bluuebunny/crossref_metadata_2025_split huggingface dataset:
POLRMT mutations impair mitochondrial transcription causing neurological disease
Authors: Oláhová Monika , Peter Bradley , Szilagyi Zsolt , Diaz-Maldonado Hector , Singh Meenakshi , Sommerville Ewen W. , Blakely Emma L. , Collier Jack J. , Hoberg Emily , Stránecký Viktor , Hartmannová Hana , Bleyer Anthony J. , McBride Kim L. , Bowden Sasigarn A. , Korandová Zuzana , Pecinová Alena , Ropers Hans-Hilger , Kahrizi Kimia , Najmabadi Hossein , Tarnopolsky Mark A. , Brady Lauren I. , Weaver K. Nicole , Prada Carlos E. , Õunap Katrin , Wojcik Monica H. , Pajusalu Sander , Syeda Safoora B. , Pais Lynn , Estrella Elicia A. , Bruels Christine C. , Kunkel Louis M. , Kang Peter B. , Bonnen Penelope E. , Mráček Tomáš , Kmoch Stanislav , Gorman Gráinne S. , Falkenberg Maria , Gustafsson Claes M. , Taylor Robert W. 
Published: February 2021

AbstractWhile >300 disease-causing variants have been identified in the mitochondrial DNA (mtDNA) polymerase γ, no mitochondrial phenotypes have been associated with POLRMT, the RNA polymerase responsible for transcription of the mitochondrial genome. Here, we characterise the clinical and molecular nature of POLRMT variants in eight individuals from seven unrelated families. Patients present with global developmental delay, hypotonia, short stature, and speech/intellectual disability in childhood; one subject displayed an indolent progressive external ophthalmoplegia phenotype. Massive parallel sequencing of all subjects identifies recessive and dominant variants in the POLRMT gene. Patient fibroblasts have a defect in mitochondrial mRNA synthesis, but no mtDNA deletions or copy number abnormalities. The in vitro characterisation of the recombinant POLRMT mutants reveals variable, but deleterious effects on mitochondrial transcription. Together, our in vivo and in vitro functional studies of POLRMT variants establish defective mitochondrial transcription as an important disease mechanism.
Symmetry breaking propulsion of magnetic microspheres in nonlinearly viscoelastic fluids
Authors: Rogowski Louis William , Ali Jamel , Zhang Xiao , Wilking James N. , Fu Henry C. , Kim Min Jun 
Published: February 2021

AbstractMicroscale propulsion impacts a diverse array of fields ranging from biology and ecology to health applications, such as infection, fertility, drug delivery, and microsurgery. However, propulsion in such viscous drag-dominated fluid environments is highly constrained, with time-reversal and geometric symmetries ruling out entire classes of propulsion. Here, we report the spontaneous symmetry-breaking propulsion of rotating spherical microparticles within non-Newtonian fluids. While symmetry analysis suggests that propulsion is not possible along the fore-aft directions, we demonstrate the existence of two equal and opposite propulsion states along the sphere’s rotation axis. We propose and experimentally corroborate a propulsion mechanism for these spherical microparticles, the simplest microswimmers to date, arising from nonlinear viscoelastic effects in rotating flows similar to the rod-climbing effect. Similar possibilities of spontaneous symmetry-breaking could be used to circumvent other restrictions on propulsion, revising notions of microrobotic design and control, drug delivery, microscale pumping, and locomotion of microorganisms.
Highly active alkyne metathesis catalysts operating under open air condition
Authors: Ge Yanqing , Huang Shaofeng , Hu Yiming , Zhang Lei , He Ling , Krajewski Sebastian , Ortiz Michael , Jin Yinghua , Zhang Wei 
Published: February 2021

AbstractAlkyne metathesis represents a rapidly emerging synthetic method that has shown great potential in small molecule and polymer synthesis. However, its practical use has been impeded by the limited availability of user-friendly catalysts and their generally high moisture/air sensitivity. Herein, we report an alkyne metathesis catalyst system that can operate under open-air conditions with a broad substrate scope and excellent yields. These catalysts are composed of simple multidentate tris(2-hydroxyphenyl)methane ligands, which can be easily prepared in multi-gram scale. The catalyst substituted with electron withdrawing cyano groups exhibits the highest activity at room temperature with excellent functional group tolerance (-OH, -CHO, -NO2, pyridyl). More importantly, the catalyst provides excellent yields (typically >90%) in open air, comparable to those operating under argon. When dispersed in paraffin wax, the active catalyst can be stored on a benchtop under ambient conditions without any decrease in activity for one day (retain 88% after 3 days). This work opens many possibilities for developing highly active user-friendly alkyne metathesis catalysts that can function in open air.
Genome-wide association studies provide insights into the genetic determination of fruit traits of pear
Authors: Zhang Ming-Yue , Xue Cheng , Hu Hongju , Li Jiaming , Xue Yongsong , Wang Runze , Fan Jing , Zou Cheng , Tao Shutian , Qin Mengfan , Bai Bing , Li Xiaolong , Gu Chao , Wu Shan , Chen Xu , Yang Guangyan , Liu Yueyuan , Sun Manyi , Fei Zhangjun , Zhang Shaoling , Wu Jun 
Published: February 2021

AbstractPear is a major fruit tree crop distributed worldwide, yet its breeding is a very time-consuming process. To facilitate molecular breeding and gene identification, here we have performed genome-wide association studies (GWAS) on eleven fruit traits. We identify 37 loci associated with eight fruit quality traits and five loci associated with three fruit phenological traits. Scans for selective sweeps indicate that traits including fruit stone cell content, organic acid and sugar contents might have been under continuous selection during breeding improvement. One candidate gene, PbrSTONE, identified in GWAS, has been functionally verified to be involved in the regulation of stone cell formation, one of the most important fruit quality traits in pear. Our study provides insights into the complex fruit related biology and identifies genes controlling important traits in pear through GWAS, which extends the genetic resources and basis for facilitating molecular breeding in perennial trees.
Harnessing peak transmission around symptom onset for non-pharmaceutical intervention and containment of the COVID-19 pandemic
Authors: Tian Liang , Li Xuefei , Qi Fei , Tang Qian-Yuan , Tang Viola , Liu Jiang , Li Zhiyuan , Cheng Xingye , Li Xuanxuan , Shi Yingchen , Liu Haiguang , Tang Lei-Han 
Published: February 2021

AbstractWithin a short period of time, COVID-19 grew into a world-wide pandemic. Transmission by pre-symptomatic and asymptomatic viral carriers rendered intervention and containment of the disease extremely challenging. Based on reported infection case studies, we construct an epidemiological model that focuses on transmission around the symptom onset. The model is calibrated against incubation period and pairwise transmission statistics during the initial outbreaks of the pandemic outside Wuhan with minimal non-pharmaceutical interventions. Mathematical treatment of the model yields explicit expressions for the size of latent and pre-symptomatic subpopulations during the exponential growth phase, with the local epidemic growth rate as input. We then explore reduction of the basic reproduction number R0 through specific transmission control measures such as contact tracing, testing, social distancing, wearing masks and sheltering in place. When these measures are implemented in combination, their effects on R0 multiply. We also compare our model behaviour to the first wave of the COVID-19 spreading in various affected regions and highlight generic and less generic features of the pandemic development.
Dopaminergic mechanism underlying reward-encoding of punishment omission during reversal learning in Drosophila
Authors: McCurdy Li Yan , Sareen Preeti , Davoudian Pasha A. , Nitabach Michael N. 
Published: February 2021

AbstractAnimals form and update learned associations between otherwise neutral sensory cues and aversive outcomes (i.e., punishment) to predict and avoid danger in changing environments. When a cue later occurs without punishment, this unexpected omission of aversive outcome is encoded as reward via activation of reward-encoding dopaminergic neurons. How such activation occurs remains unknown. Using real-time in vivo functional imaging, optogenetics, behavioral analysis and synaptic reconstruction from electron microscopy data, we identify the neural circuit mechanism through which Drosophila reward-encoding dopaminergic neurons are activated when an olfactory cue is unexpectedly no longer paired with electric shock punishment. Reduced activation of punishment-encoding dopaminergic neurons relieves depression of olfactory synaptic inputs to cholinergic neurons. Synaptic excitation by these cholinergic neurons of reward-encoding dopaminergic neurons increases their odor response, thus decreasing aversiveness of the odor. These studies reveal how an excitatory cholinergic relay from punishment- to reward-encoding dopaminergic neurons encodes the absence of punishment as reward, revealing a general circuit motif for updating aversive memories that could be present in mammals.
Characterisation of the T-cell response to Ebola virus glycoprotein amongst survivors of the 2013–16 West Africa epidemic
Authors: Tipton T. R. W. , Hall Y. , Bore J. A. , White A. , Sibley L. S. , Sarfas C. , Yuki Y. , Martin M. , Longet S. , Mellors J. , Ewer K. , Günther S. , Carrington M. , Kondé M. K. , Carroll M. W. 
Published: February 2021

AbstractZaireebolavirus (EBOV) is a highly pathogenic filovirus which can result in Ebola virus disease (EVD); a serious medical condition that presents as flu like symptoms but then often leads to more serious or fatal outcomes. The 2013–16 West Africa epidemic saw an unparalleled number of cases. Here we show characterisation and identification of T cell epitopes in surviving patients from Guinea to the EBOV glycoprotein. We perform interferon gamma (IFNγ) ELISpot using a glycoprotein peptide library to identify T cell epitopes and determine the CD4+ or CD8+ T cell component response. Additionally, we generate data on the T cell phenotype and measure polyfunctional cytokine secretion by these antigen specific cells. We show candidate peptides able to elicit a T cell response in EBOV survivors and provide inferred human leukocyte antigen (HLA) allele restriction. This data informs on the long-term T cell response to Ebola virus disease and highlights potentially important immunodominant peptides.
A role for subducted albite in the water cycle and alkalinity of subduction fluids
Authors: Hwang Gil Chan , Hwang Huijeong , Bang Yoonah , Choi Jinhyuk , Park Yong , Jeon Tae-Yeol , Chae Boknam , Jung Haemyeong , Lee Yongjae 
Published: February 2021

AbstractAlbite is one of the major constituents in the crust. We report here that albite, when subjected to hydrous cold subduction conditions, undergoes hitherto unknown breakdown into hydrated smectite, moganite, and corundum, above 2.9 GPa and 290 °C or about 90 km depth conditions, followed by subsequent breakdown of smectite into jadeite above 4.3 GPa and 435 °C or near 135 km depth. Upon the hydration into smectite, the fluid volume of the system decreases by ~14 %, whereas it increases by ~8 % upon its dehydration into jadeite. Both the hydration and dehydration depths are correlated to increases in seismicity by 93 % and 104 %, respectively, along the South Mariana trench over the past 5 years. Moreover, the formation of smectite is accompanied by the release of OH− species, which would explain the formation of moganite and expected alkalinity of the subducting fluid. Thus, we shed new insights into the mechanism of water transport and related geochemical and geophysical activities in the contemporary global subduction system.
Observation of a quantum phase transition in the quantum Rabi model with a single trapped ion
Authors: Cai M.-L. , Liu Z.-D. , Zhao W.-D. , Wu Y.-K. , Mei Q.-X. , Jiang Y. , He L. , Zhang X. , Zhou Z.-C. , Duan L.-M. 
Published: February 2021

AbstractQuantum phase transitions (QPTs) are usually associated with many-body systems in the thermodynamic limit when their ground states show abrupt changes at zero temperature with variation of a parameter in the Hamiltonian. Recently it has been realized that a QPT can also occur in a system composed of only a two-level atom and a single-mode bosonic field, described by the quantum Rabi model (QRM). Here we report an experimental demonstration of a QPT in the QRM using a171Yb+ion in a Paul trap. We measure the spin-up state population and the average phonon number of the ion as two order parameters and observe clear evidence of the phase transition via adiabatic tuning of the coupling between the ion and its spatial motion. An experimental probe of the phase transition in a fundamental quantum optics model without imposing the thermodynamic limit opens up a window for controlled study of QPTs and quantum critical phenomena.
Capturing functional two-dimensional nanosheets from sandwich-structure vermiculite for cancer theranostics
Authors: Ji Xiaoyuan , Ge Lanlan , Liu Chuang , Tang Zhongmin , Xiao Yufen , Chen Wei , Lei Zhouyue , Gao Wei , Blake Sara , De Diba , Shi Bingyang , Zeng Xiaobing , Kong Na , Zhang Xingcai , Tao Wei 
Published: February 2021

AbstractClay-based nanomaterials, especially 2:1 aluminosilicates such as vermiculite, biotite, and illite, have demonstrated great potential in various fields. However, their characteristic sandwiched structures and the lack of effective methods to exfoliate two-dimensional (2D) functional core layers (FCLs) greatly limit their future applications. Herein, we present a universal wet-chemical exfoliation method based on alkali etching that can intelligently “capture” the ultrathin and biocompatible FCLs (MgO and Fe2O3) sandwiched between two identical tetrahedral layers (SiO2 and Al2O3) from vermiculite. Without the sandwich structures that shielded their active sites, the obtained FCL nanosheets (NSs) exhibit a tunable and appropriate electron band structure (with the bandgap decreased from 2.0 eV to 1.4 eV), a conductive band that increased from −0.4 eV to −0.6 eV, and excellent light response characteristics. The great properties of 2D FCL NSs endow them with exciting potential in diverse applications including energy, photocatalysis, and biomedical engineering. This study specifically highlights their application in cancer theranostics as an example, potentially serving as a prelude to future extensive studies of 2D FCL NSs.
Evolution of immune responses to SARS-CoV-2 in mild-moderate COVID-19
Authors: Wheatley Adam K. , Juno Jennifer A. , Wang Jing J. , Selva Kevin J. , Reynaldi Arnold , Tan Hyon-Xhi , Lee Wen Shi , Wragg Kathleen M. , Kelly Hannah G. , Esterbauer Robyn , Davis Samantha K. , Kent Helen E. , Mordant Francesca L. , Schlub Timothy E. , Gordon David L. , Khoury David S. , Subbarao Kanta , Cromer Deborah , Gordon Tom P. , Chung Amy W. , Davenport Miles P. , Kent Stephen J. 
Published: February 2021

AbstractThe durability of infection-induced SARS-CoV-2 immunity has major implications for reinfection and vaccine development. Here, we show a comprehensive profile of antibody, B cell and T cell dynamics over time in a cohort of patients who have recovered from mild-moderate COVID-19. Binding and neutralising antibody responses, together with individual serum clonotypes, decay over the first 4 months post-infection. A similar decline in Spike-specific CD4+ and circulating T follicular helper frequencies occurs. By contrast, S-specific IgG+ memory B cells consistently accumulate over time, eventually comprising a substantial fraction of circulating the memory B cell pool. Modelling of the concomitant immune kinetics predicts maintenance of serological neutralising activity above a titre of 1:40 in 50% of convalescent participants to 74 days, although there is probably additive protection from B cell and T cell immunity. This study indicates that SARS-CoV-2 immunity after infection might be transiently protective at a population level. Therefore, SARS-CoV-2 vaccines might require greater immunogenicity and durability than natural infection to drive long-term protection.
Widespread signatures of natural selection across human complex traits and functional genomic categories
Authors: Zeng Jian , Xue Angli , Jiang Longda , Lloyd-Jones Luke R. , Wu Yang , Wang Huanwei , Zheng Zhili , Yengo Loic , Kemper Kathryn E. , Goddard Michael E. , Wray Naomi R. , Visscher Peter M. , Yang Jian 
Published: February 2021

AbstractUnderstanding how natural selection has shaped genetic architecture of complex traits is of importance in medical and evolutionary genetics. Bayesian methods have been developed using individual-level GWAS data to estimate multiple genetic architecture parameters including selection signature. Here, we present a method (SBayesS) that only requires GWAS summary statistics. We analyse data for 155 complex traits (n = 27k–547k) and project the estimates onto those obtained from evolutionary simulations. We estimate that, on average across traits, about 1% of human genome sequence are mutational targets with a mean selection coefficient of ~0.001. Common diseases, on average, show a smaller number of mutational targets and have been under stronger selection, compared to other traits. SBayesS analyses incorporating functional annotations reveal that selection signatures vary across genomic regions, among which coding regions have the strongest selection signature and are enriched for both the number of associated variants and the magnitude of effect sizes.
Hologenome analysis reveals dual symbiosis in the deep-sea hydrothermal vent snail Gigantopelta aegis
Authors: Lan Yi , Sun Jin , Chen Chong , Sun Yanan , Zhou Yadong , Yang Yi , Zhang Weipeng , Li Runsheng , Zhou Kun , Wong Wai Chuen , Kwan Yick Hang , Cheng Aifang , Bougouffa Salim , Van Dover Cindy Lee , Qiu Jian-Wen , Qian Pei-Yuan 
Published: February 2021

AbstractAnimals endemic to deep-sea hydrothermal vents often form obligatory symbioses with bacteria, maintained by intricate host–symbiont interactions. Most genomic studies on holobionts have not investigated both sides to similar depths. Here, we report dual symbiosis in the peltospirid snail Gigantopelta aegis with two gammaproteobacterial endosymbionts: a sulfur oxidiser and a methane oxidiser. We assemble high-quality genomes for all three parties, including a chromosome-level host genome. Hologenomic analyses reveal mutualism with nutritional complementarity and metabolic co-dependency, highly versatile in transporting and using chemical energy. Gigantopelta aegis likely remodels its immune system to facilitate dual symbiosis. Comparisons with Chrysomallon squamiferum, a confamilial snail with a single sulfur-oxidising gammaproteobacterial endosymbiont, show that their sulfur-oxidising endosymbionts are phylogenetically distant. This is consistent with previous findings that they evolved endosymbiosis convergently. Notably, the two sulfur-oxidisers share the same capabilities in biosynthesising nutrients lacking in the host genomes, potentially a key criterion in symbiont selection.
Four-dimensional vibrational spectroscopy for nanoscale mapping of phonon dispersion in BN nanotubes
Authors: Qi Ruishi , Li Ning , Du Jinlong , Shi Ruochen , Huang Yang , Yang Xiaoxia , Liu Lei , Xu Zhi , Dai Qing , Yu Dapeng , Gao Peng 
Published: February 2021

AbstractDirectly mapping local phonon dispersion in individual nanostructures can advance our understanding of their thermal, optical, and mechanical properties. However, this requires high detection sensitivity and combined spatial, energy and momentum resolutions, thus has been elusive. Here, we demonstrate a four-dimensional electron energy loss spectroscopy technique, and present position-dependent phonon dispersion measurements in individual boron nitride nanotubes. By scanning the electron beam in real space while monitoring both the energy loss and the momentum transfer, we are able to reveal position- and momentum-dependent lattice vibrations at nanometer scale. Our measurements show that the phonon dispersion of multi-walled nanotubes is locally close to hexagonal-boron nitride crystals. Interestingly, acoustic phonons are sensitive to defect scattering, while optical modes are insensitive to small voids. This work not only provides insights into vibrational properties of boron nitride nanotubes, but also demonstrates potential of the developed technique in nanoscale phonon dispersion measurements.
Direct observation of charge separation in an organic light harvesting system by femtosecond time-resolved XPS
Authors: Roth Friedrich , Borgwardt Mario , Wenthaus Lukas , Mahl Johannes , Palutke Steffen , Brenner Günter , Mercurio Giuseppe , Molodtsov Serguei , Wurth Wilfried , Gessner Oliver , Eberhardt Wolfgang 
Published: February 2021

AbstractThe ultrafast dynamics of photon-to-charge conversion in an organic light-harvesting system is studied by femtosecond time-resolved X-ray photoemission spectroscopy (TR-XPS) at the free-electron laser FLASH. This novel experimental technique provides site-specific information about charge separation and enables the monitoring of free charge carrier generation dynamics on their natural timescale, here applied to the model donor-acceptor system CuPc:C60. A previously unobserved channel for exciton dissociation into mobile charge carriers is identified, providing the first direct, real-time characterization of the timescale and efficiency of charge generation from low-energy charge-transfer states in an organic heterojunction. The findings give strong support to the emerging realization that charge separation even from energetically disfavored excitonic states is contributing significantly, indicating new options for light harvesting in organic heterojunctions.
Mitochondrial DNA editing in mice with DddA-TALE fusion deaminases
Authors: Lee Hyunji , Lee Seonghyun , Baek Gayoung , Kim Annie , Kang Beum-Chang , Seo Huiyun , Kim Jin-Soo 
Published: February 2021

AbstractDddA-derived cytosine base editors (DdCBEs), composed of the split interbacterial toxin DddAtox, transcription activator-like effector (TALE), and uracil glycosylase inhibitor (UGI), enable targeted C-to-T base conversions in mitochondrial DNA (mtDNA). Here, we demonstrate highly efficient mtDNA editing in mouse embryos using custom-designed DdCBEs. We target the mitochondrial gene, MT-ND5 (ND5), which encodes a subunit of NADH dehydrogenase that catalyzes NADH dehydration and electron transfer to ubiquinone, to obtain several mtDNA mutations, including m.G12918A associated with human mitochondrial diseases and m.C12336T that incorporates a premature stop codon, creating mitochondrial disease models in mice and demonstrating a potential for the treatment of mitochondrial disorders.