Intrinsic uncoupling of mitochondrial proton pumps. 2. Modeling studies

The thermodynamic and kinetic properties associated with intrinsic uncoupling in a six-state model of a redox proton pump have been studied by computing the flow-force relations for different degrees of coupling. Analysis of these relations shows the regulatory influence of the thermodynamic forces on the extent and relative contributions of redox slip and proton slip. Inhibition has been introduced into the model in two different ways, corresponding to possible modes of action of experimental inhibitors. Experiments relating the rate of electron transfer to delta microH at static head upon progressive inhibition of the pumps have been simulated considering (1) the limiting case that the nonzero rate of electron transfer at static head is only due to intrinsic uncoupling (no leaks) and (2) the experimentally observed case that about 30% of the nonzero rate of electron transfer at static head is due to a constant proton leakage conductance in parallel with the pumps, the rest being due to intrinsic uncoupling. The same simulations have been performed for experiments in which the rate of electron transfer is varied by varying the substrate concentration rather than by using an inhibitor. The corresponding experimental results obtained by measuring delta microH and the rate of electron transfer at different succinate concentrations in rat liver mitochondria are presented. Comparison between simulated behavior and experimental results leads to the general conclusion that the typical relationship between rate of electron transfer and delta microH found in mitochondria at static head could certainly be a manifestation of some degree of intrinsic uncoupling in the redox proton pumps.(ABSTRACT TRUNCATED AT 250 WORDS)     

Stimulation of ATP synthesis in Halobacterium halobium R1 by light-induced or artifically created proton electrochemical potential gradients across the cell membrane.

The relationship between proton movement and phosphorylation in Halo-bacterium halobium R1 has been investigated under anaerobic conditions. The light-induced changes in the bacteriorhodopsin are accompanied by proton movements across the membrane which result in pH changes in the suspending medium. The initial alkaline shift is shown to be closely paralleled by (and hence correlated with) ATP synthesis. Acidification of the medium in the presence of valinomycin, under conditions of low external potassium, brings about ATP synthesis in the dark.     

Web-based weight management programs in an integrated health care setting: a randomized, controlled trial

Objective: To assess the efficacy of a Web‐based tailored behavioral weight management program compared with Web‐based information‐only weight management materials. Research Methods and Procedures: Participants, 2862 eligible overweight and obese (BMI = 27 to 40 kg/m²) members from four regions of Kaiser Permanente's integrated health care delivery system, were randomized to receive either a tailored expert system or information‐only Web‐based weight management materials. Weight change and program satisfaction were assessed by self‐report through an Internet‐based survey at 3‐ and 6‐month follow‐up periods. Results: Significantly greater weight loss at follow‐up was found among participants assigned to the tailored expert system than among those assigned to the information‐only condition. Subjects in the tailored expert system lost a mean of 3 ± 0.3% of their baseline weight, whereas subjects in the information‐only condition lost a mean of 1.2 ± 0.4% (p < 0.0004). Participants were also more likely to report that the tailored expert system was personally relevant, helpful, and easy to understand. Notably, 36% of enrollees were African‐American, with enrollment rates higher than the general proportion of African Americans in any of the study regions. Discussion: The results of this large, randomized control trial show the potential benefit of the Web‐based tailored expert system for weight management compared with a Web‐based information‐only weight management program.     

Description of Paratetrahymena parawassi n. sp. using Morphological and Molecular Evidence and a Phylogenetic Analysis of Paratetrahymena and Other Taxonomically Ambiguous Genera in the Order Loxocephalida (Ciliophora,Oligohymenophorea)

ABSTRACT. The marine scuticociliate Paratetrahymena parawassi n. sp. is described on the basis of morphology, especially infraciliature, and the sequence of its small subunit (SSU) rRNA gene to become the second known member of its genus. Paratetrahymena and other ciliates in the order Loxocephalida possess a mixture of morphological and morphogenetic features characteristic of the subclasses Hymenostomatia and Scuticociliatia. Accordingly, we used SSU rRNA sequences to analyze the phylogeny of Paratetrahymena and three other loxocephalid genera. Paratetrahymena and Cardiostomatella vermiformis formed a moderately well‐supported clade that diverged at a deep level from all other scuticociliates, supporting separation of loxocephalids from other scuticociliates as a suprafamilial taxon. Sathrophilus holtae was a sister taxon to Paratetrahymena and Cardiostomatella in a poorly supported, unresolved relationship; nevertheless, association of all three genera into a single clade was supported by an approximately unbiased (AU) test. Any association of these genera singly or as a group with the Hymenostomatia was rejected decisively by AU tests and by a complete absence in the loxocephalids of the unique nucleotide identities that distinguish hymenostomes. Therefore, the morphological and morphogenetic similarities of loxocephalids to hymenostomes may be plesiomorphies, and the conflicting mix of scuticociliate and hymenostome characteristics seen in loxocephalids may result from differing rates of character evolution. Dexiotrichides pangi and Urocentrum, which is currently classified as a peniculid, formed a small clade that associated with hymenostomes and peritrichs. Monophyly of the Loxocephalida with Dexiotrichides and/or Urocentrum included was not rejected by AU; however, inclusion of Urocentrum in the Peniculia was rejected by AU tests. A hypothesis is offered to explain the lack of resolution of loxocephalid ciliates and Urocentrum in phylogenetic trees, namely that their phylogenetic positions are influenced by a combination of heterogeneous data and long‐branch attraction caused by poor representation of taxa in analyses. The well‐known genus Cyclidium, a member of the order Pleuronematida, was revealed to be polyphyletic as a byproduct of our analyses of loxocephalids. In particular, Cyclidium porcatum appears to fall outside the clade containing typical members of the subclass Scuticociliatia and thus invites investigation as a possible member of the order Loxocephalida.     

Electrophoretic profiles of aqueous-soluble proteins of human cerebral cortex: population and developmental characteristics

—Aqueous-soluble brain proteins from 100 adult humans have been screened by discontinuous polyacrylamide and by continuous-SDS-polyacrylamide electrophoresis for evidence of genetically determined variation. In addition 42 adult Macaca nemestrina and 36 inbred strains of mice were screened in the SDS-continuous system. No variation in position of major bands was found within species, although differences in relative intensity of staining were noted. Fetal human cerebral cortex gave profiles of aqueous-soluble proteins distinguishable from that of adults. After affinity chromatography on Concanavalin-A-agarose, adult samples gave one band on SDS-polyacrylamide gels, while fetal samples gave the same band plus an additional band, presumably representing glycoproteins.     

ANTINEOPLASTIC ACTIVITY OF CULTURED BLUE-GREEN ALGAE (CYANOPHYTA)1

A large-scale screening program was initiated to evaluate laboratory-cultured blue-green algae (cyanobacteria) as a source of novel antineoplastic agents. Approximately 1000 cyanophyte strains from diverse habitats were cultured to provide extracts for testing. The screening program identified the families Scytonemataceae and Stigonemataceae as prolific producers of novel cytotoxic compounds. Rates of rediscovery of known compounds were relatively low.