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Protein crystal structure determination with the crystallophore, a nucleating and phasing agent

Obtaining crystals and solving the phase problem remain major hurdles encountered by bio-crystallographers in their race to obtain new high-quality structures. Both issues can be overcome by the crystallophore, Tb-Xo4, a lanthanide-based molecular complex with unique nucleating and phasing properties. This article presents examples of new crystallization conditions induced by the presence of Tb-Xo4. These new crystalline forms bypass crystal defects often encountered by crystallographers, such as low-resolution diffracting samples or crystals with twinning. Thanks to Tb-Xo4's high phasing power, the structure determination process is greatly facilitated and can be extended to serial crystallography approaches.




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Protein crystal structure determination with the crystallophore, a nucleating and phasing agent

The unique nucleating and phasing capabilities of the crystallophore, Tb-Xo4, are illustrated through challenging cases.




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Small-angle neutron scattering (SANS) and spin-echo SANS measurements reveal the logarithmic fractal structure of the large-scale chromatin organization in HeLa nuclei

This paper reports on the two-scale fractal structure of chromatin organization in the nucleus of the HeLa cell.




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Crystal structure of the nucleoid-associated protein Fis (PA4853) from Pseudomonas aeruginosa

The crystal structure of Pseudomonas aeruginosa Fis is composed of an N-terminal flexible loop and a C-terminal helix–turn–helix motif.




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Don’t pick a fight with a eunuch spider. It has nothing to lose

In a recent study of the mating behavior of these Asian spiders, researchers found that 87.5 percent of males had both palps amputated during copulation.

The post Don’t pick a fight with a eunuch spider. It has nothing to lose appeared first on Smithsonian Insider.




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The origins of a torus in a galactic nucleus

One problem in unraveling the mystery of quasars is that many (perhaps most) quasar nuclei seem to be surrounded by a torus of obscuring dust that makes them difficult to study.

The post The origins of a torus in a galactic nucleus appeared first on Smithsonian Insider.




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Mitochondrial-nuclear heme trafficking is regulated by GTPases in control of mitochondrial dynamics and ER contact sites [RESEARCH ARTICLE]

Osiris Martinez-Guzman, Mathilda M. Willoughby, Arushi Saini, Jonathan V. Dietz, Iryna Bohovych, Amy E. Medlock, Oleh Khalimonchuk, and Amit R. Reddi

Heme 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.




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Canonical nucleators are dispensable for stress granule assembly in intestinal progenitors [RESEARCH ARTICLE]

Kasun Buddika, Ishara S. Ariyapala, Mary A. Hazuga, Derek Riffert, and Nicholas S. Sokol

Stressed cells downregulate translation initiation and assemble membrane-less foci termed stress granules (SGs). Extensively characterized in cultured cells, the existence of such structures in stressed adult stem cell pools remain poorly characterized. Here we report that Drosophila orthologs of mammalian SG components AGO1, ATX2, CAPRIN, eIF4E, FMRP, G3BP, LIN-28, PABP, and TIAR are enriched in adult intestinal progenitor cells where they accumulate in small cytoplasmic messenger ribonucleoprotein complexes (mRNPs). Treatment with sodium arsenite or rapamycin reorganized these mRNPs into large cytoplasmic granules. Formation of these intestinal progenitor stress granules (IPSGs) depended on polysome disassembly, led to translational downregulation, and was reversible. While canonical SG nucleators ATX2 and G3BP were sufficient for IPSG formation in the absence of stress, neither of them, nor TIAR, either individually or collectively, were required for stress-induced IPSG formation. This work therefore finds that IPSGs do not assemble via a canonical mechanism, raising the possibility that other stem cell populations employ a similar stress-response mechanism.




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The PRR14 heterochromatin tether encodes modular domains that mediate and regulate nuclear lamina targeting [RESEARCH ARTICLE]

Kelly L. Dunlevy, Valentina Medvedeva, Jade E. Wilson, Mohammed Hoque, Trinity Pellegrin, Adam Maynard, Madison M. Kremp, Jason S. Wasserman, Andrey Poleshko, and Richard A. Katz

A large fraction of epigenetically silent heterochromatin is anchored to the nuclear periphery via "tethering proteins" that function to bridge heterochromatin and the nuclear membrane or nuclear lamina. We identified previously a human tethering protein, PRR14, that binds heterochromatin through an N-terminal domain, but the mechanism and regulation of nuclear lamina association remained to be investigated. Here we identify an evolutionarily conserved PRR14 nuclear lamina binding domain (LBD) that is both necessary and sufficient for positioning of PRR14 at the nuclear lamina. We also show that PRR14 associates dynamically with the nuclear lamina, and provide evidence that such dynamics are regulated through phosphorylation-dephosphorylation of the LBD. Furthermore, we identified a PP2A phosphatase recognition motif within the evolutionarily conserved PRR14 C-terminal Tantalus domain. Disruption of this motif affected PRR14 localization to the nuclear lamina. The overall findings demonstrate a heterochromatin anchoring mechanism whereby the PRR14 tether simultaneously binds heterochromatin and the nuclear lamina through two separable, modular domains. The findings also describe an optimal PRR14 LBD fragment that could be used for efficient targeting of fusion proteins to the nuclear lamina.




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A functional in vitro cell-free system for studying DNA repair in isolated nuclei [RESEARCH ARTICLE]

Isabella Guardamagna, Elisabetta Bassi, Monica Savio, Paola Perucca, Ornella Cazzalini, Ennio Prosperi, and Lucia A. Stivala

Assessing DNA repair is an important endpoint to study the DNA damage response for investigating the biochemical mechanisms of this process and the efficacy of chemotherapy, which often uses DNA damaging compounds. Numerous in vitro methods to biochemically characterize DNA repair mechanisms have been developed so far. However, they show some limitations mainly due to the lack of chromatin organization. Here we describe a functional cell-free system to study DNA repair synthesis in vitro, using G1-phase nuclei isolated from human cells treated with different genotoxic agents. Upon incubation in the correspondent damage-activated cytosolic extracts, containing biotin-16-dUTP, nuclei are able to initiate DNA repair synthesis. The use of specific DNA synthesis inhibitors markedly decreased biotinylated dUTP incorporation, indicating the specificity of the repair response. Exogenously added human recombinant PCNA protein, but not the sensors of UV-DNA damage DDB2 or DDB1, stimulated UVC induced dUTP incorporation. In contrast, a DDB2PCNA- mutant protein, unable to associate with PCNA, interfered with DNA repair synthesis. Given its responsiveness to different type of DNA lesions, this system offers an additional tool to study DNA repair mechanisms.




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7-Iodo-5-aza-7-deazaguanine ribonucleoside: crystal structure, physical properties, base-pair stability and functionalization

The positional change of nitro­gen-7 of the RNA constituent guanosine to the bridgehead position-5 leads to the base-modified nucleoside 5-aza-7-de­aza­guanosine. Contrary to guanosine, this mol­ecule cannot form Hoogsteen base pairs and the Watson–Crick proton donor site N3—H becomes a proton-acceptor site. This causes changes in nucleobase recognition in nucleic acids and has been used to construct stable `all-purine' DNA and DNA with silver-mediated base pairs. The present work reports the single-crystal X-ray structure of 7-iodo-5-aza-7-de­aza­guanosine, C10H12IN5O5 (1). The iodinated nucleoside shows an anti conformation at the glycosylic bond and an N conformation (O4'-endo) for the ribose moiety, with an anti­periplanar orientation of the 5'-hy­droxy group. Crystal packing is controlled by inter­actions between nucleobase and sugar moieties. The 7-iodo substituent forms a contact to oxygen-2' of the ribose moiety. Self-pairing of the nucleobases does not take place. A Hirshfeld surface analysis of 1 highlights the contacts of the nucleobase and sugar moiety (O—H⋯O and N—H⋯O). The concept of pK-value differences to evaluate base-pair stability was applied to purine–purine base pairing and stable base pairs were predicted for the construction of `all-purine' RNA. Furthermore, the 7-iodo substituent of 1 was functionalized with benzo­furan to detect motional constraints by fluorescence spectroscopy.




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Meeting report - Nuclear and cytoplasmic molecular machines at work

Simon L. Bullock
Apr 6, 2020; 133:jcs245134-jcs245134
Meeting Report




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Societal and Technical Challenges Posed by Nuclear Waste Call for Attention by World Leaders

Focused attention by world leaders is needed to address the substantial challenges posed by disposal of spent nuclear fuel from reactors and high-level radioactive waste from processing such fuel for military or energy purposes.




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Fukushima Daiichi Nuclear Accident Is ‘Wake-Up Call’ for U.S. to Improve Real-Time Monitoring of Spent Fuel Pools

The 2011 Fukushima Daiichi nuclear accident should serve as a wake-up call to nuclear plant operators and regulators on the critical importance of measuring, maintaining, and restoring cooling in spent fuel pools during severe accidents and terrorist attacks, says a new report from the National Academies of Sciences, Engineering, and Medicine.




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A Domestic Electron Ion Collider Would Unlock Scientific Mysteries of Atomic Nuclei, Maintain U.S. Leadership in Accelerator Science, New Report Says

The science questions that could be answered by an electron ion collider (EIC) – a very large-scale particle accelerator – are significant to advancing our understanding of the atomic nuclei that make up all visible matter in the universe, says a new report by the National Academies of Sciences, Engineering, and Medicine.




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Breakthrough Solutions and Technologies Needed to Speed Cleanup of U.S. Nuclear Weapons Sites

A new report from the National Academies of Sciences, Engineering, and Medicine recommends changes in the way that the U.S. Department of Energy manages science and technology (S&T) development in order to accelerate the cleanup of radioactive waste and contaminated soil, groundwater, and facilities at U.S. nuclear weapons sites.




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National Academies Review of Report on Supplemental Low-Activity Waste at Hanford Nuclear Site Now Available for Public Comment

A new report from the National Academies of Sciences, Engineering, and Medicine – which reviews a separate report by a federally funded laboratory that examines options for treating low-activity radioactive waste at the Hanford Nuclear Reservation -- is available for public comment until Oct. 31.




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At Hanford, Experts and Community Members Weigh In on Nuclear Waste Disposal

In 1943, the town of Hanford in Washington State was selected by the Manhattan Project to be home to the first full-scale plutonium production reactor in the world.




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Nuclear winter would threaten nearly everyone on Earth




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Nuclear winter would threaten nearly everyone on Earth




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Sustainability assessment of different nuclear fuel cycle scenarios

A recent study has assessed the sustainability of different nuclear cycle scenarios in Europe, and suggests trade-offs are required between reducing the amount of uranium fuel needed, costs and proliferation risks.




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Fukushima’s effects on nuclear policy in Germany and the UK

The Fukushima accident in Japan has sparked international debate on nuclear energy. A new study has identified five factors which may have influenced the contrasting energy policy responses to the incident in the UK and Germany. Following the disaster, the UK is continuing to back nuclear power generation, whilst Germany is withdrawing support.




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Decommissioning is a significant part of nuclear power’s GHG impact

The greenhouse gas (GHG) emissions produced during the decommissioning phase of nuclear power plants may have been underestimated in previous assessments, new research suggests. The study estimated that the decommissioning process for a German plant resulted in 1 651 265 tonnes of CO2 (or equivalent) emissions, or 0.825 tonnes of CO2 equivalent per tonne of waste. While the researchers acknowledge that impact is highly dependent on the unique characteristics of each decommissioning project, these results raise questions as to whether this phase has been accurately assessed in earlier research.




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The effects of nuclear power cooling systems on the critically endangered European eel

A case study in Sweden has shown that critically endangered European eels are being lost when they are sucked into the local nuclear power station???s cooling system. A process to pump the eels back into the sea could be beneficial to this species, the researchers conclude.




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What threat do sunken nuclear submarines pose to fisheries?

Leakage of radioactive material from the wreck of the nuclear submarine K-159 in the Barents Sea could increase levels of radioactivity in local populations of cod by a hundred times, new research suggests. However, this level remains well below ‘safe’ standards set by the Norwegian government.




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Scientists detect a massive thermonuclear explosion from outer space

A star from a distant galaxy produced the most intense X-ray blast ever.




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Could a nuclear meltdown happen in U.S.?

There are 104 nuclear power plants in the continental United States, two of which operate in quake-prone areas and others that are in need of major upgrades.



  • Wilderness & Resources

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Nuclear skepticism around the globe

More questions are being raised about nuclear power — in the United States, Europe, Asia and Africa.



  • Wilderness & Resources

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In Germany, renewable energy could replace nuclear

If countries continue to slow the use of nuclear power can green energy be a viable alternative, and at what cost?



  • Wilderness & Resources

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Japan: A robot power everywhere except at nuclear plant

Robots need to be tailored made for their nuclear plants, and the Fukushima plant was built prior to the adoption of robots.



  • Gadgets & Electronics

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Nuclear politics come to Washington

The future looks uncertain for an industry on the brink of making huge gains in Washington this year.




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Visualize nuclear power and radiation

These maps, graphs and charts will answer your questions about radiation exposure and nuclear energy.



  • Wilderness & Resources

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New Mexico looks to expand its nuclear-waste business

The state wants to expand a nuclear-waste storage facility inside an ancient salt bed to play a bigger role in handling spent fuel from U.S. reactors.




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Nuclear radiation influences boy-to-girl ratio

New study finds that nuclear radiation from bomb tests and power plant accidents leads to the birth of more boys than girls.



  • Babies & Pregnancy

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Nuclear cars: They're not science fiction anymore

In the nuke-crazed 1950s, Ford wanted to put mini reactors in cars. That didn't fly, but now we're hearing of radioactive thorium lasers that could power a car




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Alec Baldwin knocks nuclear power, calls reactors 'filthy'

For some opponents of nuclear power, no amount of planning or patching is enough. Among those critics is actor Alec Baldwin, whose thoughts on the subject carry



  • Arts & Culture

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Sign of the times: Siemens scraps nuclear division

A historic moment for the energy industry — leading technology company Siemens abandons its nuclear division in favor of growing wind market.




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Will next-gen nuclear power be safe enough?

Next-gen nuclear plants could provide carbon-free energy, but the painfully slow process of approving better, safer reactors — not to mention real anxiety ove




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Nuclear fission scare hits wrecked Japan nuclear plant

The plant's operator found substances in a reactor which could be a result of nuclear fission, a possible setback in safely shutting down the plant.




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Fukushima chilled U.S. opinions on nuclear power

The nuclear meltdowns at the Fukushima power plant after the Japanese tsunami a year ago has made Americans more leery of nuclear power, according to a Yale Uni




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How a nuclear bomb could save Earth from an asteroid

A well-placed nuclear explosion could actually save humanity from a big asteroid hurtling toward Earth, just like in the movies, a new study suggests.




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Kodak had a 'secret' nuclear reactor

A new report reveals that the Kodak industrial facility in upstate New York was home to a small nuclear reactor filled with weapons-grade uranium for more than




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9 nightmarish nuclear fallout films

To mark the release of “The Chernobyl Diaries,” we’ve rounded up nine notable nuclear horror films that span over 50 years of murder, mayhem and reactor m



  • Arts & Culture

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Steer clear of beer when nuclear bombs drop near

Scientists reexamine and reverse a 1955 study that claimed beer and soda would be safe to drink after a nuclear bomb drops and explodes nearby.




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Satellites could detect rogue nuclear tests

The technique uses GPS and radio telescopes to detect underground nuclear tests using waves that travel from the blast into the upper atmosphere.



  • Fitness & Well-Being

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Nuclear fusion rocket could reach Mars in 30 days

Nuclear fusion could one day propel rockets that allow humans to go to Mars and back in 30 days




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Matt Damon, Michael Douglas, demand an end to nuclear weapons

Actors join other others in urging President Obama to stay true to his commitment to reduce nuclear weapons during this year's G8 summit.



  • Arts & Culture

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Worried about asteroids? Nuclear bombs could solve problem

If a dangerous asteroid pops onto the radar with no time to spare, nuclear bombs may be the best way to respond.




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Even a 'small' nuclear war could trigger catastrophic cooling

Even a relatively small regional nuclear war could trigger global cooling, damage the ozone layer and cause droughts for more than a decade.



  • Climate & Weather

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Northern lights' physics could aid in nuclear fusion

The aurora may hold the secret of a magnetic phenomenon related to the nuclear fusion powering the sun.