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.     

Open water zooplankton communities in North African wetland lakes: the CASSARINA Project

Zooplankton (Copepoda, Cladocera, Ostracoda, Rotifera and Diptera larvae) in nine North African lakes was collected from open water areas over twenty months during 1997/99. The results were used to monitor changes in the pelagic micro-invertebrate fauna of these sites with the purpose of exploring diversity structure and regional species occurrences.The studied sites formed three distinct groups based on hydrology and water quality criteria: (i) acid water with no marine connection (Megene Chitane); (ii) alkaline freshwater/brackish with no marine connection (Merja Sidi Bou Rhaba and Merja Bokka); (iii) freshwater/brackish with marine connection (Merja Zerga, Lac de Korba, Garaet El Ichkeul and three Nile Delta lakes). However, cluster analysis of the zooplankton data alone indicated four groups with Korba being separated because of its prevalence of species tolerant of summer hypersalinity.The total regional zooplanktonic species richness found was 88 taxa and these were characterized by species tolerant of widely fluctuating environmental conditions. However, some recorded species were very rare for North African freshwaters (e.g. Alonella excisa, Leydigia quadrangularis and, Ilyocryptus sordidus) and generally indicate favourable environmental conditions of low salinity and temperature. The sites influenced by marine waters generally exhibited slightly lower numbers of species but which generally demonstrate cosmopolitan distributions. Distinct seasonal patterns in species distributions were more similar to those observed in European lakes rather than to those of lower latitudes sites.Zooplankton play a key role in maintaining aquatic ecosystem quality in the North African study lakes and the community distributions described for the late 20th century help set biodiversity base-line data for future studies. If the remaining wetland lakes in this region are to persist as important resources during the 21st century, they will need to be managed in a way that ensures that aquatic diversity is maintained.     

Radiometrically determined dates and sedimentation rates for recent sediments in nine North African wetland lakes (the CASSARINA Project)

Sediment cores were collected from nine wetland lakes in Morocco, Tunisia and Egypt for the CASSARINA project investigating environmental change in Northern African wetlands. The cores were dated radiometrically by using natural (²¹⁰Pb) and artificial (¹³⁷Cs and ²⁴¹Am) radionuclides. At sites in Morocco and Tunisia with mean annual rainfall totals ranging from 500–1000 mm yr^–1, fallout records were generally satisfactory and it was possible to develop independent sediment chronologies based on the radiometric data alone. At the Egyptian sites, rainfall was less than 200 mm yr^–1 and fallout records were much less distinct. At these sites the radiometric data could only be used to give an indication of mean sedimentation rates during the past 30–40 years. By using a combination of fallout radionuclide, pollen, and macrofossil stratigraphic records it was however possible to determine a credible sediment chronology spanning the major part of the 20th century. Applying this chronology to records of spheroidal carbonaceous particles (SCP) from the same sediment cores, the onset of significant levels of atmospheric pollution in the Nile Delta is dated in all three cores to the mid 1950s. Results from a number of lakes (Sidi Bou Rhaba, Ichkeul and Korba) revealed high and accelerating siltation rates, threatening their continued existence beyond the next few decades. In contrast, sedimentation rates at all three Nile Delta sites appear to have declined in recent decades, most probably due to the impact of the Nile barrages.     

Terrestrial pollen record of recent land-use changes around nine North African lakes in the CASSARINA Project

Pollen analyses and related plant macrofossil records are presented from short cores from nine North African lakes in the EU-funded CASSARINA project. Terrestrial pollen reflects human impact on the vegetation and landscape over the last 150–100 years. Pollen changes, aided by radiometric dating, could be correlated with historical developments. The chronology of the landscape changes date other biostratigraphical records reflecting changes in the aquatic ecosystems.Three lakes in Morocco show gradually intensifying land-use over the last century. Accelerated technological development and landscape modification over the last 20 years culminated in one of the lakes being drained and cultivated during the project period. In Tunisia, a nationally unique acid-water lake is threatened by water withdrawal for increased catchment cultivation. The landscape around two other lakes is being increasingly cultivated and urbanised, and water withdrawal to support this has resulted in deleterious effects on the aquatic ecosystems, particularly at the internationally famous Garaet El Ichkeul where reed-marshes and macrophyte beds have been lost. The three lakes in the Egyptian Nile Delta are in the same hydrological system and show parallel changes in the balance between saltmarsh and reed-marsh. Control of Nile floods and year-round irrigation led to marked increases in cultivation in the delta region since ca. 1920. The Aswan High Dam (1964) had little detectable further effect. Documented planting of dates, palms, and olives and of introduced Casuarina and Eucalyptus trees provided a chronology to supplement the unsatisfactory radiometric dating of the sediments in this low-rainfall area.     

OLigonucleotide (Cyanomethyl) Phosphonates

Abstract

A dinucleoside (cyanomethyl) phosphonate has been prepared, and its properties have been studied. This compound was converted into an oligonucleotide possessing alternating (cyanomethyl) phosphonate and phosphodiester backbone groups and its hybridization to complementary DNA and RNA sequences was studied versus methylphosphonate and phosphodiester controls.     

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.