bluuebunny/crossref_metadata_2025_split huggingface dataset:
Carbonic anhydrase IX and acid transport in cancer
Authors: Becker Holger M. 
Published: December 2019

AbstractAlterations in tumour metabolism and acid/base regulation result in the formation of a hostile environment, which fosters tumour growth and metastasis. Acid/base homoeostasis in cancer cells is governed by the concerted interplay between carbonic anhydrases (CAs) and various transport proteins, which either mediate proton extrusion or the shuttling of acid/base equivalents, such as bicarbonate and lactate, across the cell membrane. Accumulating evidence suggests that some of these transporters interact both directly and functionally with CAIX to form a protein complex coined the ‘transport metabolon’. Transport metabolons formed between bicarbonate transporters and CAIX require CA catalytic activity and have a function in cancer cell migration and invasion. Another type of transport metabolon is formed by CAIX and monocarboxylate transporters. In this complex, CAIX functions as a proton antenna for the transporter, which drives the export of lactate and protons from the cell. Since CAIX is almost exclusively expressed in cancer cells, these transport metabolons might serve as promising targets to interfere with tumour pH regulation and energy metabolism. This review provides an overview of the current state of research on the function of CAIX in tumour acid/base transport and discusses how CAIX transport metabolons could be exploited in modern cancer therapy.
Energy metabolism manipulates the fate and function of tumour myeloid-derived suppressor cells
Authors: Hu Cong , Pang Bo , Lin Guangzhu , Zhen Yu , Yi Huanfa 
Published: December 2019

AbstractIn recent years, a large number of studies have been carried out in the field of immune metabolism, highlighting the role of metabolic energy reprogramming in altering the function of immune cells. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells generated during a large array of pathological conditions, such as cancer, inflammation, and infection, and show remarkable ability to suppress T-cell responses. These cells can also change their metabolic pathways in response to various pathogen-derived or inflammatory signals. In this review, we focus on the roles of glucose, fatty acid (FA), and amino acid (AA) metabolism in the differentiation and function of MDSCs in the tumour microenvironment, highlighting their potential as targets to inhibit tumour growth and enhance tumour immune surveillance by the host. We further highlight the remaining gaps in knowledge concerning the mechanisms determining the plasticity of MDSCs in different environments and their specific responses in the tumour environment. Therefore, this review should motivate further research in the field of metabolomics to identify the metabolic pathways driving the enhancement of MDSCs in order to effectively target their ability to promote tumour development and progression.
Reprogramming of fatty acid metabolism in cancer
Authors: Koundouros Nikos , Poulogiannis George 
Published: December 2019

AbstractA common feature of cancer cells is their ability to rewire their metabolism to sustain the production of ATP and macromolecules needed for cell growth, division and survival. In particular, the importance of altered fatty acid metabolism in cancer has received renewed interest as, aside their principal role as structural components of the membrane matrix, they are important secondary messengers, and can also serve as fuel sources for energy production. In this review, we will examine the mechanisms through which cancer cells rewire their fatty acid metabolism with a focus on four main areas of research. (1) The role of de novo synthesis and exogenous uptake in the cellular pool of fatty acids. (2) The mechanisms through which molecular heterogeneity and oncogenic signal transduction pathways, such as PI3K–AKT–mTOR signalling, regulate fatty acid metabolism. (3) The role of fatty acids as essential mediators of cancer progression and metastasis, through remodelling of the tumour microenvironment. (4) Therapeutic strategies and considerations for successfully targeting fatty acid metabolism in cancer. Further research focusing on the complex interplay between oncogenic signalling and dysregulated fatty acid metabolism holds great promise to uncover novel metabolic vulnerabilities and improve the efficacy of targeted therapies.
Oncogenic pathways and the electron transport chain: a dangeROS liaison
Authors: Raimondi Vittoria , Ciccarese Francesco , Ciminale Vincenzo 
Published: December 2019

AbstractDriver mutations in oncogenic pathways, rewiring of cellular metabolism and altered ROS homoeostasis are intimately connected hallmarks of cancer. Electrons derived from different metabolic processes are channelled into the mitochondrial electron transport chain (ETC) to fuel the oxidative phosphorylation process. Electrons leaking from the ETC can prematurely react with oxygen, resulting in the generation of reactive oxygen species (ROS). Several signalling pathways are affected by ROS, which act as second messengers controlling cell proliferation and survival. On the other hand, oncogenic pathways hijack the ETC, enhancing its ROS-producing capacity by increasing electron flow or by impinging on the structure and organisation of the ETC. In this review, we focus on the ETC as a source of ROS and its modulation by oncogenic pathways, which generates a vicious cycle that resets ROS levels to a higher homoeostatic set point, sustaining the cancer cell phenotype.
Defining a metabolic landscape of tumours: genome meets metabolism
Authors: Seth Nanda Chandan , Venkateswaran Sharavan Vishaan , Patani Neill , Yuneva Mariia 
Published: December 2019

AbstractCancer is a complex disease of multiple alterations occuring at the epigenomic, genomic, transcriptomic, proteomic and/or metabolic levels. The contribution of genetic mutations in cancer initiation, progression and evolution is well understood. However, although metabolic changes in cancer have long been acknowledged and considered a plausible therapeutic target, the crosstalk between genetic and metabolic alterations throughout cancer types is not clearly defined. In this review, we summarise the present understanding of the interactions between genetic drivers of cellular transformation and cancer-associated metabolic changes, and how these interactions contribute to metabolic heterogeneity of tumours. We discuss the essential question of whether changes in metabolism are a cause or a consequence in the formation of cancer. We highlight two modes of how metabolism contributes to tumour formation. One is when metabolic reprogramming occurs downstream of oncogenic mutations in signalling pathways and supports tumorigenesis. The other is where metabolic reprogramming initiates transformation being either downstream of mutations in oncometabolite genes or induced by chronic wounding, inflammation, oxygen stress or metabolic diseases. Finally, we focus on the factors that can contribute to metabolic heterogeneity in tumours, including genetic heterogeneity, immunomodulatory factors and tissue architecture. We believe that an in-depth understanding of cancer metabolic reprogramming, and the role of metabolic dysregulation in tumour initiation and progression, can help identify cellular vulnerabilities that can be exploited for therapeutic use.
Enhancing the dipolar coupling of a S-T0 qubit with a transverse sweet spot
Authors: Abadillo-Uriel J. C. , Eriksson M. A. , Coppersmith S. N. , Friesen Mark 
Published: December 2019

AbstractA fundamental challenge for quantum dot spin qubits is to extend the strength and range of qubit interactions while suppressing their coupling to the environment, since both effects have electrical origins. Key tools include the ability to take advantage of physical resources in different regimes, and to access optimal working points, sweet spots, where dephasing is minimized. Here, we explore an important resource for singlet-triplet qubits: a transverse sweet spot (TSS) that enables transitions between qubit states, a strong dipolar coupling, and leading-order protection from electrical fluctuations. Of particular interest is the possibility of transitioning between the TSS and symmetric operating points while remaining continuously protected. This arrangement is ideal for coupling qubits to a microwave cavity, because it combines tunability of the coupling with noise insensitivity. We perform simulations with $$1/f$$
1
∕
f
-type electrical noise, demonstrating that two-qubit gates mediated by a resonator can achieve fidelities >99% under realistic conditions.
TRPML1 links lysosomal calcium to autophagosome biogenesis through the activation of the CaMKKβ/VPS34 pathway
Authors: Scotto Rosato A. , Montefusco S. , Soldati C. , Di Paola S. , Capuozzo A. , Monfregola J. , Polishchuk E. , Amabile A. , Grimm C. , Lombardo A. , De Matteis M. A. , Ballabio A. , Medina D. L. 
Published: December 2019

AbstractThe lysosomal calcium channel TRPML1, whose mutations cause the lysosomal storage disorder (LSD) mucolipidosis type IV (MLIV), contributes to upregulate autophagic genes by inducing the nuclear translocation of the transcription factor EB (TFEB). Here we show that TRPML1 activation also induces autophagic vesicle (AV) biogenesis through the generation of phosphatidylinositol 3-phosphate (PI3P) and the recruitment of essential PI3P-binding proteins to the nascent phagophore in a TFEB-independent manner. Thus, TRPML1 activation of phagophore formation requires the calcium-dependent kinase CaMKKβ and AMPK, which increase the activation of ULK1 and VPS34 autophagic protein complexes. Consistently, cells from MLIV patients show a reduced recruitment of PI3P-binding proteins to the phagophore during autophagy induction, suggesting that altered AV biogenesis is part of the pathological features of this disease. Together, we show that TRPML1 is a multistep regulator of autophagy that may be targeted for therapeutic purposes to treat LSDs and other autophagic disorders.
The main pulse of the Siberian Traps expanded in size and composition
Authors: Augland L. E. , Ryabov V. V. , Vernikovsky V. A. , Planke S. , Polozov A. G. , Callegaro S. , Jerram D. A. , Svensen H. H. 
Published: December 2019

AbstractEmplacement of large volumes of (sub)volcanic rocks during the main pulse of the Siberian Traps occurred within <1 m.y., coinciding with the end-Permian mass extinction. Volcanics from outside the main Siberian Traps, e.g. Taimyr and West Siberia, have since long been correlated, but existing geochronological data cannot resolve at a precision better than ~5 m.y. whether (sub)volcanic activity in these areas actually occurred during the main pulse or later. We report the first high precision U-Pb zircon geochronology from two alkaline ultramafic-felsic layered intrusive complexes from Taimyr, showing synchronicity between these and the main Siberian Traps (sub)volcanic pulse, and the presence of a second Dinerian-Smithian pulse. This is the first documentation of felsic intrusive magmatism occurring during the main pulse, testifying to the Siberian Trap’s compositional diversity. Furthermore, the intrusions cut basal basalts of the Taimyr lava stratigraphy hence providing a minimum age of these basalts of 251.64 ± 0.11 Ma. Synchronicity of (sub)volcanic activity between Taimyr and the Siberian Traps imply that the total area of the Siberian Traps main pulse should include a ~300 000 km2 area north of Norilsk. The vast aerial extent of the (sub)volcanic activity during the Siberian Traps main pulse may explain the severe environmental consequences.
Physiological Basis of Heterosis for Nitrogen Use Efficiency of Maize
Authors: Wang Zhigang , Ma Bao-Luo , Yu Xiaofang , Gao Julin , Sun Jiying , Su Zhijun , Yu Shaobo 
Published: December 2019

AbstractEfficient use of nitrogen inputs for concurrent improvements in grain yield and nitrogen use efficiency (NUE) has been recognized as a viable strategy for sustainable agriculture development. Yet, there is little research on the possible physiological basis of maize hybrid heterosis for NUE and measurable traits that are corresponding to the NUE heterosis. A field study was conducted for two years to evaluate the heterosis for NUE and determine the relationship between NUE and its physiological components. Two commercial hybrids, ‘Xianyu335’ and ‘Zhengdan958’, and their parental inbred lines, were grown at 0 (0 N) and 150 kg N ha−1 (150 N), in a randomized complete block design with four replications each year. Compared to their parental lines, both hybrids displayed a significant heterosis, up to 466%, for NUE. N internal efficiency (NIE) accounted for 52% of the variation in heterosis for NUE, while there was generally negligible heterosis for nitrogen recovery efficiency (NRE). Heterosis for NIE and thereby for NUE in maize was ascribed to (i) an earlier establishment of pre-anthesis source for N accumulation, which phenotypically exhibited as a faster leaf appearance rate with higher maximum LAI and photosynthetic nitrogen use efficiency; (ii) a larger amount of N being remobilized from the vegetative tissues, especially from leaves, during the grain filling. Phenotypically, there was notably a rapid reduction in post-anthesis specific weights of leaf and stalk, but with maintained functionally stay-green ear leaves; and (iii) a higher productive efficiency per unit grain N, which was characterized by a reduced grain N concentration and enhanced sink strength.
Advanced microscopy analysis of the micro-nanoscale architecture of human menisci
Authors: Vetri V. , Dragnevski K. , Tkaczyk M. , Zingales M. , Marchiori G. , Lopomo N. F. , Zaffagnini S. , Bondi A. , Kennedy J. A. , Murray D. W. , Barrera O. 
Published: December 2019

AbstractThe complex inhomogeneous architecture of the human meniscal tissue at the micro and nano scale in the absence of artefacts introduced by sample treatments has not yet been fully revealed. The knowledge of the internal structure organization is essential to understand the mechanical functionality of the meniscus and its relationship with the tissue’s complex structure. In this work, we investigated human meniscal tissue structure using up-to-date non-invasive imaging techniques, based on multiphoton fluorescence and quantitative second harmonic generation microscopy complemented with Environmental Scanning Electron Microscopy measurements. Observations on 50 meniscal samples extracted from 6 human menisci (3 lateral and 3 medial) revealed fundamental features of structural morphology and allowed us to quantitatively describe the 3D organisation of elastin and collagen fibres bundles. 3D regular waves of collagen bundles are arranged in “honeycomb-like” cells that are comprised of pores surrounded by the collagen and elastin network at the micro-scale. This type of arrangement propagates from macro to the nanoscale.
Oral administration of N-acetyl cysteine prevents osteoarthritis development and progression in a rat model
Authors: Kaneko Yosuke , Tanigawa Nobuharu , Sato Yuiko , Kobayashi Tami , Nakamura Satoshi , Ito Eri , Soma Tomoya , Miyamoto Kana , Kobayashi Shu , Harato Kengo , Matsumoto Morio , Nakamura Masaya , Niki Yasuo , Miyamoto Takeshi 
Published: December 2019

AbstractThe number of osteoarthritis patients is increasing with the rise in the number of elderly people in developed countries. Osteoarthritis, which causes joint pain and deformity leading to loss of activities of daily living, is often treated surgically. Here we show that mechanical stress promotes accumulation of reactive oxygen species (ROS) in chondrocytes in vivo, resulting in chondrocyte apoptosis and leading to osteoarthritis development in a rat model. We demonstrate that mechanical stress induces ROS accumulation and inflammatory cytokine expression in cultured chondrocytes in vitro and that both are inhibited by treatment with the anti-oxidant N-acetyl cysteine (NAC). In vivo, osteoarthritis development in a rat osteoarthritis model was also significantly inhibited by oral administration of NAC. MMP13 expression and down-regulation of type II collagen in chondrocytes, both of which indicate osteoarthritis, as well as chondrocyte apoptosis in osteoarthritis rats were inhibited by NAC. Interestingly, osteoarthritis development in sham-operated control sides, likely due to disruption of normal weight-bearing activity on the control side, was also significantly inhibited by NAC. We conclude that osteoarthritis development in rats is significantly antagonized by oral NAC administration. Currently, no oral medication is available to prevent osteoarthritis development. Our work suggests that NAC may represent such a reagent and serve as osteoarthritis treatment.
Comprehensive analysis of protein acetyltransferases of human pathogen Mycobacterium tuberculosis
Authors: Xie Longxiang , Yang Wenmin , Fan Xiangyu , Xie Jianping 
Published: December 2019

Abstract
Tuberculosis (TB), a leading infectious disease caused by Mycobacterium tuberculosis strain, takes four human lives every minute globally. Paucity of knowledge on M. tuberculosis virulence and antibiotic resistance is the major challenge for tuberculosis control. We have identified 47 acetyltransferases in the M. tuberculosis, which use diverse substrates including antibiotic, amino acids, and other chemical molecules. Through comparative analysis of the protein file of the virulent M. tuberculosis H37Rv strain and the avirulent M. tuberculosis H37Ra strain, we identified one acetyltransferase that shows significant variations with N-terminal deletion, possibly influencing its physicochemical properties. We also found that one acetyltransferase has three types of post-translation modifications (lysine acetylation, succinylation, and glutarylation). The genome context analysis showed that many acetyltransferases with their neighboring genes belong to one operon. By data mining from published transcriptional profiles of M. tuberculosis exposed to diverse treatments, we revealed that several acetyltransferases may be functional during M. tuberculosis infection. Insights obtained from the present study can potentially provide clues for developing novel TB therapeutic interventions.
TRIM proteins in neuroblastoma
Authors: Xu Yonghu , Zhang Zihan , Xu Guofeng 
Published: December 2019

AbstractNeuroblastoma (NB) is the most common extracranial solid tumor in childhood. Outcome for children with high-risk NB remains unsatisfactory. Accumulating evidence suggests that tripartite motif (TRIM) family proteins express diversely in various human cancers and act as regulators of oncoproteins or tumor suppressor proteins. This review summarizes the TRIM proteins involving in NB and the underlying molecular mechanisms. We expect these new insights will provide important implications for the treatment of NB by targeting TRIM proteins.
UV and NIR size of the low-mass field galaxies: the UV compact galaxies
Authors: Cheng Cheng , Xu Cong Kevin , Xie Lizhi , Pan Zhizheng , Du Wei , Orellana-González Gustavo , Shao Xu , Wu Shumei , Leiton Roger , Huang Jia-Sheng , Dai Sophia Yu , Assmann Paulina , Araneda Nicole 
Published: December 2019

Context. Most of the massive star-forming galaxies are found to have “inside-out” stellar mass growth modes, which means the inner parts of the galaxies mainly consist of the older stellar population, while the star forming in the outskirt of the galaxy is still ongoing.
Aims. The high-resolution HST images from Hubble Deep UV Legacy Survey and Cosmic Assembly Near-infrared Deep Extragalactic Legacy Survey projects with the unprecedented depth in both F275W and F160W bands are the perfect data sets to study the forming and formed stellar distribution directly.
Methods. We selected the low redshift (0.05 <  zspec <  0.3) galaxy sample from the GOODS-North field where the HST F275W and F160W images are available. Then we measured the half light radius in F275W and F160W bands, which are the indicators of the star formation and stellar mass.
Results. By comparing the F275W and F160W half light radius, we find the massive galaxies are mainly follow the “inside-out” growth mode, which is consistent with the previous results. Moreover, the HST F275W and F160W images reveal that some of the low-mass galaxies (< 108 M⊙) have the “outside-in” growth mode: their images show a compact UV morphology, implying an ongoing star formation in the galaxy centre, while the stars in the outskirts of the galaxies are already formed. The two modes transit smoothly at stellar mass range about 108 − 9 M⊙ with a large scatter. We also try to identify the possible neighbour massive galaxies from the SDSS data, which represent the massive galaxy sample. We find that all of the spec-z selected galaxies have no massive galaxy nearby. Thus the “outside-in” mode we find in the low-mass galaxies are not likely originated from the environment.
RefPlanets: Search for reflected light from extrasolar planets with SPHERE/ZIMPOL
Authors: Hunziker S. , Schmid H. M. , Mouillet D. , Milli J. , Zurlo A. , Delorme P. , Abe L. , Avenhaus H. , Baruffolo A. , Bazzon A. , Boccaletti A. , Baudoz P. , Beuzit J. L. , Carbillet M. , Chauvin G. , Claudi R. , Costille A. , Daban J.-B. , Desidera S. , Dohlen K. , Dominik C. , Downing M. , Engler N. , Feldt M. , Fusco T. , Ginski C. , Gisler D. , Girard J. H. , Gratton R. , Henning Th. , Hubin N. , Kasper M. , Keller C. U. , Langlois M. , Lagadec E. , Martinez P. , Maire A. L. , Menard F. , Meyer M. R. , Pavlov A. , Pragt J. , Puget P. , Quanz S. P. , Rickman E. , Roelfsema R. , Salasnich B. , Sauvage J.-F. , Siebenmorgen R. , Sissa E. , Snik F. , Suarez M. , Szulágyi J. , Thalmann Ch. , Turatto M. , Udry S. , van Holstein R. G. , Vigan A. , Wildi F. 
Published: December 2019

Aims. RefPlanets is a guaranteed time observation programme that uses the Zurich IMaging POLarimeter (ZIMPOL) of Spectro-Polarimetric High-contrast Exoplanet REsearch instrument at the Very Large Telescope to perform a blind search for exoplanets in wavelengths from 600 to 900 nm. The goals of this study are the characterisation of the unprecedented high polarimetic contrast and polarimetric precision capabilities of ZIMPOL for bright targets, the search for polarised reflected light around some of the closest bright stars to the Sun, and potentially the direct detection of an evolved cold exoplanet for the first time.
Methods. For our observations of α Cen A and B, Sirius A, Altair, ɛ Eri and τ Ceti we used the polarimetricdifferential imaging (PDI) mode of ZIMPOL which removes the speckle noise down to the photon noise limit for angular separations ≿0.6′′. We describe some of the instrumental effects that dominate the noise for smaller separations and explain how to remove these additional noise effects in post-processing. We then combine PDI with angular differential imaging as a final layer of post-processing to further improve the contrast limits of our data at these separations.
Results. For good observing conditions we achieve polarimetric contrast limits of 15.0–16.3 mag at the effective inner working angle of ~0.13′′, 16.3–18.3 mag at 0.5′′, and 18.8–20.4 mag at 1.5′′. The contrast limits closer in (≾0.6′′) display a significant dependence on observing conditions, while in the photon-noise-dominated regime (≿0.6′′) the limits mainly depend on the brightness of the star and the total integration time. We compare our results with contrast limits from other surveys and review the exoplanet detection limits obtained with different detection methods. For all our targets we achieve unprecedented contrast limits. Despite the high polarimetric contrasts we are not able to find any additional companions or extended polarised light sources in the data obtained so far.