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At least 631 records · Page 35

Bacterial biofilm formation on the hyphae of ectomycorrhizal fungi: a widespread ability under controls?

Here, ectomycorrhizal (ECM) fungi establish symbiosis with roots of most trees of boreal and temperate ecosystems and are major drivers of nutrient fluxes between trees and the soil. ECM fungi constantly interact with bacteria all along their life cycle and the extended networks of hyphae provide a habitat for complex bacterial communities. Despite the important effects these bacteria can have on the growth and activities of ECM fungi, little is known about the mechanisms by which these microorganisms interact. Here we investigated the ability of bacteria to form biofilm on the hyphae of the ECM fungus Laccaria bicolor . We showed that the ability to form biofilms on the hyphae of the ECM fungus is widely shared among soil bacteria. Conversely, some fungi, belonging to the Ascomycete class, did not allow for the formation of bacterial biofilms on their surfaces. The formation of biofilms was also modulated by the presence of tree roots and ectomycorrhizae, suggesting that biofilm formation does not occur randomly in soil but that it is regulated by several biotic factors. In addition, our study demonstrated that the formation of bacterial biofilm on fungal hyphae relies on the production of networks of filaments made of extracellular DNA.

59 BASIC BIOLOGICAL SCIENCES↗

Molecular dynamics analysis of the binding of human interleukin-6 with interleukin-6 α-receptor

Human interleukin-6 (hIL-6) is a multifunctional cytokine that regulates immune and inflammatory responses in addition to metabolic and regenerative processes and cancer. hIL-6 binding to the IL-6 receptor (IL-6Rα) induces homodimerization and recruitment of the glycoprotein (gp130) to form a hexameric signaling complex. Anti-IL-6 and IL-6R antibodies are clinically approved inhibitors of IL-6 signaling pathway for treating rheumatoid arthritis and Castleman's disease, respectively. There is a potential to develop novel small molecule IL-6 antagonists derived from understanding the structural basis for IL-6/IL-6Rα interactions. In this work, we combine homology modeling with extensive molecular dynamics (MD) simulations to examine the association of hIL-6 with IL-6Rα. A comparison with MD of apo hIL-6 reveals that the binding of hIL-6 to IL-6Rα induces structural and dynamic rearrangements in the AB loop region of hIL-6, disrupting intraprotein contacts and increasing the flexibility of residues 48 to 58 of the AB loop. In contrast, due to the involvement of residues 59 to 78 in forming contacts with the receptor, these residues of the AB loop are observed to rigidify in the presence of the receptor. The binary complex is primarily stabilized by two pairs of salt bridges, Arg181 (hIL-6)- Glu182 (IL-6Rα) and Arg184 (hIL-6)- Glu183 (IL-6Rα) as well as hydrophobic and aromatic stacking interactions mediated essentially by Phe residues in both proteins. An interplay of electrostatic, hydrophobic, hydrogen bonding, and aromatic stacking interactions facilitates the formation of the hIL-6/IL-6Rα complex.

59 BASIC BIOLOGICAL SCIENCES↗

Multivalent Interactions by the Set8 Histone Methyltransferase With Its Nucleosome Substrate

Set8 is the only mammalian monomethyltransferase responsible for H4K20me1, a methyl mark critical for genomic integrity of eukaryotic cells. We present here a structural model for how Set8 uses multivalent interactions to bind and methylate the nucleosome based on crystallographic and solution studies of the Set8/nucleosome complex. Here, our studies indicate that Set8 employs its i-SET and c-SET domains to engage nucleosomal DNA 1 to 1.5 turns from the nucleosomal dyad and in doing so, it positions the SET domain for catalysis with H4 Lys20. Surprisingly, we find that a basic N-terminal extension to the SET domain plays an even more prominent role in nucleosome binding, possibly by making an arginine anchor interaction with the nucleosome H2A/H2B acidic patch. We further show that proliferating cell nuclear antigen and the nucleosome compete for binding to Set8 through this basic extension, suggesting a mechanism for how nucleosome binding protects Set8 from proliferating cell nuclear antigen-dependent degradation during the cell cycle.

59 BASIC BIOLOGICAL SCIENCES↗

Anhydrous vs Hydrated f-Element Acetate Polymers Dictated by the Stoichiometry of Protic Acidic/Basic Azole Mixtures

Continuing our investigations of ionic liquid (IL) based routes to a library of f-element/soft donor complexes which could be studied crystallographically, we have explored the dissolution of f-element salts in protic imidazole-based ILs containing only soft donors at high temperatures to drive off volatiles, including water and carboxylic or mineral acids. Here we present our results, reacting acidic and basic azoles in 1:3 or 1:1 stoichiometric compositions at elevated temperature, followed by saturation with Nd(OAc) 3 ·xH 2 O or Ce(OAc) 3 ·xH 2 O, which led to 13 new metal–acetate polymeric complexes identified by single-crystal X-ray diffraction. We found that the diversity in coordination modes of the simple acetate ligand that interfere with substitution of the softer N donors led to several readily crystallizable complexes forming two distinct groups with respect to f-element interaction with the ionic liquid precursors. When the acidic/basic azole ratio was 1:3, acetate and a neutral basic azole were found to be coordinated to the metal centers but no water, although in one case (2) water was observed in the secondary coordination sphere: [Ce(μ 2 -OAc) 3 (C 1 im)] n (1, C 1 im = 1-methylimidazole), [Nd(μ 2 -(OAc) 3 (C 1 im)] n ·nH 2 O (2), [Ce(μ 2 -OAc) 3 (C 2 im)] n (3, C 2 im = 1-ethylimidazole), [Ln(μ 2 -OAc) 3 DMF] n (Ln = Nd (4), Ce (5); dimethylformamide (DMF) was substituted for the azole mixture), and [Nd(μ 2 -OAc) 3 (C 4 im)] n (6, C 4 im = 1-butylimidazole). However, when the stoichiometric ratio was 1:1, water was always observed coordinated to the metal ions with the acidic azole included in the structure as a solvate or cocrystal, despite a higher reaction temperature: [Nd(μ 2 -OAc) 3 (OH 2 )] n ·n(1,2,3-Taz) (7, 1,2,3-Taz = 1,2,3-triazole), [Ln(μ 2 -OAc) 3 (OH 2 )] n ·n(4,5-DCim) (Ln = Nd (8), Ce (9), 4,5-DCim = 4,5-dicyanoimidazole), [Ln(μ 2 -OAc) 3 (OH 2 )] n ·n(3,5-diNH 2 -1,2,4-Taz) (Ln = Nd (10), Ce (11), 3,5-diNH 2 -1,2,4-Taz = 3,5-diamino-1,2,4-triazole), [Ce(μ 2 -OAc) 3 (OH 2 )] n ·n(3-NH 2 -1,2,4-Taz) (12, 3-NH 2 -1,2,4-Taz = 3-amino-1,2,4-triazole), and [Nd(μ 2 -OAc) 3 (OH 2 )] n ·n(5-NH 2 -Tz) (13, 5-NH2-Tz = 5-aminotetrazole). All of the compounds retain the Ln:OAc– ratio of 1:3 and form 1D polymeric chains; however, they exhibit a variety of coordination modes affecting the degree of chain condensation. The isolation of both hydrated and anhydrous products revealed different abilities of the investigated soft N-donors to compete with O-donors finding their place in the coordination sphere of the lanthanide or in the crystal lattice.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

MODELING HOST-PATHOGEN INTERACTIONS: COMPUTATIONAL BIOLOGY AND BIOINFORMATICS FOR INFECTIOUS DISEASE RESEARCH (Session introduction)

Pathogenic infections are a major cause of both human disease and loss of crop yields and animal stocks and thus cause immense damage to the worldwide economy. The significance of infectious diseases is expected to increase in an ever more connected warming world, in which new viral, bacterial and fungal pathogens can find novel hosts and ecologic niches. At the same time, the complex and sophisticated mechanisms by which diverse pathogenic agents evade defense mechanisms and subvert their hosts networks to suit their lifestyle needs is still very incompletely understood especially from a systems perspective [1]. Thus, understanding host-pathogen interactions is both an important and a scientifically fascinating topic. Recently, technology has offered the opportunity to investigate host-pathogen interactions on a level of detail and scope that offers immense computational and analytical possibilities. Genome sequencing was pioneered on some of these pathogens, and the number of strains and variants of pathogens sequenced to date vastly outnumbers the number of host genomes available. At the same time, for both plant and human hosts more and more data on population level genomic variation becomes available and offers a rich field for analysis into the genetic interactions between host and pathogen.

59 BASIC BIOLOGICAL SCIENCES↗

Supersaturated calcium carbonate solutions are classical

We will present a description of nucleation phenomena in the condensed phase that takes into account non-ideal solution effects associated with cluster-cluster interaction. To do this we employ aggregation-volume bias Monte Carlo simulation, making the estimation of free-energy of large pre-critical clusters of sizes 10-20 tractable. We will compare and contrast empirical potential and electronic structure (e.g. Density functional theory) based descriptions of molecular interaction associated with the nucleation of CaCO 3 , highlighting free-energy trends and qualitative differences in populations of pre-critical clusters as a function of supersaturation. The influence of how the precise local interaction influences the non-ideal solution behavior on the nucleation and growth processes will be highlighted. This research was supported by the US Department of Energy, Office of Science, Office of Basic Energy Sciences, Division of Chemical Sciences, Geosciences, and Biosciences.

Henzler, Katja (ORCID:0000000335905005)↗

Crystal structure of importin-α3 bound to the nuclear localization signal of Ran-binding protein 3

Ran-binding protein 3 (RanBP3) is a primarily nuclear Ran-binding protein that functions as an accessory factor in the Ran GTPase system. RanBP3 associates with Ran-specific nucleotide exchange factor RCC1 and enhances its catalytic activity towards Ran. RanBP3 also promotes CRM1-mediated nuclear export as well as CRM1-independent nuclear export of β-catenin, Smad2, and Smad3. Nuclear import of RanBP3 is dependent on the nuclear import adaptor protein importin-α and, RanBP3 is imported more efficiently by importin-α3 than by other members of the importin-α family. Protein kinase signaling pathways control nucleocytoplasmic transport through phosphorylation of RanBP3 at Ser58, immediately C-terminal to the nuclear localization signal (NLS) in the N-terminal region of RanBP3. Here we report the crystal structure of human importin-α3 bound to an N-terminal fragment of human RanBP3 containing the NLS sequence that is necessary and sufficient for nuclear import. The structure reveals that RanBP3 binds to importin-α3 residues that are strictly conserved in all seven isoforms of human importin-α at the major NLS-binding site, indicating that the region of importin-α outside the NLS-binding site, possibly the autoinhibotory importin-β1-binding domain, may be the key determinant for the preferential binding of RanBP3 to importin-α3. Computational docking simulation indicates that phosphorylation of RanBP3 at Ser58 could potentially stabilize the association of RanBP3 with importin-α through interactions between the phosphate moiety of phospho-Ser58 of RanBP3 and a cluster of basic residues (Arg96 and Lys97 in importin-α3) on armadillo repeat 1 of importin-α. - Highlights: • Ran-binding protein 3 (RanBP3) is an accessory factor in the Ran GTPase system. • The N-terminal region of RanBP3 contains a nuclear localization signal (NLS). • Crystal structure of importin-α3 bound to the NLS of RanBP3 is solved. • Phosphorylation of RanBP3 at Ser58 may modulate binding affinity to importin-α.

60 APPLIED LIFE SCIENCES↗

Nanoparticles caged with DNA nanostructures

Nanoparticles (NPs) offer many benefits in biotechnology because of their small size and unique properties. Furthermore, many applications require precise positioning of the NPs or biological targeting molecules on their surfaces. DNA cages constructed from DNA tile, origami, or wireframe nanostructures offer a promising path forward because of their simplicity and programmability that can be used to generate complex, dynamic 2D and 3D geometries. Such materials can be used to pattern DNA on NP surfaces and organize NPs into specific supramolecular structures. DNA-caged NPs can be implemented in biosensing and drug delivery applications with cavities precisely designed to encapsulate-specific biomolecules. Ultimately, such approaches provide a springboard for future DNA robot designs that will enable controlled interactions with biological systems.

59 BASIC BIOLOGICAL SCIENCES↗

Structurally Similar but Functionally Diverse ZU5 Domains in Human Erythrocyte Ankyrin

The metazoan cell membrane is highly organized. Maintaining such organization and preserving membrane integrity under different conditions are accomplished through intracellular tethering to an extensive, flexible protein network. Spectrin, the principal component of this network, is attached to the membrane through the adaptor protein ankyrin, which directly bridges the interaction between {beta}-spectrin and membrane proteins. Ankyrins have a modular structure that includes two tandem ZU5 domains. The first domain, ZU5A, is directly responsible for binding {beta}-spectrin. Here, we present a structure of the tandem ZU5 repeats of human erythrocyte ankyrin. Structural and biophysical experiments show that the second ZU5 domain, ZU5B, does not participate in spectrin binding. ZU5B is structurally similar to the ZU5 domain found in the netrin receptor UNC5b supramodule, suggesting that it could interact with other domains in ankyrin. Comparison of several ZU5 domains demonstrates that the ZU5 domain represents a compact and versatile protein interaction module.

59 BASIC BIOLOGICAL SCIENCES↗

Oxabicyclooctane-Linked Novel Bacterial Topoisomerase Inhibitors as Broad Spectrum Antibacterial Agents

Bacterial resistance is eroding the clinical utility of existing antibiotics necessitating the discovery of new agents. Bacterial type II topoisomerase is a clinically validated, highly effective, and proven drug target. This target is amenable to inhibition by diverse classes of inhibitors with alternative and distinct binding sites to quinolone antibiotics, thus enabling the development of agents that lack cross-resistance to quinolones. Described here are novel bacterial topoisomerase inhibitors (NBTIs), which are a new class of gyrase and topo IV inhibitors and consist of three distinct structural moieties. The substitution of the linker moiety led to discovery of potent broad-spectrum NBTIs with reduced off-target activity (hERG IC50 > 18 μM) and improved physical properties. AM8191 is bactericidal and selectively inhibits DNA synthesis and Staphylococcus aureus gyrase (IC50 = 1.02 μM) and topo IV (IC50 = 10.4 μM). AM8191 showed parenteral and oral efficacy (ED50) at less than 2.5 mg/kg doses in a S. aureus murine infection model. A cocrystal structure of AM8191 bound to S. aureus DNA-gyrase showed binding interactions similar to that reported for GSK299423, displaying a key contact of Asp83 with the basic amine at position-7 of the linker.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Rapid expulsion of microswimmers by a vortical flow

Interactions of microswimmers with their fluid environment are exceptionally complex. Macroscopic shear flow alters swimming trajectories in a highly nontrivial way and results in dramatic reduction of viscosity and heterogeneous bacterial distributions. Here we report on experimental and theoretical studies of rapid expulsion of microswimmers, such as motile bacteria, by a vortical flow created by a rotating microparticle. We observe a formation of a macroscopic depletion area in a high-shear region, in the vicinity of a microparticle. The rapid migration of bacteria from the shear-rich area is caused by a vortical structure of the flow rather than intrinsic random fluctuations of bacteria orientations, in stark contrast to planar shear flow. Our mathematical model reveals that expulsion is a combined effect of motility and alignment by a vortical flow. Our findings offer a novel approach for manipulation of motile microorganisms and shed light on bacteria-flow interactions.

36 MATERIALS SCIENCE↗

Long-range three-dimensional magnetic structures of the spin S =1 hexamer cluster fedotovite-like A 2 Cu 3 O ( SO 4 ) 3 ( A 2 = K 2 , NaK, Na 2 ): A neutron diffraction study

The crystal and magnetic structures of the spin S = 1 hexamer cluster fedotovite-like A 2 Cu 3 O(SO 4 ) 3 (A 2 = K 2 , NaK, Na 2 ) were studied by neutron powder diffraction at temperatures 1.6–290 K. The crystal structures in all compounds are well refined in the monoclinic space group C2/c. The basic magnetic units of the compounds are copper hexamers, which are coupled by weak superexchange interactions giving rise to three-dimensional long-range magnetic order below 3.0 < T N < 4.7 K. We have found that for A 2 = K 2 and NaK the propagation vector of the magnetic structure is k = [0,0,0], and the coupling of the Cu hexamers is ferromagnetic (FM) along the ab diagonal and antiferromagnetic along the bc diagonal. In contrast, for A = Na the propagation vector is k = [0,1,0], and the Cu hexamers are coupled antiferromagnetically (AFM) along the ab diagonal. Further, the hexamers are formed by three Cu pairs arranged along the b axis. The calculated spin expectation values $\langle s \rangle$ for the simplest symmetric spin Hamiltonian (obtained from inelastic neutron spectroscopy) of the isolated hexamers in the mean field amounted to $\langle s \rangle$ = 3/8 for the side spins Cu1 and Cu2 and $\langle s \rangle$ = 1/4 for Cu3 in the middle. The Cu spins are FM coupled in pairs and AFM between neighboring pairs. The experimental magnetic moments of the Cu 2+ ions turn out to be not completely collinear due to spin frustrations within the weak interhexamer interactions. The sizes of magnetic moments of Cu in the hexamers determined from the diffraction data are in fair agreement with the calculated values.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Colloquium: The physics of axion stars

The particle that makes up the dark matter of the Universe could be an axion or axionlike particle. A collection of axions can condense into a bound Bose-Einstein condensate called an axion star. It is possible that a significant fraction of the axion dark matter is in the form of axion stars. This would make some efforts to identify the axion as the dark matter particle more challenging, but it would also open up new possibilities. Here, the basic properties of axion stars, which can be gravitationally bound or bound by self-interactions, are summarized. Axions are naturally described by a relativistic field theory with a real scalar field, but low-energy axions can be described more simply by a classical nonrelativistic effective field theory with a complex scalar field.

79 ASTRONOMY AND ASTROPHYSICS↗

Fundamental Studies of Adhesion of Dust to PV Module Surfaces: Chemical and Physical Relationships at the Microscale

Photovoltaic (PV) module soiling is a growing area of concern for performance and reliability. This paper provides evaluations of the fundamental interactions of dust/soiling particles with several PV module surfaces. The purpose is to investigate the basic mechanisms involving the chemistry, morphology, and resulting particle adhesion to the first photon-incident surface. The evaluation and mapping of the chemistry and composition of single dust particles collected from operating PV module surfaces are presented. The first correlated direct measurements of the adhesive force of individual grains from field-operating collectors on identical PV module glass are reported, including correlations with specific compositions. Special microscale atomic force microscopy techniques are adapted to determine the force between the particle and the module glass surface. Results are presented for samples under dry and moisture-exposed conditions, confirming the effects of cementation for surfaces having soluble mineral and/or organic concentrations. Additionally, the effects of hydrocarbon fuels on the enhanced bonding of soiling particles to surfaces are determined for samples from urban and highly trafficked regions. Comparisons between glass and dust-mitigating superhydrophobic and superhydrophilic coatings are presented. Potential limitations of this proximal probe technique are discussed in terms of results and initial proof-of-concept experiments.

14 SOLAR ENERGY↗

Color symmetry and confinement as an underlying superconformal structure in holographic QCD

Dedicated to the memory of our colleague, Harald Fritzsch, who, together with Murray Gell-Mann, introduced the color quantum number as the exact symmetry responsible for the strong interaction, thus establishing quantum chromodynamics (QCD) as a fundamental non-Abelian gauge theory. A basic understanding of hadron properties, however, such as confinement and the emergence of a mass scale, from first principles QCD has remained elusive: Hadronic characteristics are not explicit properties of the QCD Lagrangian and perturbative QCD, so successful in the large transverse momentum domain, is not applicable at large distances. In this article, we shall examine how this daunting obstacle is overcome in holographic QCD with the introduction of a superconformal symmetry in anti de Sitter (AdS) space which is responsible for confinement and the introduction of a mass scale within the superconformal group. When mapped to light-front coordinates in physical spacetime, this approach incorporates supersymmetric relations between the Regge trajectories of meson, baryon and tetraquark states which can be visualized in terms of specific SU(3) C color representations of quarks. Finally, we will also briefly discuss here the implications of holographic models for QCD color transparency in view of the present experimental interest.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Controlling Matter at the Molecular Scale with DNA Circuits

In recent years, a diverse set of mechanisms have been developed that allow DNA strands with specific sequences to sense information in their environment and to control material assembly, disassembly, and reconfiguration. These sequences could serve as the inputs and outputs for DNA computing circuits, enabling DNA circuits to act as chemical information processors to program complex behavior in chemical and material systems. In this review, we describe processes that can be sensed and controlled within such a paradigm. Specifically, there are interfaces that can release strands of DNA in response to chemical signals, wavelengths of light, pH, or electrical signals, as well as DNA strands that can direct the self-assembly and dynamic reconfiguration of DNA nanostructures, regulate particle assemblies, control encapsulation, and manipulate materials including DNA crystals, hydrogels, and vesicles. These interfaces have the potential to enable chemical circuits to exert algorithmic control over responsive materials, which may ultimately lead to the development of materials that grow, heal, and interact dynamically with their environments.

59 BASIC BIOLOGICAL SCIENCES↗

The Mutualistic Niche: Mycorrhizal Symbiosis and Community Dynamics

The niche is generally viewed in terms of species' intrinsic physiological potential and limitations due to competition. Although DNA sequencing has revealed the ubiquity of beneficial microbial symbioses, the role of mutualisms in shaping species niches is not broadly recognized. In this review, I use a widespread terrestrial mutualism, the ectomycorrhizal symbiosis, to help develop the mutualistic niche concept. Using contemporary niche theory, I show how mycorrhizal symbioses expand environmental ranges (requirement niche) and influence resource use (impact niche) for both plants and fungi. Simple niche models for competition between resource specialists and generalists also predict a range of ecological phenomena, from unexpected monodominance by some tropical trees to the functional biogeography of mycorrhizal symbiosis. A niche-based view of mutualism may also help explain stability of mutualisms even in the absence of clear benefits. Furthermore, the niche is a central concept in ecology, and better integration of mutualism will more accurately reflect the positive interactions experienced by nearly all species.

59 BASIC BIOLOGICAL SCIENCES↗

Serine 363 of a hydrophobic region of Archaeal ribulose 1,5-bisphosphate carboxylase/oxygenase from Archaeoglobus fulgidus and Thermococcus kodakaraensis affects CO 2 /O 2 substrate specificity and oxygen sensitivity

Archaeal ribulose 1, 5-bisphospate carboxylase/oxygenase (RubisCO) is differentiated from other RubisCO enzymes and is classified as a form III enzyme, as opposed to the form I and form II RubisCOs typical of chemoautotrophic bacteria and prokaryotic and eukaryotic phototrophs. The form III enzyme from archaea is particularly interesting as several of these proteins exhibit unusual and reversible sensitivity to molecular oxygen, including the enzyme from Archaeoglobus fulgidus . Previous studies with A. fulgidus RbcL2 had shown the importance of Met-295 in oxygen sensitivity and pointed towards the potential significance of another residue (Ser-363) found in a hydrophobic pocket that is conserved in all RubisCO proteins. In the current study, further structure/function studies have been performed focusing on Ser-363 of A. fulgidus RbcL2; various changes in this and other residues of the hydrophobic pocket point to and definitively establish the importance of Ser-363 with respect to interactions with oxygen. In addition, previous findings had indicated discrepant CO 2 /O 2 specificity determinations of the Thermococcus kodakaraensis RubisCO, a close homolog of A. fulgidus RbcL2. As a result, it is shown here that the T. kodakaraensis enzyme exhibits a similar substrate specificity as the A. fulgidus enzyme and is also oxygen sensitive, with equivalent residues involved in oxygen interactions.

59 BASIC BIOLOGICAL SCIENCES↗