bluuebunny/crossref_metadata_2025_split huggingface dataset:
MAIT cells regulate NK cell-mediated tumor immunity
Authors: Petley Emma V. , Koay Hui-Fern , Henderson Melissa A. , Sek Kevin , Todd Kirsten L. , Keam Simon P. , Lai Junyun , House Imran G. , Li Jasmine , Zethoven Magnus , Chen Amanda X. Y. , Oliver Amanda J. , Michie Jessica , Freeman Andrew J. , Giuffrida Lauren , Chan Jack D. , Pizzolla Angela , Mak Jeffrey Y. W. , McCulloch Timothy R. , Souza-Fonseca-Guimaraes Fernando , Kearney Conor J. , Millen Rosemary , Ramsay Robert G. , Huntington Nicholas D. , McCluskey James , Oliaro Jane , Fairlie David P. , Neeson Paul J. , Godfrey Dale I. , Beavis Paul A. , Darcy Phillip K. 
Published: August 2021

AbstractThe function of MR1-restricted mucosal-associated invariant T (MAIT) cells in tumor immunity is unclear. Here we show that MAIT cell-deficient mice have enhanced NK cell-dependent control of metastatic B16F10 tumor growth relative to control mice. Analyses of this interplay in human tumor samples reveal that high expression of a MAIT cell gene signature negatively impacts the prognostic significance of NK cells. Paradoxically, pre-pulsing tumors with MAIT cell antigens, or activating MAIT cells in vivo, enhances anti-tumor immunity in B16F10 and E0771 mouse tumor models, including in the context of established metastasis. These effects are associated with enhanced NK cell responses and increased expression of both IFN-γ-dependent and inflammatory genes in NK cells. Importantly, activated human MAIT cells also promote the function of NK cells isolated from patient tumor samples. Our results thus describe an activation-dependent, MAIT cell-mediated regulation of NK cells, and suggest a potential therapeutic avenue for cancer treatment.
Genomic characterization of co-existing neoplasia and carcinoma lesions reveals distinct evolutionary paths of gallbladder cancer
Authors: Lin Jianzhen , Peng Xinxin , Dong Kun , Long Junyu , Guo Xuejiao , Li Hongyue , Bai Yi , Yang Xu , Wang Dongxu , Lu Xin , Mao Yilei , Sang Xinting , Ji Xuwo , Zhao Haitao , Liang Han 
Published: August 2021

AbstractGallbladder carcinoma is the most common cancer of the biliary tract with dismal survival largely due to delayed diagnosis. Biliary tract intraepithelial neoplasia (BilIN) is the common benign tumor that is suspected to be precancerous lesions. However, the genetic and evolutionary relationships between BilIN and carcinoma remain unclear. Here we perform whole-exome sequencing of coexisting low-grade BilIN (adenoma), high-grade BilIN, and carcinoma lesions, and normal tissues from the same patients. We identify aging as a major factor contributing to accumulated mutations and a critical role of CTNNB1 mutations in these tumors. We reveal two distinct carcinoma evolutionary paths: carcinoma can either diverge earlier and evolve more independently or form through the classic adenoma/dysplasia-carcinoma sequence model. Our analysis suggests that extensive loss-of-heterozygosity and mutation events in the initial stage tend to result in a cancerous niche, leading to the subsequent BilIN-independent path. These results reframes our understanding of tumor transformation and the evolutionary trajectory of carcinogenesis in the gallbladder, laying a foundation for the early diagnosis and effective treatment of gallbladder cancer.
Advancement in long-distance bird migration through individual plasticity in departure
Authors: Conklin Jesse R. , Lisovski Simeon , Battley Phil F. 
Published: August 2021

AbstractGlobally, bird migration is occurring earlier in the year, consistent with climate-related changes in breeding resources. Although often attributed to phenotypic plasticity, there is no clear demonstration of long-term population advancement in avian migration through individual plasticity. Using direct observations of bar-tailed godwits (Limosa lapponica) departing New Zealand on a 16,000-km journey to Alaska, we show that migration advanced by six days during 2008–2020, and that within-individual advancement was sufficient to explain this population-level change. However, in individuals tracked for the entire migration (50 total tracks of 36 individuals), earlier departure did not lead to earlier arrival or breeding in Alaska, due to prolonged stopovers in Asia. Moreover, changes in breeding-site phenology varied across Alaska, but were not reflected in within-population differences in advancement of migratory departure. We demonstrate that plastic responses can drive population-level changes in timing of long-distance migration, but also that behavioral and environmental constraints en route may yet limit adaptive responses to global change.
A squeezed quantum microcomb on a chip
Authors: Yang Zijiao , Jahanbozorgi Mandana , Jeong Dongin , Sun Shuman , Pfister Olivier , Lee Hansuek , Yi Xu 
Published: August 2021

AbstractThe optical microresonator-based frequency comb (microcomb) provides a versatile platform for nonlinear physics studies and has wide applications ranging from metrology to spectroscopy. The deterministic quantum regime is an unexplored aspect of microcombs, in which unconditional entanglements among hundreds of equidistant frequency modes can serve as critical ingredients to scalable universal quantum computing and quantum networking. Here, we demonstrate a deterministic quantum microcomb in a silica microresonator on a silicon chip. 40 continuous-variable quantum modes, in the form of 20 simultaneously two-mode squeezed comb pairs, are observed within 1 THz optical span at telecommunication wavelengths. A maximum raw squeezing of 1.6 dB is attained. A high-resolution spectroscopy measurement is developed to characterize the frequency equidistance of quantum microcombs. Our demonstration offers the possibility to leverage deterministically generated, frequency multiplexed quantum states and integrated photonics to open up new avenues in fields of spectroscopy, quantum metrology, and scalable, continuous-variable-based quantum information processing.
Enhanced NF-κB signaling in type-2 dendritic cells at baseline predicts non-response to adalimumab in psoriasis
Authors: Andres-Ejarque Rosa , Ale Hira Bahadur , Grys Katarzyna , Tosi Isabella , Solanky Shane , Ainali Chrysanthi , Catak Zeynep , Sreeneebus Hemawtee , Saklatvala Jake , Dand Nick , de Rinaldis Emanuele , Chapman Anna , Nestle Frank O. , Barnes Michael R. , Warren Richard B. , Reynolds Nick J. , Griffiths Christopher E. M. , Barker Jonathan N. , Smith Catherine H. , Di Meglio Paola ,   the PSORT Consortium, Di Meglio Paola , Emsley Richard , Evans Andrea , Payne Katherine , Stocken Deborah 
Published: August 2021

AbstractBiologic therapies have transformed the management of psoriasis, but clinical outcome is variable leaving an unmet clinical need for predictive biomarkers of response. Here we perform in-depth immunomonitoring of blood immune cells of 67 patients with psoriasis, before and during therapy with the anti-TNF drug adalimumab, to identify immune mediators of clinical response and evaluate their predictive value. Enhanced NF-κBp65 phosphorylation, induced by TNF and LPS in type-2 dendritic cells (DC) before therapy, significantly correlates with lack of clinical response after 12 weeks of treatment. The heightened NF-κB activation is linked to increased DC maturation in vitro and frequency of IL-17+ T cells in the blood of non-responders before therapy. Moreover, lesional skin of non-responders contains higher numbers of dermal DC expressing the maturation marker CD83 and producing IL-23, and increased numbers of IL-17+ T cells. Finally, we identify and clinically validate LPS-induced NF-κBp65 phosphorylation before therapy as a predictive biomarker of non-response to adalimumab, with 100% sensitivity and 90.1% specificity in an independent cohort. Our study uncovers important molecular and cellular mediators underpinning adalimumab mechanisms of action in psoriasis and we propose a blood biomarker for predicting clinical outcome.
Large-scale computational discovery and analysis of virus-derived microbial nanocompartments
Authors: Andreas Michael P. , Giessen Tobias W. 
Published: August 2021

AbstractEncapsulins are a class of microbial protein compartments defined by the viral HK97-fold of their capsid protein, self-assembly into icosahedral shells, and dedicated cargo loading mechanism for sequestering specific enzymes. Encapsulins are often misannotated and traditional sequence-based searches yield many false positive hits in the form of phage capsids. Here, we develop an integrated search strategy to carry out a large-scale computational analysis of prokaryotic genomes with the goal of discovering an exhaustive and curated set of all HK97-fold encapsulin-like systems. We find over 6,000 encapsulin-like systems in 31 bacterial and four archaeal phyla, including two novel encapsulin families. We formulate hypotheses about their potential biological functions and biomedical relevance, which range from natural product biosynthesis and stress resistance to carbon metabolism and anaerobic hydrogen production. An evolutionary analysis of encapsulins and related HK97-type virus families shows that they share a common ancestor, and we conclude that encapsulins likely evolved from HK97-type bacteriophages.
Structural dynamics of single SARS-CoV-2 pseudoknot molecules reveal topologically distinct conformers
Authors: Neupane Krishna , Zhao Meng , Lyons Aaron , Munshi Sneha , Ileperuma Sandaru M. , Ritchie Dustin B. , Hoffer Noel Q. , Narayan Abhishek , Woodside Michael T. 
Published: August 2021

AbstractThe RNA pseudoknot that stimulates programmed ribosomal frameshifting in SARS-CoV-2 is a possible drug target. To understand how it responds to mechanical tension applied by ribosomes, thought to play a key role during frameshifting, we probe its structural dynamics using optical tweezers. We find that it forms multiple structures: two pseudoknotted conformers with different stability and barriers, and alternative stem-loop structures. The pseudoknotted conformers have distinct topologies, one threading the 5′ end through a 3-helix junction to create a knot-like fold, the other with unthreaded 5′ end, consistent with structures observed via cryo-EM and simulations. Refolding of the pseudoknotted conformers starts with stem 1, followed by stem 3 and lastly stem 2; Mg2+ ions are not required, but increase pseudoknot mechanical rigidity and favor formation of the knot-like conformer. These results resolve the SARS-CoV-2 frameshift signal folding mechanism and highlight its conformational heterogeneity, with important implications for structure-based drug-discovery efforts.
Sc-compReg enables the comparison of gene regulatory networks between conditions using single-cell data
Authors: Duren Zhana , Lu Wenhui Sophia , Arthur Joseph G. , Shah Preyas , Xin Jingxue , Meschi Francesca , Li Miranda Lin , Nemec Corey M. , Yin Yifeng , Wong Wing Hung 
Published: August 2021

AbstractThe comparison of gene regulatory networks between diseased versus healthy individuals or between two different treatments is an important scientific problem. Here, we propose sc-compReg as a method for the comparative analysis of gene expression regulatory networks between two conditions using single cell gene expression (scRNA-seq) and single cell chromatin accessibility data (scATAC-seq). Our software, sc-compReg, can be used as a stand-alone package that provides joint clustering and embedding of the cells from both scRNA-seq and scATAC-seq, and the construction of differential regulatory networks across two conditions. We apply the method to compare the gene regulatory networks of an individual with chronic lymphocytic leukemia (CLL) versus a healthy control. The analysis reveals a tumor-specific B cell subpopulation in the CLL patient and identifies TOX2 as a potential regulator of this subpopulation.
Efficient and large-area all vacuum-deposited perovskite light-emitting diodes via spatial confinement
Authors: Du Peipei , Li Jinghui , Wang Liang , Sun Liang , Wang Xi , Xu Xiang , Yang Longbo , Pang Jincong , Liang Wenxi , Luo Jiajun , Ma Ying , Tang Jiang 
Published: August 2021

AbstractWith rapid advances of perovskite light-emitting diodes (PeLEDs), the large-scale fabrication of patterned PeLEDs towards display panels is of increasing importance. However, most state-of-the-art PeLEDs are fabricated by solution-processed techniques, which are difficult to simultaneously achieve high-resolution pixels and large-scale production. To this end, we construct efficient CsPbBr3 PeLEDs employing a vacuum deposition technique, which has been demonstrated as the most successful route for commercial organic LED displays. By carefully controlling the strength of the spatial confinement in CsPbBr3 film, its radiative recombination is greatly enhanced while the nonradiative recombination is suppressed. As a result, the external quantum efficiency (EQE) of thermally evaporated PeLED reaches 8.0%, a record for vacuum processed PeLEDs. Benefitting from the excellent uniformity and scalability of the thermal evaporation, we demonstrate PeLED with a functional area up to 40.2 cm2 and a peak EQE of 7.1%, representing one of the most efficient large-area PeLEDs. We further achieve high-resolution patterned perovskite film with 100 μm pixels using fine metal masks, laying the foundation for potential display applications. We believe the strategy of confinement strength regulation in thermally evaporated perovskites provides an effective way to process high-efficiency and large-area PeLEDs towards commercial display panels.
Quasiadiabatic electron transport in room temperature nanoelectronic devices induced by hot-phonon bottleneck
Authors: Weng Qianchun , Yang Le , An Zhenghua , Chen Pingping , Tzalenchuk Alexander , Lu Wei , Komiyama Susumu 
Published: August 2021

AbstractSince the invention of transistors, the flow of electrons has become controllable in solid-state electronics. The flow of energy, however, remains elusive, and energy is readily dissipated to lattice via electron-phonon interactions. Hence, minimizing the energy dissipation has long been sought by eliminating phonon-emission process. Here, we report a different scenario for facilitating energy transmission at room temperature that electrons exert diffusive but quasiadiabatic transport, free from substantial energy loss. Direct nanothermometric mapping of electrons and lattice in current-carrying GaAs/AlGaAs devices exhibit remarkable discrepancies, indicating unexpected thermal isolation between the two subsystems. This surprising effect arises from the overpopulated hot longitudinal-optical (LO) phonons generated through frequent emission by hot electrons, which induce equally frequent LO-phonon reabsorption (“hot-phonon bottleneck”) cancelling the net energy loss. Our work sheds light on energy manipulation in nanoelectronics and power-electronics and provides important hints to energy-harvesting in optoelectronics (such as hot-carrier solar-cells).
Atmospheric wavenumber-4 driven South Pacific marine heat waves and marine cool spells
Authors: Chiswell Stephen M. 
Published: August 2021

AbstractMarine heat waves (MHW) and cool spells (MCS) can both positively and negatively impact marine ecosystems with potentially large societal and economic impacts. Here, I examine the global teleconnections of MHW/MCS in the southern hemisphere and Tasman Sea. When MHW/MCS are defined with respect to a linear warming trend, there is little evidence that MHW in the Tasman Sea are changing in either frequency or intensity but may be lasting longer. MCS may be becoming weaker and less frequent. I show that MHW/MCS in the Tasman Sea co-occur with corresponding events in the Atlantic, Indian, and eastern-Pacific Oceans, and these southern hemisphere events are likely driven by stalling of a global wavenumber-4 (W4) atmospheric wave, leading to anomalously weak north-easterly winds during MHW or strong south-westerly winds during MCS. Thus, the key to predicting MHW/MCS is in understanding what causes the atmospheric W4 wave to stall.
Demonstration of the effect of stirring on nucleation from experiments on the International Space Station using the ISS-EML facility
Authors: Gangopadhyay A. K. , Sellers M. E. , Bracker G. P. , Holland-Moritz D. , Van Hoesen D. C. , Koch S. , Galenko P. K. , Pauls A. K. , Hyers R. W. , Kelton K. F. 
Published: August 2021

AbstractThe effect of fluid flow on crystal nucleation in supercooled liquids is not well understood. The variable density and temperature gradients in the liquid make it difficult to study this under terrestrial gravity conditions. Nucleation experiments were therefore made in a microgravity environment using the Electromagnetic Levitation Facility on the International Space Station on a bulk glass-forming Zr57Cu15.4Ni12.6Al10Nb5 (Vit106), as well as Cu50Zr50 and the quasicrystal-forming Ti39.5Zr39.5Ni21 liquids. The maximum supercooling temperatures for each alloy were measured as a function of controlled stirring by applying various combinations of radio-frequency positioner and heater voltages to the water-cooled copper coils. The flow patterns were simulated from the known parameters for the coil and the levitated samples. The maximum nucleation temperatures increased systematically with increased fluid flow in the liquids for Vit106, but stayed nearly unchanged for the other two. These results are consistent with the predictions from the Coupled-Flux model for nucleation.
Swimming, flying, and diving behaviors from a unified 2D potential model
Authors: Jung Sunghwan 
Published: August 2021

AbstractAnimals swim in water, fly in air, or dive into water to find mates, chase prey, or escape from predators. Even though these locomotion modes are phenomenologically distinct, we can rationalize the underlying hydrodynamic forces using a unified fluid potential model. First, we review the previously known complex potential of a moving thin plate to describe circulation and pressure around the body. Then, the impact force in diving or thrust force in swimming and flying are evaluated from the potential flow model. For the impact force, we show that the slamming or impact force of various ellipsoid-shaped bodies of animals increases with animal weight, however, the impact pressure does not vary much. For fliers, birds and bats follow a linear correlation between thrust lift force and animal weight. For swimming animals, we present a scaling of swimming speed as a balance of thrust force with drag, which is verified with biological data. Under this framework, three distinct animal behaviors (i.e., swimming, flying, and diving) are similar in that a thin appendage displaces and pressurizes a fluid, but different in regards to the surroundings, being either fully immersed in a fluid or at a fluid interface.
Human beta defensin levels and vaginal microbiome composition in post-menopausal women diagnosed with lichen sclerosus
Authors: Brunner Alexandra , Medvecz Márta , Makra Nóra , Sárdy Miklós , Komka Kinga , Gugolya Máté , Szabó Dóra , Gajdács Márió , Ostorházi Eszter 
Published: August 2021

AbstractHuman beta defensins (hBDs) may play an important role in the progression of lichen sclerosus (LS), due to their ability to induce excessive stimulation of extracellular matrix synthesis and fibroblast activation. The genetic ability of the individual to produce defensins, the presence of microbes influencing defensin production, and the sensitivity of microbes to defensins together regulate the formation of an ever-changing balance between defensin levels and microbiome composition. We investigated the potential differences in postmenopausal vaginal microbiome composition and vaginal hBD levels in LS patients compared to non-LS controls. LS patients exhibited significantly lower levels of hBD1 (p = 0.0003), and significantly higher levels of hBD2 (p = 0.0359) and hBD3 (p = 0.0002), compared to the control group. The microbiome of the LS patients was dominated by possibly harmful bacteria including Lactobacillus iners, Streptococcus anginosus or Gardnerella vaginalis known to initiate direct or indirect damage by increasing defensin level production. Our observations highlight that correcting the composition of the microbiome may be applicable in supplementary LS therapy by targeting the restoration of the beneficial flora that does not increase hBD2-3 production.
Examining the interplay between face mask usage, asymptomatic transmission, and social distancing on the spread of COVID-19
Authors: Catching Adam , Capponi Sara , Yeh Ming Te , Bianco Simone , Andino Raul 
Published: August 2021

AbstractCOVID-19’s high virus transmission rates have caused a pandemic that is exacerbated by the high rates of asymptomatic and presymptomatic infections. These factors suggest that face masks and social distance could be paramount in containing the pandemic. We examined the efficacy of each measure and the combination of both measures using an agent-based model within a closed space that approximated real-life interactions. By explicitly considering different fractions of asymptomatic individuals, as well as a realistic hypothesis of face masks protection during inhaling and exhaling, our simulations demonstrate that a synergistic use of face masks and social distancing is the most effective intervention to curb the infection spread. To control the pandemic, our models suggest that high adherence to social distance is necessary to curb the spread of the disease, and that wearing face masks provides optimal protection even if only a small portion of the population comply with social distance. Finally, the face mask effectiveness in curbing the viral spread is not reduced if a large fraction of population is asymptomatic. Our findings have important implications for policies that dictate the reopening of social gatherings.
Tautomeric equilibrium, proton affinity and mass spectrometry fragmentation of flexible hydrogen-bonded precursors and rigid $$\hbox {N}\longrightarrow \hbox {BF}_2$$ fluorescent dyes
Authors: Kaczorowska Małgorzata A. , Kaczmarek-Kędziera Anna , Ośmiałowski Borys 
Published: August 2021

AbstractThe stability of two groups of conformationally locked molecules, similar in topology, but differing only by the type of the bridge rigidifying their structure, is studied. The series of the less-rigid 2-phenacylheterocyclic compounds and their stiff difluoroboranyl derivatives are investigated for the determination of the effect of$$\hbox {NCH}_3$$NCH3/S/O replacement in a five-membered heterocyclic ring and the presence of a strong electron-donating group on the tautomeric equilibrium, protonation affinity, and fragmentation pattern observed in the structural elucidation by means of mass spectrometry technique. The results of the$$\omega $$ωB97X-D/6-311++G(d,p) calculations, the topological analysis of electron density as well as the experimental MS measurements show the importance of the number of heteroatoms, their properties, and location in the molecule for the rational design of the systems of desired stable tautomers or the favorable protonation sites. The obtained data allow for the understanding of the fundamentals of the novel highly fluorescent difluoroborates fragmentation behavior, vital for their structural elucidation with the application of high-resolution tandem mass spectrometry methods.