bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evidence for methanobactin “Theft” and novel chalkophore production in methanotrophs: impact on methanotrophic-mediated methylmercury degradation
Authors: Kang-Yun Christina S , Liang Xujun , Dershwitz Philip , Gu Wenyu , Schepers Aloys , Flatley Andrew , Lichtmannegger Josef , Zischka Hans , Zhang Lijie , Lu Xia , Gu Baohua , Ledesma Joshua C , Pelger Daly J , DiSpirito Alan A , Semrau Jeremy D 
Published: July 2021

Abstract
Aerobic methanotrophy is strongly controlled by copper, and methanotrophs are known to use different mechanisms for copper uptake. Some methanotrophs secrete a modified polypeptide—methanobactin—while others utilize a surface-bound protein (MopE) and a secreted form of it (MopE*) for copper collection. As different methanotrophs have different means of sequestering copper, competition for copper significantly impacts methanotrophic activity. Herein, we show that Methylomicrobium album BG8, Methylocystis sp. strain Rockwell, and Methylococcus capsulatus Bath, all lacking genes for methanobactin biosynthesis, are not limited for copper by multiple forms of methanobactin. Interestingly, Mm. album BG8 and Methylocystis sp. strain Rockwell were found to have genes similar to mbnT that encodes for a TonB-dependent transporter required for methanobactin uptake. Data indicate that these methanotrophs “steal” methanobactin and such “theft” enhances the ability of these strains to degrade methylmercury, a potent neurotoxin. Further, when mbnT was deleted in Mm. album BG8, methylmercury degradation in the presence of methanobactin was indistinguishable from when MB was not added. Mc. capsulatus Bath lacks anything similar to mbnT and was unable to degrade methylmercury either in the presence or absence of methanobactin. Rather, Mc. capsulatus Bath appears to rely on MopE/MopE* for copper collection. Finally, not only does Mm. album BG8 steal methanobactin, it synthesizes a novel chalkophore, suggesting that some methanotrophs utilize both competition and cheating strategies for copper collection. Through a better understanding of these strategies, methanotrophic communities may be more effectively manipulated to reduce methane emissions and also enhance mercury detoxification in situ.
Inhibition of metabotropic glutamate receptor III facilitates sensitization to alkylating chemotherapeutics in glioblastoma
Authors: Maier Julian P. , Ravi Vidhya M. , Kueckelhaus Jan , Behringer Simon P. , Garrelfs Niklas , Will Paulina , Sun Na , von Ehr Jasmin , Goeldner Jonathan M. , Pfeifer Dietmar , Follo Marie , Hannibal Luciana , Walch Axel Karl , Hofmann Ulrich G. , Beck Jürgen , Heiland Dieter Henrik , Schnell Oliver , Joseph Kevin 
Published: July 2021

AbstractGlioblastoma (GBM), the most malignant tumor of the central nervous system, is marked by its dynamic response to microenvironmental niches. In particular, this cellular plasticity contributes to the development of an immediate resistance during tumor treatment. Novel insights into the developmental trajectory exhibited by GBM show a strong capability to respond to its microenvironment by clonal selection of specific phenotypes. Using the same mechanisms, malignant GBM do develop intrinsic mechanisms to resist chemotherapeutic treatments. This resistance was reported to be sustained by the paracrine and autocrine glutamate signaling via ionotropic and metabotropic receptors. However, the extent to which glutamatergic signaling modulates the chemoresistance and transcriptional profile of the GBM remains unexplored. In this study we aimed to map the manifold effects of glutamate signaling in GBM as the basis to further discover the regulatory role and interactions of specific receptors, within the GBM microenvironment. Our work provides insights into glutamate release dynamics, representing its importance for GBM growth, viability, and migration. Based on newly published multi-omic datasets, we explored the and characterized the functions of different ionotropic and metabotropic glutamate receptors, of which the metabotropic receptor 3 (GRM3) is highlighted through its modulatory role in maintaining the ability of GBM cells to evade standard alkylating chemotherapeutics. We addressed the clinical relevance of GRM3 receptor expression in GBM and provide a proof of concept where we manipulate intrinsic mechanisms of chemoresistance, driving GBM towards chemo-sensitization through GRM3 receptor inhibition. Finally, we validated our findings in our novel human organotypic section-based tumor model, where GBM growth and proliferation was significantly reduced when GRM3 inhibition was combined with temozolomide application. Our findings present a new picture of how glutamate signaling via mGluR3 interacts with the phenotypical GBM transcriptional programs in light of recently published GBM cell-state discoveries.
Glutathione S-transferase A2 promotes hepatocellular carcinoma recurrence after liver transplantation through modulating reactive oxygen species metabolism
Authors: Ng Kevin Tak-Pan , Yeung Oscar Wai-Ho , Lam Yin Fan , Liu Jiang , Liu Hui , Pang Li , Yang Xin Xiang , Zhu Jiye , Zhang Weiyi , Lau Matthew Y. H. , Qiu Wen Qi , Shiu Hoi Chung , Lai Man Kit , Lo Chung Mau , Man Kwan 
Published: July 2021

AbstractHepatocellular carcinoma (HCC) recurrence after liver transplantation remains a significant clinical problem. Ischemia-reperfusion injury (IRI) occurred inevitably at the early phase after liver transplantation (LT) spawns a significant risk of HCC recurrence. However, their linkage and IRI-derived risk factors for HCC recurrence remain exclusive. Understanding the mechanism of post-transplantation hepatic injury could provide new strategies to prevent the later event of HCC recurrence. We demonstrated that glutathione S-transferase A2 (GSTA2) expression was significantly associated with early phase hepatic and systemic injury and ROS level after liver transplantation. Early phase circulating GSTA2 (EPCGSTA2) protein was a significant predictor of HCC recurrence and survival. Heterogeneous single nucleotide polymorphism at G335C of GSTA2 was significantly associated with poor survival of HCC recipients. Enhancement of GSTA2 could protect HCC cells against H2O2-induced cell death by compensating for the elevated ROS stress. We also demonstrated that GSTA2 played crucial roles in regulating the ROS-associated JNK and AKT signaling pathways and ROS metabolism in HCCs in responding to a dynamic ROS environment. Functionally, endogenous or exogenous upregulation of GSTA2 could promote HCC growth and invasion through activating the epithelial–mesenchymal-transition process. Targeted inhibition of GSTA2 could suppress HCC growth and metastasis. In conclusion, GSTA2 could be a novel prognostic and therapeutic target to combat HCC recurrence after liver transplantation.
Kinetically driven successive sodic and potassic alteration of feldspar
Authors: Duan Gan , Ram Rahul , Xing Yanlu , Etschmann Barbara , Brugger Joël 
Published: July 2021

AbstractThe dynamic evolutions of fluid-mineral systems driving large-scale geochemical transformations in the Earth’s crust remain poorly understood. We observed experimentally that successive sodic and potassic alterations of feldspar can occur via a single self-evolved, originally Na-only, hydrothermal fluid. At 600 °C, 2 kbar, sanidine ((K,Na)AlSi3O8) reacted rapidly with a NaCl fluid to form albite (NaAlSi3O8); over time, some of this albite was replaced by K-feldspar (KAlSi3O8), in contrast to predictions from equilibrium reaction modelling. Fluorine accelerated the process, resulting in near-complete back-replacement of albite within 1 day. These findings reveal that potassic alteration can be triggered by Na-rich fluids, indicating that pervasive sequential sodic and potassic alterations associated with mineralization in some of the world’s largest ore deposits may not necessarily reflect externally-driven changes in fluid alkali contents. Here, we show that these reactions are promoted at the micro-scale by a self-evolving, kinetically-driven process; such positive feedbacks between equilibrium and kinetic factors may be essential in driving pervasive mineral transformations.
Role of Tim4 in the regulation of ABCA1+ adipose tissue macrophages and post-prandial cholesterol levels
Authors: Magalhaes M. S. , Smith P. , Portman J. R. , Jackson-Jones L. H. , Bain C. C. , Ramachandran P. , Michailidou Z. , Stimson R. H. , Dweck M. R. , Denby L. , Henderson N. C. , Jenkins S. J. , Bénézech C. 
Published: July 2021

AbstractDyslipidemia is a main driver of cardiovascular diseases. The ability of macrophages to scavenge excess lipids implicate them as mediators in this process and understanding the mechanisms underlying macrophage lipid metabolism is key to the development of new treatments. Here, we investigated how adipose tissue macrophages regulate post-prandial cholesterol transport. Single-cell RNA sequencing and protected bone marrow chimeras demonstrated that ingestion of lipids led to specific transcriptional activation of a population of resident macrophages expressing Lyve1, Tim4, and ABCA1. Blocking the phosphatidylserine receptor Tim4 inhibited lysosomal activation and the release of post-prandial high density lipoprotein cholesterol following a high fat meal. Both effects were recapitulated by chloroquine, an inhibitor of lysosomal function. Moreover, clodronate-mediated cell-depletion implicated Tim4+ resident adipose tissue macrophages in this process. Thus, these data indicate that Tim4 is a key regulator of post-prandial cholesterol transport and adipose tissue macrophage function and may represent a novel pathway to treat dyslipidemia.
Stromal induction of BRD4 phosphorylation Results in Chromatin Remodeling and BET inhibitor Resistance in Colorectal Cancer
Authors: Wang Wenyu , Tang Yen-An , Xiao Qian , Lee Wee Chyan , Cheng Bing , Niu Zhitong , Oguz Gokce , Feng Min , Lee Puay Leng , Li Baojie , Yang Zi-huan , Chen Yu-feng , Lan Ping , Wu Xiao-Jian , Yu Qiang 
Published: July 2021

AbstractBRD4, a Bromodomain and Extraterminal (BET) protein family member, is a promising anti-cancer drug target. However, resistance to BET inhibitors targeting BRD4 is common in solid tumors. Here, we show that cancer-associated fibroblast (CAF)-activated stromal signaling, interleukin-6/8-JAK2, induces BRD4 phosphorylation at tyrosine 97/98 in colorectal cancer, resulting in BRD4 stabilization due to interaction with the deubiquitinase UCHL3. BRD4 phosphorylation at tyrosine 97/98 also displays increased binding to chromatin but reduced binding to BET inhibitors, resulting in resistance to BET inhibitors. We further show that BRD4 phosphorylation promotes interaction with STAT3 to induce chromatin remodeling through concurrent binding to enhancers and super-enhancers, supporting a tumor-promoting transcriptional program. Inhibition of IL6/IL8-JAK2 signaling abolishes BRD4 phosphorylation and sensitizes BET inhibitors in vitro and in vivo. Our study reveals a stromal mechanism for BRD4 activation and BET inhibitor resistance, which provides a rationale for developing strategies to treat CRC more effectively.
Small RNA mediated gradual control of lipopolysaccharide biosynthesis affects antibiotic resistance in Helicobacter pylori
Authors: Pernitzsch Sandy R. , Alzheimer Mona , Bremer Belinda U. , Robbe-Saule Marie , De Reuse Hilde , Sharma Cynthia M. 
Published: July 2021

AbstractThe small, regulatory RNA RepG (Regulator of polymeric G-repeats) regulates the expression of the chemotaxis receptor TlpB in Helicobacter pylori by targeting a variable G-repeat in the tlpB mRNA leader. Here, we show that RepG additionally controls lipopolysaccharide (LPS) phase variation by also modulating the expression of a gene (hp0102) that is co-transcribed with tlpB. The hp0102 gene encodes a glycosyltransferase required for LPS O-chain biosynthesis and in vivo colonization of the mouse stomach. The G-repeat length defines a gradual (rather than ON/OFF) control of LPS biosynthesis by RepG, and leads to gradual resistance to a membrane-targeting antibiotic. Thus, RepG-mediated modulation of LPS structure might impact host immune recognition and antibiotic sensitivity, thereby helping H. pylori to adapt and persist in the host.
Increasing the Hilbert space dimension using a single coupled molecular spin
Authors: Biard Hugo , Moreno-Pineda Eufemio , Ruben Mario , Bonet Edgar , Wernsdorfer Wolfgang , Balestro Franck 
Published: July 2021

AbstractQuantum technologies are expected to introduce revolutionary changes in information processing in the near future. Nowadays, one of the main challenges is to be able to handle a large number of quantum bits (qubits), while preserving their quantum properties. Beyond the usual two-level encoding capacity of qubits, multi-level quantum systems are a promising way to extend and increase the amount of information that can be stored in the same number of quantum objects. Recent work (Kues et al. 2017), has shown the possibility to use devices based on photonic integrated circuits to entangle two qudits (with “d” being the number of available states). In the race to develop a mature quantum technology with real-world applications, many possible platforms are being investigated, including those that use photons, trapped ions, superconducting and silicon circuits and molecular magnets. In this work, we present the electronic read-out of a coupled molecular multi-level quantum systems, carried by a single Tb2Pc3 molecular magnet. Owning two magnetic centres, this molecular magnet architecture permits a 16 dimensions Hilbert space, opening the possibility of performing more complex quantum algorithms.
3-hydroxy-L-kynurenamine is an immunomodulatory biogenic amine
Authors: Clement Cristina C. , D’Alessandro Angelo , Thangaswamy Sangeetha , Chalmers Samantha , Furtado Raquel , Spada Sheila , Mondanelli Giada , Ianni Federica , Gehrke Sarah , Gargaro Marco , Manni Giorgia , Cara Luisa Carlota Lopez , Runge Peter , Tsai Wanxia Li , Karaman Sinem , Arasa Jorge , Fernandez-Rodriguez Ruben , Beck Amanda , Macchiarulo Antonio , Gadina Massimo , Halin Cornelia , Fallarino Francesca , Skobe Mihaela , Veldhoen Marc , Moretti Simone , Formenti Silvia , Demaria Sandra , Soni Rajesh K. , Galarini Roberta , Sardella Roccaldo , Lauvau Gregoire , Putterman Chaim , Alitalo Kari , Grohmann Ursula , Santambrogio Laura 
Published: July 2021

AbstractTryptophan catabolism is a major metabolic pathway utilized by several professional and non-professional antigen presenting cells to maintain immunological tolerance. Here we report that 3-hydroxy-l-kynurenamine (3-HKA) is a biogenic amine produced via an alternative pathway of tryptophan metabolism. In vitro, 3-HKA has an anti-inflammatory profile by inhibiting the IFN-γ mediated STAT1/NF-κΒ pathway in both mouse and human dendritic cells (DCs) with a consequent decrease in the release of pro-inflammatory chemokines and cytokines, most notably TNF, IL-6, and IL12p70. 3-HKA has protective effects in an experimental mouse model of psoriasis by decreasing skin thickness, erythema, scaling and fissuring, reducing TNF, IL-1β, IFN-γ, and IL-17 production, and inhibiting generation of effector CD8+ T cells. Similarly, in a mouse model of nephrotoxic nephritis, besides reducing inflammatory cytokines, 3-HKA improves proteinuria and serum urea nitrogen, overall ameliorating immune-mediated glomerulonephritis and renal dysfunction. Overall, we propose that this biogenic amine is a crucial component of tryptophan-mediated immune tolerance.
IL-1B drives opposing responses in primary tumours and bone metastases; harnessing combination therapies to improve outcome in breast cancer
Authors: Tulotta Claudia , Lefley Diane V. , Moore Charlotte K. , Amariutei Ana E. , Spicer-Hadlington Amy R. , Quayle Lewis A. , Hughes Russell O. , Ahmed Khawla , Cookson Victoria , Evans Catherine A. , Vadakekolathu Jayakumar , Heath Paul , Francis Sheila , Pinteaux Emmanuel , Pockley A. Graham , Ottewell Penelope D. 
Published: July 2021

AbstractBreast cancer bone metastasis is currently incurable, ~75% of patients with late-stage breast cancer develop disease recurrence in bone and available treatments are only palliative. We have previously shown that production of the pro-inflammatory cytokine interleukin-1B (IL-1B) by breast cancer cells drives bone metastasis in patients and in preclinical in vivo models. In the current study, we have investigated how IL-1B from tumour cells and the microenvironment interact to affect primary tumour growth and bone metastasis through regulation of the immune system, and whether targeting IL-1 driven changes to the immune response improves standard of care therapy for breast cancer bone metastasis. Using syngeneic IL-1B/IL1R1 knock out mouse models in combination with genetic manipulation of tumour cells to overexpress IL-1B/IL1R1, we found that IL-1B signalling elicited an opposite response in primary tumours compared with bone metastases. In primary tumours, IL-1B inhibited growth, by impairing the infiltration of innate immune cell subsets with potential anti-cancer functions but promoted enhanced tumour cell migration. In bone, IL-1B stimulated the development of osteolytic metastases. In syngeneic models of breast cancer, combining standard of care treatments (Doxorubicin and Zoledronic acid) with the IL-1 receptor antagonist Anakinra inhibited both primary tumour growth and metastasis. Anakinra had opposite effects on the immune response compared to standard of care treatment, and its anti-inflammatory signature was maintained in the combination therapy. These data suggest that targeting IL-1B signalling may provide a useful therapeutic approach to inhibit bone metastasis and improve efficacy of current treatments for breast cancer patients.
Quantum phases and spin liquid properties of 1T-TaS2
Authors: Mañas-Valero Samuel , Huddart Benjamin M. , Lancaster Tom , Coronado Eugenio , Pratt Francis L. 
Published: July 2021

AbstractQuantum materials exhibiting magnetic frustration are connected to diverse phenomena, including high Tc superconductivity, topological order, and quantum spin liquids (QSLs). A QSL is a quantum phase (QP) related to a quantum-entangled fluid-like state of matter. Previous experiments on QSL candidate materials are usually interpreted in terms of a single QP, although theories indicate that many distinct QPs are closely competing in typical frustrated spin models. Here we report on combined temperature-dependent muon spin relaxation and specific heat measurements for the triangular-lattice QSL candidate material 1T-TaS2 that provide evidence for competing QPs. The measured properties are assigned to arrays of individual QSL layers within the layered charge density wave structure of 1T-TaS2 and their characteristic parameters can be interpreted as those of distinct Z2 QSL phases. The present results reveal that a QSL description can extend beyond the lowest temperatures, offering an additional perspective in the search for such materials.
Transcriptional programs of neoantigen-specific TIL in anti-PD-1-treated lung cancers
Authors: Caushi Justina X. , Zhang Jiajia , Ji Zhicheng , Vaghasia Ajay , Zhang Boyang , Hsiue Emily Han-Chung , Mog Brian J. , Hou Wenpin , Justesen Sune , Blosser Richard , Tam Ada , Anagnostou Valsamo , Cottrell Tricia R. , Guo Haidan , Chan Hok Yee , Singh Dipika , Thapa Sampriti , Dykema Arbor G. , Burman Poromendro , Choudhury Begum , Aparicio Luis , Cheung Laurene S. , Lanis Mara , Belcaid Zineb , El Asmar Margueritta , Illei Peter B. , Wang Rulin , Meyers Jennifer , Schuebel Kornel , Gupta Anuj , Skaist Alyza , Wheelan Sarah , Naidoo Jarushka , Marrone Kristen A. , Brock Malcolm , Ha Jinny , Bush Errol L. , Park Bernard J. , Bott Matthew , Jones David R. , Reuss Joshua E. , Velculescu Victor E. , Chaft Jamie E. , Kinzler Kenneth W. , Zhou Shibin , Vogelstein Bert , Taube Janis M. , Hellmann Matthew D. , Brahmer Julie R. , Merghoub Taha , Forde Patrick M. , Yegnasubramanian Srinivasan , Ji Hongkai , Pardoll Drew M. , Smith Kellie N. 
Published: July 2021

AbstractPD-1 blockade unleashes CD8 T cells1, including those specific for mutation-associated neoantigens (MANA), but factors in the tumour microenvironment can inhibit these T cell responses. Single-cell transcriptomics have revealed global T cell dysfunction programs in tumour-infiltrating lymphocytes (TIL). However, the majority of TIL do not recognize tumour antigens2, and little is known about transcriptional programs of MANA-specific TIL. Here, we identify MANA-specific T cell clones using the MANA functional expansion of specific T cells assay3in neoadjuvant anti-PD-1-treated non-small cell lung cancers (NSCLC). We use their T cell receptors as a ‘barcode’ to track and analyse their transcriptional programs in the tumour microenvironment using coupled single-cell RNA sequencing and T cell receptor sequencing. We find both MANA- and virus-specific clones in TIL, regardless of response, and MANA-, influenza- and Epstein–Barr virus-specific TIL each have unique transcriptional programs. Despite exposure to cognate antigen, MANA-specific TIL express an incompletely activated cytolytic program. MANA-specific CD8 T cells have hallmark transcriptional programs of tissue-resident memory (TRM) cells, but low levels of interleukin-7 receptor (IL-7R) and are functionally less responsive to interleukin-7 (IL-7) compared with influenza-specific TRM cells. Compared with those from responding tumours, MANA-specific clones from non-responding tumours express T cell receptors with markedly lower ligand-dependent signalling, are largely confined to HOBIThighTRM subsets, and coordinately upregulate checkpoints, killer inhibitory receptors and inhibitors of T cell activation. These findings provide important insights for overcoming resistance to PD-1 blockade.
Aerosol emission in professional singing of classical music
Authors: Mürbe Dirk , Kriegel Martin , Lange Julia , Rotheudt Hansjörg , Fleischer Mario 
Published: July 2021

AbstractIn this study, emission rates of aerosols emitted by professional singers were measured with a laser particle counter under cleanroom conditions. The emission rates during singing varied between 753 and 6093 particles/sec with a median of 1537 particles/sec. Emission rates for singing were compared with data for breathing and speaking. Significantly higher emission rates were found for singing. The emission enhancements between singing and speaking were between 4.0 and 99.5 with a median of 17.4, largely due to higher sound pressure levels when singing. Further, significant effects of vocal loudness were found, whereas there were no significant differences between the investigated voice classifications. The present study supports the efforts to improve the risk management in cases of possible aerogenic virus transmission, especially for choir singing.