is Peacock bass invasion Had devastating, long-term impact on Panama’s Fish By insider.si.edu Published On :: Mon, 12 Dec 2016 18:21:20 +0000 In 1969, 60 to 100 peacock bass imported from Buga, Colombia, were introduced into a pond in Panama for sport fishing. Several individuals escaped. By […] The post Peacock bass invasion Had devastating, long-term impact on Panama’s Fish appeared first on Smithsonian Insider. Full Article Animals Marine Science Research News Science & Nature Spotlight invasive species Smithsonian Tropical Research Institute
is Our Galaxy’s Black Hole is Spewing Planet-size “Spitballs” By insider.si.edu Published On :: Fri, 06 Jan 2017 19:56:12 +0000 Every few thousand years, an unlucky star wanders too close to the black hole at the center of the Milky Way. The black hole’s powerful […] The post Our Galaxy’s Black Hole is Spewing Planet-size “Spitballs” appeared first on Smithsonian Insider. Full Article Science & Nature Space Center for Astrophysics | Harvard & Smithsonian Milky Way Smithsonian Astrophysical Observatory
is Odd anatomy: flexible joint between skull and spine allow dragonfish to open wide By insider.si.edu Published On :: Wed, 01 Feb 2017 22:09:39 +0000 Food is scarce in the deep, dark regions of the ocean where barbeled dragonfishes and their relatives dwell. Known as the Stomiidae, some of these […] The post Odd anatomy: flexible joint between skull and spine allow dragonfish to open wide appeared first on Smithsonian Insider. Full Article Animals Marine Science Research News Science & Nature fishes National Museum of Natural History
is ISO: a boring Martian landing spot for NASA’s InSight probe By insider.si.edu Published On :: Wed, 08 Feb 2017 14:27:13 +0000 NASA’s InSight probe, scheduled to land on the surface of Mars in November 2018, will be boring. Boring a hole, that is. It will drill […] The post ISO: a boring Martian landing spot for NASA’s InSight probe appeared first on Smithsonian Insider. Full Article Research News Science & Nature Space astronomy astrophysics geology National Air and Space Museum planets rocks & minerals
is Simultaneous hermaphrodites: Understanding Speciation in fish called “hamlets” By insider.si.edu Published On :: Mon, 13 Mar 2017 13:51:44 +0000 New species don’t just spring out of thin air. Speciation, the evolutionary process by which new and distinct species arise, usually takes millions of years. […] The post Simultaneous hermaphrodites: Understanding Speciation in fish called “hamlets” appeared first on Smithsonian Insider. Full Article Animals Marine Science Research News Science & Nature biodiversity conservation biology endangered species fishes Tropical Research Institute
is 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
is Surprise: Distinctive new surgeonfish species makes an improbable debut By insider.si.edu Published On :: Wed, 07 Jun 2017 19:10:10 +0000 Sometimes there’s just no telling what will turn up at the local market. Fish biologist Jeff Williams of the Smithsonian’s National Museum of Natural History […] The post Surprise: Distinctive new surgeonfish species makes an improbable debut appeared first on Smithsonian Insider. Full Article Animals Marine Science Q & A Research News Science & Nature biodiversity fishes National Museum of Natural History
is Study shows ancient California Indians risked toxins from bitumen-coated bottles By insider.si.edu Published On :: Fri, 23 Jun 2017 04:10:55 +0000 Finding clean ways to store water is a challenge that humans have faced for millennia. In a new paper in Environmental Health, anthropologist Sabrina Sholts […] The post Study shows ancient California Indians risked toxins from bitumen-coated bottles appeared first on Smithsonian Insider. Full Article Anthropology History & Culture Research News Science & Nature National Museum of Natural History pollution
is Gold nanotechnology and lasers used to successfully freeze fish embryos By insider.si.edu Published On :: Thu, 13 Jul 2017 14:24:20 +0000 For more than 60 years, researchers have tried to successfully cryopreserve (or freeze) the embryo of zebrafish, a species that is an important medical model […] The post Gold nanotechnology and lasers used to successfully freeze fish embryos appeared first on Smithsonian Insider. Full Article Animals Marine Science Research News Science & Nature biodiversity conservation biology endangered species fishes Smithsonian Conservation Biology Institute Smithsonian's National Zoo
is Indestructible jaws from ancient, extinct porcupine fish reveal new species By insider.si.edu Published On :: Thu, 17 Aug 2017 15:20:36 +0000 Covered in sharp spines, when harassed the porcupine fish inflates like a balloon. Think of a small soccer ball bristling all over with nails. Most predators […] The post Indestructible jaws from ancient, extinct porcupine fish reveal new species appeared first on Smithsonian Insider. Full Article Animals Dinosaurs & Fossils Marine Science Science & Nature National Museum of Natural History new species Smithsonian Tropical Research Institute
is Locked and loaded: unique trigger design fires this ant’s snapping jaws By insider.si.edu Published On :: Thu, 31 Aug 2017 12:08:54 +0000 In conflicts between predators and prey, speed is a decided advantage, and evolution has given the trap-jaw ant a distinct advantage with spring-loaded jaws that […] The post Locked and loaded: unique trigger design fires this ant’s snapping jaws appeared first on Smithsonian Insider. Full Article Animals Research News Science & Nature insects National Museum of Natural History spiders
is Zoo scientists honored at Golden Goose By insider.si.edu Published On :: Wed, 04 Oct 2017 12:34:03 +0000 Three former scientists from the Smithsonian’s National Zoological Park–Ellen Lamirande, Don Nichols, and Allan Pessier–were honored at the sixth annual Golden Goose Award ceremony at […] The post Zoo scientists honored at Golden Goose appeared first on Smithsonian Insider. Full Article Animals Science & Nature Spotlight chytrid fungus frogs Smithsonian Conservation Biology Institute Smithsonian's National Zoo
is 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
is With voices joined in chorus, giant otter families create a distinct sound signature By insider.si.edu Published On :: Wed, 15 Nov 2017 20:05:52 +0000 With a non-stop babble of hums, grunts and shrill squeals as they argue over fish and defend their territories, the Amazon’s giant otters are one […] The post With voices joined in chorus, giant otter families create a distinct sound signature appeared first on Smithsonian Insider. Full Article Animals Research News Science & Nature conservation endangered species mammals Smithsonian Tropical Research Institute South America
is Scientists in awe of huge olfactory bulb found in turkey vulture brain By insider.si.edu Published On :: Tue, 12 Dec 2017 10:01:05 +0000 With its homely featherless head, undertaker’s charcoal coloring and association with death and decay, the turkey vulture (Cathartes aura) tops few lists as a favorite […] The post Scientists in awe of huge olfactory bulb found in turkey vulture brain appeared first on Smithsonian Insider. Full Article Animals Research News Science & Nature National Museum of Natural History
is 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
is 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
is More sky puppies! Scientists discover two new species of dog-faced bat By insider.si.edu Published On :: Mon, 15 Jan 2018 16:33:57 +0000 Flitting swiftly through the darkness above the tropical forest canopy in Central and South America, a group of cute little bats with dog-like faces have […] The post More sky puppies! Scientists discover two new species of dog-faced bat appeared first on Smithsonian Insider. Full Article Animals Research News Science & Nature bats mammals National Museum of Natural History new species Smithsonian Tropical Research Institute
is 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
is Meet the newest New World canopy beetle species. ‘Gazillions’ await discovery. By insider.si.edu Published On :: Wed, 31 Jan 2018 15:40:19 +0000 “Somber” is the adjective Smithsonian beetle expert Terry Erwin uses to describe the insects he collects on the forest floor in Peru and Ecuador. “They […] The post Meet the newest New World canopy beetle species. ‘Gazillions’ await discovery. appeared first on Smithsonian Insider. Full Article Animals Research News Science & Nature Peru
is Astronomers detect comets transiting distant stars By insider.si.edu Published On :: Thu, 01 Feb 2018 14:21:55 +0000 There are currently more than 3,500 confirmed known exoplanets thanks to the remarkable sensitivity of the Kepler spacecraft and to technological advances in space and […] The post Astronomers detect comets transiting distant stars appeared first on Smithsonian Insider. Full Article Science & Nature Space Spotlight Center for Astrophysics | Harvard & Smithsonian
is 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
is 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
is Protecting Puerto Rico’s heritage from another disaster By insider.si.edu Published On :: Wed, 09 May 2018 14:27:33 +0000 When a natural disaster strikes, it devastates lives and homes, and can even destroy a culture’s identity and history. After a disaster, humanitarian response is […] The post Protecting Puerto Rico’s heritage from another disaster appeared first on Smithsonian Insider. Full Article Art History & Culture Science & Nature
is 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
is 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
is 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
is 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
is 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
is Bond, James Bond: The ornithologist By insider.si.edu Published On :: Tue, 04 Sep 2018 13:07:54 +0000 The famous fictional British spy, James Bond (code name 007), whose action-packed exploits and international adventures are depicted in books and movies, got his name […] The post Bond, James Bond: The ornithologist appeared first on Smithsonian Insider. Full Article Animals Science & Nature Snapshot birds Caribbean Smithsonian Libraries
is 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
is Windows Server 2003 (I know it is old) and 12294 error By www.bleepingcomputer.com Published On :: 2020-05-08T09:19:37-05:00 Full Article
is Structure of Thermococcus litoralis Δ1-pyrroline-2-carboxylate reductase in complex with NADH and l-proline By scripts.iucr.org Published On :: 2020-04-29 l-Hydroxyproline (l-Hyp) is a nonstandard amino acid that is present in certain proteins, in some antibiotics and in the cell-wall components of plants. l-Hyp is the product of the post-translational modification of protein prolines by prolyl hydroxylase enzymes, and the isomers trans-3-hydroxy-l-proline (T3LHyp) and trans-4-hydroxy-l-proline (T4LHyp) are major components of mammalian collagen. T4LHyp follows two distinct degradation pathways in bacteria and mammals, while T3LHyp is metabolized by a two-step metabolic pathway that is conserved in bacteria and mammals, which involves a T3LHyp dehydratase and a Δ1-pyrroline-2-carboxylate (Pyr2C) reductase. In order to shed light on the structure and catalysis of the enzyme involved in the second step of the T3LHyp degradation pathway, the crystal structure of Pyr2C reductase from the archaeon Thermococcus litoralis DSM 5473 complexed with NADH and l-proline is presented. The model allows the mapping of the residues involved in cofactor and product binding and represents a valid model for rationalizing the catalysis of Pyr2C reductases. Full Article text
is 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
is 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
is Smithsonian ornithologist publishes new guide to the birds of Panama By insider.si.edu Published On :: Thu, 10 Feb 2011 20:15:44 +0000 This user-friendly, portable, and extensive identification guide features large color illustrations of more than 900 species; the first range maps published to show the distribution of Panama's birds and concise text that describes field marks for identification, as well as habitat, behavior, and vocalizations. The post Smithsonian ornithologist publishes new guide to the birds of Panama appeared first on Smithsonian Insider. Full Article Animals Book Review Research News Science & Nature biodiversity birds conservation biology endangered species Migratory Bird Center Smithsonian Environmental Research Center
is New book: “The Subsistence Economies of Indigenous North American Societies: A Handbook” By insider.si.edu Published On :: Tue, 19 Apr 2011 19:27:32 +0000 The new book Subsistence Economies of Indigenous North American Societies provides a comprehensive and in-depth documentation of how Native American societies met the challenges of […] The post New book: “The Subsistence Economies of Indigenous North American Societies: A Handbook” appeared first on Smithsonian Insider. Full Article Anthropology Book Review Research News Science & Nature National Museum of Natural History
is “Falling to Earth: An Apollo 15 Astronaut’s Journey to the Moon” by Al Worden with Francis French By insider.si.edu Published On :: Fri, 19 Aug 2011 15:20:42 +0000 As command module pilot for the Apollo 15 mission to the moon in 1971, Al Worden spent six days orbiting the moon, including three days completely alone, the most isolated human in existence. In Falling to Earth, Worden tells for the first time the full story around the dramatic events that shook NASA and ended his spaceflight career. The post “Falling to Earth: An Apollo 15 Astronaut’s Journey to the Moon” by Al Worden with Francis French appeared first on Smithsonian Insider. Full Article Book Review Science & Nature Space astronomy astrophysics National Air and Space Museum
is New Book: “Sweet Stuff: An American History of Sweeteners from Sugar to Sucralose” By insider.si.edu Published On :: Mon, 17 Oct 2011 14:35:38 +0000 Warner’s narrative covers the major natural sweeteners, including sugar, molasses from cane, beet sugar, corn syrup, honey and maple, as well as artificial sweeteners such as saccharin, cyclamate, aspartame and sucralose. The post New Book: “Sweet Stuff: An American History of Sweeteners from Sugar to Sucralose” appeared first on Smithsonian Insider. Full Article Book Review National Museum of American History
is New Book: “Fishes: The Animal Answer Guide” By insider.si.edu Published On :: Tue, 10 Jan 2012 14:21:43 +0000 In this fun, accessible and informative book, ichthyologists Gene Helfman, professor emeritus at the University of Georgia, and Bruce Collette, of the Division of Fishes at the Smithsonian’s National Museum of Natural History, provide accurate, entertaining, and sometimes surprising answers to more than 100 common and not-so-common questions. The post New Book: “Fishes: The Animal Answer Guide” appeared first on Smithsonian Insider. Full Article Animals Book Review Marine Science Science & Nature biodiversity fishes National Museum of Natural History
is 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
is 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
is Book Review: Double Exposure: photos of African American History & Culture By insider.si.edu Published On :: Mon, 17 Oct 2016 15:33:08 +0000 Photographs, by virtue of their static nature, not only allow us to look back to a fixed point in time, but also give us a […] The post Book Review: Double Exposure: photos of African American History & Culture appeared first on Smithsonian Insider. Full Article Art Book Review History & Culture Spotlight African American civil rights National Museum of African American History and Culture photography
is Windows 98 SE Installation Issues By www.bleepingcomputer.com Published On :: 2019-11-11T17:47:36-05:00 Full Article
is The dimeric organization that enhances the microtubule end-binding affinity of EB1 is susceptible to phosphorylation [RESEARCH ARTICLE] By jcs.biologists.org Published On :: 2020-03-09T08:45:03-07:00 Yinlong Song, Yikan Zhang, Ying Pan, Jianfeng He, Yan Wang, Wei Chen, Jing Guo, Haiteng Deng, Yi Xue, Xianyang Fang, and Xin LiangMicrotubules dynamics is regulated by the plus end-tracking proteins (+TIPs) in cells. End binding protein 1 (EB1) acts as a master regulator in +TIPs networks by targeting microtubule growing ends and recruiting other factors. However, the molecular mechanism of how EB1 binds to microtubule ends with a high affinity remains to be an open question. Using single-molecule imaging, we show that the end-binding kinetics of EB1 changes along with the polymerizing and hydrolysis rate of tubulin dimers, confirming the binding of EB1 to GTP/GDP-Pi tubulin at microtubule growing ends. The affinity of wild-type EB1 to these sites is higher than monomeric EB1 mutants, suggesting that two CH domains in the dimer contribute to the end-binding. Introducing phosphomimicking mutations into the linker domain of EB1 weakens the end-binding affinity and confers a more curved conformation to EB1 dimer without compromising dimerization, suggesting that the overall architecture of EB1 is important for the end-binding affinity. Taken together, our results provide insights into understanding how the high-affinity end-binding of EB1 can be achieved and how this activity may be regulated in cells. Full Article
is 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
is 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
is SNAP29 mediates the assembly of histidine-induced CTP synthase filaments in proximity to the cytokeratin network [RESEARCH ARTICLE] By jcs.biologists.org Published On :: 2020-03-17T03:51:28-07:00 Archan Chakraborty, Wei-Cheng Lin, Yu-Tsun Lin, Kuang-Jing Huang, Pei-Yu Wang, Yi-Feng Chang, Hsiang-Iu Wang, Kung-Ting Ma, Chun-Yen Wang, Xuan-Rong Huang, Yen-Hsien Lee, Bi-Chang Chen, Ya-Ju Hsieh, Kun-Yi Chien, Tzu-Yang Lin, Ji-Long Liu, Li-Ying Sung, Jau-Song Yu, Yu-Sun Chang, and Li-Mei PaiUnder metabolic stress, cellular components can assemble into distinct membraneless organelles for adaptation. One such example is cytidine 5'-triphosphate synthase (CTPS), which forms filamentous structures under glutamine deprivation. We have previously demonstrated that histidine (His)-mediated methylation regulates the formation of CTPS filaments to suppress enzymatic activity and preserve the CTPS protein under Gln deprivation, which promotes cancer cell growth after stress alleviation. However, it remains unclear where and how these enigmatic structures are assembled. Using CTPS-APEX2-mediated in vivo proximity labeling, we found that SNAP29 regulates the spatiotemporal filament assembly of CTPS along the cytokeratin network in a keratin 8 (KRT8)-dependent manner. Knockdown of synaptosome-associated protein 29 (SNAP29) interfered with assembly and relaxed the filament-induced suppression of CTPS enzymatic activity. Furthermore, APEX2 proximity labeling of keratin 18 (KRT18) revealed a spatiotemporal association of SNAP29 with cytokeratin in response to stress. Super-resolution imaging suggests that during CTPS filament formation, SNAP29 interacts with CTPS along the cytokeratin network. This study links the cytokeratin network to the regulation of metabolism by compartmentalization of metabolic enzymes during nutrient deprivation. Full Article
is 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
is 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