Peptide Bond Distortions from Planarity: New Insights from Quantum Mechanical Calculations and Peptide/Protein Crystal Structures

By combining quantum-mechanical analysis and statistical survey of peptide/protein structure databases we here report a thorough investigation of the conformational dependence of the geometry of peptide bond, the basic element of protein structures. Different peptide model systems have been studied by an integrated quantum mechanical approach, employing DFT, MP2 and CCSD(T) calculations, both in aqueous solution and in the gas phase. Also in absence of inter-residue interactions, small distortions from the planarity are more a rule than an exception, and they are mainly determined by the backbone ψ dihedral angle. These indications are fully corroborated by a statistical survey of accurate protein/peptide structures. Orbital analysis shows that orbital interactions between the σ system of Cα substituents and the π system of the amide bond are crucial for the modulation of peptide bond distortions. Our study thus indicates that, although long-range inter-molecular interactions can obviously affect the peptide planarity, their influence is statistically averaged. Therefore, the variability of peptide bond geometry in proteins is remarkably reproduced by extremely simplified systems since local factors are the main driving force of these observed trends. The implications of the present findings for protein structure determination, validation and prediction are also discussed

Toward a unified functional account of structural focus and negation in Hungarian

The goal of this paper is to provide a unified analysis of the function of various types of (structural) focus and the negative particle (used preverbally) in Hungarian. It is argued that the function of these elements (each inducing the inversion of verbal modifier and verb) is best understood with respect to the interpretation assigned to the verbal predicate in different contexts. By treating the verbal predicate as a schematic positive declarative clause (or “proto-statement”) in its default interpretation, it becomes possible to define the function of the elements concerned in terms of the kind of relation in which they stand with the proto-statement, the kind of relation in which the overall symbolic pattern (as a Gestalt) stands with the unmarked positive declarative clause type

The bear in Eurasian plant names: Motivations and models

Ethnolinguistic studies are important for understanding an ethnic group's ideas on the world, expressed in its language. Comparing corresponding aspects of such knowledge might help clarify problems of origin for certain concepts and words, e.g. whether they form common heritage, have an independent origin, are borrowings, or calques. The current study was conducted on the material in Slavonic, Baltic, Germanic, Romance, Finno-Ugrian, Turkic and Albanian languages. The bear was chosen as being a large, dangerous animal, important in traditional culture, whose name is widely reflected in folk plant names. The phytonyms for comparison were mostly obtained from dictionaries and other publications, and supplemented with data from databases, the co-authors' field data, and archival sources (dialect and folklore materials). More than 1200 phytonym use records (combinations of a local name and a meaning) for 364 plant and fungal taxa were recorded to help find out the reasoning behind bear-nomination in various languages, as well as differences and similarities between the patterns among them. Among the most common taxa with bear-related phytonyms were Arctostaphylos uva-ursi (L.) Spreng., Heracleum sphondylium L., Acanthus mollis L., and Allium ursinum L., with Latin loan translation contributing a high proportion of the phytonyms. Some plants have many and various bear-related phytonyms, while others have only one or two bear names. Features like form and/or surface generated the richest pool of names, while such features as colour seemed to provoke rather few associations with bears. The unevenness of bear phytonyms in the chosen languages was not related to the size of the language nor the present occurence of the Brown Bear in the region. However, this may, at least to certain extent, be related to the amount of the historical ethnolinguistic research done on the selected languages

Characterization of Anthocyanins and Their Antioxidant Activities in Indian Rose Varieties (<i>Rosa</i> × <i>hybrida</i>) Using HPLC

The present study was designed to explore the anthocyanin profile and antioxidant activities in Indian rose varieties (Rosa × hybrida). Among fifty varieties, Ashwini recorded the highest total phenolic content (427.59 ± 3.47 mg GAE/100 g) along with the highest FRAP (397.15 ± 0.82 µmol trolox/g) and DPPH free radical scavenging activity (93.47 ± 0.19%) on a fresh weight basis. A significant positive correlation was observed between total anthocyanin content, total phenolic content, and antioxidant activities. Four distinct clusters were formed according to total anthocyanins, total phenols, and antioxidant activities; white- and yellow-colored varieties were most distant from red ones. Principal component analysis revealed that variable total anthocyanin content contributed to the maximum variation among the fifty rose varieties studied. Highly anthocyanin-rich rose varieties were characterized by high-performance liquid chromatography coupled with a photodiode array detector (HPLC-PAD), which identified two major components of anthocyanins, i.e., cyanidin 3,5-di-O-glucoside and pelargonidin 3,5-di-O-glucoside. Cyanidin 3,5-di-O-glucoside was the predominant anthocyanin in red- and pink-colored varieties, whereas pelargonidin 3,5-di-O-glucoside was the major one in the orange variety. The maximum cyanidin 3,5-di-O-glucoside content was recorded in variety Ashwini (497.79 mg/100 g), whereas the maximum pelargonidin 3,5-di-O-glucoside content was recorded in Suryakiran (185.43 mg/100 g). It is suggested that the rose varieties with high anthocyanin content and antioxidant activity can be exploited as a potential source of nutraceuticals in the food industry

Pharmacovigilance [Pharmacovigilance update].

The main pharmacovigilance updates in 2014 are reviewed. Ivabradine: increased risk of cardiovascular death and myocardial infarction in patients with symptomatic angina treated with high dosages. Clopidogrel: rare observations of acquired hemophilia. Orlistat: may reduce the absorption of HIV antiretrovirals. Ponatinib: increased risk of arteriopathy and thrombosis. Axitinib: significant risk of heart failure (class effect). Tocilizumab: possible causal relationship with the emergence or aggravation of psoriasis. Lithium: hypercalcemia and hyperparathyroidism commonly observed. Sildenalfil: suspected causal association with melanoma, so far not proven, Methylphenidate: rare observations of priapism. St John's wort (Hypericum): reduced effectiveness of hormonal contraceptives, including implants