Disorder and order in unfolded and disordered peptides and proteins: A view derived from tripeptide conformational analysis. II. Tripeptides with short side chains populating asx and β‐type like turn conformations

In the preceding paper, we found that ensembles of tripeptides with long or bulky chains can include up to 20% of various turns. Here, we determine the structural and thermodynamic characteristics of GxG peptides with short polar and/or ionizable central residues (D, N, C), whose conformational distributions exhibit higher than average percentage (>20%) of turn conformations. To probe the side‐chain conformations of these peptides, we determined the ³J(H^α,H^β) coupling constants and derived the population of three rotamers with χ₁‐angles of ?60°, 180° and 60°, which were correlated with residue propensities by DFT‐calculations. For protonated GDG, the rotamer distribution provides additional evidence for asx‐turns. A comparison of vibrational spectra and NMR coupling constants of protonated GDG, ionized GDG, and the protonated aspartic acid dipeptide revealed that side chain protonation increases the pPII content at the expense of turn populations. The charged terminal groups, however, have negligible influence on the conformational properties of the central residue. Like protonated GDG, cationic GCG samples asx‐turns to a significant extent. The temperature dependence of the UVCD spectra and ³J(H^NH^α) constants suggest that the turn populations of GDG and GNG are practically temperature‐independent, indicating enthalpic and entropic stabilization. The temperature‐independent J‐coupling and UVCD spectra of GNG require a three‐state model. Our results indicate that short side chains with hydrogen bonding capability in GxG segments of proteins may serve as hinge regions for establishing compact structures of unfolded proteins and peptides. Proteins 2013. © 2012 Wiley Periodicals, Inc.     

Synthesis and FTIR Conformational Studies of Peptides From the Basic Region of c-Jun: a Critical Analysis on the Basis of CD and NMR Data

Abstract

The peptide (35 residues) corresponding to the basic subdomain (bSD) of c-Jun (residues 252–281) and its fragments NP (N-terminal peptide, 1–19) and CP (C-terminal peptide, 1635) were synthesized in stepwise solid-phase using the tert-butyloxycarbonyl/benzyl strategy. In a previous paper, we have shown that during its binding to the DNA site CRE (cAMP- responsive element) the bSD structure was converted into α-helix from an initial random coil conformation [Krebs, D., Dahmani, B., El Antri, S., Monnot, M., Convert, O., Mauffret, O., Troalen, F. & Fermandjian, S. Eur. J. Biochem. 231, 370–380 (1995)]. Our results suggested both a high flexibility and a helical potential in bSD, these two properties seeming crucial for the accommodation of the basic subdomain of c-Jun to its specific DNA targets. In this work, we assessed the conformational variability of bSD through the study of the secondary structures of its NP and CP fragments in trifluoroethanol (TFE)/²H₂O mixtures, using Fourier transform infrared (FTIR) spectroscopy. The IR results were critically analyzed in light of our previously reported circular dichroism (CD) and NMR data [Krebs, D., Dahmani, B., Monnot, M., Mauffret, O., Troalen, F. & Fermandjian, S. Eur. J. Biochem. 235, 699–712 (1996)]. Upon addition of TFE, the relative areas of the seven components of the amide I band (1700–1620 cm^?1) reflected the conversion of a large amount of random coil conformation into α-helix for the two fragments and bSD. This effect was accompanied by more subtle variations of the less populated structures, in agreement with the results of CD and NMR experiments. The IR results stipulated the conservation of the parent bSD secondary structures in both fragments; however, NP and CP peptides did not display similar random-to-α-helix stabilization pattern upon additions of TFE to aqueous solutions. The profile from CD signal at 222 nm was found sigmoidal for NP and almost linear for CP, while that corresponding to the parent peptide bSD was just in between those of its fragments. Thus, the present study confirms the high flexibility and helix propensity of the c-Jun basic subdomain and suggests that the N- and C-terminal parts of the peptide do not follow the same random-to-helix conversion profile during their complexation with DNA.     

On the limitations of standard statistical modeling in biological systems: A full Bayesian approach for biology

One of the most important scientific challenges today is the quantitative and predictive understanding of biological function. Classical mathematical and computational approaches have been enormously successful in modeling inert matter, but they may be inadequate to address inherent features of biological systems. We address the conceptual and methodological obstacles that lie in the inverse problem in biological systems modeling. We introduce a full Bayesian approach (FBA), a theoretical framework to study biological function, in which probability distributions are conditional on biophysical information that physically resides in the biological system that is studied by the scientist.     

Estimating the age structure of a buried adult population: A new statistical approach applied to archaeological digs in France

Paleodemographers have developed several methods for estimating the age structure of historical populations in absence of civil registration data. Starting from biological indicators alone, they use a reference population of known sex and age to assess the conditional distribution of the biological indicator given age. However, the small amount of data available and the unstable nature of the related statistical problem mean that most methods are disappointing. Using the most reliable reference data possible, we propose a simple statistical method, integrating the maximum amount of information included in the actual data, which quite significantly improves age estimates for a buried population. Here the method is applied to a French cemetery used from Late Antiquity to the end of the Early Middle Ages. Am J Phys Anthropol, 2013. © 2012 Wiley Periodicals, Inc.     

Molecular identification of mosquitoes (Diptera: Culicidae) in southeastern Australia

DNA barcoding is a modern species identification technique that can be used to distinguish morphologically similar species, and is particularly useful when using small amounts of starting material from partial specimens or from immature stages. In order to use DNA barcoding in a surveillance program, a database containing mosquito barcode sequences is required. This study obtained Cytochrome Oxidase I (COI) sequences for 113 morphologically identified specimens, representing 29 species, six tribes and 12 genera; 17 of these species have not been previously barcoded. Three of the 29 species ─ Culex palpalis, Macleaya macmillani, and an unknown species originally identified as Tripteroides atripes ─ were initially misidentified as they are difficult to separate morphologically, highlighting the utility of DNA barcoding. While most species grouped separately (reciprocally monophyletic), the Cx. pipiens subgroup could not be genetically separated using COI. The average conspecific and congeneric p‐distance was 0.8% and 7.6%, respectively. In our study, we also demonstrate the utility of DNA barcoding in distinguishing exotics from endemic mosquitoes by identifying a single intercepted Stegomyia aegypti egg at an international airport. The use of DNA barcoding dramatically reduced the identification time required compared with rearing specimens through to adults, thereby demonstrating the value of this technique in biosecurity surveillance. The DNA barcodes produced by this study have been uploaded to the ‘Mosquitoes of Australia–Victoria’ project on the Barcode of Life Database (BOLD), which will serve as a resource for the Victorian Arbovirus Disease Control Program and other national and international mosquito surveillance programs.     

Multidimensional biases,gaps and uncertainties in global plant occurrence information

Plants are a hyperdiverse clade that plays a key role in maintaining ecological and evolutionary processes as well as human livelihoods. Biases, gaps and uncertainties in plant occurrence information remain a central problem in ecology and conservation, but these limitations remain largely unassessed globally. In this synthesis, we propose a conceptual framework for analysing gaps in information coverage, information uncertainties and biases in these metrics along taxonomic, geographical and temporal dimensions, and apply it to all c. 370 000 species of land plants. To this end, we integrated 120 million point‐occurrence records with independent databases on plant taxonomy, distributions and conservation status. We find that different data limitations are prevalent in each dimension. Different metrics of information coverage and uncertainty are largely uncorrelated, and reducing taxonomic, spatial or temporal uncertainty by filtering out records would usually come at great costs to coverage. In light of these multidimensional data limitations, we discuss prospects for global plant ecological and biogeographical research, monitoring and conservation and outline critical next steps towards more effective information usage and mobilisation. Our study provides an empirical baseline for evaluating and improving global floristic knowledge, along with a conceptual framework that can be applied to study other hyperdiverse clades.     

Strong Interplay between Sodium and Oxygen in Kesterite Absorbers: Complex Formation,Incorporation, and Tailoring Depth Distributions

Sodium and oxygen are prevalent impurities in kesterite solar cells. Both elements are known to strongly impact performance of the kesterite devices and can be connected to efficiency improvements seen after heat treatments. The sodium distribution in the kesterite absorber is commonly reported, whereas the oxygen distribution has received less attention. Here, a direct relationship between sodium and oxygen in kesterite absorbers is established using secondary ion mass spectrometry and explained by defect analyses within the density functional theory. The calculations reveal a binding energy of 0.76 eV between the substitutional defects Na_Cu and O_S in the nearest neighbor configuration, indicating an abundance of Na? O complexes in kesterite absorbers at relevant temperatures. Oxygen incorporation is studied by introducing isotopic ¹⁸O at different stages of the Cu₂ZnSnS₄/Mo/soda‐lime glass baseline processing. It is observed that oxygen from the Mo back contact and contaminations during the sulfurization are primary contributors to the oxygen distribution. Indeed, unintentional oxygen incorporation leads to immobilization of sodium. This results in a strong correlation between sodium and oxygen, in excellent agreement with the theoretical calculations. Consequently, oxygen availability should be monitored to optimize postdeposition heat treatments to control impurities in kesterite absorbers and ultimately, the solar cell efficiency.     

Attentional bias in the radial and vertical dimensions of space

Under visual guidance, healthy subjects usually misbisect radial lines farther than, and vertical lines above the true center. It was suggested that radial and vertical misbisection depended on the presence of an attentional bias toward far/upper space. The aim of the present study was to investigate whether such attentional bias depends on a single mechanism or on separate mechanisms. Ninety participants were asked to bisect lines radially and vertically oriented. The results confirmed the presence of a consistent bisection bias farther than (radial lines), and above (vertical lines) the true center. Furthermore, there was a significant correlation between radial and vertical bisection errors. These findings suggest that a single neural mechanism is involved in producing the attentional bias toward far/upper space.