Whither biological database research?

We consider how the landscape of biological databases may evolve in the future, and what research is needed to realize this evolution. We suggest today's dispersal of diverse resources will only increase as the number and size of those resources, driving the need for semantic interoperability even more strongly. Because the complexity of the questions biologists want answered automatically continues to rapidly escalate, we will need to draw upon high-performance computing resources such as the GRID to process complex queries. Finally, we still need data, and our ways of acquiring and curating data must improve by orders of magnitude.     

Immunoglobulin allotypes among Taiwan aborigines: evidence of malarial selection could affect studies of population affinity

The aborigines of Taiwan represent the indigenous inhabitants of the island at the time of the arrival of the Chinese from the mainland. Linguistically, the aboriginal Taiwanese are related to the Malayo-Polynesian-speaking inhabitants of Indonesia and the Philippines. Three tribes occupied lowland areas while six tribes occupied highland areas. Previous studies indicate that genetic markers associated with malaria occur in lowland populations. Though the GM haplotypes are demonstrated to be very useful in the measure of population affinities, the possibility of malarial selection on this locus could affect studies of population affinity. The present work is a case study to see whether a subdivided insular population under a possible selective load will provide divergent clustering analysis depending on the population sampled. Immunoglobulin allotype (GM and KM) profiles were generated on 230 lowland and 407 highland Taiwan Aborigines from the nine tribes. A highly significant difference in GM haplotype distribution was detected between lowland and highland populations (adjusted G = 69.408, 2 df [degrees of freedom], p < 0.00001). There were no significant differences in KM*1 frequency by altitude. The Taiwan Aboriginal GM and KM frequencies were compared to data from Indonesians, Vietnamese, Thai, Malay, Chinese from Taiwan, and Ryukyu Islanders from Okinawa using cluster analysis. The lowland populations plot among the Thai (N, NC) and Malayan Aborigines. In contrast, the highland and total Taiwan Aborigine samples plot with the Indonesian, Vietnamese, and Malayan Negrito samples. Thus, depending on the populations of Taiwan Aborigines used, different conclusions could be reached. The highland population supports the published linguistic ties; however, the lowland population does not support the linguistic relationship with Indonesian populations but is more closely related to Thai and Malays, or reflects a similar selection history.     

RNA surveillance by nuclear scanning?

There are many quality-control mechanisms that ensure high fidelity of gene expression. One of these is the nonsense-mediated decay (NMD) pathway, which destroys aberrant mRNAs that contain premature termination codons generated as a result of biosynthetic errors or random and programmed gene mutations. Two complexes that initially bind to RNA in the nucleus have been suggested to be involved in NMD in the cytoplasm. Here we propose an alternative model that involves nuclear scanning, on the basis of recent evidence for nuclear translation.     

THE EFFECTS OF PHOSPHITE ON PHOSPHATE STARVATION RESPONSES OF ULVA LACTUCA (ULVALES,CHLOROPHYTA)1

Effects of phosphite (Phi) on phosphate (Pi) starvation responses were determined in Ulva lactuca L. by incubation in Pi‐limited (1 μM NaH₂PO₄) or Pi‐sufficient (100 μM NaH₂PO₄) seawater containing 0–3 mM Phi. Exposure to 1 μM NaH₂PO₄ decreased the growth rate and the content of free Pi and esterified‐P but increased the activities of extracellular alkaline phosphatase (EC 3.1.2.1) and intracellular acid phosphatase (ACP; EC 3.1.2.2); two ACP isozymes observed by activity staining on isoelectric focussing (IEF) gel were induced. The K_m value of Pi uptake rate was decreased by incubation with 1 μM NaH₂PO₄ and the decrease in K_m value was inhibited by 2 mM Phi, reflecting the operation of a high‐affinity Pi uptake system at low Pi concentrations. In the presence of Phi, the growth rate of Pi‐sufficient and Pi‐starved thalli decreased as Phi concentrations were increased from 0 to 2 mM. As Phi concentrations were increased from 0 to 2 mM, the free Pi contents in both Pi‐sufficient and Pi‐starved thalli decreased, but the esterified‐P contents in Pi‐starved thalli increased, whereas those in Pi‐sufficient thalli increased at 1 mM Phi and decreased at 2 mM Phi. Cell wall localized AP activity in both Pi‐sufficient and Pi‐starved thalli decreased as Phi concentrations were increased from 0 to 2 mM. Intracellular ACP activity in Pi‐starved thalli decreased as Phi concentrations were increased from 0 to 2 mM but was not affected in Pi‐sufficient thalli. The induction of ACP isozyme activity and high‐affinity Pi uptake system in Pi‐starved thalli was inhibited by Phi. The present investigation shows that Phi interrupts the sensing mechanisms of U. lactuca to Pi‐limiting conditions.     

Substitution bias, rapid saturation, and the use of mtDNA for nematode systematics

Only relatively recently have researchers turned to molecular methods for nematode phylogeny reconstruction. Thus, we lack the extensive literature on evolutionary patterns and phylogenetic usefulness of different DNA regions for nematodes that exists for other taxa. Here, we examine the usefulness of mtDNA for nematode phylogeny reconstruction and provide data that can be used for a priori character weighting or for parameter specification in models of sequence evolution. We estimated the substitution pattern for the mitochondrial ND4 gene from intraspecific comparisons in four species of parasitic nematodes from the family Trichostrongylidae (38-50 sequences per species). The resulting pattern suggests a strong mutational bias toward A and T, and a lower transition/transversion ratio than is typically observed in other taxa. We also present information on the relative rates of substitution at first, second, and third codon positions and on relative rates of saturation of different types of substitutions in comparisons ranging from intraspecific to interordinal. Silent sites saturate extremely quickly, presumably owing to the substitution bias and, perhaps, to an accelerated mutation rate. Results emphasize the importance of using only the most closely related sequences in order to infer patterns of substitution accurately for nematodes or for other taxa having strongly composition-biased DNA. ND4 also shows high amino acid polymorphism at both the intra- and interspecific levels, and in higher level comparisons, there is evidence of saturation at variable amino acid sites. In general, we recommend using mtDNA coding genes only for phylogenetics of relatively closely related nematode species and, even then, using only nonsynonymous substitutions and the more conserved mitochondrial genes (e.g., cytochrome oxidases). On the other hand, the high substitution rate in genes such as ND4 should make them excellent for population genetics studies, identifying cryptic species, and resolving relationships among closely related congeners when other markers show insufficient variation.      

Phylogeny of the Drosophila saltans species group based on combined analysis of nuclear and mitochondrial DNA sequences

Nucleotide sequences from two nuclear loci, alcohol dehydrogenase and internal transcribed spacer-1 of the nuclear ribosomal DNA repeats, and two mitochondrial genes, cytochrome oxidase I and cytochrome oxidase II, were determined from nine species in the Drosophila saltans species group. The partition homogeneity test and partitioned Bremer support were used to measure incongruence between phylogenetic hypotheses generated from individual partitions. Individual loci were generally congruent with each other and consistent with the previously proposed morphological hypothesis, although they differed in level of resolution. Since extreme conflict between partitions did not exist, the data were combined and analyzed simultaneously. The total evidence method gave a more resolved and highly supported phylogeny, as indicated by bootstrap proportions and decay indices, than did any of the individual analyses. The cordata and elliptica subgroups, considered to have diverged early in the history of the D. saltans group, were sister taxa to the remainder of the saltans group. The sturtevanti subgroup, represented by D. milleri and D. sturtevanti, occupies an intermediate position in this phylogeny. The saltans and parasaltans subgroups are sister clades and occupy the most recently derived portion of the phylogeny. As with previous morphological studies, phylogenetic relationships within the saltans subgroup were not satisfactorily resolved by the molecular data.      

Phylogenetic analysis supports horizontal transfer of P transposable elements

Nucleotide sequence comparisons were used to investigate the evolution of P transposable elements and the possibility that horizontal transfer has played a role in their occurrence in natural populations of Drosophila and other Diptera. The phylogeny of P elements was examined using published sequences from eight dipteran taxa and a new, partial sequence from Scaptomyza elmoi. The results from a number of different analyses are highly consistent and reveal a P-element phylogeny that contradicts the phylogeny of the species. At least three instances of horizontal transfer are necessary to explain this incongruence, but other explanations cannot be ruled out at this time.      

Deadenylylation: a mechanism controlling c-fos mRNA decay

The c-fos proto-oncogene mRNA is extremely labile and is rapidly degraded within minutes after being transported to the cytoplasm of growth factor-stimulated fibroblasts. Analysis of the structural determinants controlling c-fos message decay reveals that this message contains at least two functionally independent elements that are responsible for its short half-life. One of these determinants is an AU-rich sequence present in the 3' untranslated region of the c-fos message, whereas the other determinant, which is structurally unrelated to the AU-rich element, is located within the c-fos protein-coding sequence. Both the c-fos AU-rich element and the coding region instability determinant appear to function by facilitating rapid removal of the c-fos poly(A) tail as a first step in the mRNA degradation process.     

Granulocyte Colony-Stimulating Factor Activating HIF-1α Acts Synergistically with Erythropoietin to Promote Tissue Plasticity

Stroke and peripheral limb ischemia are serious clinical problems with poor prognosis and limited treatment. The cytokines erythropoietin (EPO) and granulocyte-colony stimulating factor (G-CSF) have been used to induce endogenous cell repair and angiogenesis. Here, we demonstrated that the combination therapy of EPO and G-CSF exerted synergistic effects on cell survival and functional recovery from cerebral and peripheral limbs ischemia. We observed that even under normoxic conditions, G-CSF activates hypoxia-inducible factor-1α (HIF-1α), which then binds to the EPO promoter and enhances EPO expression. Serum EPO level was significantly increased by G-CSF injection, with the exception of Tg-HIF-1α^+f/+f mice. The neuroplastic mechanisms exerted by EPO combined with G-CSF included enhanced expression of the antiapoptotic protein of Bcl-2, augmented neurotrophic factors synthesis, and promoted neovascularization. Further, the combination therapy significantly increased homing and differentiation of bone marrow stem cells (BMSCs) and intrinsic neural progenitor cells (INPCs) into the ischemic area. In summary, EPO in combination with G-CSF synergistically enhanced angiogenesis and tissue plasticity in ischemic animal models, leading to greater functional recovery than either agent alone.