bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ecology of inorganic sulfur auxiliary metabolism in widespread bacteriophages
Authors: Kieft Kristopher , Zhou Zhichao , Anderson Rika E. , Buchan Alison , Campbell Barbara J. , Hallam Steven J. , Hess Matthias , Sullivan Matthew B. , Walsh David A. , Roux Simon , Anantharaman Karthik 
Published: June 2021

AbstractMicrobial sulfur metabolism contributes to biogeochemical cycling on global scales. Sulfur metabolizing microbes are infected by phages that can encode auxiliary metabolic genes (AMGs) to alter sulfur metabolism within host cells but remain poorly characterized. Here we identified 191 phages derived from twelve environments that encoded 227 AMGs for oxidation of sulfur and thiosulfate (dsrA, dsrC/tusE, soxC, soxD and soxYZ). Evidence for retention of AMGs during niche-differentiation of diverse phage populations provided evidence that auxiliary metabolism imparts measurable fitness benefits to phages with ramifications for ecosystem biogeochemistry. Gene abundance and expression profiles of AMGs suggested significant contributions by phages to sulfur and thiosulfate oxidation in freshwater lakes and oceans, and a sensitive response to changing sulfur concentrations in hydrothermal environments. Overall, our study provides fundamental insights on the distribution, diversity, and ecology of phage auxiliary metabolism associated with sulfur and reinforces the necessity of incorporating viral contributions into biogeochemical configurations.
H3K27me3 demethylases alter HSP22 and HSP17.6C expression in response to recurring heat in Arabidopsis
Authors: Yamaguchi Nobutoshi , Matsubara Satoshi , Yoshimizu Kaori , Seki Motohide , Hamada Kouta , Kamitani Mari , Kurita Yuko , Nomura Yasuyuki , Nagashima Kota , Inagaki Soichi , Suzuki Takamasa , Gan Eng-Seng , To Taiko , Kakutani Tetsuji , Nagano Atsushi J. , Satake Akiko , Ito Toshiro 
Published: June 2021

AbstractAcclimation to high temperature increases plants’ tolerance of subsequent lethal high temperatures. Although epigenetic regulation of plant gene expression is well studied, how plants maintain a memory of environmental changes over time remains unclear. Here, we show that JUMONJI (JMJ) proteins, demethylases involved in histone H3 lysine 27 trimethylation (H3K27me3), are necessary for Arabidopsis thaliana heat acclimation. Acclimation induces sustained H3K27me3 demethylation at HEAT SHOCK PROTEIN22 (HSP22) and HSP17.6C loci by JMJs, poising the HSP genes for subsequent activation. Upon sensing heat after a 3-day interval, JMJs directly reactivate these HSP genes. Finally, jmj mutants fail to maintain heat memory under fluctuating field temperature conditions. Our findings of an epigenetic memory mechanism involving histone demethylases may have implications for environmental adaptation of field plants.
Spin-orbital coupling and slow phonon effects enabled persistent photoluminescence in organic crystal under isomer doping
Authors: Dou Yixuan , Demangeat Catherine , Wang Miaosheng , Xu Hengxing , Dryzhakov Bogdan , Kim Eunkyoung , Le Bahers Tangui , Lee Kwang-Sup , Attias André-Jean , Hu Bin 
Published: June 2021

AbstractWhen periodically packing the intramolecular donor-acceptor structures to form ferroelectric-like lattice identified by second harmonic generation, our CD49 molecular crystal shows long-wavelength persistent photoluminescence peaked at 542 nm with the lifetime of 0.43 s, in addition to the short-wavelength prompt photoluminescence peaked at 363 nm with the lifetime of 0.45 ns. Interestingly, the long-wavelength persistent photoluminescence demonstrates magnetic field effects, showing as crystalline intermolecular charge-transfer excitons with singlet spin characteristics formed within ferroelectric-like lattice based on internal minority/majority carrier-balancing mechanism activated by isomer doping effects towards increasing electron-hole pairing probability. Our photoinduced Raman spectroscopy reveals the unusual slow relaxation of photoexcited lattice vibrations, indicating slow phonon effects occurring in ferroelectric-like lattice. Here, we show that crystalline intermolecular charge-transfer excitons are interacted with ferroelectric-like lattice, leading to exciton-lattice coupling within periodically packed intramolecular donor-acceptor structures to evolve ultralong-lived crystalline light-emitting states through slow phonon effects in ferroelectric light-emitting organic crystal.
Activation of PARP2/ARTD2 by DNA damage induces conformational changes relieving enzyme autoinhibition
Authors: Obaji Ezeogo , Maksimainen Mirko M. , Galera-Prat Albert , Lehtiö Lari 
Published: June 2021

AbstractHuman PARP2/ARTD2 is an ADP-ribosyltransferase which, when activated by 5′-phosphorylated DNA ends, catalyses poly-ADP-ribosylation of itself, other proteins and DNA. In this study, a crystal structure of PARP2 in complex with an activating 5′-phosphorylated DNA shows that the WGR domain bridges the dsDNA gap and joins the DNA ends. This DNA binding results in major conformational changes, including reorganization of helical fragments, in the PARP2 regulatory domain. A comparison of PARP1 and PARP2 crystal structures reveals how binding to a DNA damage site leads to formation of a catalytically competent conformation. In this conformation, PARP2 is capable of binding substrate NAD+ and histone PARylation factor 1 that changes PARP2 residue specificity from glutamate to serine when initiating DNA repair processes. The structure also reveals how the conformational changes in the autoinhibitory regulatory domain would promote the flexibility needed by the enzyme to reach the target macromolecule for ADP-ribosylation.
TcpC inhibits neutrophil extracellular trap formation by enhancing ubiquitination mediated degradation of peptidylarginine deiminase 4
Authors: Ou Qian , Fang Jia-qi , Zhang Zhe-sheng , Chi Zhe , Fang Jie , Xu Di-yan , Lu Kai-zhong , Qian Meng-qing , Zhang Da-yong , Guo Jun-ping , Gao Wei , Zhang Na-ru , Pan Jian-ping 
Published: June 2021

AbstractTcpC is a multifunctional virulence factor of uropathogenicE. coli(UPEC). Neutrophil extracellular trap formation (NETosis) is a crucial anti-infection mechanism of neutrophils. Here we show the influence of TcpC on NETosis and related mechanisms. We show NETosis in the context of a pyelonephritis mouse model induced by TcpC-secreting wild-typeE. coliCFT073 (CFT073wt) and LPS-induced in vitro NETosis with CFT073wtor recombinant TcpC (rTcpC)-treated neutrophils are inhibited. rTcpC enters neutrophils through caveolin-mediated endocytosis and inhibits LPS-induced production of ROS, proinflammatory cytokines and protein but not mRNA levels of peptidylarginine deiminase 4 (PAD4). rTcpC treatment enhances PAD4 ubiquitination and accumulation in proteasomes. Moreover, in vitro ubiquitination kit analyses show that TcpC is a PAD4-targetd E3 ubiquitin-ligase. These data suggest that TcpC inhibits NETosis primarily by serving as an E3 ligase that promotes degradation of PAD4. Our findings provide a novel mechanism underlying TcpC-mediated innate immune evasion.
Tight finite-key analysis for quantum key distribution without monitoring signal disturbance
Authors: Liu Hang , Yin Zhen-Qiang , Wang Rong , Wang Ze-Hao , Wang Shuang , Chen Wei , Guo Guang-Can , Han Zheng-Fu 
Published: June 2021

AbstractUnlike traditional communication, quantum key distribution (QKD) can reach unconditional security and thus attracts intensive studies. Among all existing QKD protocols, round-robin-differential-phase-shift (RRDPS) protocol can be running without monitoring signal disturbance, which significantly simplifies its flow and improves its tolerance of error rate. Although several security proofs of RRDPS have been given, a tight finite-key analysis with a practical phase-randomized source is still missing. In this paper, we propose an improved security proof of RRDPS against the most general coherent attack based on the entropic uncertainty relation. What’s more, with the help of Azuma’s inequality, our proof can tackle finite-key effects primely. The proposed finite-key analysis keeps the advantages of phase randomization source and indicates experimentally acceptable numbers of pulses are sufficient to approach the asymptotical bound closely. The results shed light on practical QKD without monitoring signal disturbance.
Immunogenicity of Ad26.COV2.S vaccine against SARS-CoV-2 variants in humans
Authors: Alter Galit , Yu Jingyou , Liu Jinyan , Chandrashekar Abishek , Borducchi Erica N. , Tostanoski Lisa H. , McMahan Katherine , Jacob-Dolan Catherine , Martinez David R. , Chang Aiquan , Anioke Tochi , Lifton Michelle , Nkolola Joseph , Stephenson Kathryn E. , Atyeo Caroline , Shin Sally , Fields Paul , Kaplan Ian , Robins Harlan , Amanat Fatima , Krammer Florian , Baric Ralph S. , Le Gars Mathieu , Sadoff Jerald , de Groot Anne Marit , Heerwegh Dirk , Struyf Frank , Douoguih Macaya , van Hoof Johan , Schuitemaker Hanneke , Barouch Dan H. 
Published: June 2021

AbstractThe Ad26.COV2.S vaccine1–3 has demonstrated clinical efficacy against symptomatic COVID-19, including against the B.1.351 variant that is partially resistant to neutralizing antibodies1. However, the immunogenicity of this vaccine in humans against SARS-CoV-2 variants of concern remains unclear. Here we report humoral and cellular immune responses from 20 Ad26.COV2.S vaccinated individuals from the COV1001 phase I–IIa clinical trial2 against the original SARS-CoV-2 strain WA1/2020 as well as against the B.1.1.7, CAL.20C, P.1 and B.1.351 variants of concern. Ad26.COV2.S induced median pseudovirus neutralizing antibody titres that were 5.0-fold and 3.3-fold lower against the B.1.351 and P.1 variants, respectively, as compared with WA1/2020 on day 71 after vaccination. Median binding antibody titres were 2.9-fold and 2.7-fold lower against the B.1.351 and P.1 variants, respectively, as compared with WA1/2020. Antibody-dependent cellular phagocytosis, complement deposition and natural killer cell activation responses were largely preserved against the B.1.351 variant. CD8 and CD4 T cell responses, including central and effector memory responses, were comparable among the WA1/2020, B.1.1.7, B.1.351, P.1 and CAL.20C variants. These data show that neutralizing antibody responses induced by Ad26.COV2.S were reduced against the B.1.351 and P.1 variants, but functional non-neutralizing antibody responses and T cell responses were largely preserved against SARS-CoV-2 variants. These findings have implications for vaccine protection against SARS-CoV-2 variants of concern.
First-dose ChAdOx1 and BNT162b2 COVID-19 vaccines and thrombocytopenic, thromboembolic and hemorrhagic events in Scotland
Authors: Simpson C. R. , Shi T. , Vasileiou E. , Katikireddi S. V. , Kerr S. , Moore E. , McCowan C. , Agrawal U. , Shah S. A. , Ritchie L. D. , Murray J. , Pan J. , Bradley D. T. , Stock S. J. , Wood R. , Chuter A. , Beggs J. , Stagg H. R. , Joy M. , Tsang R. S. M. , de Lusignan S. , Hobbs R. , Lyons R. A. , Torabi F. , Bedston S. , O’Leary M. , Akbari A. , McMenamin J. , Robertson C. , Sheikh A. 
Published: June 2021

AbstractReports of ChAdOx1 vaccine–associated thrombocytopenia and vascular adverse events have led to some countries restricting its use. Using a national prospective cohort, we estimated associations between exposure to first-dose ChAdOx1 or BNT162b2 vaccination and hematological and vascular adverse events using a nested incident-matched case-control study and a confirmatory self-controlled case series (SCCS) analysis. An association was found between ChAdOx1 vaccination and idiopathic thrombocytopenic purpura (ITP) (0–27 d after vaccination; adjusted rate ratio (aRR) = 5.77, 95% confidence interval (CI), 2.41–13.83), with an estimated incidence of 1.13 (0.62–1.63) cases per 100,000 doses. An SCCS analysis confirmed that this was unlikely due to bias (RR = 1.98 (1.29–3.02)). There was also an increased risk for arterial thromboembolic events (aRR = 1.22, 1.12–1.34) 0–27 d after vaccination, with an SCCS RR of 0.97 (0.93–1.02). For hemorrhagic events 0–27 d after vaccination, the aRR was 1.48 (1.12–1.96), with an SCCS RR of 0.95 (0.82–1.11). A first dose of ChAdOx1 was found to be associated with small increased risks of ITP, with suggestive evidence of an increased risk of arterial thromboembolic and hemorrhagic events. The attenuation of effect found in the SCCS analysis means that there is the potential for overestimation of the reported results, which might indicate the presence of some residual confounding or confounding by indication. Public health authorities should inform their jurisdictions of these relatively small increased risks associated with ChAdOx1. No positive associations were seen between BNT162b2 and thrombocytopenic, thromboembolic and hemorrhagic events.
Central nervous system (CNS) transcriptomic correlates of human immunodeficiency virus (HIV) brain RNA load in HIV-infected individuals
Authors: Sanna Pietro Paolo , Fu Yu , Masliah Eliezer , Lefebvre Celine , Repunte-Canonigo Vez 
Published: June 2021

AbstractTo generate new mechanistic hypotheses on the pathogenesis and disease progression of neuroHIV and identify novel therapeutic targets to improve neuropsychological function in people with HIV, we investigated host genes and pathway dysregulations associated with brain HIV RNA load in gene expression profiles of the frontal cortex, basal ganglia, and white matter of HIV+ patients. Pathway analyses showed that host genes correlated with HIV expression in all three brain regions were predominantly related to inflammation, neurodegeneration, and bioenergetics. HIV RNA load directly correlated particularly with inflammation genesets representative of cytokine signaling, and this was more prominent in white matter and the basal ganglia. Increases in interferon signaling were correlated with high brain HIV RNA load in the basal ganglia and the white matter although not in the frontal cortex. Brain HIV RNA load was inversely correlated with genesets that are indicative of neuronal and synaptic genes, particularly in the cortex, indicative of synaptic injury and neurodegeneration. Brain HIV RNA load was inversely correlated with genesets that are representative of oxidative phosphorylation, electron transfer, and the tricarboxylic acid cycle in all three brain regions. Mitochondrial dysfunction has been implicated in the toxicity of some antiretrovirals, and these results indicate that mitochondrial dysfunction is also associated with productive HIV infection. Genes and pathways correlated with brain HIV RNA load suggest potential therapeutic targets to ameliorate neuropsychological functioning in people living with HIV.
DNA-PK inhibitor peposertib enhances p53-dependent cytotoxicity of DNA double-strand break inducing therapy in acute leukemia
Authors: Haines Eric , Nishida Yuki , Carr Michael I. , Montoya Rafael Heinz , Ostermann Lauren B. , Zhang Weiguo , Zenke Frank T. , Blaukat Andree , Andreeff Michael , Vassilev Lyubomir T. 
Published: June 2021

AbstractPeposertib (M3814) is a potent and selective DNA-PK inhibitor in early clinical development. It effectively blocks non-homologous end-joining repair of DNA double-strand breaks (DSB) and strongly potentiates the antitumor effect of ionizing radiation (IR) and topoisomerase II inhibitors. By suppressing DNA-PK catalytic activity in the presence of DNA DSB, M3814 potentiates ATM/p53 signaling leading to enhanced p53-dependent antitumor activity in tumor cells. Here, we investigated the therapeutic potential of M3814 in combination with DSB-inducing agents in leukemia cells and a patient-derived tumor. We show that in the presence of IR or topoisomerase II inhibitors, M3814 boosts the ATM/p53 response in acute leukemia cells leading to the elevation of p53 protein levels as well as its transcriptional activity. M3814 synergistically sensitized p53 wild-type, but not p53-deficient, AML cells to killing by DSB-inducing agents via p53-dependent apoptosis involving both intrinsic and extrinsic effector pathways. The antileukemic effect was further potentiated by enhancing daunorubicin-induced myeloid cell differentiation. Further, combined with the fixed-ratio liposomal formulation of daunorubicin and cytarabine, CPX-351, M3814 enhanced the efficacy against leukemia cells in vitro and in vivo without increasing hematopoietic toxicity, suggesting that DNA-PK inhibition could offer a novel clinical strategy for harnessing the anticancer potential of p53 in AML therapy.
Tailoring of arteriovenous graft-to-vein anastomosis angle to attenuate pathological flow fields
Authors: Williams Dillon , Leuthardt Eric C. , Genin Guy M. , Zayed Mohamed 
Published: June 2021

AbstractArteriovenous grafts are routinely placed to facilitate hemodialysis in patients with end stage renal disease. These grafts are conduits between higher pressure arteries and lower pressure veins. The connection on the vein end of the graft, known as the graft-to-vein anastomosis, fails frequently and chronically due to high rates of stenosis and thrombosis. These failures are widely believed to be associated with pathologically high and low flow shear strain rates at the graft-to-vein anastomosis. We hypothesized that consistent with pipe flow dynamics and prior work exploring vein-to-artery anastomosis angles in arteriovenous fistulas, altering the graft-to-vein anastomosis angle can reduce the incidence of pathological shear rate fields. We tested this via computational fluid dynamic simulations of idealized arteriovenous grafts, using the Bird-Carreau constitutive law for blood. We observed that low graft-to-vein anastomosis angles ($$<20^{\circ }$$

<

20
∘

) led to increased incidence of pathologically low shear rates, and that high graft-to-vein anastomosis angles ($$>40^{\circ }$$

>

40
∘

) led to increased incidence of pathologically high shear rates. Optimizations predicted that an intermediate ($$\sim 30^\circ$$

∼

30
∘

) graft-to-anastomosis angle was optimal. Our study demonstrates that graft-to-vein anastomosis angles can significantly impact pathological flow fields, and can be optimized to substantially improve arteriovenous graft patency rates.
A high-throughput microfluidic bilayer co-culture platform to study endothelial-pericyte interactions
Authors: Rogers Miles T. , Gard Ashley L. , Gaibler Robert , Mulhern Thomas J. , Strelnikov Rivka , Azizgolshani Hesham , Cain Brian P. , Isenberg Brett C. , Haroutunian Nerses J. , Raustad Nicole E. , Keegan Philip M. , Lech Matthew P. , Tomlinson Lindsay , Borenstein Jeffrey T. , Charest Joseph L. , Williams Corin 
Published: June 2021

AbstractMicrophysiological organ-on-chip models offer the potential to improve the prediction of drug safety and efficacy through recapitulation of human physiological responses. The importance of including multiple cell types within tissue models has been well documented. However, the study of cell interactions in vitro can be limited by complexity of the tissue model and throughput of current culture systems. Here, we describe the development of a co-culture microvascular model and relevant assays in a high-throughput thermoplastic organ-on-chip platform, PREDICT96. The system consists of 96 arrayed bilayer microfluidic devices containing retinal microvascular endothelial cells and pericytes cultured on opposing sides of a microporous membrane. Compatibility of the PREDICT96 platform with a variety of quantifiable and scalable assays, including macromolecular permeability, image-based screening, Luminex, and qPCR, is demonstrated. In addition, the bilayer design of the devices allows for channel- or cell type-specific readouts, such as cytokine profiles and gene expression. The microvascular model was responsive to perturbations including barrier disruption, inflammatory stimulation, and fluid shear stress, and our results corroborated the improved robustness of co-culture over endothelial mono-cultures. We anticipate the PREDICT96 platform and adapted assays will be suitable for other complex tissues, including applications to disease models and drug discovery.
Real-Time insight into in vivo redox status utilizing hyperpolarized [1-13C] N-acetyl cysteine
Authors: Yamamoto Kazutoshi , Opina Ana , Sail Deepak , Blackman Burchelle , Saito Keita , Brender Jeffrey R. , Malinowski Ronja M. , Seki Tomohiro , Oshima Nobu , Crooks Daniel R. , Kishimoto Shun , Saida Yu , Otowa Yasunori , Choyke Peter L. , Ardenkjær-Larsen Jan H. , Mitchell James B. , Linehan W. Marston , Swenson Rolf E. , Krishna Murali C. 
Published: June 2021

AbstractDrastic sensitivity enhancement of dynamic nuclear polarization is becoming an increasingly critical methodology to monitor real-time metabolic and physiological information in chemistry, biochemistry, and biomedicine. However, the limited number of available hyperpolarized 13C probes, which can effectively interrogate crucial metabolic activities, remains one of the major bottlenecks in this growing field. Here, we demonstrate [1-13C] N-acetyl cysteine (NAC) as a novel probe for hyperpolarized 13C MRI to monitor glutathione redox chemistry, which plays a central part of metabolic chemistry and strongly influences various therapies. NAC forms a disulfide bond in the presence of reduced glutathione, which generates a spectroscopically detectable product that is separated from the main peak by a 1.5 ppm shift. In vivo hyperpolarized MRI in mice revealed that NAC was broadly distributed throughout the body including the brain. Its biochemical transformation in two human pancreatic tumor cells in vitro and as xenografts differed depending on the individual cellular biochemical profile and microenvironment in vivo. Hyperpolarized NAC can be a promising non-invasive biomarker to monitor in vivo redox status and can be potentially translatable to clinical diagnosis.
Analysis of the role of Purα in the pathogenesis of Alzheimer's disease based on RNA-seq and ChIP-seq
Authors: Shi Xiaoguang , Ren Shuanglai , Zhang Bingying , Guo Shanshan , He Wenxin , Yuan Chengmin , Yang Xiaofan , Ig-lzevbekhai Kevin , Sun Tao , Wang Qinwen , Cui Jianqi 
Published: June 2021

AbstractPurine rich element binding protein A (Purα), encoded by the Purα gene, is an important transcriptional regulator that binds to DNA and RNA and is involved in processes such as DNA replication and RNA translation. Purα also plays an important role in the nervous system. To identify the function of Pura, we performed RNA sequence (RNA-seq) analysis of Purɑ-KO mouse hippocampal neuron cell line (HT22) to analyze the effect of Purα deletion on neuronal expression profiles. And combined with ChIP-seq analysis to explore the mechanism of Purα on gene regulation. In the end, totaly 656 differentially expressed genes between HT22 and Purα-KO HT22 cells have been found, which include 7 Alzheimer’s disease (AD)-related genes and 5 Aβ clearance related genes. 47 genes were regulated by Purα directly, the evidence based on CHIP-seq, which include Insr, Mapt, Vldlr, Jag1, etc. Our study provides the important informations of Purα in neuro-development. The possible regulative effects of Purα on AD-related genes consist inthe direct and indirect pathways of Purα in the pathogenesis of AD.