The relation between melanocortin 1 receptor (MC1R) variation and the generation of phenotypic diversity in the cutaneous response to ultraviolet radiation

The melanocortin 1 receptor (MC1R) is known to play an important role in determining physiological variation in human pigmentation, and consequently human susceptibility to ultraviolet radiation. A reason for wider interest is that the considerable phenotypic diversity has been in part generated by the effects of gene dosage, and the presence of a large number of mutations at this G-protein coupled receptor that are not functionally equivalent. Thus, a range of mutations at a single receptor locus can lead to a complex range of graded phenotypes.     

Discovering functional relationships: biochemistry versus genetics

Biochemists and geneticists, represented by Doug and Bill in classic essays, have long debated the merits of their methods. We revisited this issue using genomic data from the budding yeast, Saccharomyces cerevisiae, and found that genetic interactions outperformed protein interactions in predicting functional relationships between genes. However, when combined, these interaction types yielded superior performance, convincing Doug and Bill to call a truce.     

Coevolution theory of the genetic code at age thirty

The coevolution theory of the genetic code, which postulates that prebiotic synthesis was an inadequate source of all twenty protein amino acids, and therefore some of them had to be derived from the coevolving pathways of amino acid biosynthesis, has been assessed in the light of the discoveries of the past three decades. Its four fundamental tenets regarding the essentiality of amino acid biosynthesis, role of pretran synthesis, biosynthetic imprint on codon allocations and mutability of the encoded amino acids are proven by the new knowledge. Of the factors that guided the evolutionary selection of the universal code, the relative contributions of Amino Acid Biosynthesis: Error Minimization: Stereochemical Interaction are estimated to first approximation as 40,000,000:400:1, which suggests that amino acid biosynthesis represents the dominant factor shaping the code. The utility of the coevolution theory is demonstrated by its opening up experimental expansions of the code and providing a basis for locating the root of life.     

Biodegradation of phenanthrene by the indigenous microbial biomass in a zinc amended soil

AIMS: To study the effect of zinc on the biodegradation of phenanthrene by the microbial biomass in soil. METHODS AND RESULTS: Uncontaminated soil was amended with zinc and phenanthrene as single or co-contaminants, and microbial metabolic activity was measured using an intracellular dehydrogenase enzyme bioassay over 37 days. Contaminants were amended at optimum, action and double the action level specified in 'The New Dutch List' (Ministry of Housing, Spatial Planning and Environment, the Netherlands, 2000). Microbial activity in soils with zinc or phenanthrene alone indicated the presence of tolerant, albeit inhibited soil micro-organisms. A zinc concentration at the optimum level of 140 mg kg(-1) in the co-contaminated soil (phenanthrene at 40 mg kg(-1)) resulted in marginal stimulation of the rate of phenanthrene biodegradation. However, Zn2+ concentrations at the action and double the action level of zinc (720 and 1440 mg kg(-1)) inhibited phenanthrene degradation. CONCLUSIONS: Biodegradation of phenanthrene in soils co-contaminated with zinc at concentrations above the action value is impeded. SIGNIFICANCE AND IMPACT OF THE STUDY: Bioremediation efforts to remove polycyclic aromatic hydrocarbon in zinc co-contaminated soils are likely to be constrained.     

Determinants of HMGB proteins required to promote RAG1/2-recombination signal sequence complex assembly and catalysis during V(D)J recombination

Efficient assembly of RAG1/2-recombination signal sequence (RSS) DNA complexes that are competent for V(D)J cleavage requires the presence of the nonspecific DNA binding and bending protein HMGB1 or HMGB2. We find that either of the two minimal DNA binding domains of HMGB1 is effective in assembling RAG1/2-RSS complexes on naked DNA and stimulating V(D)J cleavage but that both domains are required for efficient activity when the RSS is incorporated into a nucleosome. The single-domain HMGB protein from Saccharomyces cerevisiae, Nhp6A, efficiently assembles RAG1/2 complexes on naked DNA; however, these complexes are minimally competent for V(D)J cleavage. Nhp6A forms much more stable DNA complexes than HMGB1, and a variety of mutations that destabilize Nhp6A binding to bent microcircular DNA promote increased V(D)J cleavage. One of the two DNA bending wedges on Nhp6A and the analogous phenylalanine wedge at the DNA exit site of HMGB1 domain A were found to be essential for promoting RAG1/2-RSS complex formation. Because the phenylalanine wedge is required for specific recognition of DNA kinks, we propose that HMGB proteins facilitate RAG1/2-RSS interactions by recognizing a distorted DNA structure induced by RAG1/2 binding. The resulting complex must be sufficiently dynamic to enable the series of RAG1/2-mediated chemical reactions on the DNA.     

Anaerospora hongkongensis gen. nov. sp. nov., a novel genus and species with ribosomal DNA operon heterogeneity isolated from an intravenous drug abuser with pseudobacteremia

A bacterium was isolated from the blood culture of an intravenous drug abuser with pseudobacteremia. The cells were strictly anaerobic, straight or slightly curved, sporulating, Gram-negative rods. It grew on sheep blood agar as non-hemolytic, pinpoint colonies after 48 hr of incubation at 37 C in an anaerobic environment. It was motile but did not produce catalase or cytochrome oxidase. 16S ribosomal DNA (rDNA) sequencing revealed three different copies of 16S rDNA sequences. More than 90% of the differences among them were due to differences in the lengths of the sequences. Phylogenetically, the bacterium is clustered with Dendrosporobacter, Sporomusa, and Propionispora, the other three genera of anaerobic, sporulating, Gram-negative rods. There were 8.6-11.1% differences between the 16S rDNA sequences of the bacterium and that of D. quercicolus, 4.7-15.1% differences between the 16S rDNA sequences of it and those of S. acidovorans, S. aerivorans, S. malonica, S. ovata, S. paucivorans, S. silvacetica, S. spaeroides, and S. termitida, and 7.6-13.1% differences between the 16S rDNA sequences of it and those of P. hippei and P. vibrioides. The G+C content of the bacterium (mean +/- SD) was 46.8 +/- 3.2%. For these reasons, a new genus and species, Anaerospora hongkongensis gen. nov. sp. nov., is proposed, for which HKU15T is the type strain.     

Electrostatic interactions contribute to reduced heat capacity change of unfolding in a thermophilic ribosomal protein l30e

The origin of reduced heat capacity change of unfolding (DeltaC(p)) commonly observed in thermophilic proteins is controversial. The established theory that DeltaC(p) is correlated with change of solvent-accessible surface area cannot account for the large differences in DeltaC(p) observed for thermophilic and mesophilic homologous proteins, which are very similar in structures. We have determined the protein stability curves, which describe the temperature dependency of the free energy change of unfolding, for a thermophilic ribosomal protein L30e from Thermococcus celer, and its mesophilic homologue from yeast. Values of DeltaC(p), obtained by fitting the free energy change of unfolding to the Gibbs-Helmholtz equation, were 5.3 kJ mol(-1) K(-1) and 10.5 kJ mol(-1) K(-1) for T.celer and yeast L30e, respectively. We have created six charge-to-neutral mutants of T.celer L30e. Removal of charges at Glu6, Lys9, and Arg92 decreased the melting temperatures of T.celer L30e by approximately 3-9 degrees C, and the differences in melting temperatures were smaller with increasing concentration of salt. These results suggest that these mutations destabilize T.celer L30e by disrupting favorable electrostatic interactions. To determine whether electrostatic interactions contribute to the reduced DeltaC(p) of the thermophilic protein, we have determined DeltaC(p) for wild-type and mutant T.celer L30e by Gibbs-Helmholtz and by van't Hoff analyses. A concomitant increase in DeltaC(p) was observed for those charge-to-neutral mutants that destabilize T.celer L30e by removing favorable electrostatic interactions. The crystal structures of K9A, E90A, and R92A, were determined, and no structural change was observed. Taken together, our results support the conclusion that electrostatic interactions contribute to the reduced DeltaC(p) of T.celer L30e.     

Magnetic resonance imaging findings in the brains of rabbits infected with Angiostrongylus cantonensis: a long-term investigation

Because magnetic resonance (MRI) imaging is a superior technique in delineating pathological changes in cerebral angiostrongyliasis, it should also be an optimal imaging modality in monitoring long-term changes in the brains of animals infected with Angiostrongylus cantonensis. In this study, MRI and histological techniques were used to observe the changes in the brains of 7 rabbits infected with the third-stage larvae of A. canronensis. Changes were monitored by MRI from day 0 to day 207 postinfection (PI). Hyperintense lesions on T2-weighted MR brain images were first observed on day 22 PI and hallmarks of abnormalities were noted on day 35 PI. Hyperintensities on brain MR images remained up to day 207 PI. Histological examination from days 108 to 207 PI revealed meningeal congestion, choroid plexus inflammation, infarction, granuloma with embedded larva, gliosis, and hemorrhage in the brain tissues. These findings suggest that hosts infected with A. cantonensis may undergo pathological changes in the brain tissues for more than 200 days PI. Moreover, severe abnormalities may occur as early as the fifth week PI.