Electron transfer by domain movement in cytochrome bc1

The cytochrome bc1 is one of the three major respiratory enzyme complexes residing in the inner mitochondrial membrane. Cytochrome bc1 transfers electrons from ubiquinol to cytochrome c and uses the energy thus released to form an electrochemical gradient across the inner membrane. Our X-ray crystal structures of the complex from chicken, cow and rabbit in both the presence and absence of inhibitors of quinone oxidation, reveal two different locations for the extrinsic domain of one component of the enzyme, an iron-sulphur protein. One location is close enough to the supposed quinol oxidation site to allow reduction of the Fe-S protein by ubiquinol. The other site is close enough to cytochrome c1 to allow oxidation of the Fe-S protein by the cytochrome. As neither location will allow both reactions to proceed at a suitable rate, the reaction mechanism must involve movement of the extrinsic domain of the Fe-S component in order to shuttle electrons from ubiquinol to cytochrome c1. Such a mechanism has not previously been observed in redox protein complexes.     

An endo-acting proline-specific oligopeptidase from Treponema denticola ATCC 35405: evidence of hydrolysis of human bioactive peptides

An endo-acting proline-specific oligopeptidase (prolyl oligopeptidase [POPase], EC 3.4.21.26) was purified to homogeneity from the Triton X-100 extracts of cells of Treponema denticola ATCC 35405 (a human oral spirochete) by a procedure that comprised five successive fast protein liquid chromatography steps. The POPase is a cell-associated 75- to 77-kDa protein with an isoelectric point of ca. 6.5. The enzyme hydrolyzed (optimum pH 6.5) the Pro-pNA bond in carbobenzoxy-Gly-Pro-p-nitroanilide (Z-Gly-Pro-pNA) and bonds at the carboxyl side of proline in several human bioactive peptides, such as bradykinin, substance P, neurotensin, angiotensins, oxytocin, vasopressin, and human endothelin fragment 22-38. The minimum hydrolyzable peptide size was tetrapeptide P3P2P1P'1, while the maximum substrate size was ca. 3 kDa. An imino acid residue in position P1 was absolutely necessary. The hydrolysis of Z-Gly-Pro-pNA was potently inhibited by the following, with the Ki(app) (in micromolar) in parentheses: insulin B-chain (0.7), human endothelin-1 (0.5), neuropeptide Y (1.7), substance P (32.0), T-kinin (4.0), neurotensin (5.0), and bradykinin (16.0). Chemical modification and inhibition studies suggest that the POPase is a serine endopeptidase whose activity depends on the catalytic triad of COOH ... Ser ... His but not on a metal. The amino acid sequence around the putative active-site serine is Gly-Gly-Ser-Asn-Pro-Gly. The enzyme is suggested to contain a reactive cysteinyl residue near the active site. Amino acid residues 4 to 24 of the first 24 N-terminal residues showed a homology of 71% with the POPase precursor from Flavobacterium meningosepticum and considerable homology with the Aeromonas hydrophila POPase. The ready hydrolysis of human bioactive peptides at bonds involving an imino acid residue suggests that enzymes like POPase may contribute to the chronicity of periodontal infections by participating in the peptidolytic processing of those peptides.     

Molecular characterization of erythrocyte glucose-6-phosphate dehydrogenase deficiency in Al-Ain District, United Arab Emirates

Operational skills involved in controlling a motor vehicle were measured in two groups of very healthy elderly drivers and a young control group to test the hypothesis that there are age-related declines in operational performance that may influence driver safety. An actual behind-the-wheel, standardized road test was employed using a motor vehicle equipped with sensors to record speed, braking activity, and lane position, as well as direction and magnitude of front-wheel and eye-movement excursions. The data from these sensors were used as dependent measures of operational performance. Older drivers made fewer steering and eye-movement excursions and drifted across the center line more frequently than the young control group. Younger drivers drove significantly faster and executed more braking applications than did their older counterparts. The motor-vehicle operational performance of older healthy drivers was related to visual-spatial attentional declines and the useful field of vision associated with the normal aging process.     

Effects of quinine on the mechanical frequency response of the cupula in the fish lateral line

Quinine induces changes in the motion of the cupula in the lateral line canal of the African knife-fish in response to sinusoidal water movements. Two different phases in the action of quinine on the cupular frequency response can be discerned. In the first phase the best frequency, i.e., the frequency at which the cupular vibratory displacement is maximal in response to constant-amplitude sinusoidal canal fluid displacement, shifts toward higher frequencies. During this phase, lasting about 70-100 min, the best frequency increases by a factor between 1.3 and 1.5. In the second phase, during roughly the following 90 min, the best frequency decreases gradually to a value 0.3-0.5 times that observed before the application of quinine.     

Structural and functional meta-analytic evidence for fronto-subcortical system deficit in progressive supranuclear palsy

Meta-analytic methods were used to determine the most sensitive indexes to fronto-subcortical deficit in progressive supranuclear palsy (PSP) and to further characterize the neurocognitive and related features of PSP that can provide a basis of comparison to other disorders with prominent subcortical brain lesions. Studies dating back to 1984 were gathered and calibrated to compare the neuropsychological, neuroimaging, and neurophysiological test results from 229 patients with PSP, and 357 healthy controls. The tests most sensitive to fronto-subcortical deficit in PSP were mostly neuropsychological measures that include such tests as the Stroop Task, Trail Making Test Part A, and Purdue pegboard performance. We conclude that although neuropsychological measures may be most sensitive to deficits in PSP, they are also less specific and valid indicators of fronto-subcortical brain system integrity.     

Congenital chylothorax in siblings

We describe two cases of congenital chylothorax in siblings with important differences from previously described familial cases. Our findings support the likelihood of an autosomal recessive inheritance in some cases of this condition, rather than X-linked recessive inheritance, which has also been suggested. Autopsy findings from one of these cases and others previously described suggest that the pathophysiological mechanisms involved may be variable.     

Facilitative responses to species-specific calls in cortical FM-FM neurons of the mustached bat

FM-FM neurons in the auditory cortex of the mustached bat are highly specialized for echolocation, responding facilitatively to the combination of frequency modulated (FM) components of biosonar pulse and its echo. Here we propose they are also specialized for processing bat communication calls. FM-FM neurons respond facilitatively to natural call syllable pairs, and exhibit inter-syllable interval tuning to the natural range of intervals. Our results support a role for 'combination-sensitive' neurons in communication, and suggest that cortical neurons can possess multiple distinct specialized modes of response.     

Induced magnetic fields as evidence for subsurface oceans in Europa and Callisto

The Galileo spacecraft has been orbiting Jupiter since 7 December 1995, and encounters one of the four galilean satellites-Io, Europa, Ganymede and Callisto-on each orbit. Initial results from the spacecraft's magnetometer have indicated that neither Europa nor Callisto have an appreciable internal magnetic field, in contrast to Ganymede and possibly Io. Here we report perturbations of the external magnetic fields (associated with Jupiter's inner magnetosphere) in the vicinity of both Europa and Callisto. We interpret these perturbations as arising from induced magnetic fields, generated by the moons in response to the periodically varying plasma environment. Electromagnetic induction requires eddy currents to flow within the moons, and our calculations show that the most probable explanation is that there are layers of significant electrical conductivity just beneath the surfaces of both moons. We argue that these conducting layers may best be explained by the presence of salty liquid-water oceans, for which there is already indirect geological evidence in the case of Europa.