bluuebunny/crossref_metadata_2025_split huggingface dataset:
Planetary nebulae as kinematic tracers of galaxy halos
Authors: Coccato Lodovico ,   PNS collaboration
Published: May 2017

AbstractThe kinematics and dynamical properties of galaxy stellar halos are difficult to measure, given the faint surface brightness that characterizes these regions. Gas-rich systems such as spiral galaxies can be probed using the radio Hi emission. Early-type galaxies contain less gas, therefore alternative kinematic tracers need to be used. Planetary Nebulae (PNe) can be easily detected far out in the halo thanks to their bright [Oiii] emission at 5007 Å. It is therefore possible to map the halo kinematics also in early-type galaxies, typically out to 5 effective radii or beyond. Thanks to the recent spectroscopic surveys targeting extra-galactic PNe, we can now rely on few tens of galaxies where the kinematics of the stellar halos are measured. I will discuss the most important results: (a) the relation of the stellar surface brightness and the PNe number density; (b) the velocity and velocity dispersion two-dimensional fields; (c) the radial profiles of angular momentum; and (d) the relation between the derived kinematics physical properties of the host galaxies.
Inhibition of PTP1B disrupts cell–cell adhesion and induces anoikis in breast epithelial cells
Authors: Hilmarsdottir Bylgja , Briem Eirikur , Halldorsson Skarphedinn , Kricker Jennifer , Ingthorsson Sævar , Gustafsdottir Sigrun , Mælandsmo Gunhild M , Magnusson Magnus K , Gudjonsson Thorarinn 
Published: May 2017

AbstractProtein tyrosine phosphatase 1B (PTP1B) is a well-known inhibitor of insulin signaling pathways and inhibitors against PTP1B are being developed as promising drug candidates for treatment of obesity. PTP1B has also been linked to breast cancer both as a tumor suppressor and as an oncogene. Furthermore, PTP1B has been shown to be a regulator of cell adhesion and migration in normal and cancer cells. In this study, we analyzed the PTP1B expression in normal breast tissue, primary breast cells and the breast epithelial cell line D492. In normal breast tissue and primary breast cells, PTP1B is widely expressed in both epithelial and stromal cells, with highest expression in myoepithelial cells and fibroblasts. PTP1B is widely expressed in branching structures generated by D492 when cultured in 3D reconstituted basement membrane (3D rBM). Inhibition of PTP1B in D492 and another mammary epithelial cell line HMLE resulted in reduced cell proliferation and induction of anoikis. These changes were seen when cells were cultured both in monolayer and in 3D rBM. PTP1B inhibition affected cell attachment, expression of cell adhesion proteins and actin polymerization. Moreover, epithelial to mesenchymal transition (EMT) sensitized cells to PTP1B inhibition. A mesenchymal sublines of D492 and HMLE (D492M and HMLEmes) were more sensitive to PTP1B inhibition than D492 and HMLE. Reversion of D492M to an epithelial state using miR-200c-141 restored resistance to detachment induced by PTP1B inhibition. In conclusion, we have shown that PTP1B is widely expressed in the human breast gland with highest expression in myoepithelial cells and fibroblasts. Inhibition of PTP1B in D492 and HMLE affects cell–cell adhesion and induces anoikis-like effects. Finally, cells with an EMT phenotype are more sensitive to PTP1B inhibitors making PTP1B a potential candidate for further studies as a target for drug development in cancer involving the EMT phenotype.
TXNIP regulates mitophagy in retinal Müller cells under high-glucose conditions: implications for diabetic retinopathy
Authors: Devi Takhellambam Swornalata , Somayajulu Mallika , Kowluru Renu Anjan , Singh Lalit Pukhrambam 
Published: May 2017

AbstractThioredoxin-interacting protein (TXNIP) is involved in oxidative stress and apoptosis in diabetic retinopathy. However, the role of TXNIP in the removal of damaged mitochondria (MT) via mitophagy, a process of macroautophagy, remains unexplored. Here we investigate the associated cellular and molecular mechanisms underlying mitophagy in retinal cells under diabetic conditions. For this, we maintained a rat Müller cell line (rMC1) under high-glucose (25 mM, HG) or low-glucose (5.5 mM, LG) condition for 5 days. Our data reveal that HG upregulates TXNIP in the cytosol as well as in the MT. Moreover, mitochondrial oxidative stress and membrane depolarization occur under prolonged hyperglycemia leading to fragmentation. These damaged MT are targeted to lysosome for mitophagic degradation, as is evident by co-localization of mitochondrial protein COXIV, a subunit of cytochrome c oxidase, with autophagosome marker LC3BII and the lysosomal membrane protein LAMP2A. In addition, under HG conditions, there is an accumulation of dynamin-related fission protein Drp1 and E3 ubiquitin ligase Parkin in damaged MT, suggesting their roles in mitochondrial fragmentation and ubiquitination, respectively, which is absent in LG conditions. Subsequently, ubiquitin receptors, optineurin and p62/sequestrome 1, bind to the damaged MT and target them to LC3BII autophagosomes. Conversely, TXNIP knockout via CRISPR/Cas9 and TXNIP gRNA prevents the HG-induced mitochondrial damage and mitophagy in rMC1. Last, TXNIP level is also significantly upregulated in the diabetic rat retina in vivo and induces radial glial fibrillary acidic protein expression, a marker for Müller glia activation, and the formation of LC3BII puncta, which are prevented by intravitreal injection of TXNIP siRNA. Therefore, TXNIP represents a potential target for preventing ocular complications of diabetes.
Glycolysis regulates the expansion of myeloid-derived suppressor cells in tumor-bearing hosts through prevention of ROS-mediated apoptosis
Authors: Jian Shiou-Ling , Chen Wei-Wei , Su Yu-Chia , Su Yu-Wen , Chuang Tsung-Hsien , Hsu Shu-Ching , Huang Li-Rung 
Published: May 2017

AbstractImmunotherapy aiming to rescue or boost antitumor immunity is an emerging strategy for treatment of cancers. The efficacy of immunotherapy is strongly controlled by the immunological milieu of cancer patients. Myeloid-derived suppressor cells (MDSCs) are heterogeneous immature myeloid cell populations with immunosuppressive functions accumulating in individuals during tumor progression. The signaling mechanisms of MDSC activation have been well studied. However, there is little known about the metabolic status of MDSCs and the physiological role of their metabolic reprogramming. In this study, we discovered that myeloid cells upregulated their glycolytic genes when encountered with tumor-derived factors. MDSCs exhibited higher glycolytic rate than their normal cell compartment did, which contributed to the accumulation of the MDSCs in tumor-bearing hosts. Upregulation of glycolysis prevented excess reactive oxygen species (ROS) production by MDSCs, which protected MDSCs from apoptosis. Most importantly, we identified the glycolytic metabolite, phosphoenolpyruvate (PEP), as a vital antioxidant agent able to prevent excess ROS production and therefore contributed to the survival of MDSCs. These findings suggest that glycolytic metabolites have important roles in the modulation of fitness of MDSCs and could be potential targets for anti-MDSC strategy. Targeting MDSCs with analogs of specific glycolytic metabolites, for example, 2-phosphoglycerate or PEP may diminish the accumulation of MDSCs and reverse the immunosuppressive milieu in tumor-bearing individuals.
Haploinsufficiency in the mitochondrial protein CHCHD4 reduces brain injury in a mouse model of neonatal hypoxia-ischemia
Authors: Sun Yanyan , Li Tao , Xie Cuicui , Xu Yiran , Zhou Kai , Rodriguez Juan , Han Wei , Wang Xiaoyang , Kroemer Guido , Modjtahedi Nazanine , Blomgren Klas , Zhu Changlian 
Published: May 2017

AbstractMitochondria contribute to neonatal hypoxic-ischemic brain injury by releasing potentially toxic proteins into the cytosol. CHCHD4 is a mitochondrial intermembrane space protein that plays a major role in the import of intermembrane proteins and physically interacts with apoptosis-inducing factor (AIF). The purpose of this study was to investigate the impact of CHCHD4 haploinsufficiency on mitochondrial function and brain injury after cerebral hypoxia-ischemia (HI) in neonatal mice. CHCHD4+/− and wild-type littermate mouse pups were subjected to unilateral cerebral HI on postnatal day 9. CHCHD4 haploinsufficiency reduced insult-related AIF and superoxide dismutase 2 release from the mitochondria and reduced neuronal cell death. The total brain injury volume was reduced by 21.5% at 3 days and by 31.3% at 4 weeks after HI in CHCHD4+/− mice. However, CHCHD4 haploinsufficiency had no influence on mitochondrial biogenesis, fusion, or fission; neural stem cell proliferation; or neural progenitor cell differentiation. There were no significant changes in the expression or distribution of p53 protein or p53 pathway-related genes under physiological conditions or after HI. These results suggest that CHCHD4 haploinsufficiency afforded persistent neuroprotection related to reduced release of mitochondrial intermembrane space proteins. The CHCHD4-dependent import pathway might thus be a potential therapeutic target for preventing or treating neonatal brain injury.
Chronically stressed or stress-preconditioned neurons fail to maintain stress granule assembly
Authors: Shelkovnikova Tatyana A , Dimasi Pasquale , Kukharsky Michail S , An Haiyan , Quintiero Annamaria , Schirmer Claire , Buée Luc , Galas Marie-Christine , Buchman Vladimir L 
Published: May 2017

AbstractDysregulation of stress granules (SGs) and their resident proteins contributes to pathogenesis of a number of (neuro)degenerative diseases. Phosphorylation of eIF2α is an event integrating different types of cellular stress and it is required for SG assembly. Phosphorylated eIF2α (p-eIF2α) is upregulated in the nervous system in some neurodegenerative conditions. We found that increasing p-eIF2α level by proteasomal inhibition in cultured cells, including mouse and human neurons, before a SG-inducing stress (‘stress preconditioning’), limits their ability to maintain SG assembly. This is due to upregulation of PP1 phosphatase regulatory subunits GADD34 and/or CReP in preconditioned cells and early decline of p-eIF2α levels during subsequent acute stress. In two model systems with constitutively upregulated p-eIF2α, mouse embryonic fibroblasts lacking CReP and brain neurons of tau transgenic mice, SG formation was also impaired. Thus, neurons enduring chronic stress or primed by a transient mild stress fail to maintain p-eIF2α levels following subsequent acute stress, which would compromise protective function of SGs. Our findings provide experimental evidence on possible loss of function for SGs in certain neurodegenerative diseases.
Imaging of pH in vivo using hyperpolarized 13C-labelled zymonic acid
Authors: Düwel Stephan , Hundshammer Christian , Gersch Malte , Feuerecker Benedikt , Steiger Katja , Buck Achim , Walch Axel , Haase Axel , Glaser Steffen J. , Schwaiger Markus , Schilling Franz 
Published: May 2017

AbstractNatural pH regulatory mechanisms can be overruled during several pathologies such as cancer, inflammation and ischaemia, leading to local pH changes in the human body. Here we demonstrate that 13C-labelled zymonic acid (ZA) can be used as hyperpolarized magnetic resonance pH imaging sensor. ZA is synthesized from [1-13C]pyruvic acid and its 13C resonance frequencies shift up to 3.0 p.p.m. per pH unit in the physiological pH range. The long lifetime of the hyperpolarized signal enhancement enables monitoring of pH, independent of concentration, temperature, ionic strength and protein concentration. We show in vivo pH maps within rat kidneys and subcutaneously inoculated tumours derived from a mammary adenocarcinoma cell line and characterize ZA as non-toxic compound predominantly present in the extracellular space. We suggest that ZA represents a reliable and non-invasive extracellular imaging sensor to localize and quantify pH, with the potential to improve understanding, diagnosis and therapy of diseases characterized by aberrant acid-base balance.
Tau association with synaptic vesicles causes presynaptic dysfunction
Authors: Zhou Lujia , McInnes Joseph , Wierda Keimpe , Holt Matthew , Herrmann Abigail G. , Jackson Rosemary J. , Wang Yu-Chun , Swerts Jef , Beyens Jelle , Miskiewicz Katarzyna , Vilain Sven , Dewachter Ilse , Moechars Diederik , De Strooper Bart , Spires-Jones Tara L. , De Wit Joris , Verstreken Patrik 
Published: May 2017

AbstractTau is implicated in more than 20 neurodegenerative diseases, including Alzheimer’s disease. Under pathological conditions, Tau dissociates from axonal microtubules and missorts to pre- and postsynaptic terminals. Patients suffer from early synaptic dysfunction prior to Tau aggregate formation, but the underlying mechanism is unclear. Here we show that pathogenic Tau binds to synaptic vesicles via its N-terminal domain and interferes with presynaptic functions, including synaptic vesicle mobility and release rate, lowering neurotransmission in fly and rat neurons. Pathological Tau mutants lacking the vesicle binding domain still localize to the presynaptic compartment but do not impair synaptic function in fly neurons. Moreover, an exogenously applied membrane-permeable peptide that competes for Tau-vesicle binding suppresses Tau-induced synaptic toxicity in rat neurons. Our work uncovers a presynaptic role of Tau that may be part of the early pathology in various Tauopathies and could be exploited therapeutically.
Efficient modification of λ-DNA substrates for single-molecule studies
Authors: Kim Yoori , de la Torre Armando , Leal Andrew A. , Finkelstein Ilya J. 
Published: May 2017

AbstractSingle-molecule studies of protein-nucleic acid interactions frequently require site-specific modification of long DNA substrates. The bacteriophage λ is a convenient source of high quality long (48.5 kb) DNA. However, introducing specific sequences, tertiary structures, and chemical modifications into λ-DNA remains technically challenging. Most current approaches rely on multi-step ligations with low yields and incomplete products. Here, we describe a molecular toolkit for rapid preparation of modified λ-DNA. A set of PCR cassettes facilitates the introduction of recombinant DNA sequences into the λ-phage genome with 90–100% yield. Extrahelical structures and chemical modifications can be inserted at user-defined sites via an improved nicking enzyme-based strategy. As a proof-of-principle, we explore the interactions of S. cerevisiae Proliferating Cell Nuclear Antigen (yPCNA) with modified DNA sequences and structures incorporated within λ-DNA. Our results demonstrate that S. cerevisiae Replication Factor C (yRFC) can load yPCNA onto 5′-ssDNA flaps, (CAG)13 triplet repeats, and homoduplex DNA. However, yPCNA remains trapped on the (CAG)13 structure, confirming a proposed mechanism for triplet repeat expansion. We anticipate that this molecular toolbox will be broadly useful for other studies that require site-specific modification of long DNA substrates.
PD-L1 expression in Xp11.2 translocation renal cell carcinoma: Indicator of tumor aggressiveness
Authors: Chang Kun , Qu Yuanyuan , Dai Bo , Zhao Jian-Yuan , Gan Hualei , Shi Guohai , Zhu Yiping , Shen Yijun , Zhu Yao , Zhang Hailiang , Ye Dingwei 
Published: May 2017

AbstractProgrammed death ligand-1 (PD-L1), a promising antitumor target, has proven clinical value against many malignancies. However, the PD-L1 content of Xp11.2 translocation renal cell carcinoma (Xp11.2 RCC) and its correlation with clinical outcomes remain unclear. This study aimed to investigate PD-L1 expression in Xp11.2 RCC and to assess its prognostic value. Formalin-fixed paraffin-embedded specimens from 36 adult patients that were histologically confirmed (by fluorescence in situ hybridization) were subjected to immunohistochemical analysis. Of the 36 Xp11.2 RCC patients, 9 (25.0%) had tumors with positive PD-L1 expression and 27 (75.0%) had tumors with negative PD-L1 expression. Positive PD-L1 expression correlated with advanced tumor stage (P = 0.001), regional lymph node metastasis (P < 0.001), and distant metastasis (P < 0.001). A multivariate analysis identified positive PD-L1 expression was an independent adverse prognostic factor for both progression free survival (hazard ratio: 3.7, P = 0.018) and overall survival (hazard ratio: 4.5, P = 0.034). The median PFS and OS for the whole cohort were 13.0 months (95% confidence interval [CI], 9.4–16.6 months) and 36.0 months (95% CI, 23.9–48.1 months), respectively. Our findings suggest that positive PD-L1 expression is indicative of worse clinical outcome in Xp11.2 RCC. Further studies are needed to explore the potential efficacy of targeting PD-L1 in Xp11.2 RCC.
Orbital angular momentum analysis for giant spin splitting in solids and nanostructures
Authors: Oh Sehoon , Choi Hyoung Joon 
Published: May 2017

AbstractGiant spin splitting (GSS) of electronic bands, which is several orders of magnitude greater than the standard Rashba effect has been observed in various systems including noble-metal surfaces and thin films of transition-metal dichalcogenides. Previous studies reported that orbital angular momentum (OAM) is not quenched in some GSS materials and that the atomic spin-orbit interaction (SOI) generates spin splitting in some solid states via the interorbital hopping. Although the unquenched OAM may be closely related to the interorbital hopping, their relationship is hardly studied in the aspect of using the unquenched OAM as a control parameter of GSS. Here, we analyze OAM in GSS materials by using the interorbital-hopping mechanism and first-principles calculations. We report that the interatomic hopping between different-parity orbitals, which is generated by specific broken mirror symmetry, produces k-dependent OAM, resulting in valley-dependent GSS in WSe2 monolayer, Rashba-type GSS in Au (111) surface, and Dresselhaus-type GSS in bulk HgTe. We also demonstrate systematic control of OAM by pressure, external fields, and substrates, thereby controlling the spin splitting, and discuss the temperature dependence of OAM. Our results provide a simplified picture for systematic design and control of GSS materials.
New insights into ocean sunfish (Mola mola) abundance and seasonal distribution in the northeast Atlantic
Authors: Breen Patricia , Cañadas Ana , Cadhla Oliver Ó , Mackey Mick , Scheidat Meike , Geelhoed Steve C. V. , Rogan Emer , Jessopp Mark 
Published: May 2017

AbstractThe ocean sunfish,Mola mola, is the largest teleost fish in the world. Despite being found in all oceans of the world, little is known about its abundance and factors driving its distribution. In this study we provide the first abundance estimates for sunfish in offshore waters in the northeast Atlantic and the first record of extensive sunfish presence in these waters year-round. Abundance estimates and predictive distributions for sunfish in approximately 300,000 km² of the northeast Atlantic were derived from large scale offshore aerial surveys in 2015–2016 using distance sampling techniques. Generalized additive models of sunfish density were fitted to survey data from 17,360 km of line transect effort resulting in minimum abundance estimates of 12,702 (CI: 9,864-16,357) in the summer (Density = 0.043 ind/km²) and 8,223 individuals (CI: 6,178-10,946) (Density = 0.028 ind/km²) in the winter. Density surface models predicted seasonal shifts in distribution and highlighted the importance of the mixed layer depth, possibly related to thermoregulation following deep foraging dives. The abundance estimate and estimated daily consumption of 2,600 tonnes of jellyfish in the northeast Atlantic highlights the need to re-assess the importance of this species in the pelagic ecosystem, and its role in top-down control of jellyfish blooms.
Ligand chain length drives activation of lipid G protein-coupled receptors
Authors: Troupiotis-Tsaïlaki Anastassia , Zachmann Julian , González-Gil Inés , Gonzalez Angel , Ortega-Gutiérrez Silvia , López-Rodríguez Maria L. , Pardo Leonardo , Govaerts Cedric 
Published: May 2017

AbstractSphingosine-1-phosphate (S1P) is a lipid mediator that can activate five cell membrane G protein-coupled receptors (GPCRs) which carry a variety of essential functions and are promising drug targets. S1P is composed of a polar zwitterionic head-group and a hydrophobic alkyl chain. This implies an activation mechanism of its cognate receptor that must be significantly different from what is known for prototypical GPCRs (ie receptor to small hydrophilic ligands). Here we aim to identify the structural features responsible for S1P agonism by combining molecular dynamics simulations and functional assays using S1P analogs of different alkyl chain lengths. We propose that high affinity binding involves polar interactions between the lipid head-group and receptor side chains while activation is due to hydrophobic interactions between the lipid tail and residues in a distinct binding site. We observe that ligand efficacy is directly related to alkyl chain length but also varies with receptor subtypes in correlation with the size of this binding pocket. Integrating experimental and computational data, we propose an activation mechanism for the S1P receptors involving agonist-induced conformational events that are conserved throughout class A GPCRs.
Blunted Ambiguity Aversion During Cost-Benefit Decisions in Antisocial Individuals
Authors: Buckholtz Joshua W. , Karmarkar Uma , Ye Shengxuan , Brennan Grace M. , Baskin-Sommers Arielle 
Published: May 2017

AbstractAntisocial behavior is often assumed to reflect aberrant risk processing. However, many of the most significant forms of antisocial behavior, including crime, reflect the outcomes of decisions made under conditions of ambiguity rather than risk. While risk and ambiguity are formally distinct and experimentally dissociable, little is known about ambiguity sensitivity in individuals who engage in chronic antisocial behavior. We used a financial decision-making task in a high-risk community-based sample to test for associations between sensitivity to ambiguity, antisocial behavior, and arrest history. Sensitivity to ambiguity was lower in individuals who met diagnostic criteria for Antisocial Personality Disorder. Lower ambiguity sensitivity was also associated with higher externalizing (but not psychopathy) scores, and with higher levels of aggression (but not rule-breaking). Finally, blunted sensitivity to ambiguity also predicted a greater frequency of arrests. Together, these data suggest that alterations in cost-benefit decision-making under conditions of ambiguity may promote antisocial behavior.