el In the Grand Canyon, the U.S. Postal Service still delivers mail by mule By insider.si.edu Published On :: Thu, 25 Aug 2016 09:24:04 +0000 In an age of one-hour delivery and overnight shipping, a corner of the country still gets its mail by mule. That’s right. For a small […] The post In the Grand Canyon, the U.S. Postal Service still delivers mail by mule appeared first on Smithsonian Insider. Full Article Animals History & Culture National Postal Museum
el Study shows how birds dive safely at high speeds By insider.si.edu Published On :: Thu, 06 Oct 2016 10:37:44 +0000 To surprise their prey, some species of seabirds dive into the water at speeds greater than 50 miles per hour. A human diver entering the […] The post Study shows how birds dive safely at high speeds appeared first on Smithsonian Insider. Full Article Animals Marine Science Research News Science & Nature birds National Museum of Natural History
el By simply pooping, comb jellies expel long-held scientific misconception By insider.si.edu Published On :: Mon, 28 Nov 2016 18:58:16 +0000 In 2012, under a scientist’s watchful eye, a comb jelly ate some fish, digested it, and excreted the waste out its back end. In doing […] The post By simply pooping, comb jellies expel long-held scientific misconception appeared first on Smithsonian Insider. Full Article Animals Marine Science Research News Science & Nature National Museum of Natural History
el Astronomers propose cell phone search for galactic radio bursts By insider.si.edu Published On :: Tue, 14 Feb 2017 17:43:29 +0000 Fast radio bursts (FRBs) are brief spurts of radio emission, lasting just one-thousandth of a second, whose origins are mysterious. Fewer than two dozen have […] The post Astronomers propose cell phone search for galactic radio bursts appeared first on Smithsonian Insider. Full Article Science & Nature Space astronomy astrophysics Center for Astrophysics | Harvard & Smithsonian Milky Way planets Smithsonian Astrophysical Observatory
el Trusted Sources: Why Museums and Libraries Are More Relevant Than Ever By insider.si.edu Published On :: Thu, 02 Mar 2017 13:33:36 +0000 Washington, D.C. is a city of symbols. The rites, rituals, and places that define Washington capture the aspirations of our nation and its citizens. Just […] The post Trusted Sources: Why Museums and Libraries Are More Relevant Than Ever appeared first on Smithsonian Insider. Full Article Art History & Culture Research News Science & Nature Spotlight climate change history Smithsonian Institution Archives Smithsonian Libraries
el New technique may help authorities quickly ID real and fake ivory products By insider.si.edu Published On :: Wed, 26 Apr 2017 12:48:15 +0000 Fetching close to $1,500 per pound, ivory ranks fourth in black-market traded items just behind illegal drugs, weapons, and humans. Governments across the globe are […] The post New technique may help authorities quickly ID real and fake ivory products appeared first on Smithsonian Insider. Full Article Animals Art History & Culture Research News Science & Nature Smithsonian Conservation Biology Institute Smithsonian's National Zoo
el Smithsonian Study shows relocated desert tortoises reproduce at lower rate By insider.si.edu Published On :: Wed, 24 May 2017 15:26:10 +0000 Four years after conservationists relocated 570 desert tortoises (Gopherus agassizii) in California from a threatened habitat to a new nearby location, the tortoises outwardly appeared […] The post Smithsonian Study shows relocated desert tortoises reproduce at lower rate appeared first on Smithsonian Insider. Full Article Animals Research News Science & Nature Smithsonian Conservation Biology Institute Smithsonian's National Zoo
el 3D simulations reveals why the Sun flips its magnetic field every 11 years By insider.si.edu Published On :: Thu, 27 Jul 2017 01:38:50 +0000 Using new numerical simulations and observations, scientists may now be able to explain why the Sun’s magnetic field reverses every eleven years. This significant discovery […] The post 3D simulations reveals why the Sun flips its magnetic field every 11 years appeared first on Smithsonian Insider. Full Article Research News Science & Nature Space Center for Astrophysics | Harvard & Smithsonian Smithsonian Astrophysical Observatory
el Innovation: Belly gunk from flies used to survey forest animals By insider.si.edu Published On :: Tue, 01 Aug 2017 15:14:28 +0000 The next time you swat a fly ponder this: inside its belly is the DNA of whatever it ate before landing on your picnic dinner—roadkill, […] The post Innovation: Belly gunk from flies used to survey forest animals appeared first on Smithsonian Insider. Full Article Animals Research News Science & Nature mammals Smithsonian Tropical Research Institute
el Scientists discover common sea nettle jellyfish is actually two distinct species By insider.si.edu Published On :: Mon, 16 Oct 2017 13:17:36 +0000 Chances are, if you’ve been stung by a jellyfish along the Chesapeake Bay it was by a sea nettle jellyfish–one of the most common and […] The post Scientists discover common sea nettle jellyfish is actually two distinct species appeared first on Smithsonian Insider. Full Article Animals Marine Science Research News Science & Nature Chesapeake Bay National Museum of Natural History
el DNA on 100-year-old bat from France may help fight deadly fungus in North America By insider.si.edu Published On :: Tue, 24 Oct 2017 15:26:01 +0000 A bat specimen collected in France at the end of World War I, since housed in the collections of the Smithsonian’s National Museum of Natural […] The post DNA on 100-year-old bat from France may help fight deadly fungus in North America appeared first on Smithsonian Insider. Full Article Animals Research News Science & Nature bats National Museum of Natural History Smithsonian Conservation Biology Institute
el Fifth mirror cast for Giant Magellan Telescope By insider.si.edu Published On :: Fri, 03 Nov 2017 14:12:41 +0000 The Giant Magellan Telescope Organization (GMTO) today announced that it has initiated the casting of the fifth of seven mirrors that will form the heart of […] The post Fifth mirror cast for Giant Magellan Telescope appeared first on Smithsonian Insider. Full Article Science & Nature Space Center for Astrophysics | Harvard & Smithsonian Smithsonian Astrophysical Observatory
el Happy Thanksgiving! Here are 25 fun turkey-related objects in Smithsonian collections! By insider.si.edu Published On :: Mon, 20 Nov 2017 16:57:10 +0000 “Probably no genus of birds in the American avifauna has received the amount of attention that has been bestowed upon the turkeys…there has been no […] The post Happy Thanksgiving! Here are 25 fun turkey-related objects in Smithsonian collections! appeared first on Smithsonian Insider. Full Article Animals History & Culture Science & Nature
el A new stellar X-ray “reality” show debuts By insider.si.edu Published On :: Mon, 27 Nov 2017 19:05:42 +0000 A new project using data from NASA’s Chandra X-ray Observatory and other telescopes allows people to navigate through real data of the remains of an […] The post A new stellar X-ray “reality” show debuts appeared first on Smithsonian Insider. Full Article Science & Nature Space Center for Astrophysics | Harvard & Smithsonian Chandra X-Ray Observatory
el Using genetics to help save world’s most trafficked mammal: the pangolin By insider.si.edu Published On :: Sun, 24 Dec 2017 07:12:38 +0000 One of Earth’s most evolutionarily unique species is also the world’s most trafficked mammal: pangolins, or “scaly anteaters.” A new study from the Smithsonian Conservation […] The post Using genetics to help save world’s most trafficked mammal: the pangolin appeared first on Smithsonian Insider. Full Article Animals Science & Nature Smithsonian Conservation Biology Institute Smithsonian's National Zoo
el GBT Detection Unlocks Exploration of ‘Aromatic’ Interstellar Chemistry By insider.si.edu Published On :: Thu, 11 Jan 2018 14:30:53 +0000 Astronomers had a mystery on their hands. No matter where they looked, from inside the Milky Way to distant galaxies, they observed a puzzling glow […] The post GBT Detection Unlocks Exploration of ‘Aromatic’ Interstellar Chemistry appeared first on Smithsonian Insider. Full Article Science & Nature Space Smithsonian Astrophysical Observatory
el These newly discovered pelican spiders will make you want to visit Madagascar By insider.si.edu Published On :: Thu, 11 Jan 2018 18:15:20 +0000 In 1854, a curious-looking spider was found preserved in 50 million-year-old amber. With an elongated neck-like structure and long mouthparts that protruded from the “head” […] The post These newly discovered pelican spiders will make you want to visit Madagascar appeared first on Smithsonian Insider. Full Article Animals Science & Nature National Museum of Natural History
el 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
el 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
el Scientists surprised by relentless cosmic cold front By insider.si.edu Published On :: Wed, 04 Apr 2018 16:11:37 +0000 This winter has brought many intense and powerful storms, with cold fronts sweeping across much of the United States. On a much grander scale, astronomers […] The post Scientists surprised by relentless cosmic cold front appeared first on Smithsonian Insider. Full Article Science & Nature Space Spotlight Center for Astrophysics | Harvard & Smithsonian Chandra X-Ray Observatory Smithsonian Astrophysical Observatory
el 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
el Panama: First release of endangered frogs By insider.si.edu Published On :: Wed, 11 Jul 2018 15:17:18 +0000 Ninety Limosa harlequin frogs (Atelopus limosus) bred in human care are braving the elements of the wild after Smithsonian scientists sent them out into the […] The post Panama: First release of endangered frogs appeared first on Smithsonian Insider. Full Article Animals Research News Science & Nature Spotlight Smithsonian Conservation Biology Institute
el Newly discovered snakes use curved teeth to pry snails from their shells By insider.si.edu Published On :: Thu, 12 Jul 2018 06:37:04 +0000 Five new species of snail-eating snake, from a group of snakes affectionately known to scientists as “goo-eaters,” have been discovered by a team working in […] The post Newly discovered snakes use curved teeth to pry snails from their shells appeared first on Smithsonian Insider. Full Article Animals Research News Science & Nature Ecuador endangered species National Museum of Natural History new species Peru snakes
el The crane that fell for her keeper By insider.si.edu Published On :: Tue, 07 Aug 2018 19:36:20 +0000 The post The crane that fell for her keeper appeared first on Smithsonian Insider. Full Article Animals History & Culture Science & Nature Spotlight captive breeding Smithsonian Conservation Biology Institute
el A solar probe is on its way to touch the sun. The Smithsonian built the tool that will measure the sun without melting By insider.si.edu Published On :: Mon, 20 Aug 2018 15:59:47 +0000 Smithsonian scientists have joined NASA and other organizations this summer to do something incredible: launch a spacecraft, the Parker Solar Probe, into space and have […] The post A solar probe is on its way to touch the sun. The Smithsonian built the tool that will measure the sun without melting appeared first on Smithsonian Insider. Full Article Science & Nature Space Smithsonian Astrophysical Observatory
el 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
el 1855>744<3666 Yahoo mail phone number for technical help By www.bleepingcomputer.com Published On :: 2020-05-08T08:08:44-05:00 Full Article
el Sbcglobal customer helpline number 18882468183 You have to contact us By www.bleepingcomputer.com Published On :: 2020-05-08T08:25:54-05:00 Full Article
el Sbcglobal customer helpline phone number 18882468183 You have to contact us By www.bleepingcomputer.com Published On :: 2020-05-08T08:27:56-05:00 Full Article
el The crystal structure of the TonB-dependent transporter YncD reveals a positively charged substrate-binding site By scripts.iucr.org Published On :: 2020-04-27 The outer membrane of Gram-negative bacteria is highly impermeable to hydrophilic molecules of larger than 600 Da, protecting these bacteria from toxins present in the environment. In order to transport nutrients across this impermeable membrane, Gram-negative bacteria utilize a diverse family of outer-membrane proteins called TonB-dependent transporters. The majority of the members of this family transport iron-containing substrates. However, it is becoming increasingly clear that TonB-dependent transporters target chemically diverse substrates. In this work, the structure and phylogenetic distribution of the TonB-dependent transporter YncD are investigated. It is shown that while YncD is present in some enteropathogens, including Escherichia coli and Salmonella spp., it is also widespread in Gammaproteobacteria and Betaproteobacteria of environmental origin. The structure of YncD was determined, showing that despite a distant evolutionary relationship, it shares structural features with the ferric citrate transporter FecA, including a compact positively charged substrate-binding site. Despite these shared features, it is shown that YncD does not contribute to the growth of E. coli in pure culture under iron-limiting conditions or with ferric citrate as an iron source. Previous studies of transcriptional regulation in E. coli show that YncD is not induced under iron-limiting conditions and is unresponsive to the ferric uptake regulator (Fur). These observations, combined with the data presented here, suggest that YncD is not responsible for the transport of an iron-containing substrate. Full Article text
el Crystal and solution structures of fragments of the human leucocyte common antigen-related protein By scripts.iucr.org Published On :: 2020-04-15 Leucocyte common antigen-related protein (LAR) is a post-synaptic type I transmembrane receptor protein that is important for neuronal functionality and is genetically coupled to neuronal disorders such as attention deficit hyperactivity disorder (ADHD). To understand the molecular function of LAR, structural and biochemical studies of protein fragments derived from the ectodomain of human LAR have been performed. The crystal structure of a fragment encompassing the first four FNIII domains (LARFN1–4) showed a characteristic L shape. SAXS data suggested limited flexibility within LARFN1–4, while rigid-body refinement of the SAXS data using the X-ray-derived atomic model showed a smaller angle between the domains defining the L shape compared with the crystal structure. The capabilities of the individual LAR fragments to interact with heparin was examined using microscale thermophoresis and heparin-affinity chromatography. The results showed that the three N-terminal immunoglobulin domains (LARIg1–3) and the four C-terminal FNIII domains (LARFN5–8) both bound heparin, while LARFN1–4 did not. The low-molecular-weight heparin drug Innohep induced a shift in hydrodynamic volume as assessed by size-exclusion chromatography of LARIg1–3 and LARFN5–8, while the chemically defined pentameric heparin drug Arixtra did not. Together, the presented results suggest the presence of an additional heparin-binding site in human LAR. Full Article text
el 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
el “Darwin: A Graphic Biography,” new release from Smithsonian Books By insider.si.edu Published On :: Mon, 04 Feb 2013 15:38:43 +0000 Now, for the first time, Charles Darwin's life is portrayed pictorially in an illustrated biography in graphic novel-style for all ages to enjoy. The post “Darwin: A Graphic Biography,” new release from Smithsonian Books appeared first on Smithsonian Insider. Full Article Book Review Science & Nature science education
el ‘The Wrong Wrights’: A Graphic Novel from Smithsonian Books By insider.si.edu Published On :: Mon, 22 Feb 2016 16:39:55 +0000 In the first volume of the Secret Smithsonian Adventures graphic-novel series from Smithsonian Books, The Wrong Wrights, four middle-school kids visit the Smithsonian’s National Air […] The post ‘The Wrong Wrights’: A Graphic Novel from Smithsonian Books appeared first on Smithsonian Insider. Full Article Book Review History & Culture Spotlight aviation National Air and Space Museum
el Accidentally deleting all data By www.bleepingcomputer.com Published On :: 2019-09-07T17:22:44-05:00 Full Article
el Histone H1 eviction by the histone chaperone SET reduces cell survival following DNA damage [RESEARCH ARTICLE] By jcs.biologists.org Published On :: 2020-03-17T03:51:28-07:00 Imke K. Mandemaker, Di Zhou, Serena T. Bruens, Dick H. Dekkers, Pernette J. Verschure, Raghu R. Edupuganti, Eran Meshorer, Jeroen A. Demmers, and Jurgen A. MarteijnMany chromatin remodeling and modifying proteins are involved in the DNA damage response by stimulating repair or inducing DNA damage signaling. Interestingly, here we identified that down regulation of the H1-interacting protein SET results in increased resistance to a wide variety of DNA damaging agents. We found that this increased resistance is not the result of an inhibitory effect of SET on DNA repair, but rather the consequence of a suppressed apoptotic response to DNA damage. We further provide evidence that the histone chaperone SET is responsible for the eviction of H1 from chromatin. Knock down of H1 in SET-depleted cells resulted in re-sensitization of cells to DNA damage, suggesting that the increased DNA damage resistance in SET-depleted cells is the result of enhanced retention of H1 on chromatin. Finally, clonogenic survival assays show that SET and p53 are epistatic in attenuating DNA damage-induced cell death. Altogether, our data show a role for SET in the DNA damage response as a regulator of cell survival following genotoxic stress. Full Article
el STRIPAK-PP2A regulates Hippo-Yorkie signaling to suppress retinal fate in the Drosophila eye disc peripodial epithelium [RESEARCH ARTICLE] By jcs.biologists.org Published On :: 2020-03-17T03:51:28-07:00 Scott J. Neal, Qingxiang Zhou, and Francesca PignoniThe specification of organs, tissues and cell types results from cell fate restrictions enacted by nuclear transcription factors under the control of conserved signaling pathways. The progenitor epithelium of the Drosophila compound eye, the eye imaginal disc, is a premier model for the study of such processes. Early in development, apposing cells of the eye disc are established as either retinal progenitors or support cells of the peripodial epithelium (PE), in a process whose genetic and mechanistic determinants are poorly understood. We have identified Protein Phosphatase 2A (PP2A), and specifically a STRIPAK-PP2A complex that includes the scaffolding and substrate-specificity components Cka, Strip and SLMAP, as a critical player in the retina-PE fate choice. We show that these factors suppress ectopic retina formation in the presumptive PE and do so via the Hippo signaling axis. STRIPAK-PP2A negatively regulates Hpo kinase, and consequently its substrate Wts, to release the transcriptional co-activator Yki into the nucleus. Thus, a modular higher-order PP2A complex refines the activity of this general phosphatase to act in a precise specification of cell fate. Full Article
el CLIC4 is a cytokinetic cleavage furrow protein that regulates cortical cytoskeleton stability during cell division [RESEARCH ARTICLE] By jcs.biologists.org Published On :: 2020-03-17T03:51:28-07:00 Eric Peterman, Mindaugas Valius, and Rytis PrekerisDuring mitotic cell division, the actomyosin cytoskeleton undergoes several dynamic changes that play key roles in progression through mitosis. While the regulators of cytokinetic ring formation and contraction are well-established, proteins that regulate cortical stability during anaphase and telophase have been understudied. Here, we describe a role for CLIC4 in regulating actin and actin-regulators at the cortex and cytokinetic cleavage furrow during cytokinesis. We first describe CLIC4 as a new component of the cytokinetic cleavage furrow that is required for successful completion of mitotic cell division. We also demonstrate that CLIC4 regulates the remodeling of sub-plasma membrane actomyosin network within the furrow by recruiting MST4 kinase and regulating ezrin phosphorylation. This work identifies and characterizes new molecular players involved in regulating cortex stiffness and blebbing during late stages of cytokinetic furrowing. Full Article
el 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
el {beta}1 integrin-mediated signaling regulates MT1-MMP phosphorylation to promote tumour cell invasion [RESEARCH ARTICLE] By jcs.biologists.org Published On :: 2020-03-23T03:21:37-07:00 Olivia R. Grafinger, Genya Gorshtein, Tyler Stirling, Megan I. Brasher, and Marc G. CoppolinoMalignant cancer cells can invade extracellular matrix (ECM) through the formation of F-actin-rich subcellular structures termed invadopodia. ECM degradation at invadopodia is mediated by matrix metalloproteinases (MMPs), and recent findings indicate that membrane-anchored membrane type 1-matrix metalloproteinase (MT1-MMP) has a primary role in this process. Maintenance of an invasive phenotype is dependent on internalization of MT1-MMP from the plasma membrane and its recycling to sites of ECM remodeling. Internalization of MT1-MMP is dependent on its phosphorylation, and here we examine the role of β1 integrin-mediated signaling in this process. Activation of β1 integrin using the antibody P4G11 induced phosphorylation and internalization of MT1-MMP and resulted in increased cellular invasiveness and invadopodium formation in vitro. We also observed phosphorylation of Src and epidermal growth factor receptor (EGFR) and an increase in their association in response to β1 integrin activation, and determined that Src and EGFR promote phosphorylation of MT1-MMP on Thr567. These results suggest that MT1-MMP phosphorylation is regulated by a β1 integrin-Src-EGFR signaling pathway that promotes recycling of MT1-MMP to sites of invadopodia formation during cancer cell invasion. Full Article
el Primary myeloid cell proteomics and transcriptomics: importance of ss tubulin isotypes for osteoclast function [RESEARCH ARTICLE] By jcs.biologists.org Published On :: 2020-04-07T06:16:39-07:00 David Guerit, Pauline Marie, Anne Morel, Justine Maurin, Christel Verollet, Brigitte Raynaud-Messina, Serge Urbach, and Anne BlangyAmong hematopoietic cells, osteoclasts (Oc) and immature dendritic cells (Dc) are closely related myeloid cells with distinct functions; Oc participate skeleton maintenance while Dc sample the environment for foreign antigens. Such specificities rely on profound modifications of gene and protein expression during Oc and Dc differentiation. We provide global proteomic and transcriptomic analyses of primary mouse Oc and Dc, based on original SILAC and RNAseq data. We established specific signatures for Oc and Dc including genes and proteins of unknown functions. In particular, we showed that Oc and Dc have the same α and β tubulin isotypes repertoire but that Oc express much more β tubulin isotype Tubb6. In both mouse and human Oc, we demonstrate that elevated expression of Tubb6 in Oc is necessary for correct podosomes organization and thus for the structure of the sealing zone, which sustains the bone resorption apparatus. Hence, lowering Tubb6 expression hindered Oc resorption activity. Overall, we highlight here potential new regulators of Oc and Dc biology and illustrate the functional importance of the tubulin isotype repertoire in the biology of differentiated cells. Full Article
el Chondrosarcoma-associated gene 1 (CSAG1) maintains the integrity of the mitotic centrosome in cells with defective p53 [RESEARCH ARTICLE] By jcs.biologists.org Published On :: 2020-04-15T01:46:56-07:00 Hem Sapkota, Jonathan D. Wren, and Gary J. GorbskyCentrosomes focus microtubules to promote mitotic spindle bipolarity, a critical requirement for balanced chromosome segregation. Comprehensive understanding of centrosome function and regulation requires a complete inventory of components. While many centrosome components have been identified, others may yet remain undiscovered. We have used a bioinformatics approach, based on "guilt by association" expression to identify novel mitotic components among the large group of predicted human proteins that have yet to be functionally characterized. Here we identify Chondrosarcoma-Associated Gene 1 (CSAG1) in maintaining centrosome integrity during mitosis. Depletion of CSAG1 disrupts centrosomes and leads to multipolar spindles more effectively in cells with compromised p53 function. Thus, CSAG1 may reflect a class of "mitotic addiction" genes whose expression is more essential in transformed cells. Full Article
el Control of assembly of extra-axonemal structures: the paraflagellar rod of trypanosomes [RESEARCH ARTICLE] By jcs.biologists.org Published On :: 2020-04-15T01:46:56-07:00 Aline A. Alves, Heloisa B. Gabriel, Maria J. R. Bezerra, Wanderley de Souza, Sue Vaughan, Narcisa L. Cunha-e-Silva, and Jack D. SunterEukaryotic flagella are complex microtubule based organelles and in many organisms there are extra-axonemal structures present, including the outer dense fibres of mammalian sperm and the paraflagellar rod (PFR) of trypanosomes. Flagellum assembly is a complex process occurring across three main compartments, the cytoplasm, the transition fibre-transition zone, and the flagellum. It begins with translation of protein components, followed by their sorting and trafficking into the flagellum, transport to the assembly site and then incorporation. Flagella are formed from over 500 proteins; the principles governing axonemal component assembly are relatively clear. However, the coordination and sites of extra-axonemal structure assembly processes are less clear.We have discovered two cytoplasmic proteins in T. brucei that are required for PFR formation, PFR assembly factors 1 and 2. Deletion of either PFR-AF1 or PFR-AF2 dramatically disrupted PFR formation and caused a reduction in the amount of major PFR proteins. The presence of cytoplasmic factors required for PFR formation aligns with the concept of processes occurring across multiple compartments to facilitate axoneme assembly and this is likely a common theme for extra-axonemal structure assembly. Full Article
el 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
el Maturation and phenotype of pathophysiological neuronal excitability of human cells in tau-related dementia [RESEARCH ARTICLE] By jcs.biologists.org Published On :: 2020-04-16T06:39:33-07:00 Olga Kopach, Noemi Esteras, Selina Wray, Dmitri A. Rusakov, and Andrey Y. AbramovFrontotemporal dementia and parkinsonism (FTDP-17) caused by the 10+16 splice-site mutation in the MAPT provides an established platform to model tau-related dementia in vitro. Human iPSC-derived neurons have been shown to recapitulate the neurodevelopmental profile of tau pathology during in vitro corticogenesis as in the adult human brain. However, the neurophysiological phenotype of these cells has remained unknown, leaving unanswered questions over the functional relevance and the gnostic power of this disease model. Here we used electrophysiology to explore the membrane properties and intrinsic excitability of the generated neurons to find that human cells mature by ~150 days of neurogenesis to become compatible with matured cortical neurons. In earlier FTDP-17, neurons, however, exhibited a depolarized resting membrane potential associated with increased resistance and reduced voltage-gated Na+- and K+-channel-mediated conductance. The Nav1.6 protein was reduced in FTDP-17. These led to a reduced cell capability of induced firing and changed action potential waveform in FTDP-17. The revealed neuropathology may thus contribute to the clinicopathological profile of the disease. This sheds new light on the significance of human models of dementia in vitro. Full Article
el 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
el 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
el Kinesin-14s and microtubule dynamics define fission yeast mitotic and meiotic spindle assembly and elongation [RESEARCH ARTICLE] By jcs.biologists.org Published On :: 2020-04-23T01:49:49-07:00 Ana Loncar, Sergio A. Rincon, Manuel Lera Ramirez, Anne Paoletti, and Phong T. TranTo segregate the chromosomes faithfully during cell division, cells assemble a spindle that captures the kinetochores and pulls them towards opposite poles. Proper spindle function requires correct interplay between microtubule motors and non-motor proteins. Defects in spindle assembly or changes in spindle dynamics are associated with diseases like cancer or developmental disorders. Here we compared mitotic and meiotic spindles in fission yeast. We show that even though mitotic and meiotic spindles undergo the typical three phases of spindle elongation, they have distinct features. We found that the relative concentration of kinesin-14 Pkl1 is decreased in meiosis I compared to mitosis, while the concentration of kinesin-5 Cut7 remains constant. We identified the second kinesin-14 Klp2 and microtubule dynamics as factors necessary for proper meiotic spindle assembly. This work defines differences between mitotic and meiotic spindles in fission yeast, and provides prospect for future comparative studies. Full Article
el En bloc TGN recruitment of Aspergillus TRAPPII reveals TRAPP maturation as unlikely to drive RAB1-to-RAB11 transition [RESEARCH ARTICLE] By jcs.biologists.org Published On :: 2020-04-23T01:49:49-07:00 M. Pinar and M. A. PenalvaTRAnsport Protein Particle (TRAPP) complexes regulate membrane traffic. TRAPPII and TRAPPIII share a core hetero-heptamer, also denoted TRAPPI. In fungi TRAPPIII and TRAPPII mediate GDP exchange on RAB1 and RAB11, respectively, regulating traffic across the Golgi, with TRAPPIII also activating RAB1 in autophagosomes. Our finding that Aspergillus nidulans TRAPPII can be assembled by addition of a TRAPPII-specific subcomplex onto core TRAPP prompted us to investigate the possibility that TRAPPI/TRAPPIII already residing in the Golgi matures into TRAPPII to determine a RAB1-to-RAB11 conversion as Golgi cisternae progress from early Golgi to TGN identity. By time-resolved microscopy we determine that the TRAPPII reporter Trs120/TRAPPC9 is recruited to existing TGN cisternae slightly before RAB11 arrives, and resides for~45 sec on them before cisternae tear off into RAB11 secretory carriers. Notably, the core TRAPP reporter Bet3/TRAPPC3 was not detectable in early Golgi cisternae, being instead recruited to TGN cisternae simultaneously with Trs120/TRAPPC9, indicating en bloc recruitment of TRAPPII to the Golgi and arguing strongly against the TRAPP maturation model. Full Article
el 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