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The crystal structure of the TonB-dependent transporter YncD reveals a positively charged substrate-binding site

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.




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Structure of the N-terminal domain of ClpC1 in complex with the antituberculosis natural product ecumicin reveals unique binding interactions

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.




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New book reveals tidal freshwater wetlands are on frontlines of global change

Tidal Freshwater Wetlands focuses on wetlands found in North America and Europe near the mouths of rivers that flow into estuaries like the Chesapeake Bay.

The post New book reveals tidal freshwater wetlands are on frontlines of global change appeared first on Smithsonian Insider.




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New book reveals Ice Age mariners from Europe were America’s first inhabitants

Some of the earliest humans to inhabit America came from Europe according to a new book "Across Atlantic Ice: The Origin of America's Clovis Culture."

The post New book reveals Ice Age mariners from Europe were America’s first inhabitants appeared first on Smithsonian Insider.




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Automated 3D light-sheet screening with high spatiotemporal resolution reveals mitotic phenotypes [TOOLS AND RESOURCES]

Björn Eismann, Teresa G. Krieger, Jürgen Beneke, Ruben Bulkescher, Lukas Adam, Holger Erfle, Carl Herrmann, Roland Eils, and Christian Conrad

3D cell cultures enable the in vitro study of dynamic biological processes such as the cell cycle, but their use in high-throughput screens remains impractical with conventional fluorescent microscopy. Here, we present a screening workflow for the automated evaluation of mitotic phenotypes in 3D cell cultures by light-sheet microscopy. After sample preparation by a liquid handling robot, cell spheroids are imaged for 24 hours in toto with a dual-view inverted selective plane illumination microscope (diSPIM) with a much improved signal-to-noise ratio, higher imaging speed, isotropic resolution and reduced light exposure compared to a spinning disc confocal microscope. A dedicated high-content image processing pipeline implements convolutional neural network based phenotype classification. We illustrate the potential of our approach by siRNA knock-down and epigenetic modification of 28 mitotic target genes for assessing their phenotypic role in mitosis. By rendering light-sheet microscopy operational for high-throughput screening applications, this workflow enables target gene characterization or drug candidate evaluation in tissue-like 3D cell culture models.




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A genetic interaction map centered on cohesin reveals auxiliary factors in sister chromatid cohesion [RESEARCH ARTICLE]

Su Ming Sun, Amandine Batte, Mireille Tittel-Elmer, Sophie van der Horst, Tibor van Welsem, Gordon Bean, Trey Ideker, Fred van Leeuwen, and Haico van Attikum

Eukaryotic chromosomes are replicated in interphase and the two newly duplicated sister chromatids are held together by the cohesin complex and several cohesin auxiliary factors. Sister chromatid cohesion is essential for accurate chromosome segregation during mitosis, yet has also been implicated in other processes, including DNA damage repair, transcription and DNA replication. To assess how cohesin and associated factors functionally interconnect and coordinate with other cellular processes, we systematically mapped genetic interactions of 17 cohesin genes centered on quantitative growth measurements of >52,000 gene pairs in budding yeast. Integration of synthetic genetic interactions unveiled a cohesin functional map that constitutes 373 genetic interactions, revealing novel functional connections with post-replication repair, microtubule organization and protein folding. Accordingly, we show that the microtubule-associated protein Irc15 and the prefoldin complex members Gim3, Gim4 and Yke2 are new factors involved in sister chromatid cohesion. Our genetic interaction map thus provides a unique resource for further identification and functional interrogation of cohesin proteins. Since mutations in cohesin proteins have been associated with cohesinopathies and cancer, it may also identify cohesin interactions relevant in disease etiology.




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En bloc TGN recruitment of Aspergillus TRAPPII reveals TRAPP maturation as unlikely to drive RAB1-to-RAB11 transition [RESEARCH ARTICLE]

M. Pinar and M. A. Penalva

TRAnsport 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.




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Salamander DNA reveals evidence of older land connection between Central and South America

The humble salamander may provide evidence to support a controversial claim that North and South America were joined together much earlier than previously thought. The […]

The post Salamander DNA reveals evidence of older land connection between Central and South America appeared first on Smithsonian Insider.




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Glittering, mesmerizing, lifesaving: Hospital exhibit showcases minerals used in medicine

Have an upset stomach? Pop a chalky, chewable antacid. Maybe you’ve got a painful cut or burn. No problem; reach for a healing ointment or […]

The post Glittering, mesmerizing, lifesaving: Hospital exhibit showcases minerals used in medicine appeared first on Smithsonian Insider.



  • Earth Science
  • Science & Nature
  • National Museum of Natural History

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A new method for in situ structural investigations of nano-sized amorphous and crystalline materials using mixed-flow reactors

Structural investigations of amorphous and nanocrystalline phases forming in solution are historically challenging. Few methods are capable of in situ atomic structural analysis and rigorous control of the system. A mixed-flow reactor (MFR) is used for total X-ray scattering experiments to examine the short- and long-range structure of phases in situ with pair distribution function (PDF) analysis. The adaptable experimental setup enables data collection for a range of different system chemistries, initial supersaturations and residence times. The age of the sample during analysis is controlled by adjusting the flow rate. Faster rates allow for younger samples to be examined, but if flow is too fast not enough data are acquired to average out excess signal noise. Slower flow rates form older samples, but at very slow speeds particles settle and block flow, clogging the system. Proper background collection and subtraction is critical for data optimization. Overall, this MFR method is an ideal scheme for analyzing the in situ structures of phases that form during crystal growth in solution. As a proof of concept, high-resolution total X-ray scattering data of amorphous and crystalline calcium phosphates and amorphous calcium carbonate were collected for PDF analysis.




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Elastic propagation of fast electron vortices through amorphous materials

This work studies the elastic scattering behavior of electron vortices when propagating through amorphous samples. A formulation of the multislice approach in cylindrical coordinates is used to theoretically investigate the redistribution of intensity between different angular momentum components due to scattering. To corroborate and elaborate on our theoretical results, extensive numerical simulations are performed on three model systems (Si3N4, Fe0.8B0.2, Pt) for a wide variety of experimental parameters to quantify the purity of the vortices, the net angular momentum transfer, and the variability of the results with respect to the random relative position between the electron beam and the scattering atoms. These results will help scientists to further improve the creation of electron vortices and enhance applications involving them.




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X-ray diffraction from strongly bent crystals and spectroscopy of X-ray free-electron laser pulses

The use of strongly bent crystals in spectrometers for pulses of a hard X-ray free-electron laser is explored theoretically. Diffraction is calculated in both dynamical and kinematical theories. It is shown that diffraction can be treated kinematically when the bending radius is small compared with the critical radius given by the ratio of the Bragg-case extinction length for the actual reflection to the Darwin width of this reflection. As a result, the spectral resolution is limited by the crystal thickness, rather than the extinction length, and can become better than the resolution of a planar dynamically diffracting crystal. As an example, it is demonstrated that spectra of the 12 keV pulses can be resolved in the 440 reflection from a 20 µm-thick diamond crystal bent to a radius of 10 cm.




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A clouded leopard cub, a Przewalski’s horse and a red panda cub were all recently born at the Smithsonian’s National Zoo

As you read here
In a 24-hour-period between July 9 and 10, 2009 a clouded leopard cub, a Przewalski's horse, and a red panda cub were all born at Smithsonian's National Zoo's Conservation and Research Center in Front Royal, Virginia.

The post A clouded leopard cub, a Przewalski’s horse and a red panda cub were all recently born at the Smithsonian’s National Zoo appeared first on Smithsonian Insider.




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Coral biologist Mary Hagedorn speaks about her research to conserve our ocean’s corals

Dr. Mary Hagedorn, a marine biologist at the Smithsonian Institution, talks about her research to understand and conserve our oceans' corals. To meet more scientists, visit https://insider.si.edu.

The post Coral biologist Mary Hagedorn speaks about her research to conserve our ocean’s corals appeared first on Smithsonian Insider.




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Scientists at a new National Zoo laboratory use DNA to diagnose illnesses and discover new species of animals

Researchers at the Smithsonian's National Zoo's new genetics lab use animal DNA to diagnose new diseases, discover new species help in conservation efforts and solve mysteries.

The post Scientists at a new National Zoo laboratory use DNA to diagnose illnesses and discover new species of animals appeared first on Smithsonian Insider.




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National Zoo veterinarian Katharine Hope is in charge of the health of 2,000 animals from 400 different species.

National Zoo Veterinarian Katharine Hope treats about 2,000 animals from 400 different species. She and her colleagues care for a variety of animals, from small baby flamingos to adult Asian elephants, so there's no such thing as an average day.

The post National Zoo veterinarian Katharine Hope is in charge of the health of 2,000 animals from 400 different species. appeared first on Smithsonian Insider.




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Roland Kays, curator of mammals at the New York State Museum, discusses a new Smithsonian Website for sharing camera-trap images of wild animals

The post Roland Kays, curator of mammals at the New York State Museum, discusses a new Smithsonian Website for sharing camera-trap images of wild animals appeared first on Smithsonian Insider.






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Meet our Scientist Rachel Page. She studies frog-eating bats, and other animals, in Panama

Meet Rachel Page, a Smithsonian scientist in Panama who studies frog-eating bats (fringe-lipped bats), among other topics. Her current research focuses on learning and memory in neotropical bats, combining field studies with laboratory experiments to learn about predator cognition and its effects on the evolution of their prey.

The post Meet our Scientist Rachel Page. She studies frog-eating bats, and other animals, in Panama appeared first on Smithsonian Insider.




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Can animals take a selfie?

Yes! When an animal trips a “camera trap” as a part of a project between the North Carolina Museum of Natural Sciences and the Smithsonian. […]

The post Can animals take a selfie? appeared first on Smithsonian Insider.




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Keeping zoo animals happy, healthy

 The zoo extends the collecting mission of the Smithsonian into the realm of the living. From the Series: Stories From the Vault: Random? http://bit.ly/2gfy5hO

The post Keeping zoo animals happy, healthy appeared first on Smithsonian Insider.




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Study reveals hazards of the high-wire life for bromeliads

Botanists Gerhard Zotz of the Smithsonian Tropical Research Institute and Stefan Wester of the University of Oldenburg in Germany decided to take a closer look at these high-wire bromeliads. They were interested to find out how the growth and survival rates of these plants on electrical cables compared to the growth and survival of plants of the same species growing in trees--their natural environment.

The post Study reveals hazards of the high-wire life for bromeliads appeared first on Smithsonian Insider.




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The Encyclopedia of Life is a global effort to document all 1.8 million named species of animals, plants and other life forms on Earth

The Encyclopedia of Life is an unprecedented global effort to document all 1.8 million named species of animals, plants and other forms of life on Earth. For the first time in the history of the planet, scientists, students, and citizens will have multi-media access to all known living species, even those that have just been discovered. The Field Museum of Natural History, Harvard University, Marine Biological Laboratory, Smithsonian Institution, and Biodiversity Heritage Library joined together to initiate the project, bringing together species and software experts from across the world. Lean more at www.eol.org

The post The Encyclopedia of Life is a global effort to document all 1.8 million named species of animals, plants and other life forms on Earth appeared first on Smithsonian Insider.




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DNA sequencing reveals simple vegetables in ancient Roman medicines

Recent analysis using DNA sequencing of ancient Roman pills found aboard a ship that sank in Italy’s Gulf of Baratti between 140 -120 B.C, has revealed that the medicines consist of material from simple garden plants, namely carrot, radish, parsley, celery, wild onion and cabbage.

The post DNA sequencing reveals simple vegetables in ancient Roman medicines appeared first on Smithsonian Insider.




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Fossil reveals 48-million year history of zombie ants

A 48 million-year-old fossilized leaf has revealed the oldest known evidence of a macabre part of nature – parasites taking control of their hosts to turn them into zombies.

The post Fossil reveals 48-million year history of zombie ants appeared first on Smithsonian Insider.




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New project will improve access to thousands of scientific field books, journals and notes in Smithsonian collections

In 1909, naturalist Dr. Edgar A. Mearns joined Theodore Roosevelt and scientists from the Smithsonian and New York’s American Museum of Natural History on an […]

The post New project will improve access to thousands of scientific field books, journals and notes in Smithsonian collections appeared first on Smithsonian Insider.




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Wild ginseng in steep decline in Maryland, survey reveals: Q&A with Smithsonian botanist Christopher Puttock

Despite many laws to protect it, a new survey reveals wild ginseng in Maryland is on the decline.

The post Wild ginseng in steep decline in Maryland, survey reveals: Q&A with Smithsonian botanist Christopher Puttock appeared first on Smithsonian Insider.




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Going for the gut: DNA from beetle stomachs reveals complex network

Going for the gut will soon become standard protocol for scientists working to unravel the complex living web of interactions between plants and animals on […]

The post Going for the gut: DNA from beetle stomachs reveals complex network appeared first on Smithsonian Insider.




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Loss of animals spells doom for diversity of rainforest trees

Soon after a dirt road through the forests of Lambir Hills National Park in Borneo was improved in 1987, local markets selling the meat of […]

The post Loss of animals spells doom for diversity of rainforest trees appeared first on Smithsonian Insider.




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3D study of teeth in modern mammals opens window to extinct animal diets

By charting the slopes and crags on animals’ teeth as if they were mountain ranges, scientists at the Smithsonian’s National Museum of Natural History have […]

The post 3D study of teeth in modern mammals opens window to extinct animal diets appeared first on Smithsonian Insider.




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Of mice and macchiato: Bird Friendly coffee gives a paw-up to small mammals as well

Finding a mouse in your morning coffee might give you an unwelcome jolt, but there’s a strong connection between small mammals, birds and the plantations […]

The post Of mice and macchiato: Bird Friendly coffee gives a paw-up to small mammals as well appeared first on Smithsonian Insider.





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A first: New website reveals origin of genetic samples and date collected

For the first time, a new public database will link genetic data with records of where and when the samples it was taken from were […]

The post A first: New website reveals origin of genetic samples and date collected appeared first on Smithsonian Insider.




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Study reveals soil fungi has final say in survival of seeds from tropical trees

How specific fungi interact with seeds in tropical forest soils may be the ultimate arbiter in the struggle for survival among tropical trees. “Depending on […]

The post Study reveals soil fungi has final say in survival of seeds from tropical trees appeared first on Smithsonian Insider.




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Nonlinear optical organic–inorganic crystals: synthesis, structural analysis and verification of harmonic generation in tri-(o-chloroanilinium nitrate)

The structural and nonlinear optical properties of a new anilinium hybrid crystal of chemical formula (C6H7NCl+·NO3−)3 have been investigated. The crystal structure was determined from single-crystal X-ray diffraction measurements performed at a temperature of 100 K which show that the compound crystallizes in a noncentrosymmetric space group (Pna21). The structural analysis was coupled with Hirshfeld surface analysis to evaluate the contribution of the different intermolecular interactions to the formation of supramolecular assemblies in the solid state that exhibit nonlinear optical features. This analysis reveals that the studied compound is characterized by a three-dimensional network of hydrogen bonds and the main contributions are provided by the O...H, C...H, H...H and Cl...H interactions, which alone represent ∼85% of the total contributions to the Hirshfeld surfaces. It is noteworthy that the halogen...H contributions are quite comparable with those of the H...H contacts. The nonlinear optical properties were investigated by nonlinear diffuse femtosecond-pulse reflectometry and the obtained results were compared with those of the reference material LiNbO3. The hybrid crystals exhibit notable second (SHG) and third (THG) harmonic generation which confirms its polarity is generated by the different intermolecular interactions. These measurements also highlight that the THG signal of the new anilinium compound normalized to its SHG counterpart is more pronounced than for LiNbO3.




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Reducing dynamical electron scattering reveals hydrogen atoms

Compared with X-rays, electron diffraction faces a crucial challenge: dynamical electron scattering compromises structure solution and its effects can only be modelled in specific cases. Dynamical scattering can be reduced experimentally by decreasing crystal size but not without a penalty, as it also reduces the overall diffracted intensity. In this article it is shown that nanometre-sized crystals from organic pharmaceuticals allow positional refinement of the hydrogen atoms, even whilst ignoring the effects of dynamical scattering during refinement. To boost the very weak diffraction data, a highly sensitive hybrid pixel detector was employed. A general likelihood-based computational approach was also introduced for further reducing the adverse effects of dynamic scattering, which significantly improved model accuracy, even for protein crystal data at substantially lower resolution.




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Ab initio phasing of the diffraction of crystals with translational disorder

To date X-ray protein crystallography is the most successful technique available for the determination of high-resolution 3D structures of biological molecules and their complexes. In X-ray protein crystallography the structure of a protein is refined against the set of observed Bragg reflections from a protein crystal. The resolution of the refined protein structure is limited by the highest angle at which Bragg reflections can be observed. In addition, the Bragg reflections alone are typically insufficient (by a factor of two) to determine the structure ab initio, and so prior information is required. Crystals formed from an imperfect packing of the protein molecules may also exhibit continuous diffraction between and beyond these Bragg reflections. When this is due to random displacements of the molecules from each crystal lattice site, the continuous diffraction provides the necessary information to determine the protein structure without prior knowledge, to a resolution that is not limited by the angular extent of the observed Bragg reflections but instead by that of the diffraction as a whole. This article presents an iterative projection algorithm that simultaneously uses the continuous diffraction as well as the Bragg reflections for the determination of protein structures. The viability of this method is demonstrated on simulated crystal diffraction.




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Bounding the regularity radius for regular crystals




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89 percent increase in loyalty program fraud, Forter reveals

(The Paypers) Forter has released the seventh edition of its Fraud Attack Index, tracking shifting behaviours...




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A genetic interaction map centered on cohesin reveals auxiliary factors in sister chromatid cohesion

Su Ming Sun
Apr 16, 2020; 0:jcs.237628v1-jcs.237628
Articles




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Automated 3D light-sheet screening with high spatiotemporal resolution reveals mitotic phenotypes

Björn Eismann
Apr 15, 2020; 0:jcs.245043v1-jcs.245043
TOOLS AND RESOURCES




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Why animals eat what they eat

Full Text:

What an animal eats is a fundamental aspect of its biology, but surprisingly, the evolution of diet had not been studied across the animal kingdom until now. Scientists at the University of Arizona report several unexpected findings from taking a deep dive into the evolutionary history of more than one million animal species and going back 800 million years, when the first animals appeared on our planet. The study revealed several surprising key insights: Many species living today that are carnivorous, meaning they eat other animals, can trace this diet back to a common ancestor more than 800 million years ago; A plant-based, or herbivorous, diet is not the evolutionary driver for new species that it was believed to be; Closely related animals tend to share the same dietary category -- plant-eating, meat-eating, or both. This finding implies that switching between dietary lifestyles is not something that happens easily and often over the course of evolution.

Image credit: Daniel Stolte/UANews




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Alexion's Buyout of Portola Pharmaceuticals Gets Investors' Blood Flowing

Source: Streetwise Reports   05/05/2020

Shares of Portola Pharmaceuticals traded 130% higher after the company reported that it has received an $18 per share buyout offer from Alexion Pharmaceuticals.

Commercial-stage biotechnology company Portola Pharmaceuticals Inc. (PTLA:NASDAQ), which focuses on blood-related disorders, and global biopharmaceuticals firm Alexion Pharmaceuticals Inc. (ALXN:NASDAQ) announced that they have entered into a definitive merger agreement for Portola to be acquired by Alexion.

The acquisition is said to provide a key addition to Alexion's diversified commercial portfolio. The report indicated that the merger agreement has already been unanimously approved each of the company's boards of directors.

The report explained that "Portola's commercialized medicine, Andexxa® [coagulation factor Xa (recombinant), inactivated-zhzo], marketed as Ondexxya® in Europe, is the first and only approved Factor Xa inhibitor reversal agent, and has demonstrated transformative clinical value by rapidly reversing the anticoagulant effects of Factor Xa inhibitors rivaroxaban and apixaban in severe and uncontrolled bleeding."

Portola's President and CEO Scott Garland commented, "In developing and launching Andexxa, Portola has established a strong foundation for changing the standard of care for patients receiving Factor Xa inhibitors that experience a major, life-threatening bleed. Andexxa rapidly reverses the pharmacologic effect of rivaroxaban and apixaban within two minutes, reducing anti-Factor Xa activity by 92 percent...Given their enhanced resources, global footprint and proven commercial expertise, we look forward to working with Alexion to maximize the value of Andexxa. With their commitment to commercial excellence, together, we will be able to drive stronger utilization of Andexxa, increase penetration and accelerate adoption in the critical care setting."

Ludwig Hantson, Ph.D., CEO of Alexion, remarked, "The acquisition of Portola represents an important next step in our strategy to diversify beyond C5. Andexxa is a strategic fit with our existing portfolio of transformative medicines and is well-aligned with our demonstrated expertise in hematology, neurology and critical care...We believe Andexxa has the potential to become the global standard of care for patients who experience life-threatening bleeds while taking Factor Xa inhibitors apixaban and rivaroxaban. By leveraging Alexion's strong operational and sales infrastructure and deep relationships in hospital channels, we are well positioned to expand the number of patients helped by Andexxa, while also driving value for shareholders."

The firms advised that "under the terms of the merger agreement, a subsidiary of Alexion will commence a tender offer to acquire all of the outstanding shares of Portola's common stock at a price of $18 per share in cash." Alexion plans to fund the purchase with existing cash on hand and the transaction is expected to close in Q3/20. The purchase is subject to approval by a majority interest of Portola's common stockholders tendering their shares along with ordinary closing conditions and regulatory approvals. The company noted that "following successful completion of the tender offer, Alexion will acquire all remaining shares not tendered in the offer at the same price of $18 per share through a merger."

Alexion is a global biopharmaceutical company based in Boston, Mass., with offices in 50 countries worldwide. The company states that it has been "the global leader in complement biology and inhibition for more than 20 years and that it has developed and commercializes two approved complement inhibitors to treat patients with paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome, as well as the first and only approved complement inhibitor to treat anti-acetylcholine receptor antibody-positive generalized myasthenia gravis and neuromyelitis optica spectrum disorder."

Portola is headquartered in South San Francisco, Calif., and is a commercial-stage biopharmaceutical company focused on treating patients with serious blood-related disorders. Specifically, the company is engaged in developing and commercializing novel therapeutics in order to advance the fields of thrombosis and other hematologic conditions. The firm listed that its first two commercialized products are Andexxa® and Bevyxxa® (betrixaban), and that it is also advancing and developing cerdulatinib, a SYK/JAK inhibitor for use in treatment of hematologic cancers.

Portola Pharmaceuticals started off the day with a market capitalization of around $609.0 million with approximately 78.5 million shares outstanding and a short interest of about 23.0%. PTLA shares opened 130% higher today at $17.85 (+$10.09, +130.03%) over yesterday's $7.85 closing price. The stock has traded today between $17.71 and $17.91 per share and is currently trading at $17.83 (+$10.07, +129.77%).

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Disclosure:
1) Stephen Hytha compiled this article for Streetwise Reports LLC and provides services to Streetwise Reports as an independent contractor. He or members of his household own securities of the following companies mentioned in the article: None. He or members of his household are paid by the following companies mentioned in this article: None.
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6) This article does not constitute medical advice. Officers, employees and contributors to Streetwise Reports are not licensed medical professionals. Readers should always contact their healthcare professionals for medical advice.




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Animals, Insects, etc in alphabetical order (with an image if you wish)




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A~Z Animals




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New Rapyd report on disbursement reveals how consumers across Asia prefer to be paid

The 2020 State of Disbursements: APAC Outlook Report by Rapyd...




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Congratulations Mike_Walsh: our newest Moderator!




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Antibiotic Use in Food Animals Contributes to Microbe Resistance

Bacteria that resist antibiotics can be passed from food animals to humans, but not enough is known to determine the public health risks posed by such transmission, says a new report by a committee of the National Research Council.




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Marijuanas Components Have Potential as Medicine - Clinical Trials, Drug Development Should Proceed

Marijuanas active components are potentially effective in treating pain, nausea, the anorexia of AIDS wasting, and other symptoms, and should be tested rigorously in clinical trials.