A basis set for peptides for the variational approach to conformational kinetics

Although Markov state models have proven to be powerful tools in resolving the complex features of biomolecular kinetics, the discretization of the conformational space has been a bottleneck since the advent of the method. A recently introduced variational approach, which uses basis functions instead of crisp conformational states, opened up a route to construct kinetic models in which the discretization error can be controlled systematically. Here, we develop and test a basis set for peptides to be used in the variational approach. The basis set is constructed by combining local residue-centered kinetic modes that are obtained from kinetic models of terminally blocked amino acids. Using this basis set, we model the conformational kinetics of two hexapeptides with sequences VGLAPG and VGVAPG. Six basis functions are sufficient to represent the slow kinetic modes of these peptides. The basis set also allows for a direct interpretation of the slow kinetic modes without an additional clustering in the space of the dominant eigenvectors. Moreover, changes in the conformational kinetics due to the exchange of leucine in VGLAPG to valine in VGVAPG can be directly quantified by comparing histograms of the basis set expansion coefficients

Molecular dynamics simulations data of the twenty encoded amino acids in different force fields

We present extensive all-atom Molecular Dynamics (MD) simulation data of the twenty encoded amino acids in explicit water, simulated with different force fields. The termini of the amino acids have been capped to ensure that the dynamics of the Φ and ψ torsion angles are analogues to the dynamics within a peptide chain. We use representatives of each of the four major force field families: AMBER ff-99SBILDN [1], AMBER ff-03 [2], OPLS-AA/L [3], CHARMM27 [4] and GROMOS43a1 [5,6]. Our data represents a library and test bed for method development for MD simulations and for force fields development. Part of the data set has been previously used for comparison of the dynamic properties of force fields (Vitalinietal.,2015) [7] and for the construction of peptide basis functions for the variational approach to molecular kinetics [8]

Dynamic Properties of Force Fields

Molecular-dynamics simulations are increasingly used to study dynamic properties of biological systems. With this development, the ability of force fields to successfully predict relaxation timescales and the associated conformational exchange processes moves into focus. We assess to what extent the dynamic properties of model peptides (Ac-A-NHMe, Ac-V-NHMe, AVAVA, A10) differ when simulated with different force fields (AMBER ff99SB-ILDN, AMBER ff03, OPLS-AA/L, CHARMM27, and GROMOS43a1). The dynamic properties are extracted using Markov state models. For single-residue models (Ac-A-NHMe, Ac-V-NHMe), the slow conformational exchange processes are similar in all force fields, but the associated relaxation timescales differ by up to an order of magnitude. For the peptide systems, not only the relaxation timescales, but also the conformational exchange processes differ considerably across force fields. This finding calls the significance of dynamic interpretations of molecular-dynamics simulations into question

Synthesis of imine congeners of resveratrol and evaluation of their anti-platelet activity

Resveratrol (3,5,4\u2032-trihydroxy-trans-stilbene) is a cardioprotective phytochemical occurring in many plant products. In this study, a new series of imine congeners of resveratrol has been synthesized in which the imine moiety replaced the double bond in the structure of resveratrol. In addition, the in vitro antiplatelet activity of these resveratrol derivatives has been evaluated against adenosine diphosphate (ADP), arachidonic acid (AA), and collagen as platelet aggregation inducers. In general, the synthesized compounds were active as antiplatelet agents, and, therefore, the imine functional group may be considered as an effective replacement for a double bond in resveratrol for developing new and promising antiplatelet drugs

Characterization of the biogenic volatile organic compounds (BVOCs) and analysis of the PR1 molecular marker in Vitis vinifera L. inoculated with the nematode Xiphinema index

Upon pathogen attack, plants very quickly undergo rather complex physico-chemical changes, such as the production of new chemicals or alterations in membrane and cell wall properties, to reduce disease damages. An underestimated threat is represented by root parasitic nematodes. In Vitis vinifera L., the nematode Xiphinema index is the unique vector of Grapevine fanleaf virus, responsible for fanleaf degeneration, one of the most widespread and economically damaging diseases worldwide. The aim of this study was to investigate changes in the emission of biogenic volatile organic compounds (BVOCs) in grapevines attacked by X. index. BVOCs play a role in plant defensive mechanisms and are synthetized in response to biotic damages. In our study, the BVOC profile was altered by the nematode feeding process. We found a decrease in \u3b2-ocimene and limonene monoterpene emissions, as well as an increase in \u3b1-farnesene and \u3b1-bergamotene sesquiterpene emissions in nematode-treated plants. Moreover, we evaluated the PR1 gene expression. The transcript level of PR1 gene was higher in the nematode-wounded roots, while in the leaf tissues it showed a lower expression compared to control grapevines

Anticancer Effects of Wild Mountain Mentha longifolia Extract in Adrenocortical Tumor Cell Models

Mint [Mentha longifolia (L.) Hudson] is an aromatic plant that belongs to Lamiaceae family. It is traditionally used as herbal tea in Europe, Australia and North Africa and shows numerous pharmacological effects, such as spasmolytic, antioxidant, antimicrobial and anti-hemolytic. Recently, its antiproliferative role has been suggested in a small number of tumor cell models, but no data are available on adrenocortical carcinoma, a malignancy with a survival rate at 5 years of 20%\u201330% which frequently metastasize. This work aimed to study the effects of Mentha longifolia L. crude extract (ME) on two adrenocortical tumor cell models (H295R and SW13 cells). Chemical composition of ME was assessed by gas-chromatography/mass spectrometry and NMR spectroscopy analysis. Brine shrimp lethality assay showed ME effects at >0.5 \ub5g/\ub5l (p 0.5 \ub5g/\ub5l, p 0.5 \ub5g/\ub5l, p < 0.05), while Wright staining demonstrated the presence of both necrotic and apoptotic cells. Cell cycle analysis showed a strong increase in subG0/G1 phase, related to cell death. Furthermore, MAPK and PI3k/Akt pathways were modulated by Western blot analysis when treating cells with ME alone or combined with mitotane. The crude methanolic extract of wild mountain mint can decrease cell viability, vitality and survival of adrenocortical tumor cell models, in particular of SW13 cells. These data show the potential anticancer effects of ME, still more work is needed to corroborate these findings

Traditional knowledge of wild edible plants used in the northwest of the Iberian Peninsula (Spain and Portugal): a comparative study

<p>Abstract</p> <p>Background</p> <p>We compare traditional knowledge and use of wild edible plants in six rural regions of the northwest of the Iberian Peninsula as follows: Campoo, Picos de Europa, Piloña, Sanabria and Caurel in Spain and Parque Natural de Montesinho in Portugal.</p> <p>Methods</p> <p>Data on the use of 97 species were collected through informed consent semi-structured interviews with local informants. A semi-quantitative approach was used to document the relative importance of each species and to indicate differences in selection criteria for consuming wild food species in the regions studied.</p> <p>Results and discussion</p> <p>The most significant species include many wild berries and nuts (e.g. <it>Castanea sativa, Rubus ulmifolius, Fragaria vesca</it>) and the most popular species in each food-category (e.g. fruits or herbs used to prepare liqueurs such as <it>Prunus spinosa</it>, vegetables such as <it>Rumex acetosa</it>, condiments such as <it>Origanum vulgare</it>, or plants used to prepare herbal teas such as <it>Chamaemelum nobile</it>). The most important species in the study area as a whole are consumed at five or all six of the survey sites.</p> <p>Conclusion</p> <p>Social, economic and cultural factors, such as poor communications, fads and direct contact with nature in everyday life should be taken into account in determining why some wild foods and traditional vegetables have been consumed, but others not. They may be even more important than biological factors such as richness and abundance of wild edible flora. Although most are no longer consumed, demand is growing for those regarded as local specialties that reflect regional identity.</p

Cross-Talk between the Cellular Redox State and the Circadian System in Neurospora

The circadian system is composed of a number of feedback loops, and multiple feedback loops in the form of oscillators help to maintain stable rhythms. The filamentous fungus Neurospora crassa exhibits a circadian rhythm during asexual spore formation (conidiation banding) and has a major feedback loop that includes the FREQUENCY (FRQ)/WHITE COLLAR (WC) -1 and -2 oscillator (FWO). A mutation in superoxide dismutase (sod)-1, an antioxidant gene, causes a robust and stable circadian rhythm compared with that of wild-type (Wt). However, the mechanisms underlying the functions of reactive oxygen species (ROS) remain unknown. Here, we show that cellular ROS concentrations change in a circadian manner (ROS oscillation), and the amplitudes of ROS oscillation increase with each cycle and then become steady (ROS homeostasis). The ROS oscillation and homeostasis are produced by the ROS-destroying catalases (CATs) and ROS-generating NADPH oxidase (NOX). cat-1 is also induced by illumination, and it reduces ROS levels. Although ROS oscillation persists in the absence of frq, wc-1 or wc-2, its homeostasis is altered. Furthermore, genetic and biochemical evidence reveals that ROS concentration regulates the transcriptional function of WCC and a higher ROS concentration enhances conidiation banding. These findings suggest that the circadian system engages in cross-talk with the cellular redox state via ROS-regulatory factors

ordinary biodiversity the case of food

The green revolution, the biotech revolution, and other major changes in food production, distribution, and consumption have deeply subverted the relationship between humans and food. Such a drastic rupture is forcing a rethinking of that relationship and a careful consideration of which items we shall preserve and why. This essay aims at introducing a philosophical frame for assessing the biodiversity of that portion of the living realm that I call the edible environment. With such expression I intend not simply those plants and animals (including in this category, henceforth, also fish and insects) that were domesticated for human consumption, but also the thousands of species that are regularly consumed by some human population and that are regarded to some degree as wild. The visceral, existential, and identity-related relationship that link humans with the edible environment can be regarded as sui generis and can constitute a ground for explaining why it should receive a preferential treatment when it comes to preservation, propagation, and development. First of all, I discuss whether we should draw a sharp divide, when it comes to preservation efforts, between wild and domesticated species (§1); secondly, I assess whether to draw a sharp divide between natural and unnatural entities, when it comes to measurements and interventions regarding the edible environment (§2); finally, I ask what is the value of biodiversity as far as food is concerned, and how best to preserve and foster it (§3 and §4). The closing section draws some suggestions for future investigations and interventions