Representative transcript sets for evaluating a translational initiation sites predictor

<p>Abstract</p> <p>Background</p> <p>Translational initiation site (TIS) prediction is a very important and actively studied topic in bioinformatics. In order to complete a comparative analysis, it is desirable to have several benchmark data sets which can be used to test the effectiveness of different algorithms. An ideal benchmark data set should be reliable, representative and readily available. Preferably, proteins encoded by members of the data set should also be representative of the protein population actually expressed in cellular specimens.</p> <p>Results</p> <p>In this paper, we report a general algorithm for constructing a reliable sequence collection that only includes mRNA sequences whose corresponding protein products present an average profile of the general protein population of a given organism, with respect to three major structural parameters. Four representative transcript collections, each derived from a model organism, have been obtained following the algorithm we propose. Evaluation of these data sets shows that they are reasonable representations of the spectrum of proteins obtained from cellular proteomic studies. Six state-of-the-art predictors have been used to test the usefulness of the construction algorithm that we proposed. Comparative study which reports the predictors' performance on our data set as well as three other existing benchmark collections has demonstrated the actual merits of our data sets as benchmark testing collections.</p> <p>Conclusion</p> <p>The proposed data set construction algorithm has demonstrated its property of being a general and widely applicable scheme. Our comparison with published proteomic studies has shown that the expression of our data set of transcripts generates a polypeptide population that is representative of that obtained from evaluation of biological specimens. Our data set thus represents "real world" transcripts that will allow more accurate evaluation of algorithms dedicated to identification of TISs, as well as other translational regulatory motifs within mRNA sequences. The algorithm proposed by us aims at compiling a redundancy-free data set by removing redundant copies of homologous proteins. The existence of such data sets may be useful for conducting statistical analyses of protein sequence-structure relations. At the current stage, our approach's focus is to obtain an "average" protein data set for any particular organism without posing much selection bias. However, with the three major protein structural parameters deeply integrated into the scheme, it would be a trivial task to extend the current method for obtaining a more selective protein data set, which may facilitate the study of some particular protein structure.</p

Cell cyclins: triggering elements of cancer or not?

Cyclins are indispensable elements of the cell cycle and derangement of their function can lead to cancer formation. Recent studies have also revealed more mechanisms through which cyclins can express their oncogenic potential. This review focuses on the aberrant expression of G1/S cyclins and especially cyclin D and cyclin E; the pathways through which they lead to tumour formation and their involvement in different types of cancer. These elements indicate the mechanisms that could act as targets for cancer therapy

Molecular biology primer for the pediatric pathologist

Recent advances in the knowledge of molecular events of cell growth and differentiation have provided considerable gains to the understanding of neoplasia. Along with this understanding, molecular biology has yielded many new techniques of great potential for diagnostic use. This review illustrates, in general terms, current models of gene regulation, intracellular signal transduction, and the regulation of cell division that are relevant to pediatric pathologists. These concepts are used to examine the molecular pathology of three pediatric tumors: retinoblastoma, Wilms' tumor, and neuroblastoma. In addition, molecular biology techniques potentially useful to pediatric pathologists are discussed, with examples of some possible applications of these techniques. Hopefully, this review portrays the relevance of molecular biology to pediatric pathologists and serves as a useful guide to the interpretation of the molecular pathology literature

Exploring college leaders' critical incident experiences pursuant to improving campus safety policies during the mass-shooting era

Since the early 1700’s, colleges have used authority figures such as spiritual leaders, tutors, faculty members, and campus police to implement systems of institutional control and accountability for student behavior on their campuses. Despite these efforts, during the last ten generations, colleges have struggled to find the appropriate balance between college campus control and educational freedom (Geiger, 2006). Cohen and Kisker (2010) assert that the college life system was designed for controlling the often exuberant youth and for inculcating within them, discipline, morals, and character. Ideally, the colleges simply wanted the students to aspire to higher education, but immaturity levels often contributed to students’ delinquent behaviors (Cohen & Kisker, 2010). This recurring tendency in student behavior precipitated the need for more robust measures of control on college campuses. As such, by the 1800’s, many colleges embraced the unsophisticated campus policing model known as the watchman system. The watchman system enhanced authority presence on campuses, but restricted actual campus police enforcement (Sloan, 1992). Today, remnants of the watchman system still exists in modern campus policing, as indicated by campus police officers being restricted to custodial duties such as protecting the college from fire, water, and other damage, and maintaining social control with limited enforcement capabilities (Sloan, 1992; Wilson & Wilson, 2011). This restrictive approach to campus policing has fundamentally shaped the policing model on college campuses today – reflecting a culture of perceived complacency and amateurism (Wilson & Wilson, 2011). In recent years, colleges have faced numerous unconventional threats to campus safety including: radical protests, sexual assaults and mass shooting attacks; most of which the colleges and their campus police agencies have been underprepared to handle (U.S. Department of Justice, 2005; Karjane, Fisher, & Cullen, 2005). This lack of preparedness has historically been associated with college administrators’ influence over campus security policy. In Gelber (1972), college presidents were identified as the primary policymaking authority on college campuses; while campus security offices assumed a secondary role in the decision-making process. Today, despite the unprecedented increases in violent campus crime, college presidents continue to maintain the status quo of reinforcing the historical practice of restricting campus police authority through policy and practice. Sloan (1992) found that since the Mid-to-late 1960s, colleges and campus police agencies across the country have remained relatively autonomous. However, in order for administrators to maintain authoritative control over campus police operations, some colleges made their chief of police accountable to the vice president of student affairs or directly to the president of the college (Sloan, 1992; Gelber, 1972). Many law enforcement practitioners have widely criticized the practice of hedging campus police authority because it acrimoniously impacts critical incident preparedness and response on college campuses. From a practical standpoint, there is insufficient evidence indicating that college leaders (college president and college police chiefs) are risk-conscious of impediments to critical incident management and emergent threats to campus safety based on their past experiences. However, as suggested by Whitfield (2004), college and university leaders can no longer avoid looking outside of their internal walls for impending threats and preparing for the problems that can result from them. Based on this premise, several emergent unconventional threats to college safety were presented in this study and practical recommendations were made for college leaders and politicians to consider in preparing for and mitigating the outcomes of critical incidents during the Mass-shooting Era

Chromosome mapping of human CDC25A and CDC25B phosphatases

The human CDC25 tyrosine phosphatases trigger activation of CDC2 by removing inhibitory phosphates; thus the genes encoding these phosphatases may be suspected as potential oncogenes due to their role in promoting cell division. To date, three human CDC25 genes have been identified: CDC25A, B, and C. This communication describes the mapping of CDC25A to chromosome 3p21 and CDC25B to chromosome 20p13 by fluorescence in situ hybridization with confirmation by the polymerase chain reaction of hamster-human somatic cell hybrid DNA. 3p21 is near an area frequently involved in karyotypic abnormalities in renal carcinomas, small cell carcinomas of the lung, and benign tumors of the salivary gland. 20p13 does not seem to be a common area for karyotypic alteration in tumors. Mapping of these genes to their chromosomal loci may help identify tumors with abnormal regulation of CDC25 genes due to genomic alterations

Isolation of the Rb-related p130 through its interaction with CDK2 and cyclins

A two-hybrid protein interaction screen was used to isolate cDNAs encoding human proteins that can interact with human CDK2 in yeast. A new member of the retinoblastoma susceptibility gene family, Rbr-2 (Rb-related), was obtained. The sequence of the Rbr-2 protein shares ~50% identity with p107 and homology to Rb within the pocket domain. Several lines of evidence indicate that Rbr-2 is the adenovirus E1A-associated p130. Like Rb and p107, p130(Rbr-2) can bind to viral oncoproteins, SV40 large T antigen, and adenovirus E1A through its pocket domain. Although p130(Rbr-2) does not bind to CDK2 in vitro, it can interact with cyclins, with a clear preference for D-type cyclins. Because both CDK2 and p130(Rbr-2) show affinity for cyclins, we suggest that p130(Rbr-2) and CDK2 interacted through a yeast-derived cyclin bridge in the two-hybrid screen. The gene encoding p130(Rbr-2) mapped to 16q13, a region of frequent genomic alteration in human tumors

Chromosomal mapping of human CDK2, CDK4, and CDK5 cell cycle kinase genes

Cyclin dependent kinases (CDK's) are kinases that interact with cyclins and regulate cell division. Genomic clones encoding human CDK2, CDK4, and CDK5 were obtained and mapped to their respective chromosomal loci using fluorescence in situ hybridization on human lymphocyte metaphase spreads. Interestingly, CDK2 and CDK4 were located at the same position, 12q13, and CDK5 was mapped to 7q36. 12q13 has been shown to be associated with chromosome alterations such as amplifications and translocations in solid tumors. 7q36 does not appear to be a major site of chromosome alterations in tumors. As CDK2 and CDK4 appear to be important in regulating the human cell cycle, it is possible that the alterations of the 12q13 locus in tumors may involve changes in the regulation of CDK2 and CDK4 genes

Chromosomal mapping of the human genes CKS1 to 8q21 and CKS2 to 9q22

The human cdk2/cyclin A kinase complex is a key regulator of the events of S phase. This complex contains several proteins involved in regulating its catalytic activity, including one or more of the CKS proteins, which have recently been shown to inhibit the activation of the cdk2 kinase. To investigate whether the CKS genes may be altered in human neoplasia, we mapped the chromosome locations of CKS1 and CKS2 by fluorescence in situ hybridization (FISH). CKS1 was localized to 8q21, a locus that is seldom grossly altered in cancer. The localization of CKS2 to 9q22 places it very near to a putative tumour suppressor locus suggested to be responsible for susceptibility to the Basal Cell Nervus Syndrome (BCNS or Gorlin's syndrome) familial cancer disorder. Six fibroblast cell lines isolated from patients with BCNS were demonstrated by FISH to have both copies of CKS2 present. Partial sequencing of a genomic clone of CKS2 revealed that the open reading frame lies over three exons. Examination of the six cell lines by SSCP and PCR-based sequencing of the parts of the three exons coding for the full length protein demonstrated no consistent divergence from the reported cDNA sequence in any exon. It is unlikely that CKS2 is the BCNS tumour suppressor gene

Chromosomal mapping of the genes for the human CDK2/cyclin A-associated proteins p19 (SKP1A and SKP1B) and p45 (SKP2)

Many gene products associated with the cyclin-dependant kinases (CDKs) have been shown to regulate the active kinase complex during the transition points of the cell cycle. Some of these proteins have been implicated in human neoplasia, acting as either oncoproteins or tumour suppressors. The CDK2/cyclin A kinase complex can complex with several proteins, including p21, and PCNA or p45, p19, and p9. It was previously shown that at least two of these proteins, p19 and p45, are abnormally regulated in transformed cell lines. We describe here the mapping by fluorescence in situ hybridization of the gene for the CDK2/cyclin A-associated protein p45 (SKP2) to 5p13 and the p19-related genes p19A (SKP1A) and p19B (SKP1B) to 7q11.2 and 12p12, respectively. All three of these loci are associated with karyotypic alterations, known amplifications, or suspected tumor suppressor genes