Transition metal-mediated cyclizations and synthesis of annonaceous acetogenin analogs

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Evolution of embryonic developmental period in the marine bird families Alcidae and Spheniscidae: roles for nutrition and predation?

Background: Nutrition and predation have been considered two primary agents of selection important in theevolution of avian life history traits. The relative importance of these natural selective forces in the evolution of avianembryonic developmental period (EDP) remain poorly resolved, perhaps in part because research has tended to focuson a single, high taxonomic-level group of birds: Order Passeriformes. The marine bird families Alcidae (auks) andSpheniscidae (penguins) exhibit marked variation in EDP, as well as behavioural and ecological traits ultimately linkedto EDP. Therefore, auks and penguins provide a unique opportunity to assess the natural selective basis of variation in akey life-history trait at a low taxonomic-level. We used phylogenetic comparative methods to investigate the relativeimportance of behavioural and ecological factors related to nutrition and predation in the evolution of avian EDP.Results: Three behavioural and ecological variables related to nutrition and predation risk (i.e., clutch size, activitypattern, and nesting habits) were significant predictors of residual variation in auk and penguin EDP based on modelspredicting EDP from egg mass. Species with larger clutch sizes, diurnal activity patterns, and open nests hadsignificantly shorter EDPs. Further, EDP was found to be longer among birds which forage in distant offshore waters,relative to those that foraged in near shore waters, in line with our predictions, but not significantly so.Conclusion: Current debate has emphasized predation as the primary agent of selection driving avian life historydiversification. Our results suggest that both nutrition and predation have been important selective forces in theevolution of auk and penguin EDP, and highlight the importance of considering these questions at lower taxonomicscales. We suggest that further comparative studies on lower taxonomic-level groups will continue to constructivelyinform the debate on evolutionary determinants of avian EDP, as well as other life history parameters

Influence of photoperiod and running wheel access on the entrainment of split circadian rhythms in hamsters

BACKGROUND: In the laboratory, behavioral and physiological states of nocturnal rodents alternate, with a period near 24 h, between those appropriate for the night (e.g., elevated wheel-running activity and high melatonin secretion) and for the day (e.g., rest and low melatonin secretion). Under appropriate 24 h light:dark:light:dark conditions, however, rodents may be readily induced to express bimodal rest/activity cycles that reflect a global temporal reorganization of the central neural pacemaker in the hypothalamus. We examine here how the relative length of the light and dark phases of the environmental cycle influences this rhythm splitting and the necessity of a running wheel for expression of this entrainment condition. RESULTS: Rhythm splitting was observed in wheel-running and general locomotion of Siberian and Syrian hamsters. The latter also manifest split rhythms in body temperature. Access to a running wheel was necessary neither for the induction nor maintenance of this entrainment pattern. While rhythms were only transiently split in many animals with two 5 h nights, the incidence of splitting was greater with twice daily nights of shorter duration. Removal of running wheels altered the body temperature rhythm but did not eliminate its clear bimodality. CONCLUSION: The expression of entrained, split circadian rhythms exhibits no strict dependence on access to a running wheel, but can be facilitated by manipulation of ambient lighting conditions. These circadian entrainment patterns may be of therapeutic value to human shift-workers and others facing chronobiological challenges

Perylene-Based Covalent Organic Frameworks for Acid Vapor Sensing.

Traditionally, the properties and functions of covalent organic frameworks (COFs) are defined by their constituting building blocks, while the chemical bonds that connect the individual subunits have not attracted much attention as functional components of the final material. We have developed a new series of dual-pore perylene-based COFs and demonstrated that their imine bonds can be protonated reversibly, causing significant protonation-induced color shifts toward the near-infrared, while the structure and crystallinity of the frameworks are fully retained. Thin films of these COFs are highly sensitive colorimetric acid vapor sensors with a detection limit as low as 35 μg L-1 and a response range of at least 4 orders of magnitude. Since the acidochromism in our COFs is a cooperative phenomenon based on electronically coupled imines, the COFs can be used to determine simultaneously the concentration and protonation strength of nonaqueous acid solutions, in which pH electrodes are not applicable, and to distinguish between different acids. Including the imine bonds as function-determining constituents of the framework provides an additional handle for constructing multifunctional COFs and extending the range of their possible applications

The Structure of the Fusion Glycoprotein of Newcastle Disease Virus Suggests a Novel Paradigm for the Molecular Mechanism of Membrane Fusion

AbstractBackground: Membrane fusion within the Paramyxoviridae family of viruses is mediated by a surface glycoprotein termed the “F”, or fusion, protein. Membrane fusion is assumed to involve a series of structural transitions of F from a metastable (prefusion) state to a highly stable (postfusion) state. No detail is available at the atomic level regarding the metastable form of these proteins or regarding the transitions accompanying fusion.Results: The three-dimensional structure of the fusion protein of Newcastle disease virus (NDV-F) has been determined. The trimeric NDV-F molecule is organized into head, neck, and stalk regions. The head is comprised of a highly twisted β domain and an additional immunoglobulin-like β domain. The neck is formed by the C-terminal extension of the heptad repeat region HR-A, capped by a four-helical bundle. The C terminus of HR-A is encased by a further helix HR-C and a 4-stranded β sheet. The stalk is formed by the remaining visible portion of HR-A and by polypeptide immediately N-terminal to the C-terminal heptad repeat region HR-B. An axial channel extends through the head and neck and is fenestrated by three large radial channels located approximately at the head–neck interface.Conclusion: We propose that prior to fusion activation, the hydrophobic fusion peptides in NDV-F are sequestered within the radial channels within the head, with the central HR-A coiled coil being only partly formed. Fusion activation then involves, inter alia, the assembly of a complete HR-A coiled coil, with the fusion peptides and transmembrane anchors being brought into close proximity. The structure of NDV-F is fundamentally different than that of influenza virus hemagglutinin, in that the central coiled coil is in the opposite orientation with respect to the viral membrane

Deoxyribonucleic Acid Encoded and Size-Defined π-Stacking of Perylene Diimides

Natural photosystems use protein scaffolds to control intermolecular interactions that enable exciton flow, charge generation, and long-range charge separation. In contrast, there is limited structural control in current organic electronic devices such as OLEDs and solar cells. We report here the DNA-encoded assembly of π-conjugated perylene diimides (PDIs) with deterministic control over the number of electronically coupled molecules. The PDIs are integrated within DNA chains using phosphoramidite coupling chemistry, allowing selection of the DNA sequence to either side, and specification of intermolecular DNA hybridization. In this way, we have developed a “toolbox” for construction of any stacking sequence of these semiconducting molecules. We have discovered that we need to use a full hierarchy of interactions: DNA guides the semiconductors into specified close proximity, hydrophobic–hydrophilic differentiation drives aggregation of the semiconductor moieties, and local geometry and electrostatic interactions define intermolecular positioning. As a result, the PDIs pack to give substantial intermolecular π wave function overlap, leading to an evolution of singlet excited states from localized excitons in the PDI monomer to excimers with wave functions delocalized over all five PDIs in the pentamer. This is accompanied by a change in the dominant triplet forming mechanism from localized spin–orbit charge transfer mediated intersystem crossing for the monomer toward a delocalized excimer process for the pentamer. Our modular DNA-based assembly reveals real opportunities for the rapid development of bespoke semiconductor architectures with molecule-by-molecule precision

Proteomic analysis of Plasmodium falciparum histone deacetylase 1 complex proteins

Plasmodium falciparum histone deacetylases (PfHDACs) are an important class of epigenetic regulators that alter protein lysine acetylation, contributing to regulation of gene expression and normal parasite growth and development. PfHDACs are therefore under investigation as drug targets for malaria. Despite this, our understanding of the biological roles of these enzymes is only just beginning to emerge. In higher eukaryotes, HDACs function as part of multi-protein complexes and act on both histone and non-histone substrates. Here, we present a proteomics analysis of PfHDAC1 immunoprecipitates, identifying 26 putative P. falciparum complex proteins in trophozoite-stage asexual intraerythrocytic parasites. The co-migration of two of these (P. falciparum heat shock proteins 70-1 and 90) with PfHDAC1 was validated using Blue Native PAGE combined with Western blot. These data provide a snapshot of possible PfHDAC1 interactions and a starting point for future studies focused on elucidating the broader function of PfHDACs in Plasmodium parasites

Photogeneration of Spin Quintet Triplet–Triplet Excitations in DNA-Assembled Pentacene Stacks

Singlet fission (SF), an exciton-doubling process observed in certain molecular semiconductors where two triplet excitons are generated from one singlet exciton, requires correctly tuned intermolecular coupling to allow separation of the two triplets to different molecular units. We explore this using DNA-encoded assembly of SF-capable pentacenes into discrete π-stacked constructs of defined size and geometry. Precise structural control is achieved via a combination of the DNA duplex formation between complementary single-stranded DNA and the local molecular geometry that directs the SF chromophores into a stable and predictable slip-stacked configuration, as confirmed by molecular dynamics (MD) modeling. Transient electron spin resonance spectroscopy revealed that within these DNA-assembled pentacene stacks, SF evolves via a bound triplet pair quintet state, which subsequently converts into free triplets. SF evolution via a long-lived quintet state sets specific requirements on intermolecular coupling, rendering the quintet spectrum and its zero-field-splitting parameters highly sensitive to intermolecular geometry. We have found that the experimental spectra and zero-field-splitting parameters are consistent with a slight systematic strain relative to the MD-optimized geometry. Thus, the transient electron spin resonance analysis is a powerful tool to test and refine the MD-derived structure models. DNA-encoded assembly of coupled semiconductor molecules allows controlled construction of electronically functional structures, but brings with it significant dynamic and polar disorders. Our findings here of efficient SF through quintet states demonstrate that these conditions still allow efficient and controlled semiconductor operation and point toward future opportunities for constructing functional optoelectronic systems