bluuebunny/crossref_metadata_2025 huggingface dataset:
Chirality transmission in macromolecular domains
Authors: Pandey Shankar , Mandal Shankar , Danielsen Mathias Bogetoft , Brown Asha , Hu Changpeng , Christensen Niels Johan , Kulakova Alina Vitaliyivna , Song Shixi , Brown Tom , Jensen Knud J. , Wengel Jesper , Lou Chenguang , Mao Hanbin
Published: January 2022

Chiral communications exist in secondary structures of foldamers and copolymers via a network of noncovalent interactions within effective intermolecular force (IMF) range. It is not known whether long-range chiral communication exists between macromolecular tertiary structures such as peptide coiled-coils beyond the IMF distance. Harnessing the high sensitivity of single-molecule force spectroscopy, we investigate the chiral interaction between covalently linked DNA duplexes and peptide coiled-coils by evaluating the binding of a diastereomeric pair of three DNA-peptide conjugates. We find that right-handed DNA triple helices well accommodate peptide triple coiled-coils of the same handedness, but not with the left-handed coiled-coil stereoisomers. This chiral communication is effective in a range (<4.5 nm) far beyond canonical IMF distance. Small-angle X-ray scattering and molecular dynamics simulation indicate that the interdomain linkers are tightly packed via hydrophobic interactions, which likely sustains the chirality transmission between DNA and peptide domains. Our findings establish that long-range chiral transmission occurs in tertiary macromolecular domains, explaining the presence of homochiral pairing of superhelices in proteins.
Observation of localized magnetic plasmon skyrmions
Authors: Deng Zi-Lan , Shi Tan , Krasnok Alex , Li Xiangping , Alù Andrea
Published: January 2022

Optical skyrmions have recently been constructed by tailoring vectorial near-field distributions through the interference of multiple surface plasmon polaritons, offering promising features for advanced information processing, transport and storage. Here, we provide experimental demonstration of electromagnetic skyrmions based on magnetic localized spoof plasmons (LSP) showing large topological robustness against continuous deformations, without stringent external interference conditions. By directly measuring the spatial profile of all three vectorial magnetic fields, we reveal multiple π-twist target skyrmion configurations mapped to multi-resonant near-equidistant LSP eigenmodes. The real-space skyrmion topology is robust against deformations of the meta-structure, demonstrating flexible skyrmionic textures for arbitrary shapes. The observed magnetic LSP skyrmions pave the way to ultra-compact and robust plasmonic devices, such as flexible sensors, wearable electronics and ultra-compact antennas.
Photocontrolled multiple-state photochromic benzo[b]phosphole thieno[3,2-b]phosphole-containing alkynylgold(I) complex via selective light irradiation
Authors: Wu Nathan Man-Wai , Ng Maggie , Yam Vivian Wing-Wah
Published: January 2022

Photochromic materials have drawn growing attention because using light as a stimulus has been regarded as a convenient and environmental-friendly way to control properties of smart materials. While photoresponsive systems that are capable of showing multiple-state photochromism are attractive, the development of materials with such capabilities has remained a challenging task. Here we show that a benzo[b]phosphole thieno[3,2‑b]phosphole-containing alkynylgold(I) complex features multiple photoinduced color changes, in which the gold(I) metal center plays an important role in separating two photoactive units that leads to the suppression of intramolecular quenching processes of the excited states. More importantly, the exclusive photochemical reactivity of the thieno[3,2‑b]phosphole moiety of the gold(I) complex can be initiated upon photoirradiation of visible light. Stepwise photochromism of the gold(I) complex has been made possible, offering an effective strategy for the construction of multiple-state photochromic materials with multiple photocontrolled states to enhance the storage capacity of potential optical memory devices.
Proximity labeling identifies a repertoire of site-specific R-loop modulators
Authors: Yan Qingqing , Wulfridge Phillip , Doherty John , Fernandez-Luna Jose L. , Real Pedro J. , Tang Hsin-Yao , Sarma Kavitha
Published: January 2022

R-loops are three-stranded nucleic acid structures that accumulate on chromatin in neurological diseases and cancers and contribute to genome instability. Using a proximity-dependent labeling system, we identified distinct classes of proteins that regulate R-loops in vivo through different mechanisms. We show that ATRX suppresses R-loops by interacting with RNAs and preventing R-loop formation. Our proteomics screen also discovered an unexpected enrichment for proteins containing zinc fingers and homeodomains. One of the most consistently enriched proteins was activity-dependent neuroprotective protein (ADNP), which is frequently mutated in ASD and causal in ADNP syndrome. We find that ADNP resolves R-loops in vitro and that it is necessary to suppress R-loops in vivo at its genomic targets. Furthermore, deletion of the ADNP homeodomain severely diminishes R-loop resolution activity in vitro, results in R-loop accumulation at ADNP targets, and compromises neuronal differentiation. Notably, patient-derived human induced pluripotent stem cells that contain an ADNP syndrome-causing mutation exhibit R-loop and CTCF accumulation at ADNP targets. Our findings point to a specific role for ADNP-mediated R-loop resolution in physiological and pathological neuronal function and, more broadly, to a role for zinc finger and homeodomain proteins in R-loop regulation, with important implications for developmental disorders and cancers.
A universal co-solvent dilution strategy enables facile and cost-effective fabrication of perovskite photovoltaics
Authors: Zhang Hong , Darabi Kasra , Nia Narges Yaghoobi , Krishna Anurag , Ahlawat Paramvir , Guo Boyu , Almalki Masaud Hassan S. , Su Tzu-Sen , Ren Dan , Bolnykh Viacheslav , Castriotta Luigi Angelo , Zendehdel Mahmoud , Pan Linfeng , Alonso Sandy Sanchez , Li Ruipeng , Zakeeruddin Shaik M. , Hagfeldt Anders , Rothlisberger Ursula , Di Carlo Aldo , Amassian Aram , Grätzel Michael
Published: January 2022

Cost management and toxic waste generation are two key issues that must be addressed before the commercialization of perovskite optoelectronic devices. We report a groundbreaking strategy for eco-friendly and cost-effective fabrication of highly efficient perovskite solar cells. This strategy involves the usage of a high volatility co-solvent, which dilutes perovskite precursors to a lower concentration (<0.5 M) while retaining similar film quality and device performance as a high concentration (>1.4 M) solution. More than 70% of toxic waste and material cost can be reduced. Mechanistic insights reveal ultra-rapid evaporation of the co-solvent together with beneficial alteration of the precursor colloidal chemistry upon dilution with co-solvent, which in-situ studies and theoretical simulations confirm. The co-solvent tuned precursor colloidal properties also contribute to the enhancement of the stability of precursor solution, which extends its processing window thus minimizing the waste. This strategy is universally successful across different perovskite compositions, and scales from small devices to large-scale modules using industrial spin-coating, potentially easing the lab-to-fab translation of perovskite technologies.
Magnetically brightened dark electron-phonon bound states in a van der Waals antiferromagnet
Authors: Ergeçen Emre , Ilyas Batyr , Mao Dan , Po Hoi Chun , Yilmaz Mehmet Burak , Kim Junghyun , Park Je-Geun , Senthil T. , Gedik Nuh
Published: January 2022

In van der Waals (vdW) materials, strong coupling between different degrees of freedom can hybridize elementary excitations into bound states with mixed character1–3. Correctly identifying the nature and composition of these bound states is key to understanding their ground state properties and excitation spectra4,5. Here, we use ultrafast spectroscopy to reveal bound states of d-orbitals and phonons in 2D vdW antiferromagnet NiPS3. These bound states manifest themselves through equally spaced phonon replicas in frequency domain. These states are optically dark above the Néel temperature and become accessible with magnetic order. By launching this phonon and spectrally tracking its amplitude, we establish the electronic origin of bound states as localized d–d excitations. Our data directly yield electron-phonon coupling strength which exceeds the highest known value in 2D systems6. These results demonstrate NiPS3 as a platform to study strong interactions between spins, orbitals and lattice, and open pathways to coherent control of 2D magnets.
Integrating gene expression and clinical data to identify drug repurposing candidates for hyperlipidemia and hypertension
Authors: Wu Patrick , Feng QiPing , Kerchberger Vern Eric , Nelson Scott D. , Chen Qingxia , Li Bingshan , Edwards Todd L. , Cox Nancy J. , Phillips Elizabeth J. , Stein C. Michael , Roden Dan M. , Denny Joshua C. , Wei Wei-Qi
Published: January 2022

Discovering novel uses for existing drugs, through drug repurposing, can reduce the time, costs, and risk of failure associated with new drug development. However, prioritizing drug repurposing candidates for downstream studies remains challenging. Here, we present a high-throughput approach to identify and validate drug repurposing candidates. This approach integrates human gene expression, drug perturbation, and clinical data from publicly available resources. We apply this approach to find drug repurposing candidates for two diseases, hyperlipidemia and hypertension. We screen >21,000 compounds and replicate ten approved drugs. We also identify 25 (seven for hyperlipidemia, eighteen for hypertension) drugs approved for other indications with therapeutic effects on clinically relevant biomarkers. For five of these drugs, the therapeutic effects are replicated in the All of Us Research Program database. We anticipate our approach will enable researchers to integrate multiple publicly available datasets to identify high priority drug repurposing opportunities for human diseases.
DNA methylation aging and transcriptomic studies in horses
Authors: Horvath Steve , Haghani Amin , Peng Sichong , Hales Erin N. , Zoller Joseph A. , Raj Ken , Larison Brenda , Robeck Todd R. , Petersen Jessica L. , Bellone Rebecca R. , Finno Carrie J.
Published: January 2022

Cytosine methylation patterns have not yet been thoroughly studied in horses. Here, we profilen = 333 samples from 42 horse tissue types at loci that are highly conserved between mammalian species using a custom array (HorvathMammalMethylChip40). Using the blood and liver tissues from horses, we develop five epigenetic aging clocks: a multi-tissue clock, a blood clock, a liver clock and two dual-species clocks that apply to both horses and humans. In addition, using blood methylation data from three additional equid species (plains zebra, Grevy’s zebras and Somali asses), we develop another clock that applies across all equid species. Castration does not significantly impact the epigenetic aging rate of blood or liver samples from horses. Methylation and RNA data from the same tissues define the relationship between methylation and RNA expression across horse tissues. We expect that the multi-tissue atlas will become a valuable resource.
Dynamics and mechanism of dimer dissociation of photoreceptor UVR8
Authors: Li Xiankun , Liu Zheyun , Ren Haisheng , Kundu Mainak , Zhong Frank W. , Wang Lijuan , Gao Jiali , Zhong Dongping
Published: January 2022

Photoreceptors are a class of light-sensing proteins with critical biological functions. UVR8 is the only identified UV photoreceptor in plants and its dimer dissociation upon UV sensing activates UV-protective processes. However, the dissociation mechanism is still poorly understood. Here, by integrating extensive mutations, ultrafast spectroscopy, and computational calculations, we find that the funneled excitation energy in the interfacial tryptophan (Trp) pyramid center drives a directional Trp-Trp charge separation in 80 ps and produces a critical transient Trp anion, enabling its ultrafast charge neutralization with a nearby positive arginine residue in 17 ps to destroy a key salt bridge. A domino effect is then triggered to unzip the strong interfacial interactions, which is facilitated through flooding the interface by channel and interfacial water molecules. These detailed dynamics reveal a unique molecular mechanism of UV-induced dimer monomerization.
SYP72 interacts with the mechanosensitive channel MSL8 to protect pollen from hypoosmotic shock during hydration
Authors: Zhou Xuemei , Zheng Yifan , Wang Ling , Li Haiming , Guo Yingying , Li Mengdi , Sun Meng-xiang , Zhao Peng
Published: January 2022

In flowering plants, hydration of desiccated pollen grains on stigma is a prerequisite for pollen germination, during which pollen increase markedly in volume through water uptake, requiring them to survive hypoosmotic shock to maintain cellular integrity. However, the mechanisms behind the adaptation of pollen to this hypoosmotic challenge are largely unknown. Here, we identify the Qc-SNARE protein SYP72, which is specifically expressed in male gametophytes, as a critical regulator of pollen survival upon hypoosmotic shock during hydration. SYP72 interacts with the MSCS-LIKE 8 (MSL8) and is required for its localization to the plasma membrane. Intraspecies and interspecies genetic complementation experiments reveal that SYP72 paralogs and orthologs from green algae to angiosperms display conserved molecular functions and rescue the defects of Arabidopsis syp72 mutant pollen facing hypoosmotic shock following hydration. Our findings demonstrate a critical role for SYP72 in pollen resistance to hypoosmotic shock through the MSL8 cascade during pollen hydration.
Mutations in Hcfc1 and Ronin result in an inborn error of cobalamin metabolism and ribosomopathy
Authors: Chern Tiffany , Achilleos Annita , Tong Xuefei , Hill Matthew C. , Saltzman Alexander B. , Reineke Lucas C. , Chaudhury Arindam , Dasgupta Swapan K. , Redhead Yushi , Watkins David , Neilson Joel R. , Thiagarajan Perumal , Green Jeremy B. A. , Malovannaya Anna , Martin James F. , Rosenblatt David S. , Poché Ross A.
Published: January 2022

Combined methylmalonic acidemia and homocystinuria(cblC)is the most common inborn error of intracellular cobalamin metabolism and due to mutations inMethylmalonic Aciduria type C and Homocystinuria (MMACHC). Recently, mutations in the transcriptional regulatorsHCFC1andRONIN (THAP11)were shown to result in cellular phenocopies ofcblC. Since HCFC1/RONIN jointly regulateMMACHC, patients with mutations in these factors suffer from reducedMMACHCexpression and exhibit acblC-like disease. However, additional de-regulated genes and the resulting pathophysiology is unknown. Therefore, we have generated mouse models of this disease. In addition to exhibiting loss ofMmachc, metabolic perturbations, and developmental defects previously observed incblC, we uncovered reduced expression of target genes that encode ribosome protein subunits. We also identified specific phenotypes that we ascribe to deregulation of ribosome biogenesis impacting normal translation during development. These findings identify HCFC1/RONIN as transcriptional regulators of ribosome biogenesis during development and their mutation results in complex syndromes exhibiting aspects of bothcblCand ribosomopathies.
Flame retardant high-power Li-S flexible batteries enabled by bio-macromolecular binder integrating conformal fractions
Authors: Senthil Chenrayan , Kim Sun-Sik , Jung Hyun Young
Published: January 2022

Polymer binders for sulfur cathodes play a very critical role as they prerequisites for an in-situ immobilization against polysulfide shuttle and volume change, while ensuring good adhesion within active materials for ion conduction along with robust mechanical and chemical stability. Here, we demonstrate anionic surface charge facilitated bio-polymer binder for sulfur cathodes enabling excellent performance and fire safety improvement. The aqueous-processable tragacanth gum-based binder is adjusted to house high sulfur loading over 12 mg cm−2 without compromising the sulfur utility and reversibility, imparting high accessibility for Li-ions to sulfur particles about 80%. The intrinsic rod and sphere-like saccharidic conformal fraction’s multifunctional polar units act as active channels to reach the sulfur particles. As a result, the binder entraps polysulfides with 46% improvement and restrains the volume changes within 16 % even at 4 C. Moreover, the flexible Li-S battery delivers a stack gravimetric energy density of 243 Wh kg–1, demonstrating high reactivity of sulfur along with good shape conformality, which would open an avenue for the potential development of the compact and flexible high-power device.
Fast and pervasive diagenetic isotope exchange in foraminifera tests is species-dependent
Authors: Cisneros-Lazaro Deyanira , Adams Arthur , Guo Jinming , Bernard Sylvain , Baumgartner Lukas P. , Daval Damien , Baronnet Alain , Grauby Olivier , Vennemann Torsten , Stolarski Jarosław , Escrig Stéphane , Meibom Anders
Published: January 2022

Oxygen isotope compositions of fossil foraminifera tests are commonly used proxies for ocean paleotemperatures, with reconstructions spanning the last 112 million years. However, the isotopic composition of these calcitic tests can be substantially altered during diagenesis without discernible textural changes. Here, we investigate fluid-mediated isotopic exchange in pristine tests of three modern benthic foraminifera species (Ammonia sp., Haynesina germanica, and Amphistegina lessonii) following immersion into an 18O-enriched artificial seawater at 90 °C for hours to days. Reacted tests remain texturally pristine but their bulk oxygen isotope compositions reveal rapid and species-dependent isotopic exchange with the water. NanoSIMS imaging reveals the 3-dimensional intra-test distributions of 18O-enrichment that correlates with test ultra-structure and associated organic matter. Image analysis is used to quantify species level differences in test ultrastructure, which explains the observed species-dependent rates of isotopic exchange. Consequently, even tests considered texturally pristine for paleo-climatic reconstruction purposes may have experienced substantial isotopic exchange; critical paleo-temperature record re-examination is warranted.
Contact-electro-catalysis for the degradation of organic pollutants using pristine dielectric powders
Authors: Wang Ziming , Berbille Andy , Feng Yawei , Li Site , Zhu Laipan , Tang Wei , Wang Zhong Lin
Published: January 2022

Mechanochemistry has been studied for some time, but research on the reactivity of charges exchanged by contact-electrification (CE) during mechanical stimulation remains scarce. Here, we demonstrate that electrons transferred during the CE between pristine dielectric powders and water can be utilized to directly catalyze reactions without the use of conventional catalysts. Specifically, frequent CE at Fluorinated Ethylene Propylene (FEP) - water interface induces electron-exchanges, thus forming reactive oxygen species for the degradation of an aqueous methyl orange solution. Contact-electro-catalysis, by conjunction of CE, mechanochemistry and catalysis, has been proposed as a general mechanism, which has been demonstrated to be effective for various dielectric materials, such as Teflon, Nylon-6,6 and rubber. This original catalytic principle not only expands the range of catalytic materials, but also enables us to envisage catalytic processes through mechano-induced contact-electrification.
How palladium inhibits CO poisoning during electrocatalytic formic acid oxidation and carbon dioxide reduction
Authors: Chen Xiaoting , Granda-Marulanda Laura P. , McCrum Ian T. , Koper Marc T. M.
Published: January 2022

Development of reversible and stable catalysts for the electrochemical reduction of CO2is of great interest. Here, we elucidate the atomistic details of how a palladium electrocatalyst inhibits CO poisoning during both formic acid oxidation to carbon dioxide and carbon dioxide reduction to formic acid. We compare results obtained with a platinum single-crystal electrode modified with and without a single monolayer of palladium. We combine (high-scan-rate) cyclic voltammetry with density functional theory to explain the absence of CO poisoning on the palladium-modified electrode. We show how the high formate coverage on the palladium-modified electrode protects the surface from poisoning during formic acid oxidation, and how the adsorption of CO precursor dictates the delayed poisoning during CO2reduction. The nature of the hydrogen adsorbed on the palladium-modified electrode is considerably different from platinum, supporting a model to explain the reversibility of this reaction. Our results help in designing catalysts for which CO poisoning needs to be avoided.
Half-Heusler-like compounds with wide continuous compositions and tunable p- to n-type semiconducting thermoelectrics
Authors: Dong Zirui , Luo Jun , Wang Chenyang , Jiang Ying , Tan Shihua , Zhang Yubo , Grin Yuri , Yu Zhiyang , Guo Kai , Zhang Jiye , Zhang Wenqing
Published: January 2022

Half-Heusler and full-Heusler compounds were considered as independent phases with a natural composition gap. Here we report the discovery of TiRu1+xSb (x = 0.15 ~ 1.0) solid solution with wide homogeneity range and tunable p- to n-type semiconducting thermoelectrics, which bridges the composition gap between half- and full-Heusler phases. At the high-Ru end, strange glass-like thermal transport behavior with unusually low lattice thermal conductivity (~1.65 Wm−1K−1 at 340 K) is observed for TiRu1.8Sb, being the lowest among reported half-Heusler phases. In the composition range of 0.15 < x < 0.50, TiRu1+xSb shows abnormal semiconducting behaviors because tunning Ru composition results in band structure change and carrier-type variation simultaneously, which seemingly correlates with the localized d electrons. This work reveals the possibility of designing fascinating half-Heusler-like materials by manipulating the tetrahedral site occupancy, and also demonstrates the potential of tuning crystal and electronic structures simultaneously to realize intriguing physical properties.
Hypocrates is a genetically encoded fluorescent biosensor for (pseudo)hypohalous acids and their derivatives
Authors: Kostyuk Alexander I. , Tossounian Maria-Armineh , Panova Anastasiya S. , Thauvin Marion , Raevskii Roman I. , Ezeriņa Daria , Wahni Khadija , Van Molle Inge , Sergeeva Anastasia D. , Vertommen Didier , Gorokhovatsky Andrey Yu. , Baranov Mikhail S. , Vriz Sophie , Messens Joris , Bilan Dmitry S. , Belousov Vsevolod V.
Published: January 2022

The lack of tools to monitor the dynamics of (pseudo)hypohalous acids in live cells and tissues hinders a better understanding of inflammatory processes. Here we present a fluorescent genetically encoded biosensor, Hypocrates, for the visualization of (pseudo)hypohalous acids and their derivatives. Hypocrates consists of a circularly permuted yellow fluorescent protein integrated into the structure of the transcription repressor NemR fromEscherichia coli. We show that Hypocrates is ratiometric, reversible, and responds to its analytes in the 106 M−1s−1range. Solving the Hypocrates X-ray structure provided insights into its sensing mechanism, allowing determination of the spatial organization in this circularly permuted fluorescent protein-based redox probe. We exemplify its applicability by imaging hypohalous stress in bacteria phagocytosed by primary neutrophils. Finally, we demonstrate that Hypocrates can be utilized in combination with HyPerRed for the simultaneous visualization of (pseudo)hypohalous acids and hydrogen peroxide dynamics in a zebrafish tail fin injury model.
Single cell transcriptomic landscape of diabetic foot ulcers
Authors: Theocharidis Georgios , Thomas Beena E. , Sarkar Debasree , Mumme Hope L. , Pilcher William J. R. , Dwivedi Bhakti , Sandoval-Schaefer Teresa , Sîrbulescu Ruxandra F. , Kafanas Antonios , Mezghani Ikram , Wang Peng , Lobao Antonio , Vlachos Ioannis S. , Dash Biraja , Hsia Henry C. , Horsley Valerie , Bhasin Swati S. , Veves Aristidis , Bhasin Manoj
Published: January 2022

Diabetic foot ulceration (DFU) is a devastating complication of diabetes whose pathogenesis remains incompletely understood. Here, we profile 174,962 single cells from the foot, forearm, and peripheral blood mononuclear cells using single-cell RNA sequencing. Our analysis shows enrichment of a unique population of fibroblasts overexpressing MMP1, MMP3, MMP11, HIF1A, CHI3L1, and TNFAIP6 and increased M1 macrophage polarization in the DFU patients with healing wounds. Further, analysis of spatially separated samples from the same patient and spatial transcriptomics reveal preferential localization of these healing associated fibroblasts toward the wound bed as compared to the wound edge or unwounded skin. Spatial transcriptomics also validates our findings of higher abundance of M1 macrophages in healers and M2 macrophages in non-healers. Our analysis provides deep insights into the wound healing microenvironment, identifying cell types that could be critical in promoting DFU healing, and may inform novel therapeutic approaches for DFU treatment.
Alcohols electrooxidation coupled with H2 production at high current densities promoted by a cooperative catalyst
Authors: Li Zhenhua , Yan Yifan , Xu Si-Min , Zhou Hua , Xu Ming , Ma Lina , Shao Mingfei , Kong Xianggui , Wang Bin , Zheng Lirong , Duan Haohong
Published: January 2022

Electrochemical alcohols oxidation offers a promising approach to produce valuable chemicals and facilitate coupled H2 production. However, the corresponding current density is very low at moderate cell potential that substantially limits the overall productivity. Here we report the electrooxidation of benzyl alcohol coupled with H2 production at high current density (540 mA cm−2 at 1.5 V vs. RHE) over a cooperative catalyst of Au nanoparticles supported on cobalt oxyhydroxide nanosheets (Au/CoOOH). The absolute current can further reach 4.8 A at 2.0 V in a more realistic two-electrode membrane-free flow electrolyzer. Experimental combined with theoretical results indicate that the benzyl alcohol can be enriched at Au/CoOOH interface and oxidized by the electrophilic oxygen species (OH*) generated on CoOOH, leading to higher activity than pure Au. Based on the finding that the catalyst can be reversibly oxidized/reduced at anodic potential/open circuit, we design an intermittent potential (IP) strategy for long-term alcohol electrooxidation that achieves high current density (>250 mA cm−2) over 24 h with promoted productivity and decreased energy consumption.
Extensive primary production promoted the recovery of the Ediacaran Shuram excursion
Authors: Cañadas Fuencisla , Papineau Dominic , Leng Melanie J. , Li Chao
Published: January 2022

Member IV of the Ediacaran Doushantuo Formation records the recovery from the most negative carbon isotope excursion in Earth history. However, the main biogeochemical controls that ultimately drove this recovery have yet to be elucidated. Here, we report new carbon and nitrogen isotope and concentration data from the Nanhua Basin (South China), where δ13C values of carbonates (δ13Ccarb) rise from − 7‰ to −1‰ and δ15N values decrease from +5.4‰ to +2.3‰. These trends are proposed to arise from a new equilibrium in the C and N cycles where primary production overcomes secondary production as the main source of organic matter in sediments. The enhanced primary production is supported by the coexisting Raman spectral data, which reveal a systematic difference in kerogen structure between depositional environments. Our new observations point to the variable dominance of distinct microbial communities in the late Ediacaran ecosystems, and suggest that blooms of oxygenic phototrophs modulated the recovery from the most negative δ13Ccarb excursion in Earth history.
Efficient room temperature catalytic synthesis of alternating conjugated copolymers via C-S bond activation
Authors: Li Zijie , Shi Qinqin , Ma Xiaoying , Li Yawen , Wen Kaikai , Qin Linqing , Chen Hao , Huang Wei , Zhang Fengjiao , Lin Yuze , Marks Tobin J. , Huang Hui
Published: January 2022

Structural defects in conjugated copolymers are severely detrimental to the optoelectronic properties and the performance of the resulting electronic devices fabricated from them. Therefore, the much-desired precision synthesis of conjugated copolymers with highly regular repeat units is important, but presents a significant challenge to synthetic materials chemists. To this end, aryl sulfides are naturally abundant substances and offer unrealized potential in cross-coupling reactions. Here we report an efficient room temperature polycondensation protocol which implements aryl disulfide C-S activation to produce defect-minimized semiconducting conjugated copolymers with broad scope and applicability. Thus, a broad series of arylstannanes and thioethers are employed via the present protocol to afford copolymers with number-average molecular weights (Mns) of 10.0–45.0 kDa. MALDI and NMR analysis of selected copolymers reveals minimal structural defects. Moreover, the polymer trap density here is smaller and the field effect mobility higher than that in the analogous polymer synthesized through thermal-activation Stille coupling.
Overcoming resistance to immune checkpoint therapy in PTEN-null prostate cancer by intermittent anti-PI3Kα/β/δ treatment
Authors: Qi Zhi , Xu Zihan , Zhang Liuzhen , Zou Yongkang , Li Jinping , Yan Wenyu , Li Cheng , Liu Ningshu , Wu Hong
Published: January 2022

Combining immune checkpoint therapy (ICT) and targeted therapy holds great promises for broad and long-lasting anti-cancer therapies. However, combining ICT with anti-PI3K inhibitors have been challenging because the multifaceted effects of PI3K on both cancer cells and immune cells within the tumor microenvironment. Here we find that intermittent but not daily dosing of a PI3Kα/β/δ inhibitor, BAY1082439, on Pten-null prostate cancer models could overcome ICT resistance and unleash CD8+ T cell-dependent anti-tumor immunity in vivo. Mechanistically, BAY1082439 converts cancer cell-intrinsic immune-suppression to immune-stimulation by promoting IFNα/IFNγ pathway activation, β2-microglubin expression and CXCL10/CCL5 secretion. With its preferential regulatory T cell inhibition activity, BAY1082439 promotes clonal expansion of tumor-associated CD8+ T cells, most likely via tertiary lymphoid structures. Once primed, tumors remain T cell-inflamed, become responsive to anti-PD-1 therapy and have durable therapeutic effect. Our data suggest that intermittent PI3K inhibition can alleviate Pten-null cancer cell-intrinsic immunosuppressive activity and turn “cold” tumors into T cell-inflamed ones, paving the way for successful ICT.
Scn1a gene reactivation after symptom onset rescues pathological phenotypes in a mouse model of Dravet syndrome
Authors: Valassina Nicholas , Brusco Simone , Salamone Alessia , Serra Linda , Luoni Mirko , Giannelli Serena , Bido Simone , Massimino Luca , Ungaro Federica , Mazzara Pietro Giuseppe , D’Adamo Patrizia , Lignani Gabriele , Broccoli Vania , Colasante Gaia
Published: January 2022

Dravet syndrome is a severe epileptic encephalopathy caused primarily by haploinsufficiency of the SCN1A gene. Repetitive seizures can lead to endurable and untreatable neurological deficits. Whether this severe pathology is reversible after symptom onset remains unknown. To address this question, we generated a Scn1a conditional knock-in mouse model (Scn1a Stop/+) in which Scn1a expression can be re-activated on-demand during the mouse lifetime. Scn1a gene disruption leads to the development of seizures, often associated with sudden unexpected death in epilepsy (SUDEP) and behavioral alterations including hyperactivity, social interaction deficits and cognitive impairment starting from the second/third week of age. However, we showed that Scn1a gene re-activation when symptoms were already manifested (P30) led to a complete rescue of both spontaneous and thermic inducible seizures, marked amelioration of behavioral abnormalities and normalization of hippocampal fast-spiking interneuron firing. We also identified dramatic gene expression alterations, including those associated with astrogliosis in Dravet syndrome mice, that, accordingly, were rescued by Scn1a gene expression normalization at P30. Interestingly, regaining of Nav1.1 physiological level rescued seizures also in adult Dravet syndrome mice (P90) after months of repetitive attacks. Overall, these findings represent a solid proof-of-concept highlighting that disease phenotype reversibility can be achieved when Scn1a gene activity is efficiently reconstituted in brain cells.
The m6A methyltransferase METTL3 regulates muscle maintenance and growth in mice
Authors: Petrosino Jennifer M. , Hinger Scott A. , Golubeva Volha A. , Barajas Juan M. , Dorn Lisa E. , Iyer Chitra C. , Sun Hui-Lung , Arnold W. David , He Chuan , Accornero Federica
Published: January 2022

Skeletal muscle serves fundamental roles in organismal health. Gene expression fluctuations are critical for muscle homeostasis and the response to environmental insults. Yet, little is known about post-transcriptional mechanisms regulating such fluctuations while impacting muscle proteome. Here we report genome-wide analysis of mRNA methyladenosine (m6A) dynamics of skeletal muscle hypertrophic growth following overload-induced stress. We show that increases in METTL3 (the m6A enzyme), and concomitantly m6A, control skeletal muscle size during hypertrophy; exogenous delivery of METTL3 induces skeletal muscle growth, even without external triggers. We also show that METTL3 represses activin type 2 A receptors (ACVR2A) synthesis, blunting activation of anti-hypertrophic signaling. Notably, myofiber-specific conditional genetic deletion of METTL3 caused spontaneous muscle wasting over time and abrogated overload-induced hypertrophy; a phenotype reverted by co-administration of a myostatin inhibitor. These studies identify a previously unrecognized post-transcriptional mechanism promoting the hypertrophic response of skeletal muscle via control of myostatin signaling.
Targeting necroptosis in muscle fibers ameliorates inflammatory myopathies
Authors: Kamiya Mari , Mizoguchi Fumitaka , Kawahata Kimito , Wang Dengli , Nishibori Masahiro , Day Jessica , Louis Cynthia , Wicks Ian P. , Kohsaka Hitoshi , Yasuda Shinsuke
Published: January 2022

Muscle cell death in polymyositis is induced by CD8+ cytotoxic T lymphocytes. We hypothesized that the injured muscle fibers release pro-inflammatory molecules, which would further accelerate CD8+ cytotoxic T lymphocytes-induced muscle injury, and inhibition of the cell death of muscle fibers could be a novel therapeutic strategy to suppress both muscle injury and inflammation in polymyositis. Here, we show that the pattern of cell death of muscle fibers in polymyositis is FAS ligand-dependent necroptosis, while that of satellite cells and myoblasts is perforin 1/granzyme B-dependent apoptosis, using human muscle biopsy specimens of polymyositis patients and models of polymyositis in vitro and in vivo. Inhibition of necroptosis suppresses not only CD8+ cytotoxic T lymphocytes-induced cell death of myotubes but also the release of inflammatory molecules including HMGB1. Treatment with a necroptosis inhibitor or anti-HMGB1 antibodies ameliorates myositis-induced muscle weakness as well as muscle cell death and inflammation in the muscles. Thus, targeting necroptosis in muscle cells is a promising strategy for treating polymyositis providing an alternative to current therapies directed at leukocytes.
Reciprocity of thermal diffusion in time-modulated systems
Authors: Li Jiaxin , Li Ying , Cao Pei-Chao , Qi Minghong , Zheng Xu , Peng Yu-Gui , Li Baowen , Zhu Xue-Feng , Alù Andrea , Chen Hongsheng , Qiu Cheng-Wei
Published: January 2022

The reciprocity principle governs the symmetry in transmission of electromagnetic and acoustic waves, as well as the diffusion of heat between two points in space, with important consequences for thermal management and energy harvesting. There has been significant recent interest in materials with time-modulated properties, which have been shown to efficiently break reciprocity for light, sound, and even charge diffusion. However, time modulation may not be a plausible approach to break thermal reciprocity, in contrast to the usual perception. We establish a theoretical framework to accurately describe the behavior of diffusive processes under time modulation, and prove that thermal reciprocity in dynamic materials is generally preserved by the continuity equation, unless some external bias or special material is considered. We then experimentally demonstrate reciprocal heat transfer in a time-modulated device. Our findings correct previous misconceptions regarding reciprocity breaking for thermal diffusion, revealing the generality of symmetry constraints in heat transfer, and clarifying its differences from other transport processes in what concerns the principles of reciprocity and microscopic reversibility.
Climate warming may increase the frequency of cold-adapted haplotypes in alpine plants
Authors: Wessely Johannes , Gattringer Andreas , Guillaume Frédéric , Hülber Karl , Klonner Günther , Moser Dietmar , Dullinger Stefan
Published: January 2022

Modelling of climate-driven range shifts commonly treats species as ecologically homogeneous units. However, many species show intraspecific variation of climatic niches and theory predicts that such variation may lead to counterintuitive eco-evolutionary dynamics. Here, we incorporate assumed intraspecific niche variation into a dynamic range model and explore possible consequences for six high-mountain plant species of the European Alps under scenarios of twenty-first century climate warming. At the species level, the results indicate massive range loss independent of intraspecific variation. At the intraspecific level, the model predicts a decrease in the frequency of warm-adapted haplotypes in five species. The latter effect is probably driven by a combination of leading-edge colonization and priority effects within the species’ elevational range and was weakest when leading-edge expansion was constrained by mountain topography The resulting maladaptation may additionally increase the risk that alpine plants face from shrinkage of their ranges in a warming climate.
Fibroblast growth factor-21 as a novel metabolic factor for regulating thrombotic homeostasis
Authors: Li Shuai , Jia Haibo , Liu Zhihang , Wang Nan , Guo Xiaochen , Cao Muhua , Fang Fang , Yang Jiarui , Li Junyan , He Qi , Guo Rui , Zhang Teng , Kang Kai , Wang Zongbao , Liu Shijie , Cao Yukai , Jiang Xinghao , Ren Guiping , Wang Kai , Yu Bo , Xiao Wei , Li Deshan
Published: January 2022

Fibroblast growth factor-21 (FGF-21) performs a wide range of biological functions in organisms. Here, we report for the first time that FGF-21 suppresses thrombus formation with no notable risk of bleeding. Prophylactic and therapeutic administration of FGF-21 significantly improved the degree of vascular stenosis and reduced the thrombus area, volume and burden. We determined the antithrombotic mechanism of FGF-21, demonstrating that FGF-21 exhibits an anticoagulant effect by inhibiting the expression and activity of factor VII (FVII). FGF-21 exerts an antiplatelet effect by inhibiting platelet activation. FGF-21 enhances fibrinolysis by promoting tissue plasminogen activator (tPA) expression and activation, while inhibiting plasminogen activator inhibitor 1 (PAI-1) expression and activation. We further found that FGF-21 mediated the expression and activation of tPA and PAI-1 by regulating the ERK1/2 and TGF-β/Smad2 pathways, respectively. In addition, we found that FGF-21 inhibits the expression of inflammatory factors in thrombosis by regulating the NF-κB pathway.
Compensatory contribution of retinal larger vessels to perfusion density in diabetics without retinopathy
Authors: Blanco-Hernández Dulce Milagros Razo , Somilleda-Ventura Selma Alin , Chávez-Herrera Rebeca , Colas-Calvere María Guadalupe , Lima-Gómez Virgilio
Published: January 2022

Vessel and perfusion densities may decrease before diabetic retinopathy appears; it is unknown whether these changes affect the contribution of vessel density to perfusion density. This was a non-experimental, comparative, prospective, cross-sectional study in non-diabetic subjects (group 1) and diabetics without retinopathy (group 2). Vessel and perfusion densities in the superficial capillary plexus were compared between groups at the center, inner, and full regions and by field (superior, temporal, inferior, nasal) using optical coherence tomography angiography. Coefficients of determination (R2) between vessel and perfusion densities were calculated to find the contribution of larger retinal vessels to perfusion density. Percent differences were used to evaluate the contribution of these vessels to perfusion density in a regression model. There were 62 participants, 31 eyes by group; vessel and perfusion densities as well as the coefficients of determination between them were lower in group 2, especially in the nasal field (R2 0.85 vs. 0.71), which showed a higher contribution of larger retinal vessels to perfusion density. The regression model adjusted to a quadratic equation. In diabetics without retinopathy the contribution of vessel density to perfusion density may decrease; a low vessel density may increase the contribution of larger retinal vessels to perfusion density.
Clinical significance of quantitative bone SPECT/CT in the evaluation of hand and wrist pain in patients with rheumatic disease
Authors: Lim Chae Hong , Kim Hyun-Sook , Lee Kyung-Ann , Kim JongSun , Park Soo Bin
Published: January 2022

We investigated the diagnostic value of the maximum standardized uptake value (SUV) at hand and wrist joints for differentiating rheumatic diseases via bone single-photon emission computed tomography (SPECT)/computed tomography (CT). A total of 84 patients manifesting hand and wrist pain (58 women; age, 49.8 ± 15.4 years) were finally diagnosed with rheumatoid arthritis (RA, n = 42), osteoarthritis (OA, n = 16), fibromyalgia (FM, n = 2), and other rheumatic diseases (n = 24). The SUV of each patient was measured in 32 joints including the distal interphalangeal (DIP), proximal interphalangeal (PIP), metacarpophalangeal (MCP), and wrist joints bilaterally. Differences in pain and SUVs between specific rheumatic diseases were assessed using the chi-squared test or one-way analysis of variance. Using the highest SUV (hSUV) in each patient, the diagnostic performance in differentiating specific diseases was evaluated by receiver operating characteristic (ROC) curve analysis. Pain symptoms were present in 886 (33.0%) sites in a total of 2688 joints. In four joint groups (DIP, PIP, MCP, and wrist), the SUVs of joints with pain were significantly higher than those of pain-free joints (all P < 0.001). Active joint sites with higher SUVs than the median value of each joint group were the most common in RA (55.1%). RA showed the greatest hSUV in the PIP (3.0 ± 2.4), MCP (3.5 ± 3.4), and wrist (3.3 ± 1.9) joint groups. FM was characterized by the lowest hSUV of all joint groups. In ROC curve analysis, the cumulative hSUV of the PIP, MCP, and wrist joint groups showed good performance for evaluating RA (area under the curve (AUC), 0.668; P = 0.005). The summation of the hSUVs at all joint groups had an excellent predictive performance for FM (AUC, 0.878; P < 0.001). Consequently, the arthritic activity of the hand and wrist joints based on SUV differed according to specific rheumatic diseases. Quantitative SPECT/CT may provide objective information related to arthritic activity for differentiating specific rheumatic diseases.
Synthetic aircraft RS image modelling based on improved conditional GAN joint embedding network
Authors: Chen Junyu , Li Haiwei , Song Liyao , Zhang Geng , Hu Bingliang , Wang Shuang , Liu Song , Li Siyuan , Chen Tieqiao , Liu Jia
Published: January 2022

Developing an efficient and quality remote sensing (RS) technology using volume and efficient modelling in different aircraft RS images is challenging. Generative models serve as a natural and convenient simulation method. Because aircraft types belong to the fine class under the rough class, the issue of feature entanglement may occur while modelling multiple aircraft classes. Our solution to this issue was a novel first-generation realistic aircraft type simulation system (ATSS-1) based on the RS images. It realised fine modelling of the seven aircraft types based on a real scene by establishing an adaptive weighted conditional attention generative adversarial network and joint geospatial embedding (GE) network. An adaptive weighted conditional batch normalisation attention block solved the subclass entanglement by reassigning the intra-class-wise characteristic responses. Subsequently, an asymmetric residual self-attention module was developed by establishing a remote region asymmetric relationship for mining the finer potential spatial representation. The mapping relationship between the input RS scene and the potential space of the generated samples was explored through the GE network construction that used the selected prior distribution z, as an intermediate representation. A public RS dataset (OPT-Aircraft_V1.0) and two public datasets (MNIST and Fashion-MNIST) were used for simulation model testing. The results demonstrated the effectiveness of ATSS-1, promoting further development of realistic automatic RS simulation.
Multi-column modelling of lake Geneva for climate applications
Authors: Gaillard Romain , Perroud Marjorie , Goyette Stéphane , Kasparian Jérôme
Published: January 2022

The interaction between large inland water bodies and the atmosphere impacts the evolution of regional weather and climate, which in turn affects the lake dynamics, thermodynamics, ice-formation, and, therefore, ecosystems. Over the last decades, various approaches have been used to model lake thermodynamics and dynamics in standalone mode or coupled to numerical atmospheric models. We assess a turbulence-closure $$k-\epsilon$$

k
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ϵ

multi-column lake model in standalone mode as a computationally-efficient alternative to a full three-dimensional hydrodynamic model in the case of Lake Geneva. While it struggles to reproduce some short-term features, the multi-column model reasonably reproduces the seasonal mean of the thermal horizontal and vertical structures governing heat and mass exchanges between the lake surface and the lower atmosphere (stratified period, thermocline depth, stability of the water column). As it requires typically two orders of magnitude less computational ressources, it may allow a two-way coupling with a RCM on timescales or spatial resolutions where full 3D lake models are too demanding.