September 17, 2015

"Don't you love the way companies find you and spam you daily the moment you make a sideways glance towards one of their products?" Indrani Stangl asks us. It's a good question. It's all too easy to get sucked into a newsletter situation. Some of them are good, many of them are all kinds of blight. Here, Stangl goes deeper into the unsubcribe dilemma.

My inbox, like everyone else's, is brimming with newsletters, offers, coupons, and other nonsense. Why I would take the time to read a newsletter by a staffer at 'Nothing Bundt Cakes' (don't get me started on ridiculous company names) or the place I purchased dog poop bags from, is beyond me. Generally speaking I filter these directly into my trash file, but every once in a while, enough is enough. I take the time to click the 'unsubscribe' link that is in .00001 type at the very bottom of their message.

Then starts the drill....read more
By Josh Tyson | UX Magazine

             

Full Article

FDI by firms moving from China to India will help offset damage: Kotak’s Shah

Mother's Day 2020: Sara Ali Khan shares a beautiful throwback picture and thanks her 'Maa ki Maa' for creating her mommy

Working on my mental fitness, says Dominic Thiem

Experts to help TN govt get economy back on track

Lyft, Uber and Airbnb depend on travel, vacations and gatherings. That's a problem when much of the world is staying home

The committee shall submit its final reports to the government within three months time and also submit an interim report

Sara Ali Khan shared a beautiful picture of Amrita Singh and Rukhsana Sultana holding her newborn self

Priya Pradeep, a Bengaluru-based freelance business writer, shares the lessons she learnt from her mother.

Solution structure of β-amylase 2 from Arabidopsis thaliana shows the role of the conserved N-terminus in enzyme tetramer formation.

Structures of the immunodominant protein P46 from M. hyopneumoniae has been determined by X-ray crystallography and it is shown that P46 can bind a diversity of oligosaccharides, particularly xylose, which exhibits a very high affinity for this protein. Structures of a monoclonal antibody, both alone and in complex with P46, that was raised against M. hyopnemoniae cells and specifically recognizes P46 are also reported.

The title compound, C4H9N5O2+·SO42−·H2O, is the monohydrate of the commercially available compound `C4H7N5O·H2SO4·xH2O'. It is obtained by reprecipitation of C4H7N5O·H2SO4·xH2O from dilute sodium hydroxide solution with dilute sulfuric acid. The crystal structure of anhydrous 2,4,5-tri­amino-1,6-di­hydro­pyrimidin-6-one sulfate is known, although called by the authors 5-amminium-6-amino-isocytosinium sulfate [Bieri et al. (1993). Private communication (refcode HACDEU). CCDC, Cambridge, England]. In the structure, the sulfate group is deprotonated, whereas one of the amino groups is protonated (R2C—NH3+) and one is rearranged to a protonated imine group (R2C=NH2+). This arrangement is very similar to the known crystal structure of the anhydrate. Several tautomeric forms of the investigated mol­ecule are possible, which leads to questionable proton attributions. The measured data allowed the location of all hydrogen atoms from the residual electron density. In the crystal, ions and water mol­ecules are linked into a three-dimensional network by N—H⋯O and O—H⋯O hydrogen bonds.

The title compound, C10H13Cl2NO2·C6H4Cl2O, was formed from the incomplete Mannich condensation reaction of 3-amino­propan-1-ol, formaldehyde and 2,4-di­chloro­phenol in methanol. This resulted in the formation of a co-crystal of the zwitterionic Mannich base, 2,4-di­chloro-6-{[(3-hy­droxy­prop­yl)azaniumyl]­meth­yl}phenolate and the unreacted 2,4-di­chloro­phenol. The compound crystallizes in the monoclinic crystal system (in space group Cc) and the asymmetric unit contains a mol­ecule each of the 2,4-di­chloro­phenol and 2,4-di­chloro-6-{[(3-hy­droxy­prop­yl)azaniumyl]­meth­yl}phenolate. Examination of the crystal structure shows that the two components are clearly linked together by hydrogen bonds. The packing patterns are most inter­esting along the b and the c axes, where the co-crystal in the unit cell packs in a manner that shows alternating aromatic di­chloro­phenol fragments and polar hydrogen-bonded channels. The 2,4-di­chloro­phenol rings stack on top of one another, and these are held together by π–π inter­actions. The crystal studied was refined as an inversion twin.

The title mol­ecular salt, C9H12N3O2S+·HSO4−, was obtained through the protonation of the azomethine N atom in a sulfuric acid medium. The crystal com­prises two entities, a thio­semicarbazide cation and a hydrogen sulfate anion. The cation is essentially planar and is further stabilized by a strong intra­molecular O—H⋯N hydrogen bond. In the crystal, a three-dimensional network is established through O—H⋯O and N—H⋯O hydrogen bonds. A weak intermolecular C—H⋯O hydrogen bond is also observed. The hydrogen sulfate anion exhibits disorder over two sets of sites and was modelled with refined occupancies of 0.501 (6) and 0.499 (6).

The title compound, C24H18FNO3, crystallizes in the monoclinic centrosymmetric space group P21/n and its mol­ecular conformation is stabilized via C—H⋯O intra­molecular inter­actions. The supra­molecular network mainly comprises C—H⋯O, C—H⋯F and C—H⋯π inter­actions, which contribute towards the formation of the crystal structure. The different inter­molecular inter­actions have been further analysed via Hirshfeld surface analysis and fingerprint plots.

The fully automatic processing of crystals of macromolecules has presented a unique opportunity to gather information on the samples that is not usually recorded. This has proved invaluable in improving sample-location, characterization and data-collection algorithms. After operating for four years, MASSIF-1 has now processed over 56 000 samples, gathering information at each stage, from the volume of the crystal to the unit-cell dimensions, the space group, the quality of the data collected and the reasoning behind the decisions made in data collection. This provides an unprecedented opportunity to analyse these data together, providing a detailed landscape of macromolecular crystals, intimate details of their contents and, importantly, how the two are related. The data show that mosaic spread is unrelated to the size or shape of crystals and demonstrate experimentally that diffraction intensities scale in proportion to crystal volume and molecular weight. It is also shown that crystal volume scales inversely with molecular weight. The results set the scene for the development of X-ray crystallography in a changing environment for structural biology.

Indanomycin is biosynthesized by a hybrid nonribosomal peptide synthase/polyketide synthase (NRPS/PKS) followed by a number of `tailoring' steps to form the two ring systems that are present in the mature product. It had previously been hypothesized that the indane ring of indanomycin was formed by the action of IdmH using a Diels–Alder reaction. Here, the crystal structure of a selenomethionine-labelled truncated form of IdmH (IdmH-Δ99–107) was solved using single-wavelength anomalous dispersion (SAD) phasing. This truncated variant allows consistent and easy crystallization, but importantly the structure was used as a search model in molecular replacement, allowing the full-length IdmH structure to be determined to 2.7 Å resolution. IdmH is a homodimer, with the individual protomers consisting of an α+β barrel. Each protomer contains a deep hydrophobic pocket which is proposed to constitute the active site of the enzyme. To investigate the reaction catalysed by IdmH, 88% of the backbone NMR resonances were assigned, and using chemical shift perturbation of [15N]-labelled IdmH it was demonstrated that indanomycin binds in the active-site pocket. Finally, combined quantum mechanical/molecular mechanical (QM/MM) modelling of the IdmH reaction shows that the active site of the enzyme provides an appropriate environment to promote indane-ring formation, supporting the assignment of IdmH as the key Diels–Alderase catalysing the final step in the biosynthesis of indanomycin through a similar mechanism to other recently characterized Diels–Alderases involved in polyketide-tailoring reactions. An animated Interactive 3D Complement (I3DC) is available in Proteopedia at https://proteopedia.org/w/Journal:IUCrJ:S2052252519012399.

Olfactomedins are a family of modular proteins found in multicellular organisms that all contain five-bladed β-propeller olfactomedin (OLF) domains. In support of differential functions for the OLF propeller, the available crystal structures reveal that only some OLF domains harbor an internal calcium-binding site with ligands derived from a triad of residues. For the myocilin OLF domain (myoc-OLF), ablation of the ion-binding site (triad Asp, Asn, Asp) by altering the coordinating residues affects the stability and overall structure, in one case leading to misfolding and glaucoma. Bioinformatics analysis reveals a variety of triads with possible ion-binding characteristics lurking in OLF domains in invertebrate chordates such as Arthropoda (Asp–Glu–Ser), Nematoda (Asp–Asp–His) and Echinodermata (Asp–Glu–Lys). To test ion binding and to extend the observed connection between ion binding and distal structural rearrangements, consensus triads from these phyla were installed in the myoc-OLF. All three protein variants exhibit wild-type-like or better stability, but their calcium-binding properties differ, concomitant with new structural deviations from wild-type myoc-OLF. Taken together, the results indicate that calcium binding is not intrinsically destabilizing to myoc-OLF or required to observe a well ordered side helix, and that ion binding is a differential feature that may underlie the largely elusive biological function of OLF propellers.

Helical reconstruction in RELION is increasingly being used to determine the atomic structures of amyloid filaments from electron cryo-microscopy (cryo-EM) images. However, because the energy landscape of amyloid refinements is typically fraught with local optima, amyloid structure determination is often difficult. This paper aims to help RELION users in this process. It discusses aspects of helical reconstruction that are particularly relevant to amyloids, it illustrates the problem of local optima in refinement and how to detect them, and it introduces a new method to calculate 3D initial models from reference-free 2D class averages. By providing starting models that are closer to the global optimum, this method makes amyloid structure determination easier. All methods described are open-source and distributed within RELION-3.1. Their use is illustrated using a publicly available data set on tau filaments from the brain of an individual with Alzheimer's disease.

Book review

Endoplasmic reticulum (ER)-associated degradation (ERAD) is a protein quality-control pathway in eukaryotes in which misfolded ER proteins are polyubiquitylated, extracted and ultimately degraded by the proteasome. This process involves ER membrane-embedded ubiquitin E2 and E3 enzymes, as well as a soluble E2 enzyme (Ubc7 in Saccharomyces cerevisiae and UBE2G2 in mammals). E2-binding regions (E2BRs) that recruit these soluble ERAD E2s to the ER have been identified in humans and S. cerevisiae, and structures of E2–E2BR complexes from both species have been determined. In addition to sequence and structural differences between the human and S. cerevisiae E2BRs, the binding of E2BRs also elicits different biochemical outcomes with respect to E2 charging by E1 and E2 discharge. Here, the Schizosaccharomyces pombe E2BR was identified and purified with Ubc7 to resolve a 1.7 Å resolution co-crystal structure of the E2BR in complex with Ubc7. The S. pombe E2BR binds to the back side of the E2 as an α-helix and, while differences exist, it exhibits greater similarity to the human E2BR. Structure-based sequence alignments reveal differences and conserved elements among these species. Structural comparisons and biochemistry reveal that the S. pombe E2BR presents a steric impediment to E1 binding and inhibits E1-mediated charging, respectively.

The true identity of the protein found in the crystals reported by Bondoc et al. [(2019), Acta Cryst. F75, 646–651] is given.

Mycobacterium tuberculosis produces glycogen (also known as α-glucan) to help evade human immunity. This pathogen uses the GlgE pathway to generate glycogen rather than the more well known glycogen synthase GlgA pathway, which is absent in this bacterium. Thus, the building block for this glucose polymer is α-maltose-1-phosphate rather than an NDP-glucose donor. One of the routes to α-maltose-1-phosphate is now known to involve the GlgA homologue GlgM, which uses ADP-glucose as a donor and α-glucose-1-phosphate as an acceptor. To help compare GlgA (a GT5 family member) with GlgM enzymes (GT4 family members), the X-ray crystal structure of GlgM from Mycobacterium smegmatis was solved to 1.9 Å resolution. While the enzymes shared a GT-B fold and several residues responsible for binding the donor substrate, they differed in some secondary-structural details, particularly in the N-terminal domain, which would be expected to be largely responsible for their different acceptor-substrate specificities.

In southeastern Greenland, two rivers of ice named Helheim and Kangerdlugssuaq flow in spurts and starts toward the coast. They are much like any other […]

The post Astrophysical Observatory scientists are monitoring the mysterious movements of glaciers appeared first on Smithsonian Insider.

Smithsonian astronomers have just discovered a rare example of a galaxy that appears to have a pair of giant black holes. Now they are trying to determine if those black holes are partners tied together by gravity, or if one of the two has been kicked out in a cosmic breakup.

The post Double Black-Hole Mystery: Dance Partners or Breakup Survivors? appeared first on Smithsonian Insider.

Eric Silver of SAO is pursuing innovative and interdisciplinary uses of his technique for chemical imaging at the cellular level.

The post Technology developed for X-ray astronomy is being adapted to study cancer cells appeared first on Smithsonian Insider.

The extrasolar planet GJ 1214b has a radius of about 2.7 times that of the Earth and is about 6.5 times as massive putting it squarely into the class of exoplanets known as super-Earths.

The post Super-earth has an atmosphere, but is it steamy or gassy? appeared first on Smithsonian Insider.

On April 4 the Smithsonian and the Massachusetts Institute of Technology will launch VANISHED, an 8-week online/offline environmental disaster mystery game for middle-school children, meant […]

The post Smithsonian and MIT to launch online mystery game for middle-shool children appeared first on Smithsonian Insider.

The Sun has been in the news a lot lately because it's beginning to send out more flares and solar storms. Its recent turmoil is particularly newsworthy because the Sun was very quiet for an unusually long time. New computer simulations imply that the Sun's long quiet spell resulted from changing flows of hot plasma within it.

The post Mystery of the quiet Sun solved appeared first on Smithsonian Insider.

Evidence for a diversified sea-based economy among North American inhabitants dating from 12,200 to 11,400 years ago is emerging from three sites on California's Channel Islands.

The post New archaeological evidence reveals California’s Channel Islands as North America’s earliest seafaring economy appeared first on Smithsonian Insider.

A new bacterial genome sequence could help researchers solve a mystery as to how microorganisms produce a highly toxic form of mercury.

The post New bacteria genome may help solve mystery of how methylmercury is made appeared first on Smithsonian Insider.

In an event that has astronomers mystified; the famous Crab Nebula supernova remnant has erupted in an enormous flare five times more powerful than any flare previously seen from the object.

The post Recent eruptions in the Crab Nebula mystify astronomers appeared first on Smithsonian Insider.

Using 2-dimensional and 3-dimensional CT scans, Natural History Museum anthropologists found that the brain and major organs were removed and rolls of linen filled out the abdominal cavity. This mummification method is evidence of superior embalming, indicating a person of higher status.

The post Video: A mummy ‘grows’ with CT scans and 3D digital technology appeared first on Smithsonian Insider.

The Life and Morals of Jesus of Nazareth, more commonly known as the Jefferson bible, is a volume created by Thomas Jefferson containing passages he […]

The post Unlocking the mysteries of Jefferson’s bible with high-tech analysis and microscopic testing appeared first on Smithsonian Insider.

Thunder, lightning and strong winds greeted the National Zoo’s two female red panda cubs when they were born June 17, and that stormy night has […]

The post National Zoo’s red pandas named “Pili” and “Damini” for stormy night appeared first on Smithsonian Insider.

The nature of dark matter is a mystery -- a mystery that a new study has only deepened.

The post Dark matter mystery deepens appeared first on Smithsonian Insider.

Viewed from inside the SOMATOM Emotion 6CT scanner used at the Smithsonian’s National Museum of Natural History, the skeleton and internal organs of this well-preserved […]

The post Peruvian mummy as seen by a SOMATOM Emotion 6CT scanner appeared first on Smithsonian Insider.

Observations by the NASA/ESA Hubble Space Telescope have come up with a new class of planet, a waterworld enshrouded by a thick, steamy atmosphere. It’s smaller than Uranus but larger than Earth.

The post Waterworld enshrouded by a thick, steamy atmosphere is new class of planet appeared first on Smithsonian Insider.

A newly described species of toothed whale that lived some 3-4 million years ago during the Pliocene, is causing scientists to reconsider what is known about its living cold-water relatives: narwhals and belugas.

The post New fossil whale species raises mystery regarding why narwhals and belugas live only in cold water appeared first on Smithsonian Insider.

Incredibly, the narwhale’s only visible tooth is outside of its mouth. Its tusk, in fact, is a giant canine tooth—that can grow as long as 9 feet!

The post For a dentist, the narwhal’s smile is a mystery of evolution appeared first on Smithsonian Insider.

The only explanation for such symmetry across these vast distances, explains Smithsonian anthropologist Dennis Stanford, is that the method of creating the points was handed down from person to person.

The post 3-D imaging adds remarkable new understanding of North America’s mysterious Clovis people appeared first on Smithsonian Insider.