Phytochemicals: the good, the bad and the ugly?

Phytochemicals are constitutive metabolites that enable plants to overcome temporary or continuous threats integral to their environment, while also controlling essential functions of growth and reproduction. All of these roles are generally advantageous to the producing organisms but the inherent biological activity of such constituents often causes dramatic adverse consequences in other organisms that may be exposed to them. Nevertheless, such effects may be the essential indicator of desirable properties, such as therapeutic potential, especially when the mechanism of bioactivity can be delineated. Careful observation of cause and effect, followed by a coordinated approach to identify the responsible entities, has proved extremely fruitful in discovering roles for phytochemical constituents. The process is illustrated by selected examples of plants poisonous to animals and include the steroidal alkaloid toxin of Veratrum californicum (Western false hellebore), piperidine alkaloids of Lupinus species (lupines), and polyhydroxy indolizidine, pyrrolizidine and nortropane alkaloids of Astragalus and Oxytropis species (locoweeds), Castanospermum australe (Moreton Bay chestnut) and Ipomoea species (morning glories).     

Prion hypothesis: the end of the controversy?

Forty-three years have passed since it was first proposed that a protein could be the sole component of the infectious agent responsible for the enigmatic prion diseases. Many discoveries have strongly supported the prion hypothesis, but only recently has this once heretical hypothesis been widely accepted by the scientific community. In the past 3 years, researchers have achieved the 'Holy Grail' demonstration that infectious material can be generated in vitro using completely defined components. These breakthroughs have proven that a misfolded protein is the active component of the infectious agent, and that propagation of the disease and its unique features depend on the self-replication of the infectious folding of the prion protein. In spite of these important discoveries, it remains unclear whether another molecule besides the misfolded prion protein might be an essential element of the infectious agent. Future research promises to reveal many more intriguing features about the rogue prions.     

Myosin structure: does the tail wag the dog?

Previous crystal structures of the myosin head have shown two different conformations, postulated to be the beginning and the end of the actomyosin power stroke. A new crystal structure reveals a dramatically different conformation; but how does this conformation fit into the force-generating cycle of actomyosin interactions?     

Exosomes and retroviruses: the chicken or the egg?

Retroviruses appropriate pre‐existing cellular machineries to propagate. In the last decade, impressive similarities have been observed in the generation and dissemination in the host cells of retroviruses and small cellular vesicles known as exosomes. These cellular vesicles are thought to facilitate intercellular communication processes and mediate immune functions. However, their link to the retroviral life cycle has given rise to distinct hypotheses and puzzling dilemmas. Are exosomes the antecessors of retroviruses or do retroviruses merely exploit the same cellular machinery designated for exosome biosynthesis? Here, we address these fascinating evolutionary questions by reviewing recent discoveries and analysing the controversies surrounding them.     

Comparative plant development: the time of the leaf?

A key problem in developmental biology is understanding the origin of morphological innovations. Comparative studies in plants with different leaf morphologies indicate that the developmental pathway defined by KNOTTED1-type homeodomain proteins could be involved in generating different leaf forms. The differential expression of regulatory proteins has emerged as an important factor in driving morphological innovations in the plant kingdom--an idea that is well supported by quantitative trait locus analyses.     

Fibrillin protein function: the tip of the iceberg?

Fibrillins are nuclear-encoded, plastid proteins associated with chromoplast fibrils and chloroplast plastoglobules, thylakoids, photosynthetic antenna complexes, and stroma. There are 12 sub-families of fibrillins. However, only three of these sub-families have been characterized genetically or functionally. We review evidence indicating that fibrillins are involved in plastoglobule structural development, chromoplast pigment accumulation, hormonal responses, protection of the photosynthetic apparatus from photodamage, and plant resistance to a range of biotic and abiotic stresses. The area of fibrillin research has substantial growth potential and will contribute to better understanding of mechanisms of plant stress tolerance and plastid structure and function.     

Halogen bonding: the σ-hole

Halogen bonding refers to the non-covalent interactions of halogen atoms X in some molecules, RX, with negative sites on others. It can be explained by the presence of a region of positive electrostatic potential, the σ-hole, on the outermost portion of the halogen’s surface, centered on the R–X axis. We have carried out a natural bond order B3LYP analysis of the molecules CF₃X, with X = F, Cl, Br and I. It shows that the Cl, Br and I atoms in these molecules closely approximate the configuration, where the z-axis is along the R–X bond. The three unshared pairs of electrons produce a belt of negative electrostatic potential around the central part of X, leaving the outermost region positive, the σ-hole. This is not found in the case of fluorine, for which the combination of its high electronegativity plus significant sp-hybridization causes an influx of electronic charge that neutralizes the σ-hole. These factors become progressively less important in proceeding to Cl, Br and I, and their effects are also counteracted by the presence of electron-withdrawing substituents in the remainder of the molecule. Thus a σ-hole is observed for the Cl in CF₃Cl, but not in CH₃Cl. Figure Schematic representation of the atomic charge generation. The molecular electrostatic potential (MEP) is calculated using the AM1* Hamiltonian. The semiempirical MEP is then scaled to DFT or ab initio level and atomic charges are generated from it by the restrained electrostatic potential (RESP) fit method.     

Archamoebae: the ancestral eukaryotes?

The archezoan phylum Archamoebae Cavalier-Smith, 1983 is here modified by adding a new order Phreatamoebida (presently containing only Phreatamoeba) and removing the family Entamoebidae. Entamoebidae are instead tentatively placed as a class Entamoebea together with the classes Heterolobosea, Percolomonadea and Pseudociliatea in the new protozoan phylum Percolozoa Cavalier-Smith, 1991. Thus emended the phylum Archamoebae is more homogeneous; it is more distinguished from the other two phyla of the primitively amitochondrial kingdom and superkingdom Archezoa (i.e. Metamonada and Microsporidia) by having kinetids with only a single flagellum and basal body and a flagellar root consisting of a cone of evenly spaced microtubules. This unikont character of the archamoebae suggests that they may be ancestral to the tetrakont Metamonada, from which the non-flagellate Microsporidia possibly evolved. Higher eukaryotes (superkingdom Metakaryota) probably evolved from a tetrakont metamonad by the symbiotic origin of mitochondria and peroxisomes. If so, the Archamoebae are the most primitive extant phylum of eukaryotes; if molecular phylogenetic studies confirm this idea, Archamoebae will deserve intensive study, which could reveal much about the origin of the eukaryote condition and also establish what is truly universal among eukaryotes. Archamoebae, like other Archezoa, lack mitochondria and peroxisomes and have no obvious Golgi dictyosomes. Their evolutionary significance is discussed and a detailed classification is presented in which the two earlier classes are merged into a single one: Pelobiontea Page, 1976 stat. nov., containing two orders Mastigamoebida Frenzel, 1892 (Syn. Rhizo-Flagellata Kent, 1880 non Rhizomastigida auct.) (including Mastigamoeba, Mastigina, Mastigella, Pelomyxa and probably a few other genera, which have one or more flagella or cilia (motile or immotile, 9 + 2 or otherwise) in the amoeboid trophic phase), and Phreatamoebida ord. nov. (including only Phreatamoeba in the new family Phreatamoebidae, which has alternating phases of non-flagellate amoebae and uniflagellate cells). Mastigamoebida are divided into three families: Mastigamoebidae Goldschmidt, 1907; Mastigellidae fam. nov.; Pelomyxidae Schulze, 1877. Archamoebae may be uni- or multi-nucleate and either gut parasites or (more usually) free-living in soil, freshwater, or marine habitats. Some can form cysts that would probably fossilize; the earliest (1450 My old) smooth-walled fossil cells large enough to be probable eukaryotes might therefore be archamoebal cysts.     

Nitrosylation: the next phosphorylation?

Vitamin D3 plays an important role in the regulation of mineral homeostasis, cell differentiation, and proliferation. However, the exact role of vitamin D3 in vascular smooth muscle cells remains unclear. In the present study, we investigated whether vitamin D3 induces vascular endothelial growth factor (VEGF) release in aortic smooth muscle A10 cells. 1,25-Dihydroxyvitamin D3 (1,25(OH)2VD3), an active form of vitamin D3, stimulated the VEGF release while 24,25-dihydroxyvitamin D3 (24,25(OH)2VD3), an inactive form of vitamin D3, had little effect on the release. The stimulatory effect of 1,25(OH)2VD3 was dose dependent in the range between 10 pM and 10 nM. 1,25(OH)2VD3 induced the phosphorylation of p38 mitogen-activated protein (MAP) kinase but 24,25(OH)2VD3 did not. PD169316 and SB203580, specific inhibitors of p38 MAP kinase, significantly reduced the 1,25(OH)2VD3-stimulated release of VEGF. On the contrary, SB202474, a negative control for p38 MAP kinase inhibitor, had little effect on the VEGF release. PD169316 attenuated the 1,25(OH)2VD3-induced phosphorylation of p38 MAP kinase. These results strongly suggest that 1,25(OH)2VD3 stimulates the release of VEGF in aortic smooth muscle cells via p38 MAP kinase activation.     

The pen and the sword: recovering the disciplinary identity of physiology and anatomy before 1800: II: Old anatomy—the sword

Following the exploration of the disciplinary identity of physiology before 1800 in the previous paper of this pair, the present paper seeks to recover the complementary identity of the discipline of anatomy before 1800. The manual, artisanal character of anatomy is explored via some of its practitioners, with special attention being given to William Harvey and Albrecht von Haller. Attention is particularly drawn to the important role of experiment in anatomical research and practice—which has been misread by historians as physiological experiment. Although scientific status was claimed by some practitioners for the discipline, the knife remained the tool of the discipline. Finally the differences between the teleological assumptions underlying anatomy, and the ‘argument from design’ or natural theology are explored.