Classification of temporal patterns in dynamic biological networks

A general method is presented to classify temporal patterns generated by rhythmic biological networks when synaptic connections and cellular properties are known. The method is discrete in nature and relies on algebraic properties of state transitions and graph theory. Elements of the set of rhythms generated by a network are compared using a metric that quantifies the functional differences among them. The rhythms are then classified according to their location in a metric space. Examples are given, and biological implications are discussed.     

Late cytomegalovirus disease in marrow transplantation is predicted by virus load in plasma

Late occurrence of cytomegalovirus (CMV) disease after day 100 after bone marrow transplantation has become an increasing problem; whether a quantitative measurement of CMV DNA in plasma by polymerase chain reaction (P-PCR) could be predictive of such disease was investigated. In a prospective study, 117 subjects undergoing allogeneic marrow transplantation were followed for 120 days with weekly CMV blood cultures, with day 35 bronchoalveolar lavage CMV cultures, with weekly CMV P-PCR, and with clinical follow-up for an additional 1-2 years. Despite preemptive ganciclovir, CMV disease occurred in 9% of subjects, with a median time of onset of 176 days. Quantitative CMV P-PCR was associated with the late development of CMV disease (P = .01). Of 43 subjects with positive P-PCR results, 23% developed CMV disease, but no disease occurred in the 74 subjects with negative P-PCR (P < .001), despite the fact that 22% had CMV isolated from lung lavage fluid and 32% had CMV isolated from blood.     

Energy relaxation in GaInAs/AlInAs heterojunctions and GaAs/AlGaAs multiple quantum wells

We have studied electron energy relaxation in GaInAs/AlInAs heterojunctions and GaAs/AlGaAs multiple quantum wells using mobility measurements as a function of electric field and temperature, in the range 3K to 300K. The results in the range 3 to 20K show a power loss rate which is dependent on (T_e − T_l), suggesting that the energy relaxation occurs through acoustic phonon scattering. At electron temperatures greater than 20K, the experimental results are modelled using a standard expression for polar optical phonons. This modelling yields 30meV and 31meV for the polar optical phonon energy in GaAs and InGaAs respectively.     

The soluble alpha-mannosidases of Drosophila melanogaster

The alpha-mannosidases are implicated in both the catabolism of carbohydrates and the N-linked glycosylation pathway in insects, but little is known of the biochemistry of these glycosidases. In order to study the soluble alpha-mannosidases of Drosophila melanogaster we have used artificial fluorogenic substrates for detection of activity in situ following non-denaturing gel electrophoresis. This approach also permitted examination of the mannosidases present in different tissues and the sensitivity of the enzymes to known mannosidase inhibitors. Fluorogenic substrates were also used to determine the pH optima of partly purified mannosidases. We report that D. melanogaster contains several soluble alpha-mannosidase activities. Acidic mannosidases were detected in the gut, fat body and haemolymph of third-instar larvae. The major activity detected in larval guts was a neutral mannosidase presumed to be involved in digestion.     

Comparison of voice analysis systems for perturbation measurement

Dysphonic voices are often analyzed using automated voice analysis software. However, the reliability of acoustic measures obtained from these programs remains unknown, particularly when they are applied to pathological voices. This study compared perturbation measures from CSpeech, Computerized Speech Laboratory, SoundScope, and a hand marking voice analysis system. Sustained vowels from 29 male and 21 female speakers with mild to severe dysphonia were digitized, and fundamental frequency (F0), jitter, shimmer, and harmonics- or signal-to-noise ratios were computed. Commercially available acoustical analysis programs agreed well, but not perfectly, in their measures of F0. Measures of perturbation in the various analysis packages use different algorithms, provide results in different units, and often yield values for voices that violate the assumption of quasi-periodicity. As a result, poor rank order correlations between programs using similar measures of perturbation were noted. Because measures of aperiodicity apparently cannot be reliably applied to voices that are even mildly aperiodic, we question their utility in quantifying vocal quality, especially in pathological voices.     

Perception of discrimination and ethnocultural variables in a diverse group of adolescents

Despite current interest in the multi-dimensionality of culture and ethnicity there are few studies that have explored the role of discrimination with ethnocultural variables. In this study social identity theory was used as a framework to test the relation between discrimination and components of ethnic identity, and attitudes towards out-groups. A school-based survey in a large south-west metropolitan area in 1994 was undertaken with students (n=3071) of African-American, European-American, Mexican-American, and Vietnamese-American descent using multiple measures of ethnicity. Hierarchical multiple regression results indicated that two components of ethnic identity played different roles in the relation between discrimination and attitudes towards others. Consistent with social identity theory, results indicated that perception of more discrimination was predicted by high ethnic exploration, and having more negative attitudes towards out-groups. However, ethnic affirmation, which is a positive sense of belonging to one's ethnic group, was only indirectly related to discrimination through attitudes toward others. In fact, contrary to social identity theory, a stronger sense of belonging to one's group was associated with more positive attitudes toward out-groups. Results have important implications for race relations.     

Use of the cell division protein FtsZ as a means of differentiating among Bartonella species

Genes coding for homologs of the highly conserved cell division protein FtsZ were isolated from Bartonella henselae and Bartonella quintana, the causative agents of cat scratch disease and trench fever, respectively. DNA fragments coding for the ftsZ open reading frames (ORFs) were cloned into Escherichia coli following PCR amplification with primers based on the ftsZ sequence of the closely related species Bartonella bacilliformis. The amino acid sequences predicted from the cloned B. henselae and B. quintana ftsZ ORFs are 81 to 83% identical to the corresponding protein in B. bacilliformis. Like the FtsZ protein of B. bacilliformis, the B. henselae and B. quintana homologs are about twice as large as the FtsZ proteins reported in most other organisms. Localized sequence differences within the C-terminal coding regions of the Bartonella ftsZ genes were used as the basis for species-specific identification of these organisms at both the DNA and protein levels. Oligonucleotide primers which permit the amplification of an ftsZ fragment from each of the Bartonella species without amplifying DNA from the other two species were designed. Anti-FtsZ antisera raised in rabbits against synthetic peptides corresponding to the relatively divergent C-terminal regions were shown via Western blot analysis to react only with the FtsZ protein from the cognate Bartonella species. These observations raise the possibility that the differences in ftsZ sequences can be used as the basis for diagnostic tests to differentiate among these closely related pathogens.     

Structure of nitric oxide synthase oxygenase dimer with pterin and substrate

Crystal structures of the murine cytokine-inducible nitric oxide synthase oxygenase dimer with active-center water molecules, the substrate L-arginine (L-Arg), or product analog thiocitrulline reveal how dimerization, cofactor tetrahydrobiopterin, and L-Arg binding complete the catalytic center for synthesis of the essential biological signal and cytotoxin nitric oxide. Pterin binding refolds the central interface region, recruits new structural elements, creates a 30 angstrom deep active-center channel, and causes a 35 degrees helical tilt to expose a heme edge and the adjacent residue tryptophan-366 for likely reductase domain interactions and caveolin inhibition. Heme propionate interactions with pterin and L-Arg suggest that pterin has electronic influences on heme-bound oxygen. L-Arginine binds to glutamic acid-371 and stacks with heme in an otherwise hydrophobic pocket to aid activation of heme-bound oxygen by direct proton donation and thereby differentiate the two chemical steps of nitric oxide synthesis.     

Enantioselective synthesis and pharmacology of 11-hydroxy-(1'S,2'R)-dimethylheptyl-delta 8-THC

An enantioselective synthesis of the (1'S,2'R)-dimethylheptyl cannabinoid side chain has been developed and employed in the synthesis of 11-hydroxy-(1'S,2'R)-dimethylheptyl-delta 8-THC (3). Pharmacology, in vivo and in vitro, indicate (3) to be one of the most potent traditional cannabinoids known.