Diterpenoids with a novel skeleton from the liverwort Anastrophyllum minutum

Six diterpenoids with a novel carbon skeleton were isolated from the liverwort Anastrophyllum minutum. Their structures were determined by means of high field NMR spectroscopy including proton—proton and proton—carbon shift correlation 2D-techniques, NOE difference spectroscopy and high resolution mass spectrometry. Sphenolobane is the proposed name of the new skeletal type and its biogenetic origin is briefly considered. Inhibitory activity against the growth of shoots and roots of rice was shown by 3α,4α-epoxy-5α-acetoxy-18-hydroxysphenoloba-13E, 16E-diene.     

A model for sucrose transport in the maize scutellum

A model originally developed for transport of neutral substrates in bacterial systems was tested for its suitability for depicting sucrose transport across the plasmalemma of the maize scutellum cell. The model contains a sucrose—proton symporter, a negatively-charged free carrier and a neutral sucrose—proton—carrier complex. Sucrose transport is driven by the sucrose gradient and by a proton electrochemical gradient set up by a proton-translocating ATPase. The results of experiments on sucrose uptake in scutellum slices are in accord with predictions based on the model. Evidence was obtained for an electrogenic proton pump in the plasmalemma, for sucrose—proton symport and for a sucrose transport mechanism driven by both electrical potential and pH gradients. It was found that treatments (dinitrophenol, N-ethylmaleimide or HCl) causing a net proton influx into the slices also caused an efflux of sucrose. Interpretations of these results compatible with the model are given.     

Synthesis and characterization of new platinum(II) complexes containing thiazole and imidazole donors

A number of new complexes of Pt(II) of the type cis-Pt(NH₃)(L)Cl₂, where L = thiazole (Tz), 2-bromothiazole (2-Brt), benzothiazole (Bt), 2,1,3- benzothiadiazole (213-Btd), 1,2,3-benzothiadiazole (123-Btd), imidazole (Iz) and 1-methylimidazole (N-Miz) have been prepared. The complexes were characterized by infrared and UV—Vis spectroscopy, proton NMR and elemental analyses. The thiazoles and benzothiazoles were coordinated through the nitrogen heteroatom. However, both the benzothiadiazoles were coordinated through the sulfur heteroatom. Several of the complexes showed significant cytotoxic activity.     

Photo-induced electron transport and water state in Rhodospirillum rubrum chromatophores

It is shown that in bacterial chromatophores the pronounced changes in the free water content with a proton spin-spin relaxation time (T₂) of 10^?3—10^?2 s does not influence the efficiency of electron transfer from the photosynthetic reaction centre to the membrane pool of secondary acceptors. An abrupt inhibition of this process occurs only after the loss of the water with faster proton spin-spin relaxation time (T₂ of 10^?4 s). The process is reversible. The water fraction in question is obviously bound to the chromatophore proteins and forms the primary hydration layer.     

Mitochondrial uncoupling,ROS generation and cardioprotection

Mitochondrial oxidative phosphorylation is incompletely coupled, since protons translocated to the intermembrane space by specific respiratory complexes of the electron transport chain can return to the mitochondrial matrix independently of the ATP synthase —a process known as proton leak— generating heat instead of ATP. Proton leak across the inner mitochondrial membrane increases the respiration rate and decreases the electrochemical proton gradient (Δp), and is an important mechanism for energy dissipation that accounts for up to 25% of the basal metabolic rate. It is well established that mitochondrial superoxide production is steeply dependent on Δp in isolated mitochondria and, correspondingly, mitochondrial uncoupling has been identified as a cytoprotective strategy under conditions of oxidative stress, including diabetes, drug-resistance in tumor cells, ischemia-reperfusion (IR) injury or aging. Mitochondrial uncoupling proteins (UCPs) are able to lower the efficiency of oxidative phosphorylation and are involved in the control of mitochondrial reactive oxygen species (ROS) production. There is strong evidence that UCP2 and UCP3, the UCP1 homologues expressed in the heart, protect against mitochondrial oxidative damage by reducing the production of ROS. This review first analyzes the relationship between mitochondrial proton leak and ROS generation, and then focuses on the cardioprotective role of chemical uncoupling and uncoupling mediated by UCPs. This includes their protective effects against cardiac IR, a condition known to increase ROS production, and their roles in modulating cardiovascular risk factors such as obesity, diabetes and atherosclerosis.     

New names inPhanerogamae 5

103 new nomenclatural combinations are proposed for taxa of European flora, 95 for species, 8 for subspecies. Most of them have resulted from a more natural delimitation of genera. The majority of new combinations are made in the segregants ofCentourea (Acosta—16,Colymbada— 8),Hieracium (Pilosella—16),Scabiosa (Trochocephalus—14),Serratula (Klasea—13) andLeontodon (Scorzoneroides—8). Taxonomie or nomenclatural problems of some taxa (Arum orientale, Colobium taraxacoides, Klasea, Leucanthemopsis alpina agg.,Psyllium, Scorzoneroides, Tephroseris cantabrica) are discussed. Names omitted from the Index Kewensis and corrections of publication places are added (17 names).     

A new model for the agonistic binding site on the histamine H2-receptor: The catalytic triad in serine proteases as a model for the binding site of

The historical model for the agonistic binding site on the histamine H₂-receptor is based on a postulated activation mechanism: it has been suggested that the histamine monocation binds to the histamine H₂-receptor via the formation of three hydrogen bonds. The cationic ammonium group in the side chain and the —NH— group in the π-position of the imidazole act as proton donors, whereas the N— atom in the π-position of the imidazole acts as a proton acceptor. Participation of the ammonium group in H-bonding with a presumed negative charge on the receptor leads to a decrease in positive charge, which is thought to induce a tautomeric change in the imidazole ring system from N^τ-H to N^π-H. A consequence of this tautomeric shift is the donation of a proton from the receptor to the agonist on one side, while on the other side a proton is donated from the agonist to the receptor. The proposed tautomeric shift has been suggested to trigger the H₂-stimulating effect.However, this model for the constitution of the agonistic binding site and the accessory activation mechanism cannot explain the weak histamine H₂-activity of β-histine and the activity of several other recently synthesized H₂-agonists. Based on a thorough literature study and with the aid of molecular electrostatic potentials (MEPs) we demonstrate that the sulphur atom present in histamine H₂-agonists as dimaprit and 2-amino-5-(2-aminoethyl)thiazole does not function as a proton acceptor, which implicitly means that a tautomeric shift is not a prerequisite for H₂-stimulation. As a consequence, the model for the agonistic binding site is adjusted, resulting in a strong resemblance to the nature and orientation of the amino acids constituting the catalytic triad in serine proteases. Within this concept, the N^π-H tautomer of histamine is the biologically active form, in contrast with the existing model in which the N^τ-H tautomer is the active form.     

Crystal Structure of Escherichia coli-Expressed Haloarcula marismortui Bacteriorhodopsin I in the Trimeric Form

Bacteriorhodopsins are a large family of seven-helical transmembrane proteins that function as light-driven proton pumps. Here, we present the crystal structure of a new member of the family, Haloarcula marismortui bacteriorhodopsin I (HmBRI) D94N mutant, at the resolution of 2.5 Å. While the HmBRI retinal-binding pocket and proton donor site are similar to those of other archaeal proton pumps, its proton release region is extended and contains additional water molecules. The protein''s fold is reinforced by three novel inter-helical hydrogen bonds, two of which result from double substitutions relative to Halobacterium salinarum bacteriorhodopsin and other similar proteins. Despite the expression in Escherichia coli and consequent absence of native lipids, the protein assembles as a trimer in crystals. The unique extended loop between the helices D and E of HmBRI makes contacts with the adjacent protomer and appears to stabilize the interface. Many lipidic hydrophobic tail groups are discernible in the membrane region, and their positions are similar to those of archaeal isoprenoid lipids in the crystals of other proton pumps, isolated from native or native-like sources. All these features might explain the HmBRI properties and establish the protein as a novel model for the microbial rhodopsin proton pumping studies.     

Mutations in the D-channel of cytochrome c oxidase causes leakage of the proton pump

It has experimentally been found that certain mutations close to the entry point of the proton transfer channel in cytochrome c oxidase stop proton translocation but not the oxygen reduction chemistry. This effect is termed uncoupling. Since the mutations are 20 Å away from the catalytic center, this is very surprising. A new explanation for this phenomenon is suggested here, involving a local effect at the entry point of the proton channel, rather than the long range effects suggested earlier.     

Use the Protonmotive Force: Mitochondrial Uncoupling and Reactive Oxygen Species

Mitochondrial respiration results in an electrochemical proton gradient, or protonmotive force (pmf), across the mitochondrial inner membrane. The pmf is a form of potential energy consisting of charge (?ψ_m) and chemical (?pH) components, that together drive ATP production. In a process called uncoupling, proton leak into the mitochondrial matrix independent of ATP production dissipates the pmf and energy is lost as heat. Other events can directly dissipate the pmf independent of ATP production as well, such as chemical exposure or mechanisms involving regulated mitochondrial membrane electrolyte transport. Uncoupling has defined roles in metabolic plasticity and can be linked through signal transduction to physiologic events. In the latter case, the pmf impacts mitochondrial reactive oxygen species (ROS) production. Although capable of molecular damage, ROS also have signaling properties that depend on the timing, location, and quantity of their production. In this review, we provide a general overview of mitochondrial ROS production, mechanisms of uncoupling, and how these work in tandem to affect physiology and pathologies, including obesity, cardiovascular disease, and immunity. Overall, we highlight that isolated bioenergetic models—mitochondria and cells—only partially recapitulate the complex link between the pmf and ROS signaling that occurs in vivo.     

Two new species of green eyes of the genus Chlorophthalmus (Chlorophthalmidae, Aulopiformes) from the continental slope and submarine rises of the western tropical part of the Indian ocean

Two new species of mesobenthic green eyes of the genus Chlorophthalmus—Ch. mascarensis sp. n. and Ch. vityazi sp. n.—are described for the first time. The specimens were collected at submarine rises of the Maskaren Ridge and continental slope of Madagascar, respectively. The differences between the new species and other species of the genus Chlorophthalmus are analyzed.     

Classification of the gall midge tribe Aphidoletini (Diptera,Cecidomyiidae: Aphidoletidi) with descriptions of a new genus and a new species from the Kurile Islands

A new classification is proposed for the gall-midge tribe Aphidoletini including 4 subtribes, 10 genera, and 18 species: Aphidoletina—3 genera with 7 species (Aphidoletes, Tribremia, Ligulodiplosis), Monobremiina subtrib. n.—2 genera with 5 species (Monobremia, Shikotanodiplosis gen. n.), Aculeatodiplosina subtrib. n.—2 genera with 2 species (Aculeatodiplosis, Setodiplosis), and Triommatomyiina—3 genera with 4 species (Triommatomyia, Tingidoletes, Chanchudiplosis). New subtribes and a new genus with a new species are described. Shikotanodiplosis sundukovi gen. et sp. n. differs from Monobremia in a wide and curved aedeagus, basally swollen sclerotized hypoproct, and small basal lobes of the gonocoxites. Keys to the subtribes, genera, and species of Aphidoletini are given. The diagnoses of Aculeatodiplosis fasciata Fedotova et Sidorenko, 2005, Setodiplosis unifaria Fedotova, 2006, and Triommatomyia Mamaev, 1961 are supplemented with biometrical characters. Tribremia aphidophaga Marikovskij, 1956 is resurrected from synonyms of Aphidoletes aphidimyza (Rondani, 1847).     

Identifying the proton loading site cluster in the ba3 cytochrome c oxidase that loads and traps protons

Cytochrome c Oxidase (CcO) is the terminal electron acceptor in aerobic respiratory chain, reducing O₂ to water. The released free energy is stored by pumping protons through the protein, maintaining the transmembrane electrochemical gradient. Protons are held transiently in a proton loading site (PLS) that binds and releases protons driven by the electron transfer reaction cycle. Multi-Conformation Continuum Electrostatics (MCCE) was applied to crystal structures and Molecular Dynamics snapshots of the B-type Thermus thermophilus CcO. Six residues are identified as the PLS, binding and releasing protons as the charges on heme b and the binuclear center are changed: the heme a₃ propionic acids, Asp287, Asp372, His376 and Glu126B. The unloaded state has one proton and the loaded state two protons on these six residues. Different input structures, modifying the PLS conformation, show different proton distributions and result in different proton pumping behaviors. One loaded and one unloaded protonation states have the loaded/unloaded states close in energy so the PLS binds and releases a proton through the reaction cycle. The alternative proton distributions have state energies too far apart to be shifted by the electron transfers so are locked in loaded or unloaded states. Here the protein can use active states to load and unload protons, but has nearby trapped states, which stabilize PLS protonation state, providing new ideas about the CcO proton pumping mechanism. The distance between the PLS residues Asp287 and His376 correlates with the energy difference between loaded and unloaded states.     

Dihydrofolate reductase from a methotrexate-resistant Escherichia coli: Proton magnetic resonance studies of complexes with folate and methotrexate

Proton magnetic resonance studies of 1:1 complexes of E. coli dihydrofolate reductase with folate and methotrexate were performed. A resonance at 1850 Hz in 1:1 enzyme-folate was assigned as the C-7 proton of bound folate by comparison with the spectra of enzyme complexed with folate specifically deuterated at C-7. The first order rate constant for folate dissociation was calculated to be less than 110 sec^?1. Four of the five histidine residues exhibited the same pK's and chemical shifts in the two complexes with pK values of 8.0, 7.3, 6.5 and ～5. However, one histidine increased its pK by 0.7 units (6.25→6.95) and its C-2 proton resonance shifted upfield 50 Hz when folate was substituted for methotrexate. Comparison of these results with those of chemical modification and ultraviolet difference spectroscopy experiments suggests that this histidine may be in the folate binding site — possibly near the pteridine portion of that site.     

Effect of temperature on the NMR spectra of sonicated dispersions of isomers of dipalmitoylphosphatidylcholine

Sonicated dispersions of 1,2-dipalmitoylsn-glycero-3-phosphorylcholine and of 1,3-dipalmitoylglycero-2-phosphorylcholine were examined by proton nuclear magnetic resonance (NMR) as a function of temperature. The —(CH₂)_n)— peak in the spectrum of the sn-3-isomer of dipalmitoylphosphatidylcholine showed the characteristic dramatic changes in the peak intensity and width associated with the phase transition between the liquid crystalline and gel states of the phospholipid. This occurred over a 2–3°C temperature range with the midpoint of the transition at 38.5°C. With the 2-isomer the change in phase took place over a similar temperature range but the midpoint was at 33.8°C. This lower phase transition temperature is presumably the result of increased acyl chain mobility caused by the increased separation of the two acyl chains by the centre carbon of the glycerol backbone. The effect of sonication of the broadening of the range and lowering of the midpoint temperature of the phase transition from that of the corresponding unsonicated dispersions was similar with each isomer. This suggests that the overall geometry of the sonicated vesicles of the isomers is similar.     

3-deoxy-2,5-DI-O-p-nitrobenzoyl-α-D-threo-pentofuranosyl bromide,a starting material for the synthesis of nucleosides

Hydrogenation (Raney nickel) of methyl 2,3-anhydro-α- and β-D-lyxo-furanoside (3 and 12) for 12 h at $\text{60}\text{60}$ lb.in.-2 afforded methyl 3-deoxy-α- and β-D-threo pentofuranoside (4 and 13). These were p-nitrobenzoylated to give the 2,5-di-p-nitrobenzoates (5b and 14b) which, on treatment with hydrogen bromide in acetyl bromide—acetic acid—dichloromethane, afforded the title compound (6b). The structure of compound 4 was established by conversion into the previously prepared 2,5-dibenzoate 5a of known structure, and the anomeric configuration of 6b was established by comparison of its optical rotation and the signals of its anomeric proton with those of methyl 3-deoxy-D-threo-pentofuranosides.     

Introducing Titratable Water to All-Atom Molecular Dynamics at Constant pH

Recent development of titratable coions has paved the way for realizing all-atom molecular dynamics at constant pH. To further improve physical realism, here we describe a technique in which proton titration of the solute is directly coupled to the interconversion between water and hydroxide or hydronium. We test the new method in replica-exchange continuous constant pH molecular dynamics simulations of three proteins, HP36, BBL, and HEWL. The calculated pK_a values based on 10-ns sampling per replica have the average absolute and root-mean-square errors of 0.7 and 0.9 pH units, respectively. Introducing titratable water in molecular dynamics offers a means to model proton exchange between solute and solvent, thus opening a door to gaining new insights into the intricate details of biological phenomena involving proton translocation.     

Of Shifting Economies and Making Ends Meet: The Changing Role of the Accompagnant at the Fann Psychiatric Clinic in Dakar,Senegal

Since 1972, inpatients at the Fann Psychiatric Clinic have been required to have a family member or close friend—an accompagnant—stay with them for the duration of their hospitalization. In recent years, however, the role of the accompagnant has seen a dramatic transformation. This article considers the emergence of a new kind of accompagnant at Fann: the for-hire accompagnant mercenaire, who is unrelated to the patient and not employed by the clinic. Against the backdrop of Senegal’s neoliberal turn and in light of the growing prominence of the biomedical approach at Fann, the author shows how the idealized accompagnant model of family caretaking has given way to this new form of commodified care. At the same time, however, the author argues that accompagnants mercenaires regularly draw upon and establish new sets of moral codes, obligations, debts, and expectations in their day-to-day interactions with patients, family members, and staff alike. By way of a careful ethnographic examination of the evolution of the accompagnant role at Fann, this article brings into focus a complex and multidimensional picture of the shifting economies—moral and political, as well as therapeutic—within the present-day clinic.     

Aquatic insects of the Neman River and its tributaries

The aquatic insects of the Neman River and its tributaries were studied. 178 species belonging to 9 orders were found: Collembola—2 species, Ephemeroptera—33, Odonata—16, Plecoptera—10, Heteroptera—20, Coleoptera—39, Megaloptera—2, Trichoptera—54, and Lepidoptera—2 species. Two species of aquatic insects new for the Belarusian fauna were found, Pomatinus substriatus (Ph. Müller, 1806) (Coleoptera) and Brachycercus europaeus Kluge, 1991 (Ephemeroptera).