Two commonly encountered bottlenecks in the structure determination of a protein by X-ray crystallography are screening for conditions that give high-quality crystals and, in the case of novel structures, finding derivatization conditions for experimental phasing. In this study, the phasing molecule 5-amino-2,4,6-triiodoisophthalic acid (I3C) was added to a random microseed matrix screen to generate high-quality crystals derivatized with I3C in a single optimization experiment. I3C, often referred to as the magic triangle, contains an aromatic ring scaffold with three bound I atoms. This approach was applied to efficiently phase the structures of hen egg-white lysozyme and the N-terminal domain of the Orf11 protein from Staphylococcus phage P68 (Orf11 NTD) using SAD phasing. The structure of Orf11 NTD suggests that it may play a role as a virion-associated lysin or endolysin.

Many biologists are now routinely seeking to determine the three-dimensional structures of their proteins of choice, illustrating the importance of this knowledge, but also of the simplification and streamlining of structure-determination processes. Despite the fact that most software packages offer simple pipelines, for the non-expert navigating the outputs and understanding the key aspects can be daunting. Here, the structure determination of the type IV pili (TFP) protein PilA1 from Clostridioides difficile is used to illustrate the different steps involved, the key decision criteria and important considerations when using the most common pipelines and software. Molecular-replacement pipelines within CCP4i2 are presented to illustrate the more commonly used processes. Previous knowledge of the biology and structure of TFP pilins, particularly the presence of a long, N-terminal α-helix required for pilus formation, allowed informed decisions to be made during the structure-determination strategy. The PilA1 structure was finally successfully determined using ARCIMBOLDO and the ab initio MR strategy used is described.

Here, structural parameters of various structure reports on RSi2 and R2TSi3 compounds [where R is an alkaline earth metal, a rare earth metal (i.e. an element of the Sc group or a lathanide), or an actinide and T is a transition metal] are summarized. The parameters comprising composition, lattice parameters a and c, ratio c/a, formula unit per unit cell and structure type are tabulated. The relationships between the underlying structure types are presented within a group–subgroup scheme (Bärnighausen diagram). Additionally, unexpectedly missing compounds within the R2TSi3 compounds were examined with density functional theory and compounds that are promising candidates for synthesis are listed. Furthermore, a correlation was detected between the orthorhombic AlB2-like lattices of, for example, Ca2AgSi3 and the divalence of R and the monovalence of T. Finally, a potential tetragonal structure with ordered Si/T sites is proposed.

This article describes a high-efficiency experimental configuration for a self-referenced lattice comparator with a `brush beam' of synchrotron radiation from a bending magnet and two linear position-sensitive photon-counting-type X-ray detectors. The efficiency is more than ten times greater compared with the `pencil-beam' configuration and a pair of zero-dimensional detectors. A solution for correcting the systematic deviation of d-spacing measurements caused by the horizontal non-uniformity of the brush beam is provided. Also, the use of photon-counting-type one-dimensional detectors not only improves the spatial resolution of the measurements remarkably but can also adjust the sample's attitude angles easily.

Bone crystallite chemistry and structure change during bone maturation. However, these properties of bone can also be affected by limited uptake of the chemical constituents of the mineral by the animal. This makes probing the effect of bone-mineralization-related diseases a complicated task. Here it is shown that the combination of vibrational spectroscopy with two-dimensional X-ray diffraction can provide unparalleled information on the changes in bone chemistry and structure associated with different bone pathologies (phosphate deficiency) and/or health conditions (pregnancy, lactation). Using a synergistic analytical approach, it was possible to trace the effect that changes in the remodelling regime have on the bone mineral chemistry and structure in normal and mineral-deficient (hypophosphatemic) mice. The results indicate that hypophosphatemic mice have increased bone remodelling, increased carbonate content and decreased crystallinity of the bone mineral, as well as increased misalignment of crystallites within the bone tissue. Pregnant and lactating mice that are normal and hypophosphatemic showed changes in the chemistry and misalignment of the apatite crystals that can be related to changes in remodelling rates associated with different calcium demand during pregnancy and lactation.

Neutron spin-echo spectrometers with a position-sensitive detector and operating with extended time-of-flight-tagged wavelength frames are able to collect a comprehensive set of data covering a large range of wavevector and Fourier time space with only a few instrumental settings in a quasi-continuous way. Extracting all the information contained in the raw data and mapping them to a suitable physical space in the most efficient way is a challenge. This article reports algorithms employed in dedicated software, DrSpine (data reduction for spin echo), that achieves this goal and yields reliable representations of the intermediate scattering function S(Q, t) independent of the selected `binning'.

Most articles dealing with R2TSi3 compounds are only interested in one specific composite or in a series of composites with varying T elements while keeping R fixed (or vice versa). The present work gives an overview of the complete range of 2:1:3 silicides, similar those of Hoffmann & Pöttgen (2001) and Pan et al. (2013). In contrast to the work of Hoffmann & Pöttgen (2001), reasons for formation of the different symmetries and superstructures are discussed. Here, crystallographic properties are in[the] focus, whereas physical and magnetic properties are omitted because those are given by Pan et al. (2013). READS LIKE AN ABSTRACT, please re-write and remove references if possible. Should be two sentences max.

New research by astrophysicist David Kipping has revealed that in some special cases, a star can be weighed directly. Such a star must have a planet orbiting it with a moon orbiting the planet.

The post Harvard-Smithsonian astrophysicist discovers new method to weigh some distant stars appeared first on Smithsonian Insider.

A new study has revealed information about the way tungara frogs in the tropical rain forest hear, sort, and process sounds which is very similar to the way humans do. The knowledge could be applicable to communication disorders associated with hearing loss and attention deficits or difficulties.

The post Research on tungara frogs may be applicable to hearing loss/attention deficits in humans appeared first on Smithsonian Insider.

Imagine a gas giant planet spanning three times more sky than the Moon looming over the molten landscape of a lava world. This alien vista exists in the newly discovered two-planet system of Kepler-36.

The post Close encounters between planetary systems of Kepler-36 stun astrophysicists appeared first on Smithsonian Insider.

A fiery explosion on the surface of the Moon, visible to the naked eye, recently surprised NASA astronomers monitoring the Moon for meteorite strikes. Occurring […]

The post A meteorite explodes on the Moon: Q&A with geophysicist Bruce Campbell appeared first on Smithsonian Insider.

The Smithsonian is delighted to be included in this year’s Aspen Ideas Festival (June 26 – July 2 in Aspen, Colo.) which will gather some of […]

The post Three Smithsonian scientists to participate in Aspen Ideas Festival appeared first on Smithsonian Insider.

Scientists at the Smithsonian Conservation Biology Institute are celebrating the birth of a female Przewalski’s (Cha-VAL-skee) horse—the first to be born via artificial insemination. The […]

The post First wild horse species born from artificial insemination at Smithsonian Conservation Biology Institute appeared first on Smithsonian Insider.

Hot spots of mercury pollution in aquatic sediments and soils can contaminate local food webs and threaten ecosystems, but cleaning them up can be expensive […]

The post Toxicity of mercury hot spots can be reduced with application of activated carbon, researchers discover appeared first on Smithsonian Insider.

Scientists at the Smithsonian Conservation Biology Institute in Front Royal, Va., are celebrating the anniversary of the first birth of a Przewalski’s horse by artificial […]

The post First Przewalski’s horse born by artificial insemination birthday appeared first on Smithsonian Insider.

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.

Juan Martin D'Ambrosio, Veronique Albanese, Nicolas-Frederic Lipp, Lucile Fleuriot, Delphine Debayle, Guillaume Drin, and Alenka Copic

Osh6 and Osh7 are lipid transfer proteins (LTPs) that move phosphatidylserine (PS) from the endoplasmic reticulum (ER) to the plasma membrane (PM). High PS level at the PM is key for many cellular functions. Intriguingly, Osh6/7 localize to ER-PM contact sites, although they lack membrane-targeting motifs, in contrast to multidomain LTPs that both bridge membranes and convey lipids. We show that Osh6 localization to contact sites depends on its interaction with the cytosolic tail of the ER-PM tether Ist2, a homologue of TMEM16 proteins. We identify a motif in the Ist2 tail, conserved in yeasts, as the Osh6-binding region, and we map an Ist2-binding surface on Osh6. Mutations in the Ist2 tail phenocopy osh6 osh7 deletion: they decrease cellular PS levels, and block PS transport to the PM. Our study unveils an unexpected partnership between a TMEM16-like protein and a soluble LTP, which together mediate lipid transport at contact sites.

Samantha-Su Z. Taylor, Nicole L. Jacobsen, Tasha K. Pontifex, Paul Langlais, and Janis M. Burt

Connexin 37 (Cx37) expression profoundly suppresses proliferation of rat insulinoma (Rin) cells in a manner dependent on gap junction channel (GJCh) functionality and the presence and phosphorylation status of its carboxyl-terminus (CT). In Rin cells growth arrested by induced Cx37 expression, serine 319 (S319) is frequently phosphorylated. Preventing phosphorylation at this site (alanine substitution; S319A) relieved Cx37 of its growth suppressive effect whereas mimicking phosphorylation at this site (aspartate substitution; S319D) enhanced Cx37's growth suppressive properties. Like Cx37-WT, -S319D GJChs and hemichannels (HChs) preferred the closed state, rarely opening fully, and gated slowly. In contrast, Cx37-S319A channels preferred open states, opened fully, and gated rapidly. These data indicate that phosphorylation-dependent conformational differences in Cx37 protein and channel function underlie Cx37-induced growth arrest vs. growth permissive phenotypes. That the closed state of -WT and Cx37-S319D GJChs and HChs favors growth arrest suggests that rather than specific permeants mediating cell cycle arrest, the closed conformation instead supports interaction of Cx37 with growth regulatory proteins that result in growth arrest.

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.

Crystal structure identification of thin organic films entails a number of technical and methodological challenges. In particular, if molecular crystals are epitaxially grown on single-crystalline substrates a complex scenario of multiple preferred orientations of the adsorbate, several symmetry-related in-plane alignments and the occurrence of unknown polymorphs is frequently observed. In theory, the parameters of the reduced unit cell and its orientation can simply be obtained from the matrix of three linearly independent reciprocal-space vectors. However, if the sample exhibits unit cells in various orientations and/or with different lattice parameters, it is necessary to assign all experimentally obtained reflections to their associated individual origin. In the present work, an effective algorithm is described to accomplish this task in order to determine the unit-cell parameters of complex systems comprising different orientations and polymorphs. This method is applied to a polycrystalline thin film of the conjugated organic material 6,13-pentacene­quinone (PQ) epitaxially grown on an Ag(111) surface. All reciprocal vectors can be allocated to unit cells of the same lattice constants but grown in various orientations [sixfold rotational symmetry for the contact planes (102) and (102)]. The as-determined unit cell is identical to that reported in a previous study determined for a fibre-textured PQ film. Preliminary results further indicate that the algorithm is especially effective in analysing epitaxially grown crystallites not only for various orientations, but also if different polymorphs are present in the film.

Bruce Campbell, of the Center for Earth and Planetary Studies at the Smithsonian's National Air and Space Museum, is at the National Radio Astronomy Observatory in Green Bank, W. Va., to make a radar map of the Moon.

The post Smithsonian geophysicist Bruce Campbell explains his work of making a detailed radar map of the Moon appeared first on Smithsonian Insider.

Keepers at the Smithsonian's National Zoo perform an artificial insemination procedure on a pair of Stanley Cranes. A Stanley Crane chick was successfully hatched on May 23, 2011.

The post Bird keepers at the National Zoo demonstrate the art of artificially inseminating Stanley cranes appeared first on Smithsonian Insider.

The post National Zoo gorillas participate in heart disease study appeared first on Smithsonian Insider.

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.

The discovery of starch granules in the calculus on Neandertal teeth provides direct evidence that they made sophisticated, thoughtful food choices and ate more nutrient-rich plants, for example date palms, legumes and grains such as barley.

The post Starch grains found on Neandertal teeth debunks theory that dietary deficiencies caused their extinction appeared first on Smithsonian Insider.

“When you can’t breathe, nothing else matters,” once a tagline of the American Lung Association, today it might easily describe what is happening in many […]

The post Gasping for air: nutrients, warming trigger ocean oxygen deficit appeared first on Smithsonian Insider.

Crystals of the rare earth metal polytelluride LaTe1.82(1), namely, lanthanum telluride (1/1.8), have been grown by molten alkali halide flux reactions and vapour-assisted crystallization with iodine. The two-dimensionally incommensurately modulated crystal structure has been investigated by X-ray diffraction experiments. In contrast to the tetra­gonal average structure with unit-cell dimensions of a = 4.4996 (5) and c = 9.179 (1) Å at 296 (1) K, which was solved and refined in the space group P4/nmm (No. 129), the satellite reflections are not compatible with a tetra­gonal symmetry but enforce a symmetry reduction. Possible space groups have been derived by group–subgroup relationships and by consideration of previous reports on similar rare earth metal polychalcogenide structures. Two structural models in the ortho­rhom­bic superspace group, i.e. Pmmn(α,β,1 over 2)000(−α,β,1 over 2)000 (No. 59.2.51.39) and Pm21n(α,β,1 over 2)000(−α,β,1 over 2)000 (No. 31.2.51.35), with modulation wave vectors q1 = αa* + βb* + 1 over 2c* and q2 = −αa* + βb* + 1 over 2c* [α = 0.272 (1) and β = 0.314 (1)], have been established and evaluated against each other. The modulation describes the distribution of defects in the planar [Te] layer, coupled to a displacive modulation due to the formation of different Te anions. The bonding situation in the planar [Te] layer and the different Te anion species have been investigated by density functional theory (DFT) methods and an electron localizability indicator (ELI-D)-based bonding analysis on three different approximants. The temperature-dependent electrical resistance revealed a semiconducting behaviour with an estimated band gap of 0.17 eV.

A method is described for indexing grazing-incidence X-ray diffraction data of epitaxially grown thin films comprising various crystal orientations and/or polymorphs by measuring reciprocal-lattice vectors.

Elisa Reimer
Apr 23, 2020; 134:jcs246421-jcs246421
Articles

Evidence exists linking three cancers and two other health problems with chemicals used in herbicides in the Vietnam War, a committee of the Institute of Medicine (IOM) has concluded.

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.

Good morning and welcome. There has been unprecedented interest in recent years about whether marijuana or its constituent compounds should be used as medicine. Since 1996, voters in seven states have approved the medical use of marijuana.

No justification currently exists for completely abandoning chemical pesticides, says a new report from the National Academies National Research Council.

A new data network that integrates emerging research on the molecular makeup of diseases with clinical data on individual patients could drive the development of a more accurate classification of disease and ultimately enhance diagnosis and treatment, says a new report from the National Research Council.

Research to date on the effect of capital punishment on homicide rates is not useful in determining whether the death penalty increases, decreases, or has no effect on these rates, says a new report from the National Research Council.

The Institute of Medicine today presented the 2012 Gustav O. Lienhard Award to Donald M. Berwick, a physician whose work has catalyzed a national movement to improve health care quality and safety.

A new report from the National Research Council has upheld the listing of styrene as “reasonably anticipated to be a human carcinogen” in the National Toxicology Program’s 12th Report on Carcinogens (RoC).

The Institute of Medicine today presented the Gustav O. Lienhard Award to Linda Aiken, Claire M. Fagin Leadership Professor of Nursing at the University of Pennsylvania School of Nursing, for her rigorous research demonstrating the importance of nursing care and work environments in achieving safe, effective, patient-centered, and affordable health care.

The National Academy of Sciences and the National Academy of Medicine are launching a major initiative to guide decision making about controversial new research involving human gene editing.

In the United States, most long-distance trips begin in one metropolitan region and end in another less than 500 miles away.

The best indicator of whether a disabled adult who receives Social Security benefits is capable of managing his or her benefits is evidence of real-world performance of meeting his or her own basic needs, rather than an office-based assessment of financial competence, says a new report from the National Academies of Sciences, Engineering, and Medicine.

Bullying is a serious public health problem, with significant short- and long-term psychological consequences for both the targets and perpetrators of such behavior, and requires a commitment to developing preventive and interventional policies and practices that could make a tangible difference in the lives of many children, says a new report from the National Academies of Sciences, Engineering, and Medicine.

To make the world safer against future infectious disease threats, national health systems should be strengthened, the World Health Organization’s emergency and outbreak response activities should be consolidated and bolstered, and research and development should be enhanced, says a new Policy Forum article that appears in the May 19 edition of PLOS Medicine.

A new report from the National Academies of Sciences, Engineering, and Medicine that examines the regulations governing federally funded research recommends that Congress authorize and the president appoint an independent national commission to examine and update the ethical, legal, and institutional frameworks governing research involving human subjects.

In response to alarming evidence of high rates of depression and suicide among U.S. health care workers, the National Academy of Medicine is launching a wide-ranging “action collaborative” of multiple organizations to promote clinician well-being and resilience.

The National Academies Committee on Genetically Engineered Crops - Past Experiences and Future Prospects authored an almost 600-page landmark report, released in May 2016. It was perhaps the most comprehensive analysis of genetically engineered crops to date.

As the nation discusses repealing and replacing the Affordable Care Act, the National Academy of Medicine today released a publication on crosscutting priorities that provides a succinct blueprint to address challenges to Americans’ health and health care that span beyond debates over insurance coverage.

Assistive products and technologies – such as wheelchairs, upper-limb prostheses, and hearing and speech devices – hold promise for partially or fully mitigating the effects of impairments and enabling people with disabilities to work, but in some cases environmental and personal factors create additional barriers to employment, says a new report from the National Academies of Sciences, Engineering, and Medicine.

Cognitive training, blood pressure management for people with hypertension, and increased physical activity all show modest but inconclusive evidence that they can help prevent cognitive decline and dementia, but there is insufficient evidence to support a public health campaign encouraging their adoption, says a new report from the National Academies of Sciences, Engineering, and Medicine.