Legal Remedies for “Cloud-Seeding” Activities: Nuisance or Trespass?

Intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs) of proteins are very common and instrumental for cellular signaling. Recently, a number of studies have investigated the kinetic binding mechanisms of IDPs and IDRs. These results allow us to draw conclusions about the energy landscape for the coupled binding and folding of disordered proteins. The association rate constants of IDPs cover a wide range (10(5)-10(9) M-1 s(-1)) and are largely governed by long-range charge-charge interactions, similarly to interactions between well-folded proteins. Off-rate constants also differ significantly among IDPs (with half-lives of up to several minutes) but are usually around 0.1-1000 s(-1), allowing for rapid dissociation of complexes. Likewise, affinities span from pM to mu M suggesting that the low-affinity high-specificity concept for IDPs is not straightforward. Overall, it appears that binding precedes global folding although secondary structure elements such as helices may form before the protein-protein interaction. Short IDPs bind in apparent two-state reactions whereas larger IDPs often display complex multi-step binding reactions. While the two extreme cases of two-step binding (conformational selection and induced fit) or their combination into a square mechanism is an attractive model in theory, it is too simplistic in practice. Experiment and simulation suggest a more complex energy landscape in which IDPs bind targets through a combination of conformational selection before binding (e. g., secondary structure formation) and induced fit after binding (global folding and formation of short-range intermolecular interactions)

The kinetics of folding of the NSH2 domain from p85

SH2 domains are protein domains that mediate protein-protein interaction through the recognition and binding of specific sequences containing phosphorylated tyrosines. The p85 protein is the regulatory subunit of the heterodimeric enzyme PI3K, an important enzyme involved in several molecular pathways. In this work we characterize the folding kinetics of the NSH2 domain of p85. Our data clearly reveal peculiar folding kinetics, characterized by an apparent mismatch between the observed folding and unfolding kinetics. Taking advantage of double mixing stopped flow experiments and site directed mutagenesis we demonstrate that such behavior is due to the cis/trans isomerization of the peptide bond between D73 and P74, being in a cis conformation in the native protein. Our data are discussed in comparison with previous works on the folding of other SH2 domains

Wet and dry accelerated aging tests in a spray chamber to understand the effects of acid rain frequencies on bronze corrosion

We have conducted controlled laboratory experiments using a series of bronze alloys exposed to frequent, repeated wet and dry cycles, to simulate frequent acid rain exposure and study the resultant corrosion processes in bronze artifacts exposed to an outdoor urban environment. To simulate rainwater and condensation, a spray chamber for the corrosion tests was assembled, which delivered homogeneous vapor diffusion and drop deposition. Three bi-component bronzes, with 3%, 7% and 20% tin content, were subjected to seven days of controlled wet and dry cycles, and analyzed at precise intervals. Electrochemical impedance spectroscopy and spectrocolorimetry results were combined to show the different phases of corrosion. The patinas on all three samples at the end of the exposure period were studied with scanning electron microscopy to show the morphology of corrosion products; they were also analyzed by X-ray diffraction. The sample containing 7% tin produces a patina that is unstable and frequently dissolved. Partial patina dissolution also occurs during exposure for the 3% tin sample, but the effects are less pronounced. Because it reacts the least with the environment, the 20% tin sample demonstrates intermediate behavior (between the 7% and the 3% tin samples). However, the patina is less protective than the 3% tin sample patina

Understanding the mechanism of binding between Gab2 and the C terminal SH3 domain from Grb2

Gab2 is a large disordered protein that regulates several cellular signalling pathways and is overexpressed in different forms of cancer. Because of its disordered nature, a detailed characterization of the mechanisms of recognition between Gab2 and its physiological partners is particularly difficult. Here we provide a detailed kinetic characterization of the binding reaction between Gab2 and the C-terminal SH3 domain of the growth factor receptor-bound protein 2 (Grb2). We demonstrate that Gab2 folds upon binding following an induced fit type mechanism, whereby recognition is characterized by the formation of an intermediate, in which Gab2 is primarily disordered. In this scenario, folding of Gab2 into the bound conformation occurs only after binding. However, an alanine scanning of the proline residues of Gab2 suggests that the intermediate contains some degree of native-like structure, which might play a role for the recognition event to take place. The results, which represent a fundamental step forward in the understanding of this functional proteinprotein interaction, are discussed on the light of previous structural works on these proteins

Larix decidua Bark as a Source of Phytoconstituents: An LC-MS Study

Larix decidua bark is a waste of the timber industry and is widely diffused in Northern Italy. This material can be considered a good source of antioxidants and phytoconstituents with possible use in cosmetic or nutraceutical products. In this study, simple extraction of larch bark was performed using mixtures of ethanol/water. Furthermore, the phytochemical composition of larch bark extract was studied using LC-MS(n) methods and the main constituents were identified as flavonoids, spiro-polyphenols, and procyanidins. To confirm the identification by LC-MS semi-preparative HPLC was performed in order to isolate the main constituents and verify the structures by \ub9H-NMR. Antioxidant properties were studied using an in vitro approach combining DPPH assay and LC-MS in order to establish different roles of the various classes of phytochemicasl of the extract. DPPH activity of some of the isolated compounds was also assessed. The overall results indicate this waste material as a good source of antioxidant compounds, mainly procyanidins, whichresulted the most active constituents in the DPPH assay

Dissecting Inter-domain Cooperativity in the Folding of a Multi Domain Protein.

Correct protein folding underlies all cellular functions. While there are detailed descriptions and a good understanding of protein folding pathways for single globular domains there is a paucity of quantitative data regarding folding of multidomain proteins. We have here investigated the folding of a three-domain supramodule from the protein PSD-95, consisting of one PDZ domain, one SH3 domain and one guanylate kinase-like (GK) domain. This supramodule has previously been shown to work as one functional unit with regard to ligand binding. We used equilibrium and kinetic folding experiments to demonstrate that the PDZ domain folds faster and independently from the SH3-GK tandem, which folds as one cooperative unit. However, concurrent folding of the PDZ domain slows down folding of SH3-GK by non-native interactions, resulting in an off-pathway folding intermediate. Our data contribute to an emerging description of multidomain protein folding in which individual domains cannot a priori be viewed as separate folding units

Traffic-induced vibrations on a simple frame: Influence of external action coherence on structural response

The study of the traffic-induced response of a simple frame structure is presented. In particular, the effect of the spatial correlation, among the traffic-induced ground displacements, is discussed by means of a parametric study to achieve the purpose of outlining those configurations yielding the less-conservative structural response. Ground excitations are estimated by the model of Hunt (J. Sound Vib. 1991; 1:41–51; J. Sound Vib. 1991; 1:53–70) assuming a quarter-car vehicle model moving on an uneven roadway placed on the top of a homogeneous half-space. The structure consists of a rigid slab supported by four columns and subjected by traffic-induced forces suitably condensed in its center of mass. Copyright © 2008 John Wiley & Sons, Ltd

Archaeometric study of mortars from the Pisa's Cathedral Square (Italy)

The present work is focused on the study of forty-two mortars used in the construction of both Roman buildings, old Pisa’s Cathedral and Modern structures in the Miracles Square (Italy). This area, included since 1987 in the World Heritage List of the UNESCO, is famous for the presence of an important historical complex built in the Middle Ages (the Cathedral, the Baptistery, the Leaning Tower and the Monumental Cemetery). The archaeologists discovered some structures related to more ancient periods: the Roman domus (1st–5th centuries) and the older cathedral with its foundations and crypt (10th century). Based on OM, XRF, XRPD, TG-DSC and SEM-EDS analyses, the main characteristics of binder and aggregate of the mortars have been determined, and some raw materials used for the production of the analysed binding materials have been identified