Synthesis and characterization of three covalently linked porphyrin-phthalocyanine pentamers with nucleophilic substitution

In this paper the synthetic methods of three covalently linked porphyrin-phthalocyanine heteropentamers, containing four units of porphyrin linked to a central phthalocyanine (Mpor-LPc; M = 2H, Fe, L = Zn, Fe), are described. The synthetic strategy is on the basis of nucleophilic substitution reactions between [1,8,15,22-tetra nitro phthalocyanines] and [5-(4-hydroxy phenyl)-10,15,20-triphenyl porphyrins] as the phenolic alcohols. Porphyrins are linked with oxygen as spacer through meso position of phenyl group to phthalocyanines. These macromolecules were characterized by ¹H NMR, UV-Vis, IR, fluorescence and mass spectroscopy. The electronic absorption spectrums of the hetero-dyad systems changed significantly upon coupling and showed a great red shift in the phthalocyanine Q-bands. These changes confirm the electron-donating effects of the porphyrin units and the extension of conjugated п-systems. The emission spectra of the products supports intramolecular energy and charge transfer between the sub-units.     

Physiological roles of animal succinate thiokinases Specific association of the guanine nucleotide-linked enzyme with haem biosynthesis

The discovery of two distinct succinate thiokinases in mammalian tissues, one (G-STK) specific for GDP/GTP and the other (A-STK) for ADP/ATP, poses the question of their differential metabolic roles. Evidence has suggested that the A-STK functions in the citric acid cycle in the direction of succinyl-CoA breakdown (and ATP formation) whereas one role of the G-STK appears to be the re-cycling of succinate to succinyl-CoA (at the expense of GTP) for the purpose of ketone body activation. A third metabolic participation of succinyl-CoA is in haem biosynthesis. This communication shows that in chemically induced hepatic porphyria, when the demand for succinyl-CoA is increased, it is the level of G-STK only which is elevated, that of A-STK being unaffected. The results implicate G-STK in the provision of succinyl-CoA for haem biosynthesis, a conclusion which is further supported by the observation of a high G-STK/A-STK ratio in bone marrow.     

A test of a model for planktivorous filter feeding by bream Abramis brama

Synopsis The planktivorous feeding of bream, Abramis brama on Daphnia hyalina and Bosmina coregoni was analyzed in a stepwise regression analysis with the average size (and standard deviation) of consumed organisms as dependent variable and the size of the fish, the average size (and standard deviation) of the organisms and their density in the environment as independent variables. Three basic predictions on filter feeding were formulated and tested. It was predicted that the (average) prey size should increase with fish size, but that the standard deviation should decline. Secondly the prey size should be strongly correlated with the prey size available and thirdly the prey density should have little effect on the size selection. These hypotheses could not be rejected for bream>10 cm feeding on B. coregoni and for bream>20 cm feeding on D. hyalina. The hypotheses were not valid for smaller bream as these acted as particulate or combined filter- and particulate feeders.     

Interference by DDT and cyclodiene types of insecticides with chloroplast-associated reactions

The effects of DDT, some of its analogs, and selected cyclodiene insecticides on isolated spinach (Spinacea oleracea L.) thylakoids were identified, characterized, and compared to responses induced by selected herbicides. Except for endrin, the insecticides inhibited light-induced electron transport, altered chlorophyll fluorescence transients, and competitively displaced [14C]atrazine [2-chloro-4-(ethylamino)-6-(isopropylamino)-s-triazine], a known photosystem II inhibitor, from the membranes. The insecticides appeared to act at, or near B, the secondary electron acceptor of photo-system II. Binding of DDT and dieldrin was estimated at 900 and 2200 molecules, respectively, per photosynthetic unit (490 chlorophyll molecules). The insecticides also inhibited valinomycin-induced swelling of the thylakoid membrane. Whereas inhibition of electron transport can be attributed to interaction by the insecticides with a proteinaceous component of the thylakoid membrane, interference with the action of valinomycin may involve interaction with lipoidal constituents of the membrane.     

Size composition, growth and sexual maturity of Callinectes latimanus (Rath.) in two Ghanaian lagoons

Blue crabs Callinectes latimanus (Rath.) trapped from two lagoons were sexed, measured and weighed. The eggs of the mature females were counted to determine fecundity, and the spermatophores of the males were counted to determine the size of sexual maturity. Sizes at maturity of both male and female crabs were determined. The methods employed and the results are discussed.     

Effects of diphenyl ether herbicides on porphyrin accumulation by cultured hepatocytes

Several diphenyl ether herbicides, such as acifluorfen methyl, have been previously shown to cause large accumulations of the heme and chlorophyll precursor, protoporphyrin, in plants. Lightinduced herbicidal damage is mediated by the photoactive porphyrin. Here we investigate whether diphenyl ether herbicides can affect porphyrin synthesis in rat and chick hepatocytes. In rat hepatocyte cultures, protoporphyrin, as well as coproporphyrin, accumulated after treatment with acifluorfen or acifluorfen methyl. Combination of acifluorfen methyl with an esterase inhibitor to prevent the conversion of acifluorfen methyl to acifluorfen resulted in a greater accumulation of porphyrins than caused by acifluorfen methyl or acifluorfen alone. In vitro enzyme studies of hepatic mitochondria isolated from rat and chick embryos demonstrated that protopor-phyrinogen oxidase, the penultimate enzyme of heme biosynthesis, was inhibited by low concentrations of acifluorfen, nitrofen, or acifluorfen methyl with the latter being the most potent inhibitor. These findings indicate that diphenyl ether treatment can cause protoporphyrin accumulation in rat hepatocyte cultures and suggest that this accumulation was associated with the inhibition of protoporphyrinogen oxidase. In cultured chick embryo hepatocytes, treatment with acifluorfen methyl plus an esterase inhibitor caused massive accumulation of uroporphyrin rather than protoporphyrin or coproporphyrin. Specific isozymes of cytochrome P450 were also induced in chick embryo hepatocytes. These effects were not observed in the absence of an esterase inhibitor. These results suggest that diphenyl ether herbicides can cause uroporphyrin accumulation similar to that induced by other cytochrome P450-inducing chemicals such as polyhalogenated aromatic hydrocarbons in the chick hepatocyte system.     

Substrate binding to Src: A new perspective on tyrosine kinase substrate recognition from NMR and molecular dynamics

Most signal transduction pathways in humans are regulated by protein kinases through phosphorylation of their protein substrates. Typical eukaryotic protein kinases are of two major types: those that phosphorylate‐specific sequences containing tyrosine (~90 kinases) and those that phosphorylate either serine or threonine (~395 kinases). The highly conserved catalytic domain of protein kinases comprises a smaller N lobe and a larger C lobe separated by a cleft region lined by the activation loop. Prior studies find that protein tyrosine kinases recognize peptide substrates by binding the polypeptide chain along the C‐lobe on one side of the activation loop, while serine/threonine kinases bind their substrates in the cleft and on the side of the activation loop opposite to that of the tyrosine kinases. Substrate binding structural studies have been limited to four families of the tyrosine kinase group, and did not include Src tyrosine kinases. We examined peptide‐substrate binding to Src using paramagnetic‐relaxation‐enhancement NMR combined with molecular dynamics simulations. The results suggest Src tyrosine kinase can bind substrate positioning residues C‐terminal to the phosphoacceptor residue in an orientation similar to serine/threonine kinases, and unlike other tyrosine kinases. Mutagenesis corroborates this new perspective on tyrosine kinase substrate recognition. Rather than an evolutionary split between tyrosine and serine/threonine kinases, a change in substrate recognition may have occurred within the TK group of the human kinome. Protein tyrosine kinases have long been therapeutic targets, but many marketed drugs have deleterious off‐target effects. More accurate knowledge of substrate interactions of tyrosine kinases has the potential for improving drug selectivity.     

Finite element analysis of Stryker Xia pedicle screw in artificial bone samples with and without supplemental cement augmentation

A validated, using in vitro biomechanical testing, finite element model was used to evaluate the affects of (1) cement augmentation and (2) an intact posterior cortex in osteoporotic bone. The presence of augmentation and/or a posterior cortical cortex increased the stabilization of the pedicle screw 2–5 fold. Placement of cement influenced failure load and toggle; with distal placement having the largest increase in failure load and decrease in cephalad–caudad toggle. The presence of posterior cortex caused a decrease in the amount of toggle, a proximal shift of the center of rotation and an increase in the maximum failure force.