Reverse Conservation Analysis Reveals the Specificity Determining Residues of Cytochrome P450 Family 2 (CYP 2)

The concept of conservation of amino acids is widely used to identify important alignment positions of orthologs. The assumption is that important amino acid residues will be conserved in the protein family during the evolutionary process. For paralog alignment, on the other hand, the opposite concept can be used to identify residues that are responsible for specificity. Assuming that the function-specific or ligand-specific residue positions will have higher diversity since they are under evolutionary pressure to fit the target specificity, these function-specific or ligand-specific residues positions will have a lower degree of conservation than other positions in a highly conserved paralog alignment. This study assessed the ability of reverse conservation analysis to identify function-specific and ligand-specific residue positions in closely related paralog

Socioeconomic Costs of Overactive Bladder and Stress Urinary Incontinence in Korea

Purpose We quantified and described the economic burden of overactive bladder and stress urinary incontinence in Korea. We calculated direct costs by identifying public and private data sources that contain population-based data on resource utilization by patients with stress urinary incontinence and overactive bladder. Methods For estimating indirect costs (productivity loss), the human capital approach was applied. Data were collected from several institutes, including the Health Insurance Review Agency. Results The estimated total economic cost in treating overactive bladder was 117 billion Korean Won (KRW, the currency of South Koea) in 2006 and 145 billion KRW in 2007. The estimated total cost in treating stress urinary incontinence was 122 billion KRW in 2006 and 59 billion KRW in 2007. Conclusions By quantifying the total economic costs of overactive bladder and stress urinary incontinence, this study provides an important perspective in Korea. Because the average age of the Korean population is rapidly increasing, this study provides important information on the direct and indirect costs of overactive bladder and stress urinary incontinence for an aging society

Structural effects of clinically observed mutations in JAK2 exons 13-15: comparison with V617F and exon 12 mutations

<p>Abstract</p> <p>Background</p> <p>The functional relevance of many of the recently detected JAK2 mutations, except V617F and exon 12 mutants, in patients with chronic myeloproliferative neoplasia (MPN) has been significantly overlooked. To explore atomic-level explanations of the possible mutational effects from those overlooked mutants, we performed a set of molecular dynamics simulations on clinically observed mutants, including newly discovered mutations (K539L, R564L, L579F, H587N, S591L, H606Q, V617I, V617F, C618R, L624P, whole exon 14-deletion) and control mutants (V617C, V617Y, K603Q/N667K).</p> <p>Results</p> <p>Simulation results are consistent with all currently available clinical/experimental evidence. The simulation-derived putative interface, not possibly obtained from static models, between the kinase (JH1) and pseudokinase (JH2) domains of JAK2 provides a platform able to explain the mutational effect for all mutants, including presumably benign control mutants, at the atomic level.</p> <p>Conclusion</p> <p>The results and analysis provide structural bases for mutational mechanisms of JAK2, may advance the understanding of JAK2 auto-regulation, and have the potential to lead to therapeutic approaches. Together with recent mutation profiling results demonstrating the breadth of clinically observed JAK2 mutations, our findings suggest that molecular testing/diagnostics of JAK2 should extend beyond V617F and exon 12 mutations, and perhaps should encompass most of the pseudo-kinase domain-coding region.</p

Multiple Property Tolerance Analysis for the Evaluation of Missense Mutations

Computational prediction of the impact of a mutation on protein function is still not accurate enough for clinical diagnostics without additional human expert analysis. Sequence alignment-based methods have been extensively used but their results highly depend on the quality of the input alignments and the choice of sequences. Incorporating the structural information with alignments improves prediction accuracy. Here, we present a conservation of amino acid properties method for mutation prediction, Multiple Properties Tolerance Analysis (MuTA), and a new strategy, MuTA/S, to incorporate the solvent accessible surface (SAS) property into MuTA. Instead of combining multiple features by machine learning or mathematical methods, an intuitive strategy is used to divide the residues of a protein into different groups, and in each group the properties used is adjusted

Missing link in community psychiatry: When a patient with schizophrenia was expelled from her home

Treatment and disposition of homeless patients with schizophrenia represent a great challenge in clinical practice. We report a case of this special population, and discuss the development of homelessness, the difficulty in disposition, their utilization of health services, and possible applications of mandatory community treatment in this group of patients. A 51-year-old homeless female was brought to an emergency department for left femur fracture caused by an assault. She was diagnosed with schizophrenia about 20 years ago but received little help from mental health services over the decades. During hospitalization, her psychotic symptoms were only partially responsive to treatment. Her family refused to handle caretaking duties. The social welfare system was mobilized for long-term disposition. Homeless patients with schizophrenia are characterized by family disruption, poor adherence to health care, and multiple emergency visits and hospitalization. We hope this article can provide information about the current mental health policy to medical personnel. It is possible that earlier intervention and better outcome can be achieved by utilizing mandatory community treatment in the future, as well as preventing patients with schizophrenia from losing shelters

Initial Experience with Laparoendoscopic Single-Site Surgery by Use of a Homemade Transumbilical Port in Urology

Purpose: We present our initial experience with laparoendoscopic single-site surgery (LESS) by a single surgeon in the urologic field. Materials and Methods: From May 2009 to April 2010, 30 consecutive patients underwent LESS including seven cases of nephrectomy, five cases of nephroureterectomy with bladder cuff excision, four cases of ureterolithotomy, eight cases of marsupialization, and six cases of varicocelectomy. We performed a retrospective analysis of the medical records of the above patients. The single port was made with a surgical glove and an Alexis?? wound retractor (Applied Medical, Rancho Santa Margarita, CA, USA). The wound retractor was put into the peritoneal space through an umbilical incision, and a laparoscopic triangle was secured by crossing both instruments. All operations were performed by the transperitoneal approach. Results: Mean patient age was 54.8 years. Mean operative time was 171.2??109.1 minutes. Mean estimated blood loss was 265.0??395.5 ml. Mean incision length was 3.2??1.4 cm. Mean length of hospitalization was 5.2??2.9 days. There was one laparoscopic conversion and two open conversions. There were two cases of transient ileus that improved with conservative treatment. Mean visual analogue pain scales on the operative day and first postoperative day were 6.3/10 and 3.1/10, respectively. Conclusions: In our experience, LESS for urologic surgery is feasible, safe, and clinically applicable. We consider the homemade single-port device to be a relatively cost-effective and convenient device. If surgical instruments for LESS and appropriate ports specified for LESS are developed, LESS would be a surgical treatment technique that could be used as an alternative to the conventional types of laparoscopic surgery. ?? The Korean Urological Association, 2010

Comparative Interactomes of VRK1 and VRK3 with Their Distinct Roles in the Cell Cycle of Liver Cancer

Vaccinia-related kinase 1 (VRK1) and VRK3 are members of the VRK family of serine/threonine kinases and are principally localized in the nucleus. Despite the crucial roles of VRK1/VRK3 in physiology and disease, the molecular and functional interactions of VRK1/VRK3 are poorly understood. Here, we identified over 200 unreported VRK1/VRK3-interacting candidate proteins by affinity purification and LC-MS/MS. The networks of VRK1 and VRK3 interactomes were found to be associated with important biological processes such as the cell cycle, DNA repair, chromatin assembly, and RNA processing. Interactions of interacting proteins with VRK1/VRK3 were confirmed by biochemical assays. We also found that phosphorylations of XRCC5 were regulated by both VRK1/VRK3, and that of CCNB1 was regulated by VRK3. In liver cancer cells and tissues, VRK1/VRK3 were highly upregulated and its depletion affected cell cycle progression in the different phases. VRK3 seemed to affect S phase progression and G2 or M phase entry and exit, whereas VRK1 affects G1/S transition in the liver cancer, which could be explained by different interacting candidate proteins. Thus, this study not only provides a resource for investigating the unidentified functions of VRK1/VRK3, but also an insight into the regulatory roles of VRK1/VRK3 in biological processes.11Ysciescopuskc

Study on Practical Measures for the Development of Korean Track and Field

PURPOSE In this study, in-depth interviews were conducted with track-and-field athletes and leaders who participated in the Tokyo Olympics. The study aimed to present practical measures for the development of Korean track and field, which people at the forefront of Korean track and field thought. METHODS In-depth interviews were conducted using semi-structured questions for a total of five track-and-field national athletes and four track and field coaches. RESULTS A total of 39 subcategories and 104 concepts were derived with regard to four research questions: the process up to the Tokyo Olympics, the actual condition of Korean track and field, a comparison with track-and-field power nation, and practical measures for becoming track-and-field power nation. CONCLUSIONS Practical measures are needed to improve and develop the competitiveness of Korean track and field, which is expected to improve its competitiveness and help develop Korean track and field in the future