Synthesis and biological activity of linear and cyclic enkephalins modified at the Gly3-Phe4 amide bond

As part of our continuing effort to define structure-activity relationships for enkephalin and design enzymatically resistant analogs, we report the synthesis and biological activities of linear and cyclic enkephalin analogs modified at the Gly3-Phe4 amide bond. The partial retro-inverso enkephalin analog Tyr-D-Ala-gGly-(R,S)-mPhe-Leu-NH2 and its cyclic counterpart, Tyr-cyclo[D-A2 bu-gGly-(R,S)-mPhe-Leu-], were synthesized as diastereomeric mixtures using solution methodology. The racemic benzylmalonate allowed the linear analog to be synthesized by fragment coupling at the reversed bond. Cyclization of the second analog was carried out at high concentration, eliminating formation of polymer by the use of an insoluble base. All gem-diaminoalkyl residues were prepared by conversion of peptidyl amides with benzene iodonium bis(trifluoroacetate). Diastereomers of both compounds were separable by reverse phase HPLC but those of the linear compound racemized rapidly under conditions of testing and were therefore tested together. All analogs tested had activities ranging from 6 to 14% of the activity of Leu enkephalin, indicating that the Gly3-Phe4 amide bond is important, though not crucial, for receptor binding.     

Wheat dwarf virus, a geminivirus of graminaceous plants needs splicing for replication.

By analysing mRNAs with the polymerase chain reaction (PCR) and by studying in vitro generated mutants we have identified an intron in the genome of wheat dwarf virus (WDV), a geminivirus of cereals. Polypeptides whose expression is essential for the replication of the viral DNA have been defined. They are encoded by two distinct overlapping open reading frames (ORFs). The joining of these two ORFs by deletion of the intron as well as the introduction of a frameshift mutation within the intron do not prevent replication of the viral genome in suspension culture cells. In contrast to WDV, the geminiviruses of dicotyledonous plants possess a single continuous ORF, highly homologous to the two individual ones of WDV. We propose that mRNA splicing is a common feature of all geminiviruses of the Gramineae and might contribute to their host class specificity. The existence of a functional intron is a novel finding for the plant viruses.     

Microbodies (peroxisomes) in the toad,Bufo marinus

Summary Microbodies (peroxisomes), a group of cytoplasmic organelles enriched in catalase, are demonstrated in the toad, Bufo marinus, by light and electron microscopy by means of a cytochemical staining procedure that demonstrates the peroxidatic activity of catalase with diaminobenzidine (DAB). Amphibian microbodies are similar to those of other classes in their fine structure and localization in hepatocytes and kidney, where they are prominent in the proximal tubular cells. Nucleoids are present only in renal microbodies. In the proximal renal tubule an unusual group of large brown granules are identified as lysosomes by their acid phosphatase, -glucosaminidase and -glucuronidase activities.This work was supported by U.S. Public Health Service Grants Nos. NS-06856 and HD 00674. We wish to thank Dr. Richard M. Hays who generously supplied us with toads; Dr. Alex B. Novikoff for making available facilities for ultramicrotomy, Miss Betty De Prest for technical assistance; Miss Marianne Van Hooren for preparation of the photomicrographs.     

Examination of the bactericidal and opsonic activity of normal human serum for a mucoid and nonmucoid strain ofPseudomonas aeruginosa

The bactericidal and opsonic activity of fresh human serum (FHS) for a mucoid strain ofPseudomonas aeruginosa, 144M, and its spontaneous nonmucoid revertant, 144NM, was examined. Strain 144M was sensitive to the bactericidal activity of FHS, but strain 144NM was not. This bactericidal activity was due to the combined interaction of IgG and IgM with complement, activated through both pathways. Neither 144M nor 144NM was ingested by human polymorphonuclear leukocytes (PMNL) without FHS. Whereas maximal phagocytosis of 144M required only 5% FHS, comparable ingestion of 144NM required 25% FHS. Maximal phagocytosis of either 144M or 144NM required IgG, IgM, and complement. However, 144M required a heat-sensitive opsonic IgG, whereas 144NM required a heat-resistant IgG. Using selective absorption techniques, the targets for bactericidal and opsonic immunoglobulins on 144M and 144NM appeared to be different, suggesting that the variant 144NM had one or more altered, absent, or inaccessible cell surface components that account for differences in response to FHS and PMNL.     

A model for traveling bands of chemotactic bacteria.

A theoretical model is used to study band formation by chemotactic populations of Escherichia coli. The model includes the bacterial response to attractant gradients, the chemotactic sensitivity of the bacteria to the concentration of the attractant, and population growth. For certain values of the parameters in the model, traveling bands of bacteria form and propagate with or without growth. Under specific growth conditions the band profile is maintained and the band propagates at constant speed. These predictions are in general agreement with the experiment results of J. Adler and earlier theoretical work by L. Segel and his collaborators. However, our theory differs in several important respects from the latter efforts. Suggestions are made for further experiments to test the proposed model and to clarify the nature of the processes which lead to band formation.     

Points of departure for a constructive critique of the Bolivarian Revolution

From what Left position, both intellectually and politically, does one formulate a critique of the Chávez-led Bolivarian Revolution without aligning with a right-wing opposition? For starters, we need reliable evidence of the achievements, problems, and mistakes of the Bolivarian project. At the same time, any engagement with social change in Venezuela necessitates attention to one’s positionality as well as scholarly and activist categories of analysis and practice.