Improving the quality of protein structure models by selecting from alignment alternatives

Background  

In the area of protein structure prediction, recently a lot of effort has gone into the development of Model Quality Assessment Programs (MQAPs). MQAPs distinguish high quality protein structure models from inferior models. Here, we propose a new method to use an MQAP to improve the quality of models. With a given target sequence and template structure, we construct a number of different alignments and corresponding models for the sequence. The quality of these models is scored with an MQAP and used to choose the most promising model. An SVM-based selection scheme is suggested for combining MQAP partial potentials, in order to optimize for improved model selection.     

FRASS: the web-server for RNA structural comparison

Background  

The impressive increase of novel RNA structures, during the past few years, demands automated methods for structure comparison. While many algorithms handle only small motifs, few techniques, developed in recent years, (ARTS, DIAL, SARA, SARSA, and LaJolla) are available for the structural comparison of large and intact RNA molecules.     

Bayesian adaptive sequence alignment algorithms

The selection of a scoring matrix and gap penalty parameters continues to be an important problem in sequence alignment. We describe here an algorithm, the 'Bayes block aligner, which bypasses this requirement. Instead of requiring a fixed set of parameter settings, this algorithm returns the Bayesian posterior probability for the number of gaps and for the scoring matrices in any series of interest. Furthermore, instead of returning the single best alignment for the chosen parameter settings, this algorithm returns the posterior distribution of all alignments considering the full range of gapping and scoring matrices selected, weighing each in proportion to its probability based on the data. We compared the Bayes aligner with the popular Smith-Waterman algorithm with parameter settings from the literature which had been optimized for the identification of structural neighbors, and found that the Bayes aligner correctly identified more structural neighbors. In a detailed examination of the alignment of a pair of kinase and a pair of GTPase sequences, we illustrate the algorithm's potential to identify subsequences that are conserved to different degrees. In addition, this example shows that the Bayes aligner returns an alignment-free assessment of the distance between a pair of sequences.      

黄檗丛枝菌根真菌鉴定

目的：利用形态学特征与Nested-PCR技术鉴定黄檗丛枝菌根真菌。方法：采用酸性品红染色法挑选黄檗丛枝菌根。同时,利用湿筛法获得AM真菌孢子,进行形态学鉴定。运用Nested-PCR技术,对黄檗粗提DNA进行特异性扩增,采用blastn进行序列相似性比较。并构建系统进化树,确定侵染黄檗根系的AM真菌。结果：编号为HDAM-1的AM真菌孢子,形态特征与G．intraradices的特征描述一致。Nested-PCR检测到约455bp的目的片段,其序列与G．intraradices（DQ469118）相似性最高,达97．8％,有11个碱基的差异。系统进化树显示该序列在基于25S rDNA的进化树中与G．intraradices（DQ469118．1）处于同一分支,确定G．intraradices侵染黄檗根系。结论：将形态学特征与Nested-PCR技术相结合鉴定AM真菌,不仅简易、经济,而且能够提高研究结果的可靠性。     

Anti-inflammatory effect of rosiglitazone is not reflected in expression of NFκB-related genes in peripheral blood mononuclear cells of patients with type 2 diabetes mellitus

Background

The aim of this study is to perform a cost-effectiveness comparison between palpation-guided thyroid fine-needle aspiration biopsies (P-FNA) and ultrasound-guided thyroid FNA biopsies (USG-FNA).

Methods

Each nodule was considered as a case. Diagnostic steps were history and physical examination, TSH measurement, Tc^99m thyroid scintigraphy for nodules with a low TSH level, initial P-FNA versus initial USG-FNA, repeat USG-FNA for nodules with initial inadequate P-FNA or USG-FNA, hemithyroidectomy for inadequate repeat USG-FNA. American Thyroid Association thyroid nodule management guidelines were simulated in estimating the cost of P-FNA strategy. American Association of Clinical Endocrinologists guidelines were simulated for USG-FNA strategy. Total costs were estimated by adding the cost of each diagnostic step to reach a diagnosis for 100 nodules. Strategy cost was found by dividing the total cost to 100. Incremental cost-effectiveness ratio (ICER) was calculated by dividing the difference between strategy cost of USG-FNA and P-FNA to the difference between accuracy of USG-FNA and P-FNA. A positive ICER indicates more and a negative ICER indicates less expense to achieve one more additional accurate diagnosis of thyroid cancer for USG-FNA.

Results

Seventy-eight P-FNAs and 190 USG-FNAs were performed between April 2003 and May 2008. There were no differences in age, gender, thyroid function, frequency of multinodular goiter, nodule location and diameter (median nodule diameter: 18.4 mm in P-FNA and 17.0 mm in USG-FNA) between groups. Cytology results in P-FNA versus USG-FNA groups were as follows: benign 49% versus 62% (p = 0.04), inadequate 42% versus 29% (p = 0.03), malignant 3% (p = 1.00) and indeterminate 6% (p = 0.78) for both. Eleven nodules from P-FNA and 18 from USG-FNA group underwent surgery. The accuracy of P-FNA was 0.64 and USG-FNA 0.72. Unit cost of P-FNA was 148 Euros and USG-FNA 226 Euros. The cost of P-FNA strategy was 534 Euros and USG-FNA strategy 523 Euros. Strategy cost includes the expense of repeat USG-FNA for initial inadequate FNAs and surgery for repeat inadequate USG-FNAs. ICER was -138 Euros.

Conclusion

Universal application of USG-FNA for all thyroid nodules is cost-effective and saves 138 Euros per additional accurate diagnosis of benign versus malignant thyroid nodular disease.

Trial registration

ClinicalTrials.gov, NCT00571090     

Clinical and Bacteriological Studies with Clindamycin

Fifty patients have been treated with clindamycin, a chemical analogue of lincomycin. Forty-four responded satisfactorily to treatment. Gastrointestinal side-effects were rare though five patients developed rashes. Most recently isolated staphylococci are clindamycin-sensitive.     

Multiple levels of regulation of megakaryocytopoiesis

A working hypothesis for the regulation of megakaryocytopoiesis is described on the basis of current data. The hypothesis proposes that in vivo megakaryocytes are generated by 1) the expansion of clonable progenitor cells into immature megakaryocytes by locally produced (and regulated) interleukin-3 (IL-3) and 2) the development and maturation of immature megakaryocytes by a dual system; by a lineage specific mechanism involving thrombopoietic stimuli in the steady state and thrombocytopenic conditions, and by a lineage nonspecific mechanism via IL-3 in damaged or reconstituting marrow. The hypothesis predicts that if IL-3 is a significant in vivo regulator of megakaryocyte formation and development, receptor for IL-3 should be present on megakaryocytes and may be vestigially on platelets. Small but significant levels of 125I IL-3 were found to bind to platelets from normal mice. The level of binding on platelets was found to be enhanced sevenfold from mice that had received high levels of irradiation followed by bone marrow transplantation. This contrasted with a twofold increase in the level of binding to platelets from mice made acutely thrombocytopenic with antiplatelet serum. The data suggest that IL-3 may be involved in the in vivo regulation of murine megakaryocytopoiesis and may be a significant factor in rebound thrombopoiesis following bone marrow damage.