de Did ripening fruit help hominids develop complex hands? By insider.si.edu Published On :: Thu, 12 May 2016 11:32:13 +0000 One of the primary features that distinguish hominids such as chimpanzees, gorillas and humans from the rest of the animal kingdom are uniquely dexterous hands. […] The post Did ripening fruit help hominids develop complex hands? appeared first on Smithsonian Insider. Full Article Animals Anthropology Research News Science & Nature evolution mammals Smithsonian's National Zoo Tropical Research Institute
de Smithsonian Study reveals Decline of Genetic Diversity in Wild Cheetahs By insider.si.edu Published On :: Tue, 21 Jun 2016 19:23:58 +0000 The planet’s last stronghold of wild cheetahs (Acinonyx jubatus) is losing genetic diversity at an alarming rate according to a new study from the Smithsonian […] The post Smithsonian Study reveals Decline of Genetic Diversity in Wild Cheetahs appeared first on Smithsonian Insider. Full Article Animals Research News Science & Nature Spotlight Smithsonian Conservation Biology Institute Smithsonian's National Zoo
de Discovery in Smithsonian collection broadens understanding of rare North American leech By insider.si.edu Published On :: Wed, 06 Jul 2016 17:44:03 +0000 Thanks to a recent reassessment of specimens preserved in jars of alcohol at the Smithsonian’s National Museum of Natural History, New Hampshire is now on […] The post Discovery in Smithsonian collection broadens understanding of rare North American leech appeared first on Smithsonian Insider. Full Article Animals Research News Science & Nature amphibian National Museum of Natural History
de New bright orange-red scorpionfish discovered deep in Caribbean By insider.si.edu Published On :: Mon, 25 Jul 2016 14:57:04 +0000 Meet Scorpaenodes barrybrowni is a scorpionfish species newly discovered by Smithsonian scientists using a manned submersible in the deep-reef waters of the Caribbean island of Curaçao. It […] The post New bright orange-red scorpionfish discovered deep in Caribbean appeared first on Smithsonian Insider. Full Article Animals Marine Science Research News Science & Nature Spotlight conservation biology fishes National Museum of Natural History new species Tropical Research Institute
de First hooded crane hatches @ SCBI By insider.si.edu Published On :: Fri, 29 Jul 2016 11:02:40 +0000 The Smithsonian Conservation Biology Institute (SCBI) hatched its first hooded crane chick June 14. The chick was born as the result of artificial insemination. The […] The post First hooded crane hatches @ SCBI appeared first on Smithsonian Insider. Full Article Animals Science & Nature Spotlight birds conservation biology endangered species Smithsonian Conservation Biology Institute Smithsonian's National Zoo
de Why Birds Really Matter: President Jimmy Carter By insider.si.edu Published On :: Sat, 20 Aug 2016 08:49:14 +0000 President Jimmy Carter, an avid birder, talks about the importance of bird conservation and why birds really matter. Step outside your house in the morning […] The post Why Birds Really Matter: President Jimmy Carter appeared first on Smithsonian Insider. Full Article Animals Science & Nature biodiversity birds conservation biology endangered species extinction Migratory Bird Center Smithsonian Conservation Biology Institute
de 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
de Making the Smithsonian’s New “Sidedoor” podcast series a reality By insider.si.edu Published On :: Wed, 26 Oct 2016 13:08:11 +0000 There’s something exciting and strange about having an idea. It can come suddenly. Unexpectedly. Randomly. Intensely. Ideas can uninvitingly appear full-forced and bright—like the cliché […] The post Making the Smithsonian’s New “Sidedoor” podcast series a reality appeared first on Smithsonian Insider. Full Article Art History & Culture Meet Our People Science & Nature
de 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
de 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
de 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
de Paleo-detectives energize great whale mystery: how & when baleen evolved By insider.si.edu Published On :: Fri, 07 Apr 2017 18:20:24 +0000 A bizarre change occurs in the mouth of a humpback whale during its development in the womb. Several dozen tooth buds sprout in a row […] The post Paleo-detectives energize great whale mystery: how & when baleen evolved appeared first on Smithsonian Insider. Full Article Animals Dinosaurs & Fossils Marine Science Research News Science & Nature evolution fossils mammals National Museum of Natural History
de Whale tagging in Southeast Pacific provides data for species protection By insider.si.edu Published On :: Fri, 14 Apr 2017 10:38:23 +0000 Whales from both poles migrate long distances to breed in tropical waters. Smithsonian scientist Hector M. Guzman and Fernando Félix at the Salinas Whale Museum […] The post Whale tagging in Southeast Pacific provides data for species protection appeared first on Smithsonian Insider. Full Article Animals Marine Science Research News Science & Nature Spotlight conservation mammals Smithsonian Tropical Research Institute whales
de 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
de 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
de Study determines microscopic water bears will be Earth’s last survivors By insider.si.edu Published On :: Wed, 19 Jul 2017 16:53:32 +0000 The world’s most indestructible species, the tardigrade, an eight-legged micro-animal, also known as the water bear, will survive until the Sun dies, according to a […] The post Study determines microscopic water bears will be Earth’s last survivors appeared first on Smithsonian Insider. Full Article Animals Marine Science Research News Science & Nature Space Spotlight asteroids astronomy astrophysics Center for Astrophysics | Harvard & Smithsonian extinction Smithsonian Astrophysical Observatory
de Laser beams unveil secrets locked inside primitive stone spear points By insider.si.edu Published On :: Fri, 28 Jul 2017 15:22:42 +0000 In a new study in which one of humankind’s most high-tech tools was used to analyze one of its most primitive, scientists have uncovered evidence […] The post Laser beams unveil secrets locked inside primitive stone spear points appeared first on Smithsonian Insider. Full Article Anthropology Science & Nature National Museum of Natural History
de 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
de 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
de Eons before viral kitten videos, ancient Egyptians adored cats By insider.si.edu Published On :: Fri, 22 Sep 2017 12:49:04 +0000 Cats are notoriously fickle—purring in your lap one second, then swiping you with an indignant claw the next. One thing is certain however when it […] The post Eons before viral kitten videos, ancient Egyptians adored cats appeared first on Smithsonian Insider. Full Article Anthropology Art History & Culture Arthur M. Sackler Gallery
de 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
de 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
de 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
de Early indicator of cheetah pregnancy identified By insider.si.edu Published On :: Fri, 15 Dec 2017 09:42:42 +0000 A new study from the Smithsonian Conservation Biology Institute (SCBI) is helping make headway in an area of animal management that has historically proven challenging: […] The post Early indicator of cheetah pregnancy identified appeared first on Smithsonian Insider. Full Article Animals Research News Science & Nature Spotlight Smithsonian Conservation Biology Institute Smithsonian's National Zoo
de Jaguar conservation depends on neighbor attitudes By insider.si.edu Published On :: Fri, 29 Dec 2017 12:44:34 +0000 According to a new survey of residents living near two major national parks in Panama, jaguars deserve increased protection. Nature and wildlife are considered national […] The post Jaguar conservation depends on neighbor attitudes appeared first on Smithsonian Insider. Full Article Animals Research News Science & Nature Spotlight biodiversity conservation conservation biology endangered species mammals Tropical Research Institute
de 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
de 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
de 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
de Meet the world’s weirdest whale By insider.si.edu Published On :: Thu, 15 Feb 2018 20:25:00 +0000 Swimming in the frigid waters of the Arctic and surfacing in narrow gaps in the sea ice to breathe, the narwhal is one of the […] The post Meet the world’s weirdest whale appeared first on Smithsonian Insider. Full Article Animals Marine Science Science & Nature National Museum of Natural History whales
de Underpaid women “computers” mapped the universe in the 19th century By insider.si.edu Published On :: Tue, 27 Mar 2018 11:49:04 +0000 Every day, astronomers at the Harvard-Smithsonian Center for Astrophysics depend on computers to help them solve the mysteries of the universe, just as they did […] The post Underpaid women “computers” mapped the universe in the 19th century appeared first on Smithsonian Insider. Full Article Science & Nature Space astrophysics Center for Astrophysics | Harvard & Smithsonian
de 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
de 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
de 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
de Windows Server 2016: Audio In/Out through Remote Desktop to Thinclients By www.bleepingcomputer.com Published On :: 2020-03-17T19:52:46-05:00 Full Article
de Windows Server unattended.xml file License Agreement By www.bleepingcomputer.com Published On :: 2020-04-18T03:42:38-05:00 Full Article
de Use GPO to Import Safe Senders & Auto Download External Email Content By www.bleepingcomputer.com Published On :: 2020-04-28T01:51:44-05:00 Full Article
de 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
de 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
de 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
de “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
de 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
de New Book: “Birds of South Asia: The Ripley Guide” By insider.si.edu Published On :: Thu, 18 Oct 2012 17:21:43 +0000 When it comes to the birds of South Asia, Pamela Rasmussen wrote the book on it. Literally. Twice. The post New Book: “Birds of South Asia: The Ripley Guide” appeared first on Smithsonian Insider. Full Article Animals Book Review Science & Nature birds conservation biology National Museum of Natural History
de Accidentally deleting all data By www.bleepingcomputer.com Published On :: 2019-09-07T17:22:44-05:00 Full Article
de Win95b not detecting pcmcia network card *pulling my hair out* By www.bleepingcomputer.com Published On :: 2019-10-28T18:08:00-05:00 Full Article
de DE-cadherin and Myosin II balance regulates furrow length for onset of polygon shape in syncytial Drosophila embryos [RESEARCH ARTICLE] By jcs.biologists.org Published On :: 2020-04-07T06:45:08-07:00 Bipasha Dey and Richa RikhyCell shape morphogenesis from spherical to polygonal occurs in epithelial cell formation in metazoan embryogenesis. In syncytial Drosophila embryos, the plasma membrane incompletely surrounds each nucleus and is organized as a polygonal epithelial-like array. Each cortical syncytial division cycle shows circular to polygonal plasma membrane transition along with furrow extension between adjacent nuclei from interphase to metaphase. In this study, we assess the relative contribution of DE-cadherin and Myosin II at the furrow for polygonal shape transition. We show that polygonality initiates during each cortical syncytial division cycle when the furrow extends from 4.75 to 5.75 µm. Polygon plasma membrane organization correlates with increased junctional tension, increased DE-cadherin and decreased Myosin II mobility. DE-cadherin regulates furrow length and polygonality. Decreased Myosin II activity allows for polygonality to occur at a lower length than controls. Increased Myosin II activity leads to loss of lateral furrow formation and complete disruption of polygonal shape transition. Our studies show that DE-cadherin-Myosin II balance regulates an optimal lateral membrane length during each syncytial cycle for polygonal shape transition. Full Article
de 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
de The small GTPase Rab32 resides on lysosomes to regulate mTORC1 signaling [RESEARCH ARTICLE] By jcs.biologists.org Published On :: 2020-04-15T01:46:56-07:00 Kristina Drizyte-Miller, Jing Chen, Hong Cao, Micah B. Schott, and Mark A. McNivenEpithelial cells such as liver-resident hepatocytes rely heavily on the Rab family of small GTPases to perform membrane trafficking events that dictate cell physiology and metabolism. Not surprisingly, disruption of several Rabs can manifest in metabolic diseases or cancer. Rab32 is expressed in many secretory epithelial cells but its role in cellular metabolism is virtually unknown. In this study, we find that Rab32 associates with lysosomes and regulates proliferation and cell size of Hep3B hepatoma and HeLa cells. Specifically, we identify that Rab32 supports mTORC1 signaling under basal and amino acid stimulated conditions. Consistent with inhibited mTORC1, an increase in nuclear TFEB localization and lysosome biogenesis is also observed in Rab32-depleted cells. Finally, we find that Rab32 interacts with mTOR kinase and that loss of Rab32 reduces the association of mTOR and mTORC1 pathway proteins with lysosomes, suggesting that Rab32 regulates lysosomal mTOR trafficking. In summary, these findings suggest that Rab32 functions as a novel regulator of cellular metabolism through supporting mTORC1 signaling. Full Article
de 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
de 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
de 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