bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanism of filament formation in UPA-promoted CARD8 and NLRP1 inflammasomes
Authors: Robert Hollingsworth L. , David Liron , Li Yang , Griswold Andrew R. , Ruan Jianbin , Sharif Humayun , Fontana Pietro , Orth-He Elizabeth L. , Fu Tian-Min , Bachovchin Daniel A. , Wu Hao
Published: January 2021

NLRP1 and CARD8 are related cytosolic sensors that upon activation form supramolecular signalling complexes known as canonical inflammasomes, resulting in caspase−1 activation, cytokine maturation and/or pyroptotic cell death. NLRP1 and CARD8 use their C-terminal (CT) fragments containing a caspase recruitment domain (CARD) and the UPA (conserved in UNC5, PIDD, and ankyrins) subdomain for self-oligomerization, which in turn form the platform to recruit the inflammasome adaptor ASC (apoptosis-associated speck-like protein containing a CARD) or caspase-1, respectively. Here, we report cryo-EM structures of NLRP1-CT and CARD8-CT assemblies, in which the respective CARDs form central helical filaments that are promoted by oligomerized, but flexibly linked, UPAs surrounding the filaments. Through biochemical and cellular approaches, we demonstrate that the UPA itself reduces the threshold needed for NLRP1-CT and CARD8-CT filament formation and signalling. Structural analyses provide insights on the mode of ASC recruitment by NLRP1-CT and the contrasting direct recruitment of caspase-1 by CARD8-CT. We also discover that subunits in the central NLRP1CARD filament dimerize with additional exterior CARDs, which roughly doubles its thickness and is unique among all known CARD filaments. Finally, we engineer and determine the structure of an ASCCARD–caspase-1CARD octamer, which suggests that ASC uses opposing surfaces for NLRP1, versus caspase-1, recruitment. Together these structures capture the architecture and specificity of the active NLRP1 and CARD8 inflammasomes in addition to key heteromeric CARD-CARD interactions governing inflammasome signalling.
A four-electron Zn-I2 aqueous battery enabled by reversible I−/I2/I+ conversion
Authors: Zou Yiping , Liu Tingting , Du Qijun , Li Yingying , Yi Haibo , Zhou Xing , Li Zhuxin , Gao Lujie , Zhang Lan , Liang Xiao
Published: January 2021

Electrochemically reversible redox couples that embrace more electron transfer at a higher potential are the eternal target for energy storage batteries. Here, we report a four-electron aqueous zinc-iodine battery by activating the highly reversible I2/I+ couple (1.83 V vs. Zn/Zn2+) in addition to the typical I−/I2 couple (1.29 V). This is achieved by intensive solvation of the aqueous electrolyte to yield ICl inter-halogens and to suspend its hydrolysis. Experimental characterization and modelling reveal that limited water activity and sufficient free chloride ions in the electrolyte are crucial for the four-electron process. The merits of the electrolyte also afford to stabilize Zn anode, leading to a reliable Zn-I2 aqueous battery of 6000 cycles. Owing to high operational voltage and capacity, energy density up to 750 Wh kg−1 based on iodine mass was achieved (15–20 wt% iodine in electrode). It pushes the Zn-I2 battery to a superior level among these available aqueous batteries.
Resilin-mimetics as a smart biomaterial platform for biomedical applications
Authors: Balu Rajkamal , Dutta Naba K. , Dutta Ankit K. , Choudhury Namita Roy
Published: January 2021

Intrinsically disordered proteins have dramatically changed the structure–function paradigm of proteins in the 21st century. Resilin is a native elastic insect protein, which features intrinsically disordered structure, unusual multi-stimuli responsiveness and outstanding resilience. Advances in computational techniques, polypeptide synthesis methods and modular protein engineering routines have led to the development of novel resilin-like polypeptides (RLPs) including modular RLPs, expanding their applications in tissue engineering, drug delivery, bioimaging, biosensors, catalysis and bioelectronics. However, how the responsive behaviour of RLPs is encoded in the amino acid sequence level remains elusive. This review summarises the milestones of RLPs, and discusses the development of modular RLP-based biomaterials, their current applications, challenges and future perspectives. A perspective of future research is that sequence and responsiveness profiling of RLPs can provide a new platform for the design and development of new modular RLP-based biomaterials with programmable structure, properties and functions.
EGFR/SRC/ERK-stabilized YTHDF2 promotes cholesterol dysregulation and invasive growth of glioblastoma
Authors: Fang Runping , Chen Xin , Zhang Sicong , Shi Hui , Ye Youqiong , Shi Hailing , Zou Zhongyu , Li Peng , Guo Qing , Ma Li , He Chuan , Huang Suyun
Published: January 2021

Glioblastoma (GBM) is the most common type of adult malignant brain tumor, but its molecular mechanisms are not well understood. In addition, the knowledge of the disease-associated expression and function of YTHDF2 remains very limited. Here, we show that YTHDF2 overexpression clinically correlates with poor glioma patient prognosis. EGFR that is constitutively activated in the majority of GBM causes YTHDF2 overexpression through the EGFR/SRC/ERK pathway. EGFR/SRC/ERK signaling phosphorylates YTHDF2 serine39 and threonine381, thereby stabilizes YTHDF2 protein. YTHDF2 is required for GBM cell proliferation, invasion, and tumorigenesis. YTHDF2 facilitates m6A-dependent mRNA decay of LXRA and HIVEP2, which impacts the glioma patient survival. YTHDF2 promotes tumorigenesis of GBM cells, largely through the downregulation of LXRα and HIVEP2. Furthermore, YTHDF2 inhibits LXRα-dependent cholesterol homeostasis in GBM cells. Together, our findings extend the landscape of EGFR downstream circuit, uncover the function of YTHDF2 in GBM tumorigenesis, and highlight an essential role of RNA m6A methylation in cholesterol homeostasis.
Interaction between SNAI2 and MYOD enhances oncogenesis and suppresses differentiation in Fusion Negative Rhabdomyosarcoma
Authors: Pomella Silvia , Sreenivas Prethish , Gryder Berkley E. , Wang Long , Milewski David , Cassandri Matteo , Baxi Kunal , Hensch Nicole R. , Carcarino Elena , Song Young , Chou Hsien-Chao , Yohe Marielle E. , Stanton Benjamin Z. , Amadio Bruno , Caruana Ignazio , De Stefanis Cristiano , De Vito Rita , Locatelli Franco , Chen Yidong , Chen Eleanor Y. , Houghton Peter , Khan Javed , Rota Rossella , Ignatius Myron S.
Published: January 2021

Rhabdomyosarcoma (RMS) is an aggressive pediatric malignancy of the muscle, that includes Fusion Positive (FP)-RMS harboring PAX3/7-FOXO1 and Fusion Negative (FN)-RMS commonly with RAS pathway mutations. RMS express myogenic master transcription factors MYOD and MYOG yet are unable to terminally differentiate. Here, we report that SNAI2 is highly expressed in FN-RMS, is oncogenic, blocks myogenic differentiation, and promotes growth. MYOD activates SNAI2 transcription via super enhancers with striped 3D contact architecture. Genome wide chromatin binding analysis demonstrates that SNAI2 preferentially binds enhancer elements and competes with MYOD at a subset of myogenic enhancers required for terminal differentiation. SNAI2 also suppresses expression of a muscle differentiation program modulated by MYOG, MEF2, and CDKN1A. Further, RAS/MEK-signaling modulates SNAI2 levels and binding to chromatin, suggesting that the differentiation blockade by oncogenic RAS is mediated in part by SNAI2. Thus, an interplay between SNAI2, MYOD, and RAS prevents myogenic differentiation and promotes tumorigenesis.
π-Extended perylene diimide double-heterohelicenes as ambipolar organic semiconductors for broadband circularly polarized light detection
Authors: Zhang Li , Song Inho , Ahn Jaeyong , Han Myeonggeun , Linares Mathieu , Surin Mathieu , Zhang Hui-Jun , Oh Joon Hak , Lin Jianbin
Published: January 2021

Despite great challenges, the development of new molecular structures with multiple and even conflicting characteristics are eagerly pursued for exploring advanced applications. To develop high-performance chiral organic semiconducting molecules, a distorted π-system is required for strong coupling with circularly polarized light (CPL), whereas planar π-stacking systems are necessary for high charge-carrier mobility. To address this dilemma, in this work, we introduce a skeleton merging approach through distortion of a perylene diimide (PDI) core with four fused heteroaromatics to form an ortho-π-extended PDI double-[7]heterohelicene. PDI double helicene inherits a high dissymmetry factor from the helicene skeleton, and the extended π-planar system concurrently maintains a high level of charge transport properties. In addition, ortho-π-extension of the PDI skeleton brings about near-infrared (NIR) light absorption and ambipolar charge transport abilities, endowing the corresponding organic phototransistors with high photoresponsivity of 450 and 120 mA W−1 in p- and n-type modes respectively, along with a high external quantum efficiency (89%) under NIR light irradiations. Remarkably, these multiple characteristics enable high-performance broadband CPL detections up to NIR spectral region with chiral organic semiconductors.
Asynchronicity of endemic and emerging mosquito-borne disease outbreaks in the Dominican Republic
Authors: Petrone Mary E. , Earnest Rebecca , Lourenço José , Kraemer Moritz U. G. , Paulino-Ramirez Robert , Grubaugh Nathan D. , Tapia Leandro
Published: January 2021

Mosquito-borne viruses threaten the Caribbean due to the region’s tropical climate and seasonal reception of international tourists. Outbreaks of chikungunya and Zika have demonstrated the rapidity with which these viruses can spread. Concurrently, dengue fever cases have climbed over the past decade. Sustainable disease control measures are urgently needed to quell virus transmission and prevent future outbreaks. Here, to improve upon current control methods, we analyze temporal and spatial patterns of chikungunya, Zika, and dengue outbreaks reported in the Dominican Republic between 2012 and 2018. The viruses that cause these outbreaks are transmitted by Aedes mosquitoes, which are sensitive to seasonal climatological variability. We evaluate whether climate and the spatio-temporal dynamics of dengue outbreaks could explain patterns of emerging disease outbreaks. We find that emerging disease outbreaks were robust to the climatological and spatio-temporal constraints defining seasonal dengue outbreak dynamics, indicating that constant surveillance is required to prevent future health crises.
Dynamics of cascades on burstiness-controlled temporal networks
Authors: Unicomb Samuel , Iñiguez Gerardo , Gleeson James P. , Karsai Márton
Published: January 2021

Burstiness, the tendency of interaction events to be heterogeneously distributed in time, is critical to information diffusion in physical and social systems. However, an analytical framework capturing the effect of burstiness on generic dynamics is lacking. Here we develop a master equation formalism to study cascades on temporal networks with burstiness modelled by renewal processes. Supported by numerical and data-driven simulations, we describe the interplay between heterogeneous temporal interactions and models of threshold-driven and epidemic spreading. We find that increasing interevent time variance can both accelerate and decelerate spreading for threshold models, but can only decelerate epidemic spreading. When accounting for the skewness of different interevent time distributions, spreading times collapse onto a universal curve. Our framework uncovers a deep yet subtle connection between generic diffusion mechanisms and underlying temporal network structures that impacts a broad class of networked phenomena, from spin interactions to epidemic contagion and language dynamics.
Potent DNA gyrase inhibitors bind asymmetrically to their target using symmetrical bifurcated halogen bonds
Authors: Kolarič Anja , Germe Thomas , Hrast Martina , Stevenson Clare E. M. , Lawson David M. , Burton Nicolas P. , Vörös Judit , Maxwell Anthony , Minovski Nikola , Anderluh Marko
Published: January 2021

Novel bacterial type II topoisomerase inhibitors (NBTIs) stabilize single-strand DNA cleavage breaks by DNA gyrase but their exact mechanism of action has remained hypothetical until now. We have designed a small library of NBTIs with an improved DNA gyrase-binding moiety resulting in low nanomolar inhibition and very potent antibacterial activity. They stabilize single-stranded cleavage complexes and, importantly, we have obtained the crystal structure where an NBTI binds gyrase–DNA in a single conformation lacking apparent static disorder. This directly proves the previously postulated NBTI mechanism of action and shows that they stabilize single-strand cleavage through asymmetric intercalation with a shift of the scissile phosphate. This crystal stucture shows that the chlorine forms a halogen bond with the backbone carbonyls of the two symmetry-related Ala68 residues. To the best of our knowledge, such a so-called symmetrical bifurcated halogen bond has not been identified in a biological system until now.
Giant topological longitudinal circular photo-galvanic effect in the chiral multifold semimetal CoSi
Authors: Ni Zhuoliang , Wang K. , Zhang Y. , Pozo O. , Xu B. , Han X. , Manna K. , Paglione J. , Felser C. , Grushin A. G. , de Juan F. , Mele E. J. , Wu Liang
Published: January 2021

The absence of mirror symmetry, or chirality, is behind striking natural phenomena found in systems as diverse as DNA and crystalline solids. A remarkable example occurs when chiral semimetals with topologically protected band degeneracies are illuminated with circularly polarized light. Under the right conditions, the part of the generated photocurrent that switches sign upon reversal of the light’s polarization, known as the circular photo-galvanic effect, is predicted to depend only on fundamental constants. The conditions to observe quantization are non-universal, and depend on material parameters and the incident frequency. In this work, we perform terahertz emission spectroscopy with tunable photon energy from 0.2 –1.1 eV in the chiral topological semimetal CoSi. We identify a large longitudinal photocurrent peaked at 0.4 eV reaching  ~550 μ A/V2, which is much larger than the photocurrent in any chiral crystal reported in the literature. Using first-principles calculations we establish that the peak originates only from topological band crossings, reaching 3.3 ± 0.3 in units of the quantization constant. Our calculations indicate that the quantized circular photo-galvanic effect is within reach in CoSi upon doping and increase of the hot-carrier lifetime. The large photo-conductivity suggests that topological semimetals could potentially be used as novel mid-infrared detectors.
Visualising G-quadruplex DNA dynamics in live cells by fluorescence lifetime imaging microscopy
Authors: Summers Peter A. , Lewis Benjamin W. , Gonzalez-Garcia Jorge , Porreca Rosa M. , Lim Aaron H. M. , Cadinu Paolo , Martin-Pintado Nerea , Mann David J. , Edel Joshua B. , Vannier Jean Baptiste , Kuimova Marina K. , Vilar Ramon
Published: January 2021

Guanine rich regions of oligonucleotides fold into quadruple-stranded structures called G-quadruplexes (G4s). Increasing evidence suggests that these G4 structures form in vivo and play a crucial role in cellular processes. However, their direct observation in live cells remains a challenge. Here we demonstrate that a fluorescent probe (DAOTA-M2) in conjunction with fluorescence lifetime imaging microscopy (FLIM) can identify G4s within nuclei of live and fixed cells. We present a FLIM-based cellular assay to study the interaction of non-fluorescent small molecules with G4s and apply it to a wide range of drug candidates. We also demonstrate thatDAOTA-M2can be used to study G4 stability in live cells. Reduction ofFancJandRTEL1expression in mammalian cells increases theDAOTA-M2lifetime and therefore suggests an increased number of G4s in these cells, implying thatFancJandRTEL1play a role in resolving G4 structures in cellulo.
Continued preference for suboptimal habitat reduces bat survival with white-nose syndrome
Authors: Hopkins Skylar R. , Hoyt Joseph R. , White J. Paul , Kaarakka Heather M. , Redell Jennifer A. , DePue John E. , Scullon William H. , Kilpatrick A. Marm , Langwig Kate E.
Published: January 2021

Habitat alteration can influence suitability, creating ecological traps where habitat preference and fitness are mismatched. Despite their importance, ecological traps are notoriously difficult to identify and their impact on host–pathogen dynamics remains largely unexplored. Here we assess individual bat survival and habitat preferences in the midwestern United States before, during, and after the invasion of the fungal pathogen that causes white-nose syndrome. Despite strong selection pressures, most hosts continued to select habitats where disease severity was highest and survival was lowest, causing continued population declines. However, some individuals used refugia where survival was higher. Over time, a higher proportion of the total population used refugia than before pathogen arrival. Our results demonstrate that host preferences for habitats with high disease-induced mortality can create ecological traps that threaten populations, even in the presence of accessible refugia.
Room-temperature photonic logical qubits via second-order nonlinearities
Authors: Krastanov Stefan , Heuck Mikkel , Shapiro Jeffrey H. , Narang Prineha , Englund Dirk R. , Jacobs Kurt
Published: January 2021

Recent progress in nonlinear optical materials and microresonators has brought quantum computing with bulk optical nonlinearities into the realm of possibility. This platform is of great interest, not only because photonics is an obvious choice for quantum networks, but also as a promising route to quantum information processing at room temperature. We propose an approach for reprogrammable room-temperature photonic quantum logic that significantly simplifies the realization of various quantum circuits, and in particular, of error correction. The key element is the programmable photonic multi-mode resonator that implements reprogrammable bosonic quantum logic gates, while using only the bulk χ(2) nonlinear susceptibility. We theoretically demonstrate that just two of these elements suffice for a complete, compact error-correction circuit on a bosonic code, without the need for measurement or feed-forward control. Encoding and logical operations on the code are also easily achieved with these reprogrammable quantum photonic processors. An extrapolation of current progress in nonlinear optical materials and photonic circuits indicates that such circuitry should be achievable within the next decade.
Organ-specific, multimodal, wireless optoelectronics for high-throughput phenotyping of peripheral neural pathways
Authors: Kim Woo Seok , Hong Sungcheol , Gamero Milenka , Jeevakumar Vivekanand , Smithhart Clay M. , Price Theodore J. , Palmiter Richard D. , Campos Carlos , Park Sung Il
Published: January 2021

The vagus nerve supports diverse autonomic functions and behaviors important for health and survival. To understand how specific components of the vagus contribute to behaviors and long-term physiological effects, it is critical to modulate their activity with anatomical specificity in awake, freely behaving conditions using reliable methods. Here, we introduce an organ-specific scalable, multimodal, wireless optoelectronic device for precise and chronic optogenetic manipulations in vivo. When combined with an advanced, coil-antenna system and a multiplexing strategy for powering 8 individual homecages using a single RF transmitter, the proposed wireless telemetry enables low cost, high-throughput, and precise functional mapping of peripheral neural circuits, including long-term behavioral and physiological measurements. Deployment of these technologies reveals an unexpected role for stomach, non-stretch vagal sensory fibers in suppressing appetite and demonstrates the durability of the miniature wireless device inside harsh gastric conditions.
Gut microbiota impact on the peripheral immune response in non-alcoholic fatty liver disease related hepatocellular carcinoma
Authors: Behary Jason , Amorim Nadia , Jiang Xiao-Tao , Raposo Anita , Gong Lan , McGovern Emily , Ibrahim Ragy , Chu Francis , Stephens Carlie , Jebeili Hazem , Fragomeli Vincenzo , Koay Yen Chin , Jackson Miriam , O’Sullivan John , Weltman Martin , McCaughan Geoffrey , El-Omar Emad , Zekry Amany
Published: January 2021

The gut microbiota is reported to modulate the immune response in hepatocellular carcinoma (HCC). Here, we employ metagenomic and metabolomic studies to characterise gut microbiota in patients with non-alcoholic fatty liver disease (NAFLD) related cirrhosis, with or without HCC, and evaluate its effect on the peripheral immune response in an ex vivo model. We find that dysbiosis characterises the microbiota of patients with NAFLD-cirrhosis, with compositional and functional shifts occurring with HCC development. Gene function of the microbiota in NAFLD-HCC supports short chain fatty acid production, and this is confirmed by metabolomic studies. Ex vivo studies show that bacterial extracts from the NAFLD-HCC microbiota, but not from the control groups, elicit a T cell immunosuppressive phenotype, characterised by expansion of regulatory T cells and attenuation of CD8 + T cells. Our study suggest that the gut microbiota in NAFLD-HCC is characterised by a distinctive microbiome/metabolomic profile, and can modulate the peripheral immune response.
Microbial production of multiple short-chain primary amines via retrobiosynthesis
Authors: Kim Dong In , Chae Tong Un , Kim Hyun Uk , Jang Woo Dae , Lee Sang Yup
Published: January 2021

Bio-based production of many chemicals is not yet possible due to the unknown biosynthetic pathways. Here, we report a strategy combining retrobiosynthesis and precursor selection step to design biosynthetic pathways for multiple short-chain primary amines (SCPAs) that have a wide range of applications in chemical industries. Using direct precursors of 15 target SCPAs determined by the above strategy,Streptomyces viridifaciens vlmDencoding valine decarboxylase is examined as a proof-of-concept promiscuous enzyme both in vitro and in vivo for generating SCPAs from their precursors.Escherichia coliexpressing the heterologousvlmDproduces 10 SCPAs by feeding their direct precursors. Furthermore, metabolically engineeredE. colistrains are developed to produce representative SCPAs from glucose, including the one producing 10.67 g L−1ofiso-butylamine by fed-batch culture. This study presents the strategy of systematically designing biosynthetic pathways for the production of a group of related chemicals as demonstrated by multiple SCPAs as examples.
Conditional quantum operation of two exchange-coupled single-donor spin qubits in a MOS-compatible silicon device
Authors: Ma̧dzik Mateusz T. , Laucht Arne , Hudson Fay E. , Jakob Alexander M. , Johnson Brett C. , Jamieson David N. , Itoh Kohei M. , Dzurak Andrew S. , Morello Andrea
Published: January 2021

Silicon nanoelectronic devices can host single-qubit quantum logic operations with fidelity better than 99.9%. For the spins of an electron bound to a single-donor atom, introduced in the silicon by ion implantation, the quantum information can be stored for nearly 1 second. However, manufacturing a scalable quantum processor with this method is considered challenging, because of the exponential sensitivity of the exchange interaction that mediates the coupling between the qubits. Here we demonstrate the conditional, coherent control of an electron spin qubit in an exchange-coupled pair of 31P donors implanted in silicon. The coupling strength, J = 32.06 ± 0.06 MHz, is measured spectroscopically with high precision. Since the coupling is weaker than the electron-nuclear hyperfine coupling A ≈ 90 MHz which detunes the two electrons, a native two-qubit controlled-rotation gate can be obtained via a simple electron spin resonance pulse. This scheme is insensitive to the precise value of J, which makes it suitable for the scale-up of donor-based quantum computers in silicon that exploit the metal-oxide-semiconductor fabrication protocols commonly used in the classical electronics industry.
Conformational and migrational dynamics of slipped-strand DNA three-way junctions containing trinucleotide repeats
Authors: Hu Tianyu , Morten Michael J. , Magennis Steven W.
Published: January 2021

Expansions of CAG/CTG trinucleotide repeats in DNA are the cause of at least 17 degenerative human disorders, including Huntington’s Disease. Repeat instability is thought to occur via the formation of intrastrand hairpins during replication, repair, recombination, and transcription though relatively little is known about their structure and dynamics. We use single-molecule Förster resonance energy transfer to study DNA three-way junctions (3WJs) containing slip-outs composed of CAG or CTG repeats. 3WJs that only have repeats in the slip-out show two-state behavior, which we attribute to conformational flexibility at the 3WJ branchpoint. When the triplet repeats extend into the adjacent duplex, additional dynamics are observed, which we assign to interconversion of positional isomers. We propose a branchpoint migration model that involves conformational rearrangement, strand exchange, and bulge-loop movement. This migration has implications for how repeat slip-outs are processed by the cellular machinery, disease progression, and their development as drug targets.
Predicting postoperative peritoneal metastasis in gastric cancer with serosal invasion using a collagen nomogram
Authors: Chen Dexin , Liu Zhangyuanzhu , Liu Wenju , Fu Meiting , Jiang Wei , Xu Shuoyu , Wang Guangxing , Chen Feng , Lu Jianping , Chen Hao , Dong Xiaoyu , Li Guoxin , Chen Gang , Zhuo Shuangmu , Yan Jun
Published: January 2021

Accurate prediction of peritoneal metastasis for gastric cancer (GC) with serosal invasion is crucial in clinic. The presence of collagen in the tumour microenvironment affects the metastasis of cancer cells. Herein, we propose a collagen signature, which is composed of multiple collagen features in the tumour microenvironment of the serosa derived from multiphoton imaging, to describe the extent of collagen alterations. We find that a high collagen signature is significantly associated with a high risk of peritoneal metastasis (P < 0.001). A competing-risk nomogram including the collagen signature, tumour size, tumour differentiation status and lymph node metastasis is constructed. The nomogram demonstrates satisfactory discrimination and calibration. Thus, the collagen signature in the tumour microenvironment of the gastric serosa is associated with peritoneal metastasis in GC with serosal invasion, and the nomogram can be conveniently used to individually predict the risk of peritoneal metastasis in GC with serosal invasion after radical surgery.
Large-area and efficient perovskite light-emitting diodes via low-temperature blade-coating
Authors: Chu Shenglong , Chen Wenjing , Fang Zhibin , Xiao Xun , Liu Yan , Chen Jia , Huang Jinsong , Xiao Zhengguo
Published: January 2021

Large-area light-emitting diodes (LEDs) fabricated by mass-production techniques are needed for low-cost flat-panel lighting. Nevertheless, it is still challenging to fabricate efficient large-area LEDs using organic small molecules (OLEDs), quantum dots (QLEDs), polymers (PLEDs), and recently-developed hybrid perovskites (PeLEDs) due to difficulties controlling film uniformity. To that end, we report sol-gel engineering of low-temperature blade-coated methylammonium lead iodide (MAPbI3) perovskite films. The precipitation, gelation, aging, and phase transformation stages are dramatically shortened by using a diluted, organoammonium-excessed precursor, resulting in ultra-flat large-area films (54 cm2) with roughness reaching 1 nm. The external quantum efficiency of doctor-bladed PeLEDs reaches 16.1%, higher than that of best-performing blade-coated OLEDs, QLEDs, and PLEDs. Furthermore, benefitting from the throughput of the blade-coating process and cheap materials, the expected cost of the emissive layer is projected to be as low as 0.02 cents per cm2, emphasizing its application potential.
HIV-1 diversity considerations in the application of the Intact Proviral DNA Assay (IPDA)
Authors: Kinloch Natalie N. , Ren Yanqin , Conce Alberto Winiffer D. , Dong Winnie , Khadka Pragya , Huang Szu Han , Mota Talia M. , Wilson Andrew , Shahid Aniqa , Kirkby Don , Harris Marianne , Kovacs Colin , Benko Erika , Ostrowski Mario A. , Del Rio Estrada Perla M. , Wimpelberg Avery , Cannon Christopher , Hardy W. David , MacLaren Lynsay , Goldstein Harris , Brumme Chanson J. , Lee Guinevere Q. , Lynch Rebecca M. , Brumme Zabrina L. , Jones R. Brad
Published: January 2021

The Intact Proviral DNA Assay (IPDA) was developed to address the critical need for a scalable method for intact HIV-1 reservoir quantification. This droplet digital PCR-based assay simultaneously targets two HIV-1 regions to distinguish genomically intact proviruses against a large background of defective ones, and its application has yielded insights into HIV-1 persistence. Reports of assay failures however, attributed to HIV-1 polymorphism, have recently emerged. Here, we describe a diverse North American cohort of people with HIV-1 subtype B, where the IPDA yielded a failure rate of 28% due to viral polymorphism. We further demonstrate that within-host HIV-1 diversity can lead the IPDA to underestimate intact reservoir size, and provide examples of how this phenomenon could lead to erroneous interpretation of clinical trial data. While the IPDA represents a major methodological advance, HIV-1 diversity should be addressed before its widespread adoption as a principal readout in HIV-1 remission trials.
Host and viral determinants for efficient SARS-CoV-2 infection of the human lung
Authors: Chu Hin , Hu Bingjie , Huang Xiner , Chai Yue , Zhou Dongyan , Wang Yixin , Shuai Huiping , Yang Dong , Hou Yuxin , Zhang Xi , Yuen Terrence Tsz-Tai , Cai Jian-Piao , Zhang Anna Jinxia , Zhou Jie , Yuan Shuofeng , To Kelvin Kai-Wang , Chan Ivy Hau-Yee , Sit Ko-Yung , Foo Dominic Chi-Chung , Wong Ian Yu-Hong , Ng Ada Tsui-Lin , Cheung Tan To , Law Simon Ying-Kit , Au Wing-Kuk , Brindley Melinda A. , Chen Zhiwei , Kok Kin-Hang , Chan Jasper Fuk-Woo , Yuen Kwok-Yung
Published: January 2021

Understanding the factors that contribute to efficient SARS-CoV-2 infection of human cells may provide insights on SARS-CoV-2 transmissibility and pathogenesis, and reveal targets of intervention. Here, we analyze host and viral determinants essential for efficient SARS-CoV-2 infection in both human lung epithelial cells and ex vivo human lung tissues. We identify heparan sulfate as an important attachment factor for SARS-CoV-2 infection. Next, we show that sialic acids present on ACE2 prevent efficient spike/ACE2-interaction. While SARS-CoV infection is substantially limited by the sialic acid-mediated restriction in both human lung epithelial cells and ex vivo human lung tissues, infection by SARS-CoV-2 is limited to a lesser extent. We further demonstrate that the furin-like cleavage site in SARS-CoV-2 spike is required for efficient virus replication in human lung but not intestinal tissues. These findings provide insights on the efficient SARS-CoV-2 infection of human lungs.
SLE non-coding genetic risk variant determines the epigenetic dysfunction of an immune cell specific enhancer that controls disease-critical microRNA expression
Authors: Hou Guojun , Harley Isaac T. W. , Lu Xiaoming , Zhou Tian , Xu Ning , Yao Chao , Qin Yuting , Ouyang Ye , Ma Jianyang , Zhu Xinyi , Yu Xiang , Xu Hong , Dai Dai , Ding Huihua , Yin Zhihua , Ye Zhizhong , Deng Jun , Zhou Mi , Tang Yuanjia , Namjou Bahram , Guo Ya , Weirauch Matthew T. , Kottyan Leah C. , Harley John B. , Shen Nan
Published: January 2021

Since most variants that impact polygenic disease phenotypes localize to non-coding genomic regions, understanding the consequences of regulatory element variants will advance understanding of human disease mechanisms. Here, we report that the systemic lupus erythematosus (SLE) risk variant rs2431697 as likely causal for SLE through disruption of a regulatory element, modulating miR-146a expression. Using epigenomic analysis, genome-editing and 3D chromatin structure analysis, we show that rs2431697 tags a cell-type dependent distal enhancer specific for miR-146a that physically interacts with the miR-146a promoter. NF-kB binds the disease protective allele in a sequence-specific manner, increasing expression of this immunoregulatory microRNA. Finally, CRISPR activation-based modulation of this enhancer in the PBMCs of SLE patients attenuates type I interferon pathway activation by increasing miR-146a expression. Our work provides a strategy to define non-coding RNA functional regulatory elements using disease-associated variants and provides mechanistic links between autoimmune disease risk genetic variation and disease etiology.
Structures of human dual oxidase 1 complex in low-calcium and high-calcium states
Authors: Wu Jing-Xiang , Liu Rui , Song Kangcheng , Chen Lei
Published: January 2021

Dual oxidases (DUOXs) produce hydrogen peroxide by transferring electrons from intracellular NADPH to extracellular oxygen. They are involved in many crucial biological processes and human diseases, especially in thyroid diseases. DUOXs are protein complexes co-assembled from the catalytic DUOX subunits and the auxiliary DUOXA subunits and their activities are regulated by intracellular calcium concentrations. Here, we report the cryo-EM structures of human DUOX1-DUOXA1 complex in both high-calcium and low-calcium states. These structures reveal the DUOX1 complex is a symmetric 2:2 hetero-tetramer stabilized by extensive inter-subunit interactions. Substrate NADPH and cofactor FAD are sandwiched between transmembrane domain and the cytosolic dehydrogenase domain of DUOX. In the presence of calcium ions, intracellular EF-hand modules might enhance the catalytic activity of DUOX by stabilizing the dehydrogenase domain in a conformation that allows electron transfer.
Exposure to pesticides in utero impacts the fetal immune system and response to vaccination in infancy
Authors: Prahl Mary , Odorizzi Pamela , Gingrich David , Muhindo Mary , McIntyre Tara , Budker Rachel , Jagannathan Prasanna , Farrington Lila , Nalubega Mayimuna , Nankya Felistas , Sikyomu Esther , Musinguzi Kenneth , Naluwu Kate , Auma Ann , Kakuru Abel , Kamya Moses R. , Dorsey Grant , Aweeka Francesca , Feeney Margaret E.
Published: January 2021

The use of pesticides to reduce mosquito vector populations is a cornerstone of global malaria control efforts, but the biological impact of most pesticides on human populations, including pregnant women and infants, is not known. Some pesticides, including carbamates, have been shown to perturb the human immune system. We measure the systemic absorption and immunologic effects of bendiocarb, a commonly used carbamate pesticide, following household spraying in a cohort of pregnant Ugandan women and their infants. We find that bendiocarb is present at high levels in maternal, umbilical cord, and infant plasma of individuals exposed during pregnancy, indicating that it is systemically absorbed and trans-placentally transferred to the fetus. Moreover, bendiocarb exposure is associated with numerous changes in fetal immune cell homeostasis and function, including a dose-dependent decrease in regulatory CD4 T cells, increased cytokine production, and inhibition of antigen-driven proliferation. Additionally, prenatal bendiocarb exposure is associated with higher post-vaccination measles titers at one year of age, suggesting that its impact on functional immunity may persist for many months after birth. These data indicate that in utero bendiocarb exposure has multiple previously unrecognized biological effects on the fetal immune system.
Selective capture of carbon dioxide from hydrocarbons using a metal-organic framework
Authors: Qazvini Omid T. , Babarao Ravichandar , Telfer Shane G.
Published: January 2021

Efficient and sustainable methods for carbon dioxide capture are highly sought after. Mature technologies involve chemical reactions that absorb CO2,but they have many drawbacks. Energy-efficient alternatives may be realised by porous physisorbents with void spaces that are complementary in size and electrostatic potential to molecular CO2. Here, we present a robust, recyclable and inexpensive adsorbent termed MUF-16. This metal-organic framework captures CO2with a high affinity in its one-dimensional channels, as determined by adsorption isotherms, X-ray crystallography and density-functional theory calculations. Its low affinity for other competing gases delivers high selectivity for the adsorption of CO2over methane, acetylene, ethylene, ethane, propylene and propane. For equimolar mixtures of CO2/CH4and CO2/C2H2, the selectivity is 6690 and 510, respectively. Breakthrough gas separations under dynamic conditions benefit from short time lags in the elution of the weakly-adsorbed component to deliver high-purity hydrocarbon products, including pure methane and acetylene.
High-resolution single-cell 3D-models of chromatin ensembles during Drosophila embryogenesis
Authors: Sun Qiu , Perez-Rathke Alan , Czajkowsky Daniel M. , Shao Zhifeng , Liang Jie
Published: January 2021

Single-cell chromatin studies provide insights into how chromatin structure relates to functions of individual cells. However, balancing high-resolution and genome wide-coverage remains challenging. We describe a computational method for the reconstruction of large 3D-ensembles of single-cell (sc) chromatin conformations from population Hi-C that we apply to study embryogenesis in Drosophila. With minimal assumptions of physical properties and without adjustable parameters, our method generates large ensembles of chromatin conformations via deep-sampling. Our method identifies specific interactions, which constitute 5–6% of Hi-C frequencies, but surprisingly are sufficient to drive chromatin folding, giving rise to the observed Hi-C patterns. Modeled sc-chromatins quantify chromatin heterogeneity, revealing significant changes during embryogenesis. Furthermore, >50% of modeled sc-chromatin maintain topologically associating domains (TADs) in early embryos, when no population TADs are perceptible. Domain boundaries become fixated during development, with strong preference at binding-sites of insulator-complexes upon the midblastula transition. Overall, high-resolution 3D-ensembles of sc-chromatin conformations enable further in-depth interpretation of population Hi-C, improving understanding of the structure-function relationship of genome organization.
Plasma ctDNA is a tumor tissue surrogate and enables clinical-genomic stratification of metastatic bladder cancer
Authors: Vandekerkhove Gillian , Lavoie Jean-Michel , Annala Matti , Murtha Andrew J. , Sundahl Nora , Walz Simon , Sano Takeshi , Taavitsainen Sinja , Ritch Elie , Fazli Ladan , Hurtado-Coll Antonio , Wang Gang , Nykter Matti , Black Peter C. , Todenhöfer Tilman , Ost Piet , Gibb Ewan A. , Chi Kim N. , Eigl Bernhard J. , Wyatt Alexander W.
Published: January 2021

Molecular stratification can improve the management of advanced cancers, but requires relevant tumor samples. Metastatic urothelial carcinoma (mUC) is poised to benefit given a recent expansion of treatment options and its high genomic heterogeneity. We profile minimally-invasive plasma circulating tumor DNA (ctDNA) samples from 104 mUC patients, and compare to same-patient tumor tissue obtained during invasive surgery. Patient ctDNA abundance is independently prognostic for overall survival in patients initiating first-line systemic therapy. Importantly, ctDNA analysis reproduces the somatic driver genome as described from tissue-based cohorts. Furthermore, mutation concordance between ctDNA and matched tumor tissue is 83.4%, enabling benchmarking of proposed clinical biomarkers. While 90% of mutations are identified across serial ctDNA samples, concordance for serial tumor tissue is significantly lower. Overall, our exploratory analysis demonstrates that genomic profiling of ctDNA in mUC is reliable and practical, and mitigates against disease undersampling inherent to studying archival primary tumor foci. We urge the incorporation of cell-free DNA profiling into molecularly-guided clinical trials for mUC.
High efficiency hierarchical porous composite microfiltration membrane for high-temperature particulate matter capturing
Authors: Gui Wanyuan , Qu Yuhai , Liang Yongfeng , Wang Yanli , Zhang Hui , Luan Benli , Lin Junpin
Published: January 2021

Porous intermetallic membrane with extensive interconnected pores are potential candidates as functional materials for high-temperature particulate matter (PM) capturing. However, fabrication of intermetallic membrane with a combined performance of high filtration efficiency and high-temperature oxidation resistance remains a challenge. To tackle this issue, a hierarchical micro-/nano-dual-scale sized pores was constructed on the inner cell walls of a porous support through mutual diffusion and chemical reaction. Benefited from its hierarchical micro/nano-dual-scaled pore structural features, the high Nb containing TiAl-based porous composite microfiltration membrane demonstrates ultrahigh PM>2.5removal efficiency (99.58%) and favorable oxidation/sulfidation performance at high temperature. These features, combined with our experimental design strategy, provide insight into designing high-temperature PM filtration membrane materials with enhanced performance and durability.
A single vaccination with four-segmented Rift Valley fever virus prevents vertical transmission of the wild-type virus in pregnant ewes
Authors: Wichgers Schreur Paul J. , Oymans Judith , Kant Jet , van de Water Sandra , Kollár Anna , Dehon Yves , Soós Pál , Pénzes Zoltán , van Keulen Lucien , Kortekaas Jeroen
Published: January 2021

Rift Valley fever virus (RVFV) is a mosquito-transmitted bunyavirus that causes severe outbreaks among wild and domesticated ruminants, of which sheep are the most susceptible. Outbreaks are characterised by high mortality rates among new-born lambs and abortion storms, in which all pregnant ewes in a flock may abort their foetuses. In endemic areas, Rift Valley fever (RVF) can be controlled by vaccination with either inactivated or live-attenuated vaccines. Inactivated vaccines are safe for animals during all physiological stages, including pregnancy. However, optimal efficacy of these vaccines depends on multiple vaccinations and yearly re-vaccination. Live-attenuated vaccines are generally highly efficacious after a single vaccination, but currently available live-attenuated vaccines may transmit to the ovine foetus, resulting in stillbirths, congenital malformations or abortion. We have previously reported the development of a novel live-attenuated RVFV vaccine, named RVFV-4s. This vaccine virus was created by splitting the M genome segment and deleting the major virulence determinant NSs, and was shown to be safe even for the most susceptible species, including pregnant ewes. The demonstrated efficacy and safety profile suggests that RVFV-4s holds promise for veterinary and human application. The RVFV-4s vaccine for veterinary application, here referred to as vRVFV-4s, was shown to provide complete protection after a single vaccination of lambs, goats and cattle. In this work, we evaluated the efficacy of the vRVFV-4s vaccine in pregnant ewes. Anticipating on the extremely high susceptibility of pregnant ewes for RVFV, both a single vaccination and double vaccination were evaluated in two independent experiments. The combined results suggest that a single vaccination with vRVFV-4s is sufficient to protect pregnant ewes and to prevent transmission to the ovine foetus.
Hormonal and transcriptional analyses provides new insights into the molecular mechanisms underlying root thickening and isoflavonoid biosynthesis in Callerya speciosa (Champ. ex Benth.) Schot
Authors: Yao Shaochang , Lan Zuzai , Huang Rongshao , Tan Yong , Huang Ding , Gu Jinyuan , Pan Chunliu
Published: January 2021

Callerya speciosa (Champ. ex Benth.) Schot is a traditional Chinese medicine characterized by tuberous roots as the main organ of isoflavonoid accumulation. Root thickening and isoflavonoid accumulation are two major factors for yield and quality of C. speciosa. However, the underlying mechanisms of root thickening and isoflavonoid biosynthesis have not yet been elucidated. Here, integrated morphological, hormonal and transcriptomic analyses of C. speciosa tuberous roots at four different ages (6, 12, 18, 30 months after germination) were performed. The growth cycle of C. speciosa could be divided into three stages: initiation, rapid-thickening and stable-thickening stage, which cued by the activity of vascular cambia. Endogenous changes in phytohormones were associated with developmental changes during root thickening. Jasmonic acid might be linked to the initial development of tuberous roots. Abscisic acid seemed to be essential for tuber maturation, whereas IAA, cis-zeatin and gibberellin 3 were considered essential for rapid thickening of tuberous roots. A total of 4337 differentially expressed genes (DEGs) were identified during root thickening, including 15 DEGs participated in isoflavonoid biosynthesis, and 153 DEGs involved in starch/sucrose metabolism, hormonal signaling, transcriptional regulation and cell wall metabolism. A hypothetical model of genetic regulation associated with root thickening and isoflavonoid biosynthesis in C. speciosa is proposed, which will help in understanding the underlying mechanisms of tuberous root formation and isoflavonoid biosynthesis.
Photocatalytic degradation of organic dye and tetracycline by ternary Ag2O/AgBr–CeO2 photocatalyst under visible-light irradiation
Authors: Su Fu , Li Pengpeng , Huang Jianshu , Gu Meijuan , Liu Zhiying , Xu Yanhua
Published: January 2021

In this work, CeO2 nanosheets decorated with Ag2O and AgBr are successfully fabricated via a simple sediment-precipitation method. The as-prepared ternary Ag2O/AgBr–CeO2 composite with double Z-scheme construction was analyzed by various analytical techniques. Ag nanoparticles (NPs) used as the electron medium could reduce the recombination of photoelectrons and holes, thus leading to the improvement of photocatalytic performance of these catalysts. Due to the unique structure and composite advantages, the optimal Ag2O/AgBr–CeO2 photocatalysts exhibit the superior tetracycline (TC) degradation efficiency of 93.23% and favorable stability with near-initial capacity under visible light irradiation. This ternary Z-scheme structure materials will be the well-promising photocatalysts or the purification of antibiotic wastewater.
First evidence of virus-like particles in the bacterial symbionts of Bryozoa
Authors: Vishnyakov A. E. , Karagodina N. P. , Lim-Fong G. , Ivanov P. A. , Schwaha T. F. , Letarov A. V. , Ostrovsky A. N.
Published: January 2021

Bacteriophage communities associated with humans and vertebrate animals have been extensively studied, but the data on phages living in invertebrates remain scarce. In fact, they have never been reported for most animal phyla. Our ultrastructural study showed for the first time a variety of virus-like particles (VLPs) and supposed virus-related structures inside symbiotic bacteria in two marine species from the phylum Bryozoa, the cheilostomes Bugula neritina and Paralicornia sinuosa. We also documented the effect of VLPs on bacterial hosts: we explain different bacterial ‘ultrastructural types’ detected in bryozoan tissues as stages in the gradual destruction of prokaryotic cells caused by viral multiplication during the lytic cycle. We speculate that viruses destroying bacteria regulate symbiont numbers in the bryozoan hosts, a phenomenon known in some insects. We develop two hypotheses explaining exo- and endogenous circulation of the viruses during the life-cycle of B. neritina. Finally, we compare unusual ‘sea-urchin’-like structures found in the collapsed bacteria in P. sinuosa with so-called metamorphosis associated contractile structures (MACs) formed in the cells of the marine bacterium Pseudoalteromonas luteoviolacea which are known to trigger larval metamorphosis in a polychaete worm.