Structural basis of GC-1 selectivity for thyroid hormone receptor isoforms

Background

Multiple protein templates are commonly used in manual protein structure prediction. However, few automated algorithms of selecting and combining multiple templates are available.

Results

Here we develop an effective multi-template combination algorithm for protein comparative modeling. The algorithm selects templates according to the similarity significance of the alignments between template and target proteins. It combines the whole template-target alignments whose similarity significance score is close to that of the top template-target alignment within a threshold, whereas it only takes alignment fragments from a less similar template-target alignment that align with a sizable uncovered region of the target. We compare the algorithm with the traditional method of using a single top template on the 45 comparative modeling targets (i.e. easy template-based modeling targets) used in the seventh edition of Critical Assessment of Techniques for Protein Structure Prediction (CASP7). The multi-template combination algorithm improves the GDT-TS scores of predicted models by 6.8% on average. The statistical analysis shows that the improvement is significant (p-value < 10^-4). Compared with the ideal approach that always uses the best template, the multi-template approach yields only slightly better performance. During the CASP7 experiment, the preliminary implementation of the multi-template combination algorithm (FOLDpro) was ranked second among 67 servers in the category of high-accuracy structure prediction in terms of GDT-TS measure.

Conclusion

We have developed a novel multi-template algorithm to improve protein comparative modeling.     

Horizontal transmission, vertical inactivation, and stochastic loss of mariner-like transposable elements

Horizontal transmission has been well documented as a major mechanism for the dissemination of mariner-like elements (MLEs) among species. Less well understood are mechanisms that limit vertical transmission of MLEs resulting in the "spotty" or discontinuous distribution observed in closely related species. In this article we present evidence that the genome of the common ancestor of the melanogaster species subgroup of Drosophila contained an MLE related to the mellifera (honey bee) subfamily. Horizontal transmission, approximately 3-10 MYA, is strongly suggested by the observation that the sequence of the MLE in Drosophila erecta is 97% identical in nucleotide sequence with that of an MLE in the cat flea, Ctenocephalides felis. The D. erecta MLE has a spotty distribution among species in the melanogaster subgroup. The element has a high copy number in D. erecta and D. orena, a moderate copy number in D. teissieri and D. yakuba, and was apparently lost ("stochastic loss") in the lineage leading to D. melanogaster, D. simulans, D. mauritiana, and D. sechellia. In D. erecta, most copies are concentrated in the heterochromatin. Two copies from D. erecta, denoted De12 and De19, were cloned and sequenced, and they appear to be nonfunctional ("vertical inactivation"). It therefore appears that the predominant mode of MLE evolution is vertical inactivation and stochastic loss balanced against occasional reinvasion of lineages by horizontal transmission.      

Budding yeast morphogenesis: signalling, cytoskeleton and cell cycle

Yeast-like fungi such as Saccharomyces cerevisiae exhibit a range of cell types differing in cell shape, gene expression and growth pattern. Signal transduction pathways mediate transitions between different cell types. Nutritional signals induce rounded yeast-form cells either to enter invasive growth as elongated filamentous cells or to arrest to prepare for stationary phase, conjugation, or meiosis. An emerging theme is that development critically depends upon differential regulation of vegetative functions, including cytoskeletal organization and cell cycle progression, as much as on the expression of cell type specific gene products.     

Warthin''s tumour: unusual vs. common morphological findings in fine needle aspiration biopsies

Fine needle aspiration biopsies (FNA) of 47 Warthin's tumours confirmed by histology were re-evaluated for cytomorphological findings. The majority of aspirates (37/47) contained a typical background with proteinaceous substance and cell debris, along with cellular elements represented by oncocytic, lymphoid, and mast cells with degranulated cytoplasm. Uncommon cellular findings were true squamous cells (1/47), atypical cells with vacuoles (1/47), osteoclastic giant cells (1/47), epithelioid cells (1/47), mast cells with preserved granules in cytoplasm (3/47), and siderophages (4/47). Uncommon findings in the background were corpora amylacea-like structures and homogeneous bright red droplets. Squamous cells and atypical cells with vacuoles caused diagnostic difficulties in distinguishing a Warthin's tumour from a squamous cell or mucoepidermoid carcinoma. However, other unusual cellular and background findings were not worrying; therefore, they are merely regarded as a curiosity in the cytomorphological appearance of the tumour.     

Water in the Avian Egg Overall Budget of Incubation

The loss of mass in eggs during incubation was examined andevidence is presented to show that this is essentially due toloss of water. The mean fraction of water lost by diffusionthroughout incubation is 0.150 ± 0.025 S D per gram ofegg and 0.162 ± 0.026 S D per gram of egg content for81 species. The water fraction of fresh eggs and of hatchingeggs was examined in 32 species divided according to maturityat hatching, and found to be very similar within each category(83% in altricial 83% in semi-altricial 78% in semi-precocial72% in precocial eggs). The 11% difference between the altricialand precocial categories is statistically significant. Duringincubation, dry matter is metabolized increasing the water fractionwhich is further increased by metabolic water production. Hence,water loss during incubation is mandatory if the relative watercontent of an egg at the end of incubation is to remain essentiallythe same as at the beginning. Equations are developed whichallow one to estimate the difference between diffusive waterloss and the total water loss in altricial and piecocial eggscaused by additional water loss during pipping and hatching.     

Gas Exchange of the Avian Egg Time, Structure, and Function

Data are presented for oxygen consumption water loss duringincubation water vapor conductance of the shell and pore numberof avian eggs and the way in which these values relate not onlyto egg mass but also to incubation time. It is proposed thatall these functions are proportional to the product of egg massand rate of development where the latter is defined as the inverseof incubation time. These interrelationships account at theend of incubation for similar O₂ and CO₂ tensions in the airspace of eggs utilization of calories (0.5 kcal g^–1) andwater loss (15 g g^–1)     

Statistical properties of the variation at linked microsatellite loci: implications for the history of human Y chromosomes [published erratum appears in Mol Biol Evol 1997 Mar;14(3):354]

It has recently been suggested that observed levels of variation at microsatellite loci can be used to infer patterns of selection in genomes and to assess demographic history. In order to evaluate the feasibility of these suggestions it is necessary to know something about how levels of variation at microsatellite loci are expected to fluctuate due simply to stochasticity in the processes of mutation and inheritance (genetic sampling). Here we use recently derived properties of the stepwise mutation model to place confidence intervals around the variance in repeat score that is expected at mutation-drift equilibrium and outline a statistical test for whether an observed value differs significantly from expectation. We also develop confidence intervals for the time course of the buildup of variation following a complete elimination of variation, such as might be caused by a selective sweep or an extreme population bottleneck. We apply these methods to the variation observed at human Y-specific microsatellites. Although a number of authors have suggested the possibility of a very recent sweep, our analyses suggest that a sweep or extreme bottleneck is unlikely to have occurred anytime during the last approximately 74,000 years. To generate this result we use a recently estimated mutation rate for microsatellite loci of 5.6 x 10(-4) along with the variation observed at autosomal microsatellite loci to estimate the human effective population size. This estimate is 18,000, implying an effective number of 4,500 Y chromosomes. One important general conclusion to emerge from this study is that in order to reject mutation-drift equilibrium at a set of linked microsatellite loci it is necessary to have an unreasonably large number of loci unless the observed variance is far below that expected at mutation-drift equilibrium.      

Effects of carbon dioxide exposure on early brain development in rats

The developing brain is vulnerable to environmental factors. We investigated the effects of air that contained 0.05, 0.1 and 0.3% CO₂ on the hippocampus, prefrontal cortex (PFC) and amygdala. We focused on the circuitry involved in the neurobiology of anxiety, spatial learning, memory, and on insulin-like growth factor-1 (IGF-1), which is known to play a role in early brain development in rats. Spatial learning and memory were impaired by exposure to 0.3% CO₂ air, while exposure to 0.1 and 0.3% CO₂ air elevated blood corticosterone levels, intensified anxiety behavior, increased superoxide dismutase (SOD) enzyme activity and MDA levels in hippocampus and PFC; glutathione peroxidase (GPx) enzyme activity decreased in the PFC with no associated change in the hippocampus. IGF-1 levels were decreased in the blood, PFC and hippocampus by exposure to both 0.1 and 0.3% CO₂. In addition, apoptosis was increased, while cell numbers were decreased in the CA1 regions of hippocampus and PFC after 0.3% CO₂ air exposure in adolescent rats. A positive correlation was found between the blood IGF-1 level and apoptosis in the PFC. We found that chronic exposure to 0.3% CO₂ air decreased IGF-1 levels in the serum, hippocampus and PFC, and increased oxidative stress. These findings were associated with increased anxiety behavior, and impaired memory and learning.     

Kill rates and food consumption of leopards in Bardia National Park, Nepal

This is the first study presenting data on kill rates and food consumption among Asian leopardsPanthera pardus Linnaeus, 1758. In Bardia National Park, Nepal, we found leopard kills by searching within areas with clusters of locations from radio collared leopards (2 males and 1 female with 2 cubs aged 4–9 months). We used two tracking schemes, 24-h intensive radio-tracking and daily monitoring, and we defined food consumption as the product of average prey live weight and proportion consumed. The three leopards consumed 89.2 kg of meat from five chitalAxis axis, one domestic dog and two birds during 19 days of 24-h intensive tracking, rendering an average (± SE) daily food intake of 4.7 ± 0.3 kgper capita. Twenty-five prey items (14 chital, one muntjacMuntiacus muntjak, four primates and six birds) were found during 180 days of daily monitoring of the female. All edible biomass was consumed in all kills, except for three chital, and the rate of kill consumption was positively related to the age of her cubs. The average daily food consumption of the female was 4.0 ± 0.3 kg/day, the kill rate (days/kill) including all prey categories was 5.6 ± 0.4 days, and the kill rate of ungulates was 10.6 ±0.7 days. Our food consumption estimates are higher than reported from arid African environments. We suggest that the high food consumption rate in our study is a consequence of a release from time-energy constraints due to high prey abundance.