate the expression of M2 cytokine IL-10 by 84.5%; while the dual-effect of Zn2+ and BMP-2 peptide can increase M2 macrophages recruitment by up to 124.7% in vivo and upregulate the expression of M2 cytokine IL-10 by 171%. These benefits eventually significantly enhance bone-implant mechanical fixation (203.3 N) and new bone ingrowth (82.1%) compared to the bare TiO2 (98.6 N and 45.1%, respectively). Taken together, the dual-effect coating can be utilized to synergistically modulate the osteoimmune microenvironment at the bone-implant interface, enhancing bone regeneration for successful implantation.
A proximity biotinylation-based approach to identify protein-E3 ligase interactions induced by PROTACs and molecular glues
Authors: Yamanaka Satoshi , Horiuchi Yuto , Matsuoka Saya , Kido Kohki , Nishino Kohei , Maeno Mayaka , Shibata Norio , Kosako Hidetaka , Sawasaki Tatsuya
Published: January 2022

Proteolysis-targeting chimaeras (PROTACs) as well as molecular glues such as immunomodulatory drugs (IMiDs) and indisulam are drugs that induce interactions between substrate proteins and an E3 ubiquitin ligases for targeted protein degradation. Here, we develop a workflow based on proximity-dependent biotinylation by AirID to identify drug-induced neo-substrates of the E3 ligase cereblon (CRBN). Using AirID-CRBN, we detect IMiD-dependent biotinylation of CRBN neo-substrates in vitro and identify biotinylated peptides of well-known neo-substrates by mass spectrometry with high specificity and selectivity. Additional analyses reveal ZMYM2 and ZMYM2-FGFR1 fusion protein—responsible for the 8p11 syndrome involved in acute myeloid leukaemia—as CRBN neo-substrates. Furthermore, AirID-DCAF15 and AirID-CRBN biotinylate neo-substrates targeted by indisulam and PROTACs, respectively, suggesting that this approach has the potential to serve as a general strategy for characterizing drug-inducible protein–protein interactions in cells.
Alloy information helps prioritize material criticality lists
Authors: Graedel T. E. , Reck Barbara K. , Miatto Alessio
Published: January 2022

Materials scientists employ metals and alloys that involve most of the periodic table. Nonetheless, materials scientists rarely take material criticality and reuse potential into account. In this work, we expand upon lists of “critical materials” generated by national and regional governments by showing that many materials are employed predominantly as alloying elements, which can be a deterrent to recovery and reuse at end of product life and, likely as a consequence, have low functional end-of-life recycling rates, among other problematic characteristics. We thereby single out six metals for enhanced concern: dysprosium, samarium, vanadium, niobium, tellurium, and gallium. From that perspective, the use of critical metals in low concentrations in alloys unlikely to be routinely recycled should be avoided if possible. If not, provision should be made for better identification and more efficient recycling so that materials designated as critical can have increased potential for more than a single functional use.
Targeted editing and evolution of engineered ribosomes in vivo by filtered editing
Authors: Radford Felix , Elliott Shane D. , Schepartz Alanna , Isaacs Farren J.
Published: January 2022

Genome editing technologies introduce targeted chromosomal modifications in organisms yet are constrained by the inability to selectively modify repetitive genetic elements. Here we describe filtered editing, a genome editing method that embeds group 1 self-splicing introns into repetitive genetic elements to construct unique genetic addresses that can be selectively modified. We introduce intron-containing ribosomes into the E. coli genome and perform targeted modifications of these ribosomes using CRISPR/Cas9 and multiplex automated genome engineering. Self-splicing of introns post-transcription yields scarless RNA molecules, generating a complex library of targeted combinatorial variants. We use filtered editing to co-evolve the 16S rRNA to tune the ribosome’s translational efficiency and the 23S rRNA to isolate antibiotic-resistant ribosome variants without interfering with native translation. This work sets the stage to engineer mutant ribosomes that polymerize abiological monomers with diverse chemistries and expands the scope of genome engineering for precise editing and evolution of repetitive DNA sequences.
Suppressing electrolyte-lithium metal reactivity via Li+-desolvation in uniform nano-porous separator
Authors: Sheng Li , Wang Qianqian , Liu Xiang , Cui Hao , Wang Xiaolin , Xu Yulong , Li Zonglong , Wang Li , Chen Zonghai , Xu Gui-Liang , Wang Jianlong , Tang Yaping , Amine Khalil , Xu Hong , He Xiangming
Published: January 2022

Lithium reactivity with electrolytes leads to their continuous consumption and dendrite growth, which constitute major obstacles to harnessing the tremendous energy of lithium-metal anode in a reversible manner. Considerable attention has been focused on inhibiting dendrite via interface and electrolyte engineering, while admitting electrolyte-lithium metal reactivity as a thermodynamic inevitability. Here, we report the effective suppression of such reactivity through a nano-porous separator. Calculation assisted by diversified characterizations reveals that the separator partially desolvates Li+ in confinement created by its uniform nanopores, and deactivates solvents for electrochemical reduction before Li0-deposition occurs. The consequence of such deactivation is realizing dendrite-free lithium-metal electrode, which even retaining its metallic lustre after long-term cycling in both Li-symmetric cell and high-voltage Li-metal battery with LiNi0.6Mn0.2Co0.2O2 as cathode. The discovery that a nano-structured separator alters both bulk and interfacial behaviors of electrolytes points us toward a new direction to harness lithium-metal as the most promising anode.
Alteration of ribosome function upon 5-fluorouracil treatment favors cancer cell drug-tolerance
Authors: Therizols Gabriel , Bash-Imam Zeina , Panthu Baptiste , Machon Christelle , Vincent Anne , Ripoll Julie , Nait-Slimane Sophie , Chalabi-Dchar Mounira , Gaucherot Angéline , Garcia Maxime , Laforêts Florian , Marcel Virginie , Boubaker-Vitre Jihane , Monet Marie-Ambre , Bouclier Céline , Vanbelle Christophe , Souahlia Guillaume , Berthel Elise , Albaret Marie Alexandra , Mertani Hichem C. , Prudhomme Michel , Bertrand Martin , David Alexandre , Saurin Jean-Christophe , Bouvet Philippe , Rivals Eric , Ohlmann Théophile , Guitton Jérôme , Dalla Venezia Nicole , Pannequin Julie , Catez Frédéric , Diaz Jean-Jacques
Published: January 2022

Mechanisms of drug-tolerance remain poorly understood and have been linked to genomic but also to non-genomic processes. 5-fluorouracil (5-FU), the most widely used chemotherapy in oncology is associated with resistance. While prescribed as an inhibitor of DNA replication, 5-FU alters all RNA pathways. Here, we show that 5-FU treatment leads to the production of fluorinated ribosomes exhibiting altered translational activities. 5-FU is incorporated into ribosomal RNAs of mature ribosomes in cancer cell lines, colorectal xenografts, and human tumors. Fluorinated ribosomes appear to be functional, yet, they display a selective translational activity towards mRNAs depending on the nature of their 5′-untranslated region. As a result, we find that sustained translation ofIGF-1RmRNA, which encodes one of the most potent cell survival effectors, promotes the survival of 5-FU-treated colorectal cancer cells. Altogether, our results demonstrate that “man-made” fluorinated ribosomes favor the drug-tolerant cellular phenotype by promoting translation of survival genes.
Nutrient supply controls the linkage between species abundance and ecological interactions in marine bacterial communities
Authors: Dai Tianjiao , Wen Donghui , Bates Colin T. , Wu Linwei , Guo Xue , Liu Suo , Su Yifan , Lei Jiesi , Zhou Jizhong , Yang Yunfeng
Published: January 2022

Nutrient scarcity is pervasive for natural microbial communities, affecting species reproduction and co-existence. However, it remains unclear whether there are general rules of how microbial species abundances are shaped by biotic and abiotic factors. Here we show that the ribosomal RNA gene operon (rrn) copy number, a genomic trait related to bacterial growth rate and nutrient demand, decreases from the abundant to the rare biosphere in the nutrient-rich coastal sediment but exhibits the opposite pattern in the nutrient-scarce pelagic zone of the global ocean. Both patterns are underlain by positive correlations between community-level rrn copy number and nutrients. Furthermore, inter-species co-exclusion inferred by negative network associations is observed more in coastal sediment than in ocean water samples. Nutrient manipulation experiments yield effects of nutrient availability on rrn copy numbers and network associations that are consistent with our field observations. Based on these results, we propose a “hunger games” hypothesis to define microbial species abundance rules using the rrn copy number, ecological interaction, and nutrient availability.
Cooperation in a fluid swarm of fuel-free micro-swimmers
Authors: Ben Zion Matan Yah , Caba Yaelin , Modin Alvin , Chaikin Paul M.
Published: January 2022

While motile bacteria display rich dynamics in dense colonies, the phoretic nature of artificial micro-swimmers restricts their activity when crowded. Here we introduce a new class of synthetic micro-swimmers that are driven solely by light. By coupling a light absorbing particle to a fluid droplet we produce a colloidal chimera that transforms optical power into propulsive thermo-capillary action. The swimmers’ internal drive allows them to operate for a long duration (days) and remain active when crowded, forming a high density fluid phase. We find that above a critical concentration, swimmers form a long lived crowded state that displays internal dynamics. When passive particles are introduced, the dense swimmer phase can re-arrange to spontaneously corral the passive particles. We derive a geometrical, depletion-like condition for corralling by identifying the role the passive particles play in controlling the effective concentration of the micro-swimmers.
Shortcuts to adiabaticity for open systems in circuit quantum electrodynamics
Authors: Yin Zelong , Li Chunzhen , Allcock Jonathan , Zheng Yicong , Gu Xiu , Dai Maochun , Zhang Shengyu , An Shuoming
Published: January 2022

Shortcuts to adiabaticity are powerful quantum control methods, allowing quick evolution into target states of otherwise slow adiabatic dynamics. Such methods have widespread applications in quantum technologies, and various shortcuts to adiabaticity protocols have been demonstrated in closed systems. However, realizing shortcuts to adiabaticity for open quantum systems has presented a challenge due to the complex controls in existing proposals. Here, we present the experimental demonstration of shortcuts to adiabaticity for open quantum systems, using a superconducting circuit quantum electrodynamics system. By applying a counterdiabatic driving pulse, we reduce the adiabatic evolution time of a single lossy mode from 800 ns to 100 ns. In addition, we propose and implement an optimal control protocol to achieve fast and qubit-unconditional equilibrium of multiple lossy modes. Our results pave the way for precise time-domain control of open quantum systems and have potential applications in designing fast open-system protocols of physical and interdisciplinary interest, such as accelerating bioengineering and chemical reaction dynamics.
Identifying optimal cycles in quantum thermal machines with reinforcement-learning
Authors: Erdman Paolo A. , Noé Frank
Published: January 2022

The optimal control of open quantum systems is a challenging task but has a key role in improving existing quantum information processing technologies. We introduce a general framework based on reinforcement learning to discover optimal thermodynamic cycles that maximize the power of out-of-equilibrium quantum heat engines and refrigerators. We apply our method, based on the soft actor-critic algorithm, to three systems: a benchmark two-level system heat engine, where we find the optimal known cycle; an experimentally realistic refrigerator based on a superconducting qubit that generates coherence, where we find a non-intuitive control sequence that outperforms previous cycles proposed in literature; a heat engine based on a quantum harmonic oscillator, where we find a cycle with an elaborate structure that outperforms the optimized Otto cycle. We then evaluate the corresponding efficiency at maximum power.
Esophageal regeneration following surgical implantation of a tissue engineered esophageal implant in a pediatric model
Authors: Sundaram Sumati , Jensen Todd , Roffidal Tina , Paquin Karissa , Wanczyk Heather , Cockman Michael D. , Shadman Shawyon , Finck Christine , Fodor William
Published: January 2022

Diseases of the esophagus, damage of the esophagus due to injury or congenital defects during fetal esophageal development, i.e., esophageal atresia (EA), typically require surgical intervention to restore esophageal continuity. The development of tissue engineered tubular structures would improve the treatment options for these conditions by providing an alternative that is organ sparing and can be manufactured to fit the exact dimensions of the defect. An autologous tissue engineered Cellspan Esophageal ImplantTM (CEI) was surgically implanted into piglets that underwent surgical resection of the esophagus. Multiple survival time points, post-implantation, were analyzed histologically to understand the tissue architecture and time course of the regeneration process. In addition, we investigated CT imaging as an “in-life” monitoring protocol to assess tissue regeneration. We also utilized a clinically relevant animal management paradigm that was essential for long term survival. Following implantation, CT imaging revealed early tissue deposition and the formation of a contiguous tissue conduit. Endoscopic evaluation at multiple time points revealed complete epithelialization of the lumenal surface by day 90. Histologic evaluation at several necropsy time points, post-implantation, determined the time course of tissue regeneration and demonstrated that the tissue continues to remodel over the course of a 1-year survival time period, resulting in the development of esophageal structural features, including the mucosal epithelium, muscularis mucosae, lamina propria, as well as smooth muscle proliferation/migration initiating the formation of a laminated adventitia. Long term survival (1 year) demonstrated restoration of oral nutrition, normal animal growth and the overall safety of this treatment regimen.
Passive transfer of Ad26.COV2.S-elicited IgG from humans attenuates SARS-CoV-2 disease in hamsters
Authors: Tostanoski Lisa H. , Chandrashekar Abishek , Patel Shivani , Yu Jingyou , Jacob-Dolan Catherine , Chang Aiquan , Powers Olivia C. , Sellers Daniel , Gardner Sarah , Barrett Julia , Sanborn Owen , Stephenson Kathryn E. , Ansel Jessica L. , Jaegle Kate , Seaman Michael S. , Porto Maciel , Lok Megan , Spence Brittany , Cayer Kathleen , Nase Danielle , Holman Shaikim , Bradette Heath , Kar Swagata , Andersen Hanne , Lewis Mark G. , Cox Freek , Tolboom Jeroen T. B. M. , de Groot Anne Marit , Heerwegh Dirk , Le Gars Mathieu , Sadoff Jerald , Wegmann Frank , Zahn Roland C. , Schuitemaker Hanneke , Barouch Dan H.
Published: January 2022

SARS-CoV-2 Spike-specific binding and neutralizing antibodies, elicited either by natural infection or vaccination, have emerged as potential correlates of protection. An important question, however, is whether vaccine-elicited antibodies in humans provide direct, functional protection from SARS-CoV-2 infection and disease. In this study, we explored directly the protective efficacy of human antibodies elicited by Ad26.COV2.S vaccination by adoptive transfer studies. IgG from plasma of Ad26.COV2.S vaccinated individuals was purified and transferred into naïve golden Syrian hamster recipients, followed by intra-nasal challenge of the hamsters with SARS-CoV-2. IgG purified from Ad26.COV2.S-vaccinated individuals provided dose-dependent protection in the recipient hamsters from weight loss following challenge. In contrast, IgG purified from placebo recipients provided no protection in this adoptive transfer model. Attenuation of weight loss correlated with binding and neutralizing antibody titers of the passively transferred IgG. This study suggests that Ad26.COV2.S-elicited antibodies in humans are mechanistically involved in protection against SARS-CoV-2.
Ciliary beating patterns map onto a low-dimensional behavioural space
Authors: Geyer Veikko F. , Howard Jonathon , Sartori Pablo
Published: January 2022

Biological systems are robust to perturbations at both the genetic and environmental levels, although these same perturbations can elicit variation in behaviour. The interplay between functional robustness and behavioural variability is exemplified at the organellar level by the beating of cilia and flagella. Cilia are motile despite wide genetic diversity between and within species, differences in intracellular concentrations of ATP and calcium, and considerable environment fluctuations in temperature and viscosity. At the same time, these perturbations result in a variety of spatio-temporal patterns that span a rich behavioural space. To investigate this behavioural space we analysed the dynamics of isolated cilia from the unicellular algae Chlamydomonas reinhardtii under many different environmental and genetic conditions. We found that, despite large changes in beat frequency and amplitude, the space of waveform shapes is low-dimensional in the sense that two features account for 80% of the observed variation. The geometry of this behavioural space accords with the predictions of a simple mechanochemical model in the low-viscosity regime. This allowed us to associate waveform shape variability with changes in only the curvature response coefficients of the dynein motors.
Delivery of affordable and scalable encapsulated allogenic/autologous mesenchymal stem cells in coagulated platelet poor plasma for dental pulp regeneration
Authors: Angelopoulos Ioannis , Trigo Cesar , Ortuzar Maria-Ignacia , Cuenca Jimena , Brizuela Claudia , Khoury Maroun
Published: January 2022

The main goal of regenerative endodontics procedures (REPs) is to revitalize teeth by the regeneration of healthy dental pulp. In this study, we evaluated the potential of combining a natural and accessible biomaterial based on Platelet Poor Plasma (PPP) as a support for dental pulp stem cells (DPSC) and umbilical cord mesenchymal stem cells (UC-MSC). A comparison study between the two cell sources revealed compatibility with the PPP based scaffold with differences noted in the proliferation and angiogenic properties in vitro. Additionally, the release of growth factors including VEGF, HGF and DMP-1, was detected in the media of cultured PPP and was enhanced by the presence of the encapsulated MSCs. Dentin-Discs from human molars were filled with PPP alone or with MSCs and implanted subcutaneously for 4 weeks in mice. Histological analysis of the MSC-PPP implants revealed a newly formed dentin-like structure evidenced by the expression of Dentin sialophosphoprotein (DSPP). Finally, DPSC induced more vessel formation around the dental discs. This study provides evidence of a cost-effective, xenofree scaffold that is compatible with either autologous or allogenic strategy for dental pulp regeneration. This attempt if successfully implemented, could make REPs treatment widely accessible, contributing in improving global health conditions.
Water availability, bedrock, disturbance by herbivores, and climate determine plant diversity in South-African savanna
Authors: Hejda Martin , Čuda Jan , Pyšková Klára , Zambatis Guin , Foxcroft Llewellyn C. , MacFadyen Sandra , Storch David , Tropek Robert , Pyšek Petr
Published: January 2022

To identify factors that drive plant species richness in South-African savanna and explore their relative importance, we sampled plant communities across habitats differing in water availability, disturbance, and bedrock, using the Kruger National Park as a model system. We made plant inventories in 60 plots of 50 × 50 m, located in three distinct habitats: (i) at perennial rivers, (ii) at seasonal rivers with water available only during the rainy season, and (iii) on crests, at least ~ 5 km away from any water source. We predicted that large herbivores would utilise seasonal rivers’ habitats less intensely than those along perennial rivers where water is available throughout the year, including dry periods. Plots on granite harboured more herbaceous and shrub species than plots on basalt. The dry crests were poorer in herb species than both seasonal and perennial rivers. Seasonal rivers harboured the highest numbers of shrub species, in accordance with the prediction of the highest species richness at relatively low levels of disturbance and low stress from the lack of water. The crests, exposed to relatively low pressure from grazing but stressed by the lack of water, are important from the conservation perspective because they harbour typical, sometimes rare savanna species, and so are seasonal rivers whose shrub richness is stimulated and maintained by the combination of moderate disturbance imposed by herbivores and position in the middle of the water availability gradient. To capture the complexity of determinants of species richness in KNP, we complemented the analysis of the above local factors by exploring large-scale factors related to climate, vegetation productivity, the character of dominant vegetation, and landscape features. The strongest factor was temperature; areas with the highest temperatures reveal lower species richness. Our results also suggest thatColophospermum mopane, a dominant woody species in the north of KNP is not the ultimate cause of the lower plant diversity in this part of the park.
Acoustic-level and language-specific processing of native and non-native phonological sequence onsets in the low gamma and theta-frequency bands
Authors: Wagner Monica , Ortiz-Mantilla Silvia , Rusiniak Mateusz , Benasich April A. , Shafer Valerie L. , Steinschneider Mitchell
Published: January 2022

Acoustic structures associated with native-language phonological sequences are enhanced within auditory pathways for perception, although the underlying mechanisms are not well understood. To elucidate processes that facilitate perception, time–frequency (T–F) analyses of EEGs obtained from native speakers of English and Polish were conducted. Participants listened to same and different nonword pairs within counterbalanced attend and passive conditions. Nonwords contained the onsets /pt/, /pət/, /st/, and /sət/ that occur in both the Polish and English languages with the exception of /pt/, which never occurs in the English language in word onset. Measures of spectral power and inter-trial phase locking (ITPL) in the low gamma (LG) and theta-frequency bands were analyzed from two bilateral, auditory source-level channels, created through source localization modeling. Results revealed significantly larger spectral power in LG for the English listeners to the unfamiliar /pt/ onsets from the right hemisphere at early cortical stages, during the passive condition. Further, ITPL values revealed distinctive responses in high and low-theta to acoustic characteristics of the onsets, which were modulated by language exposure. These findings, language-specific processing in LG and acoustic-level and language-specific processing in theta, support the view that multi scale temporal processing in the LG and theta-frequency bands facilitates speech perception.