ac This Squirrel Appreciation Day we have a few surprising squirrely facts for you By insider.si.edu Published On :: Fri, 19 Jan 2018 15:49:29 +0000 Flying through the air? Check. Surviving snake bites? Check. One of the most adorable creatures on earth? Absolutely! Do you think you know everything about […] The post This Squirrel Appreciation Day we have a few surprising squirrely facts for you appeared first on Smithsonian Insider. Full Article Animals Science & Nature National Museum of Natural History Smithsonian's National Zoo
ac Black hole blasts may transform “Mini-Neptunes” into rocky worlds By insider.si.edu Published On :: Tue, 27 Feb 2018 20:01:07 +0000 A team of astrophysicists and planetary scientists has predicted that Neptune-like planets located near the center of the Milky Way galaxy have been transformed into […] The post Black hole blasts may transform “Mini-Neptunes” into rocky worlds appeared first on Smithsonian Insider. Full Article Research News Science & Nature Space Spotlight black holes Center for Astrophysics | Harvard & Smithsonian Milky Way
ac Poachers are killing endangered Asian elephants for their skin and meat, not their tusks By insider.si.edu Published On :: Tue, 20 Mar 2018 19:51:13 +0000 Poaching wasn’t the largest conservation concern for Asian elephants, an endangered species, until satellite tracking stunned researchers. Scientists at the Smithsonian Conservation Biology Institute (SCBI) […] The post Poachers are killing endangered Asian elephants for their skin and meat, not their tusks appeared first on Smithsonian Insider. Full Article Animals History & Culture Science & Nature Smithsonian Conservation Biology Institute
ac Some dolphins cross the Pacific more easily than others. Why that matters for protecting them By insider.si.edu Published On :: Fri, 04 May 2018 11:31:12 +0000 Marine mammologist Matthew Leslie aims his crossbow from the bow of a moving boat at the dolphins riding the breaking waves below. A dolphin will […] The post Some dolphins cross the Pacific more easily than others. Why that matters for protecting them appeared first on Smithsonian Insider. Full Article Animals Marine Science Science & Nature National Museum of Natural History
ac The real history behind science fiction’s ‘2001: A Space Odyssey’ By insider.si.edu Published On :: Wed, 09 May 2018 13:05:15 +0000 When “2001: A Space Odyssey” premiered April 2, 1968 at Washington, D.C.’s Uptown Theater—not far from the Smithsonian’s National Air and Space Museum—not everyone was […] The post The real history behind science fiction’s ‘2001: A Space Odyssey’ appeared first on Smithsonian Insider. Full Article Art History & Culture Science & Nature Space National Air and Space Museum
ac Helicopter cockroach moms have protected their young for millions of years By insider.si.edu Published On :: Sat, 12 May 2018 02:37:14 +0000 Very early on, cockroach moms found out maternal care gave their offspring a better chance at survival. The cockroach parenting method—which includes feeding, guarding and […] The post Helicopter cockroach moms have protected their young for millions of years appeared first on Smithsonian Insider. Full Article Animals Dinosaurs & Fossils Science & Nature dinosaurs National Museum of Natural History
ac Five fun turtle and tortoise facts from the Smithsonian’s National Zoo By insider.si.edu Published On :: Wed, 23 May 2018 08:01:40 +0000 People often use the words turtle and tortoise interchangeably, but these reptiles have distinct differences: Turtle shells are typically more flattened and not as deeply […] The post Five fun turtle and tortoise facts from the Smithsonian’s National Zoo appeared first on Smithsonian Insider. Full Article Animals Science & Nature reptiles Smithsonian's National Zoo
ac Study of bacteria inside guts of wild Canada geese shows greater danger than earlier studies exposed By insider.si.edu Published On :: Thu, 31 May 2018 13:40:08 +0000 In the early 20th century, Canada geese were considered endangered in the U.S. So in the 1950s and 1960s, birds from the Midwest were released […] The post Study of bacteria inside guts of wild Canada geese shows greater danger than earlier studies exposed appeared first on Smithsonian Insider. Full Article Animals Research News Science & Nature birds conservation biology National Museum of Natural History veterinary medicine
ac Space is the best place to eat ice cream By insider.si.edu Published On :: Tue, 03 Jul 2018 12:08:51 +0000 Imagine a place where ice cream never drips. Ice cream lovers, how far would you be willing to go to avoid that heartbreaking moment where […] The post Space is the best place to eat ice cream appeared first on Smithsonian Insider. Full Article History & Culture Science & Nature Space National Air and Space Museum
ac Scientists track a mysterious songbird using tiny backpack locators By insider.si.edu Published On :: Tue, 07 Aug 2018 14:27:33 +0000 Little to nothing is known about how and where a small European songbird called the bluethroat spends much of the year. Now, Smithsonian scientists have […] The post Scientists track a mysterious songbird using tiny backpack locators appeared first on Smithsonian Insider. Full Article Animals History & Culture Research News Science & Nature birds endangered species Migratory Bird Center Smithsonian's National Zoo
ac How do National Zoo animals beat the heat? Bloodsicles and other frozen delicacies By insider.si.edu Published On :: Thu, 30 Aug 2018 12:00:42 +0000 When the heat and humidity of the Washington, D.C. summer sends its residents scrambling for air conditioning and iced coffee, the animal care specialists at […] The post How do National Zoo animals beat the heat? Bloodsicles and other frozen delicacies appeared first on Smithsonian Insider. Full Article Animals Science & Nature Smithsonian's National Zoo
ac Smithsonian scientists become shark detectives to track species in the Chesapeake Bay By insider.si.edu Published On :: Thu, 13 Sep 2018 15:54:37 +0000 When many people think of the Chesapeake Bay, one of the first creatures that comes to mind is the iconic blue crab. But parts of […] The post Smithsonian scientists become shark detectives to track species in the Chesapeake Bay appeared first on Smithsonian Insider. Full Article Animals Marine Science Science & Nature Chesapeake Bay Smithsonian Environmental Research Center
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ac Structure of the N-terminal domain of ClpC1 in complex with the antituberculosis natural product ecumicin reveals unique binding interactions By scripts.iucr.org Published On :: 2020-04-23 The biological processes related to protein homeostasis in Mycobacterium tuberculosis, the etiologic agent of tuberculosis, have recently been established as critical pathways for therapeutic intervention. Proteins of particular interest are ClpC1 and the ClpC1–ClpP1–ClpP2 proteasome complex. The structure of the potent antituberculosis macrocyclic depsipeptide ecumicin complexed with the N-terminal domain of ClpC1 (ClpC1-NTD) is presented here. Crystals of the ClpC1-NTD–ecumicin complex were monoclinic (unit-cell parameters a = 80.0, b = 130.0, c = 112.0 Å, β = 90.07°; space group P21; 12 complexes per asymmetric unit) and diffracted to 2.5 Å resolution. The structure was solved by molecular replacement using the self-rotation function to resolve space-group ambiguities. The new structure of the ecumicin complex showed a unique 1:2 (target:ligand) stoichiometry exploiting the intramolecular dyad in the α-helical fold of the target N-terminal domain. The structure of the ecumicin complex unveiled extensive interactions in the uniquely extended N-terminus, a critical binding site for the known cyclopeptide complexes. This structure, in comparison with the previously reported rufomycin I complex, revealed unique features that could be relevant for understanding the mechanism of action of these potential antituberculosis drug leads. Comparison of the ecumicin complex and the ClpC1-NTD-L92S/L96P double-mutant structure with the available structures of rufomycin I and cyclomarin A complexes revealed a range of conformational changes available to this small N-terminal helical domain and the minor helical alterations involved in the antibiotic-resistance mechanism. The different modes of binding and structural alterations could be related to distinct modes of action. Full Article text
ac Structural basis of carbohydrate binding in domain C of a type I pullulanase from Paenibacillus barengoltzii By scripts.iucr.org Published On :: 2020-04-23 Pullulanase (EC 3.2.1.41) is a well known starch-debranching enzyme that catalyzes the cleavage of α-1,6-glycosidic linkages in α-glucans such as starch and pullulan. Crystal structures of a type I pullulanase from Paenibacillus barengoltzii (PbPulA) and of PbPulA in complex with maltopentaose (G5), maltohexaose (G6)/α-cyclodextrin (α-CD) and β-cyclodextrin (β-CD) were determined in order to better understand substrate binding to this enzyme. PbPulA belongs to glycoside hydrolase (GH) family 13 subfamily 14 and is composed of three domains (CBM48, A and C). Three carbohydrate-binding sites identified in PbPulA were located in CBM48, near the active site and in domain C, respectively. The binding site in CBM48 was specific for β-CD, while that in domain C has not been reported for other pullulanases. The domain C binding site had higher affinity for α-CD than for G6; a small motif (FGGEH) seemed to be one of the major determinants for carbohydrate binding in this domain. Structure-based mutations of several surface-exposed aromatic residues in CBM48 and domain C had a debilitating effect on the activity of the enzyme. These results suggest that both CBM48 and domain C play a role in binding substrates. The crystal forms described contribute to the understanding of pullulanase domain–carbohydrate interactions. Full Article text
ac Structural and thermodynamic analyses of interactions between death-associated protein kinase 1 and anthraquinones By scripts.iucr.org Published On :: 2020-04-15 Death-associated protein kinase 1 (DAPK1) is a serine/threonine protein kinase that regulates apoptosis and autophagy. DAPK1 is considered to be a therapeutic target for amyloid-β deposition, endometrial adenocarcinomas and acute ischemic stroke. Here, the potent inhibitory activity of the natural anthraquinone purpurin against DAPK1 phosphorylation is shown. Thermodynamic analysis revealed that while the binding affinity of purpurin is similar to that of CPR005231, which is a DAPK1 inhibitor with an imidazopyridazine moiety, the binding of purpurin was more enthalpically favorable. In addition, the inhibition potencies were correlated with the enthalpic changes but not with the binding affinities. Crystallographic analysis of the DAPK1–purpurin complex revealed that the formation of a hydrogen-bond network is likely to contribute to the favorable enthalpic changes and that stabilization of the glycine-rich loop may cause less favorable entropic changes. The present findings indicate that purpurin may be a good lead compound for the discovery of inhibitors of DAPK1, and the observation of enthalpic changes could provide important clues for drug development. Full Article text
ac Bond-valence analyses of the crystal structures of FeMo/V cofactors in FeMo/V proteins By scripts.iucr.org Published On :: 2020-04-15 The bond-valence method has been used for valence calculations of FeMo/V cofactors in FeMo/V proteins using 51 crystallographic data sets of FeMo/V proteins from the Protein Data Bank. The calculations show molybdenum(III) to be present in MoFe7S9C(Cys)(HHis)[R-(H)homocit] (where H4homocit is homocitric acid, HCys is cysteine and HHis is histidine) in FeMo cofactors, while vanadium(III) with a more reduced iron complement is obtained for FeV cofactors. Using an error analysis of the calculated valences, it was found that in FeMo cofactors Fe1, Fe6 and Fe7 can be unambiguously assigned as iron(III), while Fe2, Fe3, Fe4 and Fe5 show different degrees of mixed valences for the individual Fe atoms. For the FeV cofactors in PDB entry 5n6y, Fe4, Fe5 and Fe6 correspond to iron(II), iron(II) and iron(III), respectively, while Fe1, Fe2, Fe3 and Fe7 exhibit strongly mixed valences. Special situations such as CO-bound and selenium-substituted FeMo cofactors and O(N)H-bridged FeV cofactors are also discussed and suggest rearrangement of the electron configuration on the substitution of the bridging S atoms. Full Article text
ac Structure of P46, an immunodominant surface protein from Mycoplasma hyopneumoniae: interaction with a monoclonal antibody By scripts.iucr.org Published On :: 2020-04-15 Mycoplasma hyopneumoniae is a prokaryotic pathogen that colonizes the respiratory ciliated epithelial cells in swine. Infected animals suffer respiratory lesions, causing major economic losses in the porcine industry. Characterization of the immunodominant membrane-associated proteins from M. hyopneumoniae may be instrumental in the development of new therapeutic approaches. Here, the crystal structure of P46, one of the main surface-antigen proteins, from M. hyopneumoniae is presented and shows N- and C-terminal α/β domains connected by a hinge. The structures solved in this work include a ligand-free open form of P46 (3.1 Å resolution) and two ligand-bound structures of P46 with maltose (2.5 Å resolution) and xylose (3.5 Å resolution) in open and closed conformations, respectively. The ligand-binding site is buried in the cleft between the domains at the hinge region. The two domains of P46 can rotate with respect to each other, giving open or closed alternative conformations. In agreement with this structural information, sequence analyses show similarities to substrate-binding members of the ABC transporter superfamily, with P46 facing the extracellular side as a functional subunit. In the structure with xylose, P46 was also bound to a high-affinity (Kd = 29 nM) Fab fragment from a monoclonal antibody, allowing the characterization of a structural epitope in P46 that exclusively involves residues from the C-terminal domain. The Fab structure in the complex with P46 shows only small conformational rearrangements in the six complementarity-determining regions (CDRs) with respect to the unbound Fab (the structure of which is also determined in this work at 1.95 Å resolution). The structural information that is now available should contribute to a better understanding of sugar nutrient intake by M. hyopneumoniae. This information will also allow the design of protocols and strategies for the generation of new vaccines against this important swine pathogen. Full Article text
ac Macromolecular X-ray crystallography: soon to be a road less travelled? By scripts.iucr.org Published On :: 2020-04-30 The number of new X-ray crystallography-based submissions to the Protein Data Bank appears to be at the beginning of a decline, perhaps signalling an end to the era of the dominance of X-ray crystallography within structural biology. This letter, from the viewpoint of a young structural biologist, applies the Copernican method to the life expectancy of crystallography and asks whether the technique is still the mainstay of structural biology. A study of the rate of Protein Data Bank depositions allows a more nuanced analysis of the fortunes of macromolecular X-ray crystallography and shows that cryo-electron microscopy might now be outcompeting crystallography for new labour and talent, perhaps heralding a change in the landscape of the field. Full Article text
ac Five funky and 5 fun facts about fishes By insider.si.edu Published On :: Sun, 29 Jan 2012 20:12:51 +0000 A selection of fascinating facts about fishes from the new book "Fishes: The Animal Answer Guide" The post Five funky and 5 fun facts about fishes appeared first on Smithsonian Insider. Full Article Animals Book Review Marine Science Science & Nature fishes National Museum of Natural History
ac New Book: “Across Atlantic Ice : The Origin of America’s Clovis Culture” By insider.si.edu Published On :: Tue, 31 Jan 2012 20:06:35 +0000 Supplying archaeological and oceanographic evidence, this book persuasively links Clovis technology with the culture of the Solutrean people who occupied France and Spain more than 20,000 years ago. The post New Book: “Across Atlantic Ice : The Origin of America’s Clovis Culture” appeared first on Smithsonian Insider. Full Article Anthropology Book Review Science & Nature National Museum of Natural History
ac New Book: “Recreating First Contact: Expeditions, Anthropology, and Popular Culture” By insider.si.edu Published On :: Wed, 30 Oct 2013 14:36:51 +0000 Between the world wars of the early Twentieth Century, an age of adventure travel and cultural exploration flourished when newly developed transport and recording technologies–particularly […] The post New Book: “Recreating First Contact: Expeditions, Anthropology, and Popular Culture” appeared first on Smithsonian Insider. Full Article Anthropology Book Review Research News Science & Nature National Museum of Natural History
ac Book: Airport Towers as Abstract Art By insider.si.edu Published On :: Mon, 07 Dec 2015 15:52:50 +0000 “My recurring theme is the transformation of the ordinary…,” explains National Air and Space Museum photographer Carolyn Russo in reference to her new book, Art […] The post Book: Airport Towers as Abstract Art appeared first on Smithsonian Insider. Full Article Art Book Review aeronautics National Air and Space Museum photography technology visual arts
ac Accidentally deleting all data By www.bleepingcomputer.com Published On :: 2019-09-07T17:22:44-05:00 Full Article
ac EML4-ALK V3 oncogenic fusion proteins promote microtubule stabilization and accelerated migration through NEK9 and NEK7 [RESEARCH ARTICLE] By jcs.biologists.org Published On :: 2020-03-17T03:51:28-07:00 Laura O'Regan, Giancarlo Barone, Rozita Adib, Chang Gok Woo, Hui Jeong Jeong, Emily L. Richardson, Mark W. Richards, Patricia A.J. Muller, Spencer J. Collis, Dean A. Fennell, Jene Choi, Richard Bayliss, and Andrew M. FryEML4-ALK is an oncogenic fusion present in ~5% non-small cell lung cancers. However, alternative breakpoints in the EML4 gene lead to distinct variants with different patient outcomes. Here, we show in cell models that EML4-ALK variant 3 (V3), which is linked to accelerated metastatic spread, causes microtubule stabilization, formation of extended cytoplasmic protrusions and increased cell migration. It also recruits the NEK9 and NEK7 kinase to microtubules via the N-terminal EML4 microtubule-binding region. Overexpression of wild-type EML4 as well as constitutive activation of NEK9 also perturb cell morphology and accelerate migration in a microtubule-dependent manner that requires the downstream kinase NEK7 but not ALK activity. Strikingly, elevated NEK9 expression is associated with reduced progression-free survival in EML4-ALK patients. Hence, we propose that EML4-ALK V3 promotes microtubule stabilization through NEK9 and NEK7 leading to increased cell migration. This represents a novel actionable pathway that could drive metastatic disease progression in EML4-ALK lung cancer. Full Article
ac Actin waves transport RanGTP to the neurite tip to regulate non-centrosomal microtubules in neurons [RESEARCH ARTICLE] By jcs.biologists.org Published On :: 2020-04-06T07:46:57-07:00 Yung-An Huang, Chih-Hsuan Hsu, Ho-Chieh Chiu, Pei-Yu Hsi, Chris T. Ho, Wei-Lun Lo, and Eric HwangMicrotubule (MT) is the most abundant cytoskeleton in neurons and controls multiple facets of their development. While the MT-organizing center (MTOC) in mitotic cells is typically located at the centrosome, MTOC in neurons switches to non-centrosomal sites. A handful of cellular components have been shown to promote non-centrosomal MT (ncMT) formation in neurons, yet the regulation mechanism remains unknown. Here we demonstrate that the small GTPase Ran is a key regulator of ncMTs in neurons. Using an optogenetic tool that enables light-induced local production of RanGTP, we demonstrate that RanGTP promotes ncMT plus-end growth along the neurite. Additionally, we discovered that actin waves drive the anterograde transport of RanGTP. Pharmacological disruption of actin waves abolishes the enrichment of RanGTP and reduces growing ncMT plus-ends at the neurite tip. These observations identify a novel regulation mechanism of ncMTs and pinpoint an indirect connection between the actin and MT cytoskeletons in neurons. Full Article
ac Mitochondrial-nuclear heme trafficking is regulated by GTPases in control of mitochondrial dynamics and ER contact sites [RESEARCH ARTICLE] By jcs.biologists.org Published On :: 2020-04-07T06:16:39-07:00 Osiris Martinez-Guzman, Mathilda M. Willoughby, Arushi Saini, Jonathan V. Dietz, Iryna Bohovych, Amy E. Medlock, Oleh Khalimonchuk, and Amit R. ReddiHeme is a cofactor and signaling molecule that is essential for much of aerobic life. All heme-dependent processes in eukaryotes require that heme is trafficked from its site of synthesis in the mitochondria to hemoproteins located throughout the cell. However, the mechanisms governing the mobilization of heme out of the mitochondria, and the spatio-temporal dynamics of these processes, are poorly understood. Herein, using genetically encoded fluorescent heme sensors, we developed a live cell assay to monitor heme distribution dynamics between the mitochondrial inner-membrane, where heme is synthesized, and the mitochondrial matrix, cytosol, and nucleus. Surprisingly, heme trafficking to the nucleus is ~25% faster than to the cytosol or mitochondrial matrix, which are nearly identical, potentially supporting a role for heme as a mitochondrial-nuclear retrograde signal. Moreover, we discovered that the heme synthetic enzyme, 5-aminolevulinic acid synthase (ALAS), and GTPases in control of the mitochondrial dynamics machinery, Mgm1 and Dnm1, and ER contact sites, Gem1, regulate the flow of heme between the mitochondria and nucleus. Overall, our results indicate that there are parallel pathways for the distribution of bioavailable heme. Full Article
ac Micro-stepping Extended Focus reduces photobleaching and preserves structured illumination super-resolution features [TOOLS AND RESOURCES] By jcs.biologists.org Published On :: 2020-04-07T06:16:39-07:00 Xian Hu, Salma Jalal, Michael Sheetz, Oddmund Bakke, and Felix MargadantDespite progress made in confocal microscopy, even fast systems still have insufficient temporal resolution for detailed live cell volume imaging, such as tracking rapid movement of membrane vesicles in three-dimensional space. Depending on the shortfall, this may result in undersampling and/or motion artifacts that ultimately limit the quality of the imaging data. By sacrificing detailed information in the Z-direction, we propose a new imaging modality that involves capturing fast "projections" from the field of depth which shortens imaging time by approximately an order of magnitude as compared to standard volumetric confocal imaging. With faster imaging, radiation exposure to the sample is reduced, resulting in less fluorophore photobleaching and potential photodamage. The implementation minimally requires two synchronized control signals that drive a piezo stage and trigger the camera exposure. The device generating the signals has been tested on spinning disk confocals and instant structured-illumination-microscopy (iSIM) microscopes. Our calibration images show that the approach provides highly repeatable and stable imaging conditions that enable photometric measurements of the acquired data, in both standard live imaging and super-resolution modes. Full Article
ac LDL uptake-dependent phosphatidylethanolamine translocation to the cell surface promotes fusion of osteoclast-like cells [RESEARCH ARTICLE] By jcs.biologists.org Published On :: 2020-04-15T01:46:56-07:00 Victor J. F. Kitano, Yoko Ohyama, Chiyomi Hayashida, Junta Ito, Mari Okayasu, Takuya Sato, Toru Ogasawara, Maki Tsujita, Akemi Kakino, Jun Shimada, Tatsuya Sawamura, and Yoshiyuki HakedaOsteoporosis is associated with vessel diseases attributed to hyperlipidemia, and bone resorption by multinucleated osteoclasts is related to lipid metabolism. In this study, we generated low-density lipoprotein receptor (LDLR)/lectin-like oxidized LDL receptor-1 (LOX-1) double knockout (dKO) mice. We found that, like LDLR single KO (sKO), LDLR/LOX-1 dKO impaired cell-cell fusion of osteoclast-like cells (OCLs). LDLR/LOX-1 dKO and LDLR sKO preosteoclasts exhibited decreased uptake of LDL. The cell surface cholesterol levels of both LDLR/LOX-1 dKO and LDLR sKO osteoclasts were lower than the levels of wild-type OCLs. Additionally, the amount of phosphatidylethanolamine (PE) on the cell surface was attenuated in LDLR/LOX-1 dKO and LDLR sKO pre-OCLs, while the PE distribution in wild-type OCLs was concentrated on the filopodia in contact with neighboring cells. Abrogation of the ATP binding cassette G1 (ABCG1) transporter, which transfers PE to the cell surface, caused decreased PE translocation to the cell surface and subsequent cell-cell fusion. The findings of this study indicate the involvement of a novel cascade (LDLR~ABCG1~PE translocation to cell surface~cell-cell fusion) in multinucleation of OCLs. Full Article
ac A genetic interaction map centered on cohesin reveals auxiliary factors in sister chromatid cohesion [RESEARCH ARTICLE] By jcs.biologists.org Published On :: 2020-04-16T06:39:33-07:00 Su Ming Sun, Amandine Batte, Mireille Tittel-Elmer, Sophie van der Horst, Tibor van Welsem, Gordon Bean, Trey Ideker, Fred van Leeuwen, and Haico van AttikumEukaryotic chromosomes are replicated in interphase and the two newly duplicated sister chromatids are held together by the cohesin complex and several cohesin auxiliary factors. Sister chromatid cohesion is essential for accurate chromosome segregation during mitosis, yet has also been implicated in other processes, including DNA damage repair, transcription and DNA replication. To assess how cohesin and associated factors functionally interconnect and coordinate with other cellular processes, we systematically mapped genetic interactions of 17 cohesin genes centered on quantitative growth measurements of >52,000 gene pairs in budding yeast. Integration of synthetic genetic interactions unveiled a cohesin functional map that constitutes 373 genetic interactions, revealing novel functional connections with post-replication repair, microtubule organization and protein folding. Accordingly, we show that the microtubule-associated protein Irc15 and the prefoldin complex members Gim3, Gim4 and Yke2 are new factors involved in sister chromatid cohesion. Our genetic interaction map thus provides a unique resource for further identification and functional interrogation of cohesin proteins. Since mutations in cohesin proteins have been associated with cohesinopathies and cancer, it may also identify cohesin interactions relevant in disease etiology. Full Article
ac Compartmentalization of adenosine metabolism in cancer cells and its modulation during acute hypoxia [RESEARCH ARTICLE] By jcs.biologists.org Published On :: 2020-04-21T05:32:09-07:00 Karolina Losenkova, Mariachiara Zuccarini, Marika Karikoski, Juha Laurila, Detlev Boison, Sirpa Jalkanen, and Gennady G. YegutkinExtracellular adenosine mediates diverse anti-inflammatory, angiogenic and vasoactive effects and becomes an important therapeutic target for cancer, which has been translated into clinical trials. This study was designed to comprehensively assess adenosine metabolism in prostate and breast cancer cells. We identified cellular adenosine turnover as a complex cascade, comprised of (a) the ectoenzymatic breakdown of ATP via sequential nucleotide pyrophosphatase/phosphodiesterase-1, ecto-5’-nucleotidase/CD73 and adenosine deaminase reactions, and ATP re-synthesis through counteracting adenylate kinase and nucleoside diphosphokinase; (b) the uptake of nucleotide-derived adenosine via equilibrative nucleoside transporters; and (c) the intracellular adenosine phosphorylation into ATP by adenosine kinase and other nucleotide kinases. The exposure of cancer cells to 1% O2 for 24 hours triggered ~2-fold up-regulation of CD73, without affecting nucleoside transporters, adenosine kinase activity and cellular ATP content. The ability of adenosine to inhibit the tumor-initiating potential of breast cancer cells via receptor-independent mechanism was confirmed in vivo using a xenograft mouse model. The existence of redundant pathways controlling extracellular and intracellular adenosine provides a sufficient justification for reexamination of the current concepts of cellular purine homeostasis and signaling in cancer. Full Article
ac F-BAR domain protein Syndapin regulates actomyosin dynamics during apical cap remodeling in syncytial Drosophila embryos [SHORT REPORT] By jcs.biologists.org Published On :: 2020-04-23T01:49:49-07:00 Aparna Sherlekar, Gayatri Mundhe, Prachi Richa, Bipasha Dey, Swati Sharma, and Richa RikhyBranched actin networks driven by Arp2/3 collaborate with actomyosin filaments in processes such as cell migration. The syncytial Drosophila blastoderm embryo also shows expansion of apical caps by Arp2/3 driven actin polymerization in interphase and buckling at contact edges by MyosinII to form furrows in metaphase. Here we study the role of Syndapin (Synd), an F-BAR domain containing protein in apical cap remodelling prior to furrow extension. synd depletion showed larger apical caps. STED super-resolution and TIRF microscopy showed long apical actin protrusions in caps in interphase and short protrusions in metaphase in control embryos. synd depletion led to sustained long protrusions even in metaphase. Loss of Arp2/3 function in synd mutants partly reverted defects in apical cap expansion and protrusion remodelling. MyosinII levels were decreased in synd mutants and MyosinII mutant embryos have been previously reported to have expanded caps. We propose that Syndapin function limits branching activity during cap expansion and affects MyosinII distribution in order to shift actin remodeling from apical cap expansion to favor lateral furrow extension. Full Article
ac A new brain mitochondrial sodium-sensitive potassium channel: effect of sodium ions on respiratory chain activity [RESEARCH ARTICLE] By jcs.biologists.org Published On :: 2020-04-23T01:49:49-07:00 Javad Fahanik-babaei, Bahareh Rezaee, Maryam Nazari, Nihad Torabi, Reza Saghiri, Remy Sauve, and Afsaneh EliassiWe have determined the electropharmacological properties of a new potassium channel from brain mitochondrial membrane by planar lipid bilayer method. Our results showed the presence of a channel with a conductance of 150 pS at potentials between 0 and –60 mV in 200 cis/50 trans mM KCl solutions.The channel was voltage-independent, with an open probability value ~0.6 at different voltages. ATP did not affect current amplitude and Po at positive and negative voltages. Notably, adding iberiotoxin, charybdotoxin, lidocaine, and margatoxin had no effect on the channel behavior. Similarly, no changes were observed by decreasing the cis-pH to 6. Interestingly, the channel was inhibited by adding sodium in a dose dependent manner. Our results also indicated a significant increase in mitochondrial complex IV activity and membrane potential and decrease in complex I activity and mitochondrial ROS production in the presence of sodium ions.We propose that inhibition of mitochondrial K+ transport by Na ions on K+ channel opening may be important for cell protection and ATP synthesis. Full Article
ac Osh6 requires Ist2 for localization to the ER-PM contacts and efficient phosphatidylserine transport [RESEARCH ARTICLE] By jcs.biologists.org Published On :: 2020-04-23T01:49:49-07:00 Juan Martin D'Ambrosio, Veronique Albanese, Nicolas-Frederic Lipp, Lucile Fleuriot, Delphine Debayle, Guillaume Drin, and Alenka CopicOsh6 and Osh7 are lipid transfer proteins (LTPs) that move phosphatidylserine (PS) from the endoplasmic reticulum (ER) to the plasma membrane (PM). High PS level at the PM is key for many cellular functions. Intriguingly, Osh6/7 localize to ER-PM contact sites, although they lack membrane-targeting motifs, in contrast to multidomain LTPs that both bridge membranes and convey lipids. We show that Osh6 localization to contact sites depends on its interaction with the cytosolic tail of the ER-PM tether Ist2, a homologue of TMEM16 proteins. We identify a motif in the Ist2 tail, conserved in yeasts, as the Osh6-binding region, and we map an Ist2-binding surface on Osh6. Mutations in the Ist2 tail phenocopy osh6 osh7 deletion: they decrease cellular PS levels, and block PS transport to the PM. Our study unveils an unexpected partnership between a TMEM16-like protein and a soluble LTP, which together mediate lipid transport at contact sites. Full Article
ac Cdc24 interacts with the septins to create a positive feedback during bud site assembly in yeast [RESEARCH ARTICLE] By jcs.biologists.org Published On :: 2020-04-29T02:35:34-07:00 Julian Chollet, Alexander Dünkler, Anne Bäuerle, Laura Vivero-Pol, Medhanie A. Mulaw, Thomas Gronemeyer, and Nils JohnssonYeast cells select the position of their new bud at the beginning of each cell cycle. The recruitment of the septins to this prospective bud site is one of the critical events in a complex assembly pathway that culminates in the outgrowth of a new daughter cell. Hereby, the septin-rods follow the high concentration of Cdc42GTP that is generated by the focused localization of its GEF Cdc24. We show that shortly before budding Cdc24 not only activates Cdc42 but also transiently interacts with Cdc11, the septin subunit that caps both ends of the septin rods. Mutations in Cdc24 reducing the affinity to Cdc11 impair septin recruitment and decrease the stability of the polarity patch. The interaction between septins and Cdc24 thus reinforces bud assembly at sites where septin structures are formed. Once the septins polymerize into the ring, Cdc24 is found at the cortex of the bud and directs its further outgrowth from this position. Full Article
ac Glucocorticoids rapidly inhibit cell migration through a novel, non-transcriptional HDAC6 pathway [RESEARCH ARTICLE] By jcs.biologists.org Published On :: 2020-05-07T00:45:50-07:00 Stephen Kershaw, David J. Morgan, James Boyd, David G. Spiller, Gareth Kitchen, Egor Zindy, Mudassar Iqbal, Magnus Rattray, Chris M. Sanderson, Andrew Brass, Claus Jorgensen, Tracy Hussell, Laura C. Matthews, and David W. RayGlucocorticoids (GCs) act through the glucocorticoid receptor (GR) to regulate immunity, energy metabolism, and tissue repair. Upon ligand binding, activated GR mediates cellular effects by regulating gene expression, but some GR effects can occur rapidly without new transcription. We show GCs rapidly inhibit cell migration, in response to both GR agonist and antagonist ligand binding. The inhibitory effect on migration is prevented by GR knockdown with siRNA, confirming GR specificity, but not by actinomycin D treatment, suggesting a non-transcriptional mechanism. We identified a rapid onset increase in microtubule polymerisation following glucocorticoid treatment, identifying cytoskeletal stabilisation as the likely mechanism of action. HDAC6 overexpression, but not knockdown of αTAT1, rescued the GC effect, implicating HDAC6 as the GR effector. Consistent with this hypothesis, ligand-dependent cytoplasmic interaction between GR and HDAC6 was demonstrated by quantitative imaging. Taken together, we propose that activated GR inhibits HDAC6 function and thereby increases the stability of the microtubule network to reduce cell motility. We therefore report a novel, non-transcriptional mechanism whereby GCs impair cell motility through inhibition of HDAC6 and rapid reorganization of the cell architecture. Full Article
ac Smithsonian’s National Gem Collection acquires a yellow fluorite from Tanzania By insider.si.edu Published On :: Wed, 21 Oct 2009 17:52:20 +0000 Fluorite is well known and prized for its rich variety of colors, most commonly pale green, purple, yellow, orange, blue, pink and colorless. “We acquired this specimen because it is a very nice quality fluorite with an attractive color and it is large enough to be exhibited,” Curator Jeff Post says. The post Smithsonian’s National Gem Collection acquires a yellow fluorite from Tanzania appeared first on Smithsonian Insider. Full Article Earth Science Science & Nature geology National Gem Collection National Museum of Natural History new acquisitions
ac Cullinan Blue Diamond Necklace By insider.si.edu Published On :: Thu, 30 Sep 2010 08:43:18 +0000 The Cullinan Blue Diamond Necklace, featuring a bow motif with nine sparkling and extremely rare blue diamonds, recently joined the National Gem Collection in the […] The post Cullinan Blue Diamond Necklace appeared first on Smithsonian Insider. Full Article Earth Science Science & Nature Spotlight geology National Gem Collection National Museum of Natural History
ac National Museum of Natural History acquires gemstones in honor of its 100th anniversary By insider.si.edu Published On :: Wed, 03 Nov 2010 18:07:32 +0000 The Smithsonian’s National Museum of Natural History recently acquired four remarkable gemstones and jewelry pieces for the Smithsonian’s National Gem Collection in celebration of the 100th anniversary of the museum. The post National Museum of Natural History acquires gemstones in honor of its 100th anniversary appeared first on Smithsonian Insider. Full Article Earth Science Science & Nature geology National Gem Collection National Museum of Natural History new acquisitions rocks & minerals
ac A hot new island has just surfaced in the Red Sea. What’s going on? Smithsonian scientists explain. By insider.si.edu Published On :: Wed, 11 Jan 2012 16:45:25 +0000 The new island visible in the satellite photograph is the top of a giant shield volcano located on the rift axis in the Red Sea where the continental plates of Africa and Arabia are pulling apart. The post A hot new island has just surfaced in the Red Sea. What’s going on? Smithsonian scientists explain. appeared first on Smithsonian Insider. Full Article Earth Science Marine Science Science & Nature National Museum of Natural History
ac Photos reveal recent activity in moon’s crust By insider.si.edu Published On :: Tue, 28 Feb 2012 13:03:20 +0000 New images from NASA's Lunar Reconnaissance Orbiter (LRO) spacecraft show the moon's crust is being stretched, forming minute valleys in a few small areas on the lunar surface. The post Photos reveal recent activity in moon’s crust appeared first on Smithsonian Insider. Full Article Earth Science Science & Nature Space astronomy astrophysics geology National Air and Space Museum rocks & minerals
ac Mexico’s Popocatepetl volcano active again By insider.si.edu Published On :: Thu, 03 May 2012 19:24:02 +0000 According to the weekly report of the Smithsonian’s Global Volcanism Program, gas-and-ash plumes rose nearly one mile above the crater of Mexico’s Popocatépetl volcano from […] The post Mexico’s Popocatepetl volcano active again appeared first on Smithsonian Insider. Full Article Earth Science Science & Nature Spotlight volcanoes
ac Pieces of rare meteorite land at five different academic institutions By insider.si.edu Published On :: Thu, 22 Aug 2013 13:46:37 +0000 The main mass of a rare meteorite that exploded over California’s Sierra foothills in April 2012 will be preserved for current and future scientific discoveries, […] The post Pieces of rare meteorite land at five different academic institutions appeared first on Smithsonian Insider. Full Article Earth Science Research News Science & Nature astronomy astrophysics geology meteorites National Museum of Natural History new acquisitions
ac Climate change to impact even deep-ocean ecosystems By insider.si.edu Published On :: Tue, 24 Jun 2014 15:05:49 +0000 Even tiny crustaceans scuttling across the deepest, darkest depths of the ocean floor will feel the effects of climate change, according to a new study […] The post Climate change to impact even deep-ocean ecosystems appeared first on Smithsonian Insider. Full Article Animals Earth Science Marine Science Research News Science & Nature climate change conservation biology