Folding Mechanism and Aggregation Propensity of the KH0 Domain of FMRP and Its R138Q Pathological Variant

The K-homology (KH) domains are small, structurally conserved domains found in proteins of different origins characterized by a central conserved βααβ “core” and a GxxG motif in the loop between the two helices of the KH core. In the eukaryotic KHI type, additional αβ elements decorate the “core” at the C-terminus. Proteins containing KH domains perform different functions and several diseases have been associated with mutations in these domains, including those in the fragile X mental retardation protein (FMRP). FMRP is an RNA-binding protein crucial for the control of RNA metabolism whose lack or mutations lead to fragile X syndrome (FXS). Among missense mutations, the R138Q substitution is in the KH0 degenerated domain lacking the classical GxxG motif. By combining equilibrium and kinetic experiments, we present a characterization of the folding mechanism of the KH0 domain from the FMRP wild-type and of the R138Q variant showing that in both cases the folding mechanism implies the accumulation of an on-pathway transient intermediate. Moreover, by exploiting a battery of biophysical techniques, we show that the KH0 domain has the propensity to form amyloid-like aggregates in mild conditions in vitro and that the R138Q mutation leads to a general destabilization of the protein and to an increased fibrillogenesis propensity.     

Extracellular Acidosis Differentially Regulates Estrogen Receptor β-Dependent EMT Reprogramming in Female and Male Melanoma Cells

Clinical outcomes of melanoma patients pointed out a gender disparity that supports a correlation between sex hormone activity on estrogen receptors (ER) and melanoma development and progression. Here, we found that the epithelial-to-mesenchymal transition (EMT) of melanoma cells induced by extracellular acidosis, which is a crucial hallmark of solid cancers, correlates with the expression of ERβ, the most representative ER on melanoma cells. Extracellular acidosis induces an enhanced expression of ERβ in female cells and EMT markers remain unchanged, while extracellular acidosis did not induce the expression of ERβ in male cells and EMT was strongly promoted. An inverse relationship between ERβ expression and EMT markers in melanoma cells of different sex exposed to extracellular acidosis was revealed by two different technical approaches: florescence-activated cell sorting of high ERβ expressing cell subpopulations and ERβ receptor silencing. Finally, we found that ERβ regulates EMT through NF-κB activation. These results demonstrate that extracellular acidosis drives a differential ERβ regulation in male and female melanoma cells and that this gender disparity might open new perspectives for personalized therapeutic approaches.     

Controlling DNA Bundle Size and Spatial Arrangement in Self-assembled Arrays on Superhydrophobic Surface

Nano-Micro Letters - The use of superhydrophobic surfaces (SHSs) is now emerging as an attractive platform for the realization of one-dimensional (1D) nanostructures with potential applications in...     

Climbing Plant‐Inspired Micropatterned Devices for Reversible Attachment

Climbing plants have evolved over millions of years and have adapted to unpredictable scenarios in unique ways. These crucial features make plants an outstanding biological model for scientists and engineers. Inspired by the ratchet‐like attachment mechanism of the hook‐climber Galium aparine, a novel micropatterned flexible mechanical interlocker is fabricated using a 3D direct laser lithography technique. The artificial hooks are designed based on a morphometric analysis of natural hooks. They are characterized in terms of pull‐off and shear forces, both in an array and as individual hooks. The microprinted hooks array shows high values of pull‐off forces (up to F_⊥ ≈ 0.4 N cm^?2) and shear forces (up to F_// ≈ 13.8 N cm^?2) on several rough surfaces (i.e., abrasive materials, fabrics, and artificial skin tissues). The contact separation forces of individual artificial hooks are estimated when loads with different orientations are applied (up to F ≈ 0.26 N). In addition, a patterned tape with directional microhooks is integrated into a mobile platform to demonstrate its climbing ability on inclined surfaces of up to 45°. This research opens up new opportunities for prototyping the next generation of mechanical interlockers, particularly for soft‐ and microrobotics, the textile industry, and biomedical fields.     

Evaluation of pure‐component adsorption properties of silicalite based on the Langmuir and Sips models

The Langmuir and Sips models parameters were estimated for the adsorption of several light gases and hydrocarbons (H₂, CH₄, CO₂, CO, N₂, C₂H₆, C₃H₈, n‐C₄H₁₀) in silicalite along with their functionality with temperature. This is a scientific attempt to resume and reconcile the number of available experimental data and supply scientists and other operators with the adsorption properties of silicalite within a wider range of temperature and pressure. Furthermore, to provide readers with more detailed information on where each of the two models work better, the analysis is divided into three temperature ranges: low‐temperature, high‐temperature, and whole temperature range. As a result, it is found that the Langmuir model works well in the whole temperature range for the light gases considered but not for the other hydrocarbons, for which it is better to use the Sips model by splitting calculation over low‐ and high‐temperature range. © 2015 American Institute of Chemical Engineers AIChE J, 61: 3911–3922, 2015     

Accelerating Scientific Discovery Through Computation and Visualization II

This is the second in a series of articles describing a wide variety of projects at NIST that synergistically combine physical science and information science. It describes, through examples, how the Scientific Applications and Visualization Group (SAVG) at NIST has utilized high performance parallel computing, visualization, and machine learning to accelerate research. The examples include scientific collaborations in the following areas: (1) High Precision Energies for few electron atomic systems, (2) Flows of suspensions, (3) X-ray absorption, (4) Molecular dynamics of fluids, (5) Nanostructures, (6) Dendritic growth in alloys, (7) Screen saver science, (8) genetic programming.     

Geothermal energy and the dissemination of information: the role of the International Geothermal Association

The International Geothermal Association (IGA), founded on 6 July 1988, is an international, worldwide, non-profit and non-governmental association whose objective and mission is to promote the research and utilization of geothermal resources, through the compilation, publication, and dissemination of scientific and technical data and information. The Information Committee (IC) of the IGA is responsible for advising the IGA Board on policies concerned with the collection, compilation, publication, exchange and dissemination of geothermal information, including information on utilization, development, technical findings, scientific research, meetings, publications and Association activities. The Committee is also responsible for the implementation of information policies determined by the Board.     

Substrate Selection for Full Exploitation of Organic Semiconductor Films: Epitaxial Rubrene on β‐Alanine Single Crystals

Rubrene (RUB) is one of the most studied organic semiconductors because, in the orthorhombic single‐crystal phase, it exhibits a record exciton diffusion length and one of the highest charge carrier mobilities ever reported. Here, thin films of oriented crystalline RUB are successfully grown in vacuum on millimeter‐sized (010)‐β‐alanine (β‐ala) single crystals with a step‐growth protocol, exploiting organic epitaxy. The experimental characterization demonstrates that these RUB films grow in the orthorhombic polymorph with the (100)_RUB plane in contact with the (010)_β‐ala surface and with precise azimuthal orientations. A complementary study of the RUB(100)/β‐ala(010) interface, performed by computational simulations, confirms the epitaxial relations expected by considering the molecular scale corrugations of the surfaces. Moreover, thanks to the wide transparency region of β‐ala, the RUB absorption bands in the UV range are directly detected for the first time. Finally, removal of the water‐soluble substrate enables the integration of the films in field effect transistors as high quality active organic layers. The characteristics of such RUB‐based devices confirm the quality and versatility of epitaxial thin films for use in organic electronics.