Modeling the tetraphenylalanine-PEG hybrid amphiphile: from DFT calculations on the peptide to molecular dynamics simulations on the conjugate

The conformational properties of the hybrid amphiphile formed by the conjugation of a hydrophobic peptide with four phenylalanine (Phe) residues and hydrophilic poly(ethylene glycol), have been investigated using quantum mechanical calculations and atomistic molecular dynamics simulations. The intrinsic conformational preferences of the peptide were examined using the building-up search procedure combined with B3LYP/ 6-31G(d) geometry optimizations, which led to the identification of 78, 78, and 92 minimum energy structures for the peptides containing one, two, and four Phe residues. These peptides tend to adopt regular organizations involving turn-like motifs that define ribbon or helicallike arrangements. Furthermore, calculations indicate that backbone ... side chain interactions involving the N-H of the amide groups and the pi clouds of the aromatic rings play a crucial role in Phe-containing peptides. On the other hand,MD simulations on the complete amphiphile in aqueous solution showed that the polymer fragment rapidly unfolds maximizing the contacts with the polar solvent, even though the hydrophobic peptide reduce the number of waters of hydration with respect to an individual polymer chain of equivalent molecular weight. In spite of the small effect of the peptide in the hydrodynamic properties of the polymer, we conclude that the two counterparts of the amphiphile tend to organize as independent modules.

Structural characterization of a new crystal form of the four-way Holliday junction formed by the DNA sequence d(CCGGTACCGG)2: sequence versus lattice?

DNA-strand exchange is a vital step in the recombination process, of which a key intermediate is the four-way DNA Holliday junction formed transiently in most living organisms. Here, the single-crystal structure at a resolution of 2.35 Å of such a DNA junction formed by d(CCGGTACCGG)2, which has crystallized in a more highly symmetrical packing mode to that previously observed for the same sequence, is presented. In this case, the structure is isomorphous to the mismatch sequence d(CCGGGACCGG)2, which reveals the roles of both lattice and DNA sequence in determining the junction geometry. The helices cross at the larger angle of 43.0° (the previously observed angle for this sequence was 41.4°) as a right-handed X. No metal cations were observed; the crystals were grown in the presence of only group I counter-cations.

A comparison among four different retrieval methods for ice-cloud properties using data from CloudSat, CALIPSO, and MODIS

The A-Train constellation of satellites provides a new capability to measure vertical cloud profiles that leads to more detailed information on ice-cloud microphysical properties than has been possible up to now. A variational radar–lidar ice-cloud retrieval algorithm (VarCloud) takes advantage of the complementary nature of the CloudSat radar and Cloud–Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO) lidar to provide a seamless retrieval of ice water content, effective radius, and extinction coefficient from the thinnest cirrus (seen only by the lidar) to the thickest ice cloud (penetrated only by the radar). In this paper, several versions of the VarCloud retrieval are compared with the CloudSat standard ice-only retrieval of ice water content, two empirical formulas that derive ice water content from radar reflectivity and temperature, and retrievals of vertically integrated properties from the Moderate Resolution Imaging Spectroradiometer (MODIS) radiometer. The retrieved variables typically agree to within a factor of 2, on average, and most of the differences can be explained by the different microphysical assumptions. For example, the ice water content comparison illustrates the sensitivity of the retrievals to assumed ice particle shape. If ice particles are modeled as oblate spheroids rather than spheres for radar scattering then the retrieved ice water content is reduced by on average 50% in clouds with a reflectivity factor larger than 0 dBZ. VarCloud retrieves optical depths that are on average a factor-of-2 lower than those from MODIS, which can be explained by the different assumptions on particle mass and area; if VarCloud mimics the MODIS assumptions then better agreement is found in effective radius and optical depth is overestimated. MODIS predicts the mean vertically integrated ice water content to be around a factor-of-3 lower than that from VarCloud for the same retrievals, however, because the MODIS algorithm assumes that its retrieved effective radius (which is mostly representative of cloud top) is constant throughout the depth of the cloud. These comparisons highlight the need to refine microphysical assumptions in all retrieval algorithms and also for future studies to compare not only the mean values but also the full probability density function.

Provider diversity in the English NHS: a study of recent developments in four local health economies

Objectives: The overall objective of the research was to assess the impact of provider diversity on quality and innovation in the English NHS. The aims were to map the extent of diverse provider activity, identify the differences in performance between Third Sector Organisations (TSOs), for-profit private enterprises, and incumbent organisations within the NHS, and the factors that affect the entry and growth of new private and TSOs. Methods: Case studies of four Local Health Economies (LHEs). Data included: semi-structured interviews with 48 managerial and clinical staff from NHS organizations and providers from the private and Third Sector; some documentary evidence; a focus group with service users; and routine data from the Care Quality Commission and Companies House. Data collection was mainly between November 2008 and November 2009. Results: Involvement of diverse providers in the NHS is limited. Commissioners’ local strategies influence degrees of diversity. Barriers to the entry for TSOs include lack of economies of scale in the bidding process. Private providers have greater concern to improve patient pathways and patient experience, whereas TSOs deliver quality improvements by using a more holistic approach and a greater degree of community involvement. Entry of new providers drives NHS Trusts to respond by making improvements. Information sharing diminishes as competition intensifies. Conclusions: There is scope to increase the participation of diverse providers in the NHS, but care must be taken not to damage public accountability, overall productivity, equity and NHS providers (especially acute hospitals, which are likely to remain in the NHS) in the process.

Tarabotti fra storia e storiografia: miti, fatti e alcune questioni più generali

This article presents the state of the arts about suor Arcangela Tarabotti, once "little less than a foot-note" well-known to scholars only (even if by Benedetto Croce, the most important of all XXth century Italian historians) and nowadays a literary case and a well-recognised proto-feminist, whose works are now all translated into English. The article examins the fortune (or misfortune) she enjoyed over the centuries, the reasons of her current international success, her life according to real documents and to her more fantasist accounts, the archives research and recent publications on her. It also explores the theoretical issues currently in place within Italian women's studies, moving from the 1970s' emphasis on witches, to the 1980s' passion for women saints, and the current obsession with queens and "winners", in order to prove that Arcangela Tarabotti was someonw unique who paid an enormous price for her bravery and outspokness, having been cloistered without a religious vocation.

Typification of four North American club-chollas: the names of four Engelmannian species from Mexico and Southwestern United States

The names Opuntia bulbispina, O. clavata, O. emoryi and O. grahamii, originally proposed by George Engelmann between 1848 and 1856, are reviewed and typified after new findings of previously unknown voucher specimens. Original materials collected by some of the collaborators employed by Engelmann during the Mexican Boundary Survey were discovered in a loan from the Torrey Herbarium at the New York Botanical Garden (NY). Many of the materials include fragments of stems and fruits, and others include only sectioned flowers and some seeds. Particularly good descriptions of the species here concerned were published in Engelmann’s “Synopsis of the Cactaceae” in 1857, and exceptional illustrations were produced by Paulus Roetter and printed in “Cactaceae of the Boundary” in 1859. The problems surrounding some previous typifications of these names range from typification of joint lectotypes to illegitimate typifications of illustrations when original material was known to exist. The materials selected for typification were collected by the Mexican Boundary Survey and are lodged at the herbaria of the Missouri Botanical Garden (MO) and the New York Botanical Garden (NY); some are illustrations published by Engelmann.

Adaptive evolution of four microcephaly genes and the evolution of brain size in anthropoid primates

The anatomical basis and adaptive function of the expansion in primate brain size have long been studied; however, we are only beginning to understand the genetic basis of these evolutionary changes. Genes linked to human primary microcephaly have received much attention as they have accelerated evolutionary rates along lineages leading to humans. However, these studies focus narrowly on apes, and the link between microcephaly gene evolution and brain evolution is disputed. We analyzed the molecular evolution of four genes associated with microcephaly (ASPM, CDK5RAP2, CENPJ, MCPH1) across 21 species representing all major clades of anthropoid primates. Contrary to prevailing assumptions, positive selection was not limited to or intensified along the lineage leading to humans. In fact we show that all four loci were subject to positive selection across the anthropoid primate phylogeny. We developed clearly defined hypotheses to explicitly test if selection on these loci was associated with the evolution of brain size. We found positive relationships between both CDK5RAP2 and ASPM and neonatal brain mass and somewhat weaker relationships between these genes and adult brain size. In contrast, there is no evidence linking CENPJ and MCPH1 to brain size evolution. The stronger association of ASPM and CDK5RAP2 evolution with neonatal brain size than with adult brain size is consistent with these loci having a direct effect on prenatal neuronal proliferation. These results suggest that primate brain size may have at least a partially conserved genetic basis. Our results contradict a previous study that linked adaptive evolution of ASPM to changes in relative cortex size; however, our analysis indicates that this conclusion is not robust. Our finding that the coding regions of two widely expressed loci has experienced pervasive positive selection in relation to a complex, quantitative developmental phenotype provides a notable counterexample to the commonly asserted hypothesis that cisregulatory regions play a dominant role in phenotypic evolution. Key words: ASPM, MCPH1, CDK5RAP2, CENPJ, brain, neurogenesis, primates.