Plk1 plays a pivotal role in cell proliferation and is considered an attractive target for anti-cancer therapy. The noncatalytic polo-box domain (PBD) of Plk1 forms a phosphoepitope-binding module for protein-protein interaction. Here, we report the identification of minimal phosphopeptides that specifically interacted with the PBD of Plk1, but not the two closely-related Plk2 and Plk3. Comparative binding studies and analyses of crystal structures of the Plk1 PBD in complex with the minimal phosphopeptides revealed that the C-terminal SpT dipeptide functions as a high affinity anchor, whereas the N-terminal residues are critical for providing both specificity and affinity to the interaction. Inhibition of the Plk1 PBD by phospho-Thr mimetic peptides was sufficient to induce mitotic arrest and apoptotic cell death. Thus, the mode of the minimal peptide and PBD interaction may provide a template for designing anti-Plk1 therapeutic agents.
We have characterized the global gene expression patterns of Arabidopsis pollen using Serial Analysis of Gene Expression (SAGE). A total of 21,237 SAGE tags were sequenced and 4,211 unique tags were identified. Interestingly, the number of unique tags in pollen was low compared with the SAGE library of the leaf constructed on a similar scale. The transcript profiles of pollen reflect accurately the characteristics of pollen as a reproductive organ. Functional classification of the expressed genes reveals that those involved in cellular biogenesis such as polygalacturonase, pectate lyase, and pectin methylesterase make up more than 40% of the total transcripts. However, genes involved in energy and protein synthesis, which are prevalent in leaves, were expressed at a relatively low level. The expression level of the great majority of transcripts was unaffected by cold treatment at 0°C for 72 h, whereas pollen tube growth and seed production were substantially reduced. Interestingly, many genes thought to be responsible for cold acclimation such as COR, lipid transfer protein, and ␤-amylase, that are highly induced in Arabidopsis leaves, were only expressed at their normal level or weakly induced in the pollen. The expression patterns of the cold-responsive transcripts identified by SAGE were confirmed by microarray analysis. Our results strongly suggest that poor accumulation of proteins that play a role in stress tolerance may be why Arabidopsis pollen is cold sensitive.The functional and biochemical features of specific cell types are determined by their particular gene expression profiles. Such global gene expression patterns can be represented by a "transcriptome", which reveals the identity and the level of expression of each expressed gene in a defined population of cells (Velculescu et al., 1997). The transcriptome can be modulated by both external and internal factors, and thereby provide not only information useful for the understanding of the basic cellular biology but also a global view of biological responses over environmental stimuli.Gene expression profiles can be obtained and compared by various methods, such as RNA-DNA hybridization measurements, subtractive hybridization, subtraction libraries, and differential display. However, these methods have been limited in providing overall gene expression patterns due to their technical shortcoming. The recent DNA microarray technique allows large-scale quantitative gene expression analysis. Especially, it has been possible to cover most of the genome in GeneChips for several model systems. However, in many experimental systems, it is still limited by the fact that it only analyzes arbitrarily chosen genes. Another technology, Serial Analysis of Gene Expression (SAGE), in part overcomes this limitation. SAGE allows simultaneous, comparative, and quantitative analysis of genespecific, 9-to 10-bp sequence tags (Velculescu et al., 1995). The expression patterns of any population of transcripts can be evaluated qualitatively and quantitatively by identifying...
The growth of the maxillary sinus continues until the 3rd decade in males and the 2nd decade in females. Therefore, a maxillary sinus operation affecting the bony structures before these ages might affect the development of the sinus and needs to be performed carefully.
Adenoid hypertrophy is known as the most common cause of nasal obstruction in children; thus, adenoidectomy with, or without, tonsillectomy is one of the most commonly performed surgical procedures in the paediatric population. Although many methods have been suggested, few studies have reported on how to assess adenoid size, pre-operatively. Acoustic rhinometry is an objective technique as well as a non-invasive method, which can be easily used in young children. This study confirmed that acoustic rhinometry is a non-invasive and objective technique for assessing the geometry of the nasal cavity and nasopharynx. Forty children were evaluated using symptomology, two different radiological measurements and acoustic rhinometry; the results were compared with endoscopic findings. Clinical symptoms and A/N ratio measured with Fujioka's method significantly correlated with the endoscopic assessment findings (r = 0.769 and 0.604 respectively). Significant increases in the cross-sectional area and volume of the nasopharynx were observed at the adenoid notch after adenoidectomy (p<0.005 andp<0.005, respectively). Acoustic rhinometry showed a high degree of correlation of which adenoid occupied the nasopharyngeal airway under endoscopic examination (r = 0.771). Thus, the study concluded that acoustic rhinometry can be as good an objective method for measuring adenoid sizes as endoscopy and can be used as one of the pre-operative examination tools for adenoidectomy.
Formation of a DNA loop by AraC proteins bound at the aral and araO2 sites, whose center-to-center distance is 211 base pairs, is necessary for repression of the araBAD promoter, PBAD, of Escherichia coli. To determine the upper and lower size limits of the loop, we constructed PBADreporter gene fusion plasmids with various spacings between aral and araO2 and measured their levels of expression. Spacings larger than about 500 base pairs resulted in elimination of detectable repression. No lower limit to spacing was found, suggesting that AraC protein itself possesses significant flexibility and its bending substantially aids formation of small loops. As the spacing between aral and araO2 varied, the activity of PBAD oscillated with an 11.1-base-pair periodicity, implying that the in vivo helical repeat of this DNA is 1.1 base pairs per turn.
AbstractÐEfficient and effective buffering of disk blocks in main memory is critical for better file system performance due to a wide speed gap between main memory and hard disks. In such a buffering system, one of the most important design decisions is the block replacement policy that determines which disk block to replace when the buffer is full. In this paper, we show that there exists a spectrum of block replacement policies that subsumes the two seemingly unrelated and independent Least Recently Used (LRU) and Least Frequently Used (LFU) policies. The spectrum is called the LRFU (Least Recently/Frequently Used) policy and is formed by how much more weight we give to the recent history than to the older history. We also show that there is a spectrum of implementations of the LRFU that again subsumes the LRU and LFU implementations. This spectrum is again dictated by how much weight is given to recent and older histories and the time complexity of the implementations lies between O(1) (the time complexity of LRU) and ylog P n (the time complexity of LFU), where n is the number of blocks in the buffer. Experimental results from trace-driven simulations show that the performance of the LRFU is at least competitive with that of previously known policies for the workloads we considered.
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