Computer Folding of Parallel DNA G-Quadruplex: Hitchhiker's Guide to the Conformational Space.

Guanine quadruplexes (GQs) play crucial roles in various biological processes, and understanding their folding pathways provides insight into their stability, dynamics, and functions. This knowledge aids in designing therapeutic strategies, as GQs are potential targets for anticancer drugs and other therapeutics. Although experimental and theoretical techniques have provided valuable insights into different stages of the GQ folding, the structural complexity of GQs poses significant challenges, and our understanding remains incomplete.

Determination of α lamellae orientation in a β-Ti alloy using electron backscatter diffraction.

The spatial orientation of α lamellae in a metastable β-Ti matrix of Timetal LCB (Ti-6.8 Mo-4.5 Fe-1.

Late onset and regional heterogeneity of synaptic deficits in cortical PV interneurons of mice.

Epilepsy and epileptiform patterns of cortical activity are highly prevalent in autism spectrum disorders (ASDs), but the neural substrates and pathophysiological mechanisms underlying the onset of cortical dysfunction in ASD remains elusive. Reduced cortical expression of Parvalbumin (PV) has been widely observed in ASD mouse models and human postmortem studies, suggesting a crucial role of PV interneurons (PVINs) in ASD pathogenesis. mice carrying a Δ13-16 deletion in SHANK3 exhibit cortical hyperactivity during postnatal development and reduced sensory responses in cortical GABAergic interneurons in adulthood.

The relationship between fear of falling and functional ability following a multi-component fall prevention program: an analysis of clinical data.

Objectives: The first objective was to evaluate clinical data from a multi-component fall prevention program. The second objective was to explore the relationship between physical function and fear of falling (FoF).

Methods: Adults (N = 287, mean age = 76 years) who participated in the Building Balance Program between 2011-2020 were assessed with five physical function measures and two FoF measures.

Automatic Learning of Hydrogen-Bond Fixes in the AMBER RNA Force Field.

The capability of current force fields to reproduce RNA structural dynamics is limited. Several methods have been developed to take advantage of experimental data in order to enforce agreement with experiments. Here, we extend an existing framework which allows arbitrarily chosen force-field correction terms to be fitted by quantification of the discrepancy between observables back-calculated from simulation and corresponding experiments.

Toward Convergence in Folding Simulations of RNA Tetraloops: Comparison of Enhanced Sampling Techniques and Effects of Force Field Modifications.

Atomistic molecular dynamics simulations represent an established technique for investigation of RNA structural dynamics. Despite continuous development, contemporary RNA simulations still suffer from suboptimal accuracy of empirical potentials (force fields, ffs) and sampling limitations. Development of efficient enhanced sampling techniques is important for two reasons.

W-RESP: Well-Restrained Electrostatic Potential-Derived Charges. Revisiting the Charge Derivation Model.

Representation of electrostatic interactions by a Coulombic pairwise potential between atom-centered partial charges is a fundamental and crucial part of empirical force fields used in classical molecular dynamics simulations. The broad success of the AMBER force-field family originates mainly from the restrained electrostatic potential (RESP) charge model, which derives partial charges to reproduce the electrostatic field around the molecules. However, the description of the electrostatic potential around molecules by standard RESP may be biased for some types of molecules.

Novel α + β Zr Alloys with Enhanced Strength.

Low-alloyed zirconium alloys are widely used in nuclear applications due to their low neutron absorption cross-section. These alloys, however, suffer from limited strength. Well-established guidelines for the development of Ti alloys were applied to design new two-phase ternary Zr alloys with improved mechanical properties.

The Effect of Hot Working on the Mechanical Properties of High Strength Biomedical Ti-Nb-Ta-Zr-O Alloy.

Beta titanium alloy Ti-35Nb-6Ta-7Zr-0.7O (wt%) was developed as a material intended for the manufacturing of a stem of a hip joint replacement. This alloy contains only biocompatible elements and possesses a very high yield strength already in the cast condition (900 MPa).

Transformation Pathway upon Heating of Metastable Titanium Alloy Ti-15Mo Investigated by Neutron Diffraction.

A transformation pathway during thermal treatment of metastable β Ti-15Mo alloy was investigated by in situ neutron diffraction. The evolution of individual phases α , β , and ω was investigated during linear heating with two heating rates of 1.9 ∘ C / min and 5 ∘ C / min and during aging at 450 ∘ C .

Local-to-global signal transduction at the core of a Mn sensing riboswitch.

The widespread Mn-sensing yybP-ykoY riboswitch controls the expression of bacterial Mn homeostasis genes. Here, we first determine the crystal structure of the ligand-bound yybP-ykoY riboswitch aptamer from Xanthomonas oryzae at 2.96 Å resolution, revealing two conformations with docked four-way junction (4WJ) and incompletely coordinated metal ions.

Anomalous X-ray diffraction from ω nanoparticles in β-Ti(Mo) single crystals.

Anomalous X-ray diffraction (AXRD) is a technique which makes use of effects occurring near the energy of an absorption edge of an element present in the studied sample. The intensity of the diffracted radiation exhibits an anomalous decrease when the primary beam energy matches the energy needed to excite an electron from an atomic orbital. The characteristics of this step are sensitive to the concentration of the `anomalous' element and its spatial distribution in the sample.

Toolbox of Diverse Linkers for Navigating the Cellular Efficacy Landscape of Stapled Peptides.

Stapled peptides have great potential as modulators of protein-protein interactions (PPIs). However, there is a vast landscape of chemical features that can be varied for any given peptide, and identifying a set of features that maximizes cellular uptake and subsequent target engagement remains a key challenge. Herein, we present a systematic analysis of staple functionality on the peptide bioactivity landscape in cellular assays.

Oxytocin facilitates adaptive fear and attenuates anxiety responses in animal models and human studies-potential interaction with the corticotropin-releasing factor (CRF) system in the bed nucleus of the stria terminalis (BNST).

Despite its relatively well-understood role as a reproductive and pro-social peptide, oxytocin (OT) tells a more convoluted story in terms of its modulation of fear and anxiety. This nuanced story has been obscured by a great deal of research into the therapeutic applications of exogenous OT, driving more than 400 ongoing clinical trials. Drawing from animal models and human studies, we review the complex evidence concerning OT's role in fear learning and anxiety, clarifying the existing confusion about modulation of fear versus anxiety.

Structural characterization of semi-heusler/light metal composites prepared by spark plasma sintering.

A composite of powders of semi-Heusler ferromagnetic shape memory and pure titanium was successfully prepared by spark plasma sintering at the temperature of 950 °C. Sintering resulted in the formation of small precipitates and intermetallic phases at the heterogeneous interfaces. Various complementary experimental methods were used to fully characterize the microstructure.

Computationally-guided optimization of small-molecule inhibitors of the Aurora A kinase-TPX2 protein-protein interaction.

Free energy perturbation theory, in combination with enhanced sampling of protein-ligand binding modes, is evaluated in the context of fragment-based drug design, and used to design two new small-molecule inhibitors of the Aurora A kinase-TPX2 protein-protein interaction.

Increasing strength of a biomedical Ti-Nb-Ta-Zr alloy by alloying with Fe, Si and O.

Low-modulus biomedical beta titanium alloys often suffer from low strength which limits their use as load-bearing orthopaedic implants. In this study, twelve different Ti-Nb-Zr-Ta based alloys alloyed with Fe, Si and O additions were prepared by arc melting and hot forging. The lowest elastic modulus (65GPa) was achieved in the benchmark TNTZ alloy consisting only of pure β phase with low stability due to the 'proximity' to the β to α'' martensitic transformation.

Mapping monthly rainfall erosivity in Europe.

Rainfall erosivity as a dynamic factor of soil loss by water erosion is modelled intra-annually for the first time at European scale. The development of Rainfall Erosivity Database at European Scale (REDES) and its 2015 update with the extension to monthly component allowed to develop monthly and seasonal R-factor maps and assess rainfall erosivity both spatially and temporally. During winter months, significant rainfall erosivity is present only in part of the Mediterranean countries.

Allosteric modulation of AURKA kinase activity by a small-molecule inhibitor of its protein-protein interaction with TPX2.

The essential mitotic kinase Aurora A (AURKA) is controlled during cell cycle progression via two distinct mechanisms. Following activation loop autophosphorylation early in mitosis when it localizes to centrosomes, AURKA is allosterically activated on the mitotic spindle via binding to the microtubule-associated protein, TPX2. Here, we report the discovery of AurkinA, a novel chemical inhibitor of the AURKA-TPX2 interaction, which acts via an unexpected structural mechanism to inhibit AURKA activity and mitotic localization.

Newly developed Ti-Nb-Zr-Ta-Si-Fe biomedical beta titanium alloys with increased strength and enhanced biocompatibility.

Beta titanium alloys are promising materials for load-bearing orthopaedic implants due to their excellent corrosion resistance and biocompatibility, low elastic modulus and moderate strength. Metastable beta-Ti alloys can be hardened via precipitation of the alpha phase; however, this has an adverse effect on the elastic modulus. Small amounts of Fe (0-2 wt.

Performance of the Tachyon Time-of-Flight PET Camera.

We have constructed and characterized a time-of-flight Positron Emission Tomography (TOF PET) camera called the Tachyon. The Tachyon is a single-ring Lutetium Oxyorthosilicate (LSO) based camera designed to obtain significantly better timing resolution than the ~ 550 ps found in present commercial TOF cameras, in order to quantify the benefit of improved TOF resolution for clinically relevant tasks. The Tachyon's detector module is optimized for timing by coupling the 6.

Work-hardening induced tensile ductility of bulk metallic glasses via high-pressure torsion.

The mechanical properties of engineering materials are key for ensuring safety and reliability. However, the plastic deformation of BMGs is confined to narrow regions in shear bands, which usually result in limited ductilities and catastrophic failures at low homologous temperatures. The quasi-brittle failure and lack of tensile ductility undercut the potential applications of BMGs.

Diversity-oriented synthesis of drug-like macrocyclic scaffolds using an orthogonal organo- and metal catalysis strategy.

Small-molecule modulators of biological targets play a crucial role in biology and medicine. In this context, diversity-oriented synthesis (DOS) provides strategies toward generating small molecules with a broad range of unique scaffolds, and hence three-dimensionality, to target a broad area of biological space. In this study, an organocatalysis-derived DOS library of macrocycles was synthesized by exploiting the pluripotency of aldehydes.