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Roma M,1,2 Madhura Sen,1,2 Kundabala Mala,1,2 Nanditha Sujir,2,3 Dharnappa Poojary,2,4 Neetha J Shetty,2,5 Ramya Shenoy,2,6 Sharon Saldanha2,7 1Department of Conservative Dentistry and Endodontics, Manipal College of Dental Sciences, Mangalore, Mangalore, India; 2Manipal Academy of Higher Education, Manipal, Karnataka, India; 3Department of Oral Medicine and Radiology, Manipal College of Dental Sciences, Mangalore, Mangalore, India; 4Department of Oral & Maxillofacial Surgery, Manipal College of Dental Sciences, Mangalore, Mangalore, India; 5Department of Periodontology, Manipal College of Dental Sciences, Mangalore, Mangalore, India; 6Department of Public Health Dentistry, Manipal College of Dental Sciences, Mangalore, Mangalore, India; 7Department of Prosthodontics and Crown and Bridge, Manipal College of Dental Sciences, Mangalore, Mangalore, IndiaCorrespondence: Ramya ShenoyDepartment of Public Health Dentistry, Manipal College of Dental Sciences, Mangalore, Light House Hill Road, Mangalore, Karnataka, 575001, IndiaTel +91 9880450277Email ramya.shenoy@manipal.eduSharon SaldanhaDepartment of Prosthodontics and Crown and Bridge, Manipal College of Dental Sciences, Mangalore, Light House Hill Road, Mangalore, Karnataka, 575001, IndiaEmail sharon.saldanha@manipal.eduPurpose: To critically assess the unmet oral health needs and oral health-related quality of life among old age home inhabitants in Karnataka, India.Methods: A total of 96 older adults (males=32, 33.33%, females=64, 66.67%) aged 60 years and above, residing in old age homes were included in this cross-sectional study. The mean age of the participants included in the study was 69.25± 7.99 years. Oral health status and dental needs were assessed using the Oral Hygiene Index Simplified (OHIS) and the WHO Oral Health Assessment forms. Oral health-related quality of life was evaluated by administrating the Geriatric Oral Health Assessment Index (GOHAI) questionnaire through an interview format.Statistical Analysis: The Statistical Package for Social Sciences (SPSS) version 17 was used. Descriptive statistics was tabulated for oral health status and GOHAI scores. Student’s t-test and ANOVA were applied to check the association of the GOHAI responses with the number of years of residence in old age homes, age groups, gender, and dentition status.Results: The mean age of the participants included in the study was 69.25± 7.99 years. Twenty-six (27.1%) participants reported diabetes mellitus and hypertension. Most of the participants 89 (91.7%) visited the dentist when they had dental complaints. Among the dentulous study population, the majority of the participants had untreated dental caries indicated for dental extraction and needed periodontal therapy. Amongst the participants, 68 (70.82%) required prosthetic rehabilitation. More than 10 years of residence in old aged homes, over 80 years of age, being female, and completely edentulous groups showed lower total GOHAI scores compared to their counterparts.Conclusion: The majority of the participants showed unmet oral health needs and lower GOHAI scores indicating poor oral health-related quality of life.Keywords: developing countries, homes for aged, GOHAI, older adults, oral health, oral health-related quality of life

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cell.2007.07.018 Byline: Choel Kim (1), Cecilia Y. Cheng (1), S. Adrian Saldanha (1), Susan S. Taylor (1)(2)(3) Keywords: CELLBIO; SIGNALING Abstract: Protein kinase A (PKA) holoenzyme is one of the major receptors for cyclic adenosine monophosphate (cAMP), where an extracellular stimulus is translated into a signaling response. We report here the structure of a complex between the PKA catalytic subunit and a mutant RI regulatory subunit, RI[alpha](91-379:R333K), containing both cAMP-binding domains. Upon binding to the catalytic subunit, RI undergoes a dramatic conformational change in which the two cAMP-binding domains uncouple and wrap around the large lobe of the catalytic subunit. This large conformational reorganization reveals the concerted mechanism required to bind and inhibit the catalytic subunit. The structure also reveals a holoenzyme-specific salt bridge between two conserved residues, Glu261 and Arg366, that tethers the two adenine capping residues far from their cAMP-binding sites. Mutagenesis of these residues demonstrates their importance for PKA activation. Our structural insights, combined with the mutagenesis results, provide a molecular mechanism for the ordered and cooperative activation of PKA by cAMP. Author Affiliation: (1) Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093-0654, USA (2) Department of Pharmacology, University of California, San Diego, La Jolla, CA 92093-0654, USA (3) Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA 92093-0654, USA Article History: Received 19 December 2006; Revised 23 March 2007; Accepted 13 July 2007 Article Note: (miscellaneous) Published: September 20, 2007

Targeting sites that modulate protein-protein interactions represents an ongoing challenge for drug discovery. We have devised an assay principle, named ligand-regulated competition (LiReC), in an effort to find non-ATP competitive small-molecule regulators for type I[alpha] cAMP-dependent Protein kinase (PKA-I[alpha]), a protein complex that is implicated in disease. Our assay based on the LiReC principle utilizes a competitive fluorescent peptide probe to assess the integrity of the PKA-I[alpha] complex upon introduction of an allosteric ligand. The developed fluorescence polarization method screens for small molecules that specifically protect (antagonists) or conversely activate (agonists) this protein complex. In high-throughput format, various cyclic nucleotide-derived agonists and antagonists are successfully detected with high precision. Furthermore, assay performance (Z'-factors above 0.7) far exceeds the minimum requirement for small-molecule screening. To identify compounds that operate through novel modes of action, our method shields the ATP-binding site and purposely excludes ATP-competitive ligands. These proof-of-principle experiments highlight the potential of the LiReC technique and suggest its application to other protein complexes, thereby providing a novel approach to identify and characterize modulators (small molecules, proteins, peptides, or nucleic acids) of protein-protein systems.

Research has been conducted on the ketopantoate reductase which catalyzes the NADPH-dependent ketopantoate reduction to pantoate. The Escherichia coli panE gene encoding this ketopantoate reductase has been cloned and expressed as the native and selenomethionine-substituted proteins and the results are reported.

Abstract Background Transformation of low-grade follicular lymphoma to high-grade diffuse large B cell lymphoma (DLBCL) is known. However, the opposite is not commonly reported. In this report, we present a case of follicular lymphoma that underwent transformation to DLBCL. Three years after treatment for histologic transformation, the patient presented again with low-grade follicular lymphoma at the same site which is unusual in the natural history of follicular lymphoma. Case presentation A 50-year-old female patient presented to us with complaints of slowly progressing swelling in the neck on the left side for a duration of 1 year. Past history of the patient revealed a diagnosis of follicular lymphoma in 2004 for which the patient had taken prednisolone and chlorambucil. Details of staging were not available with the patient. After a complete work-up, she was diagnosed as DLBCL, stage IIIE. She was treated with 6 cycles of CHOP regimen. She had very good response to chemotherapy. However, she defaulted and was lost to follow-up. She presented again after 3 years with history of painless progressive swelling in the right side of the neck for the last 1 year. Examination revealed cervical lymph nodes and ascites. This time, a repeat biopsy and immunohistochemistry was suggestive of follicular lymphoma. In view of significant ascites, she was started on chemotherapy with CVP regimen. After 6 cycles, she has good partial response and resolution of ascites. She is currently on follow-up. Conclusions We have presented a case of FL that has transformed to DLBCL after 10 years of diagnosis. After HT, she was treated with CHOP chemotherapy and the patient relapsed again after 3 years with follicular lymphoma histology. This case highlights the unique and varied natural history of follicular lymphoma that may be attributed to different subclones of malignant cells that may have arisen from a common progenitor FL cell and differential effect of chemotherapy on these subclones.

Compound pooling, or multiplexing more than one compound per well during primary high-throughput screening (HTS), is a controversial approach with a long history of limited success. Many issues with this approach likely arise from long-term storage of library plates containing complex mixtures of compounds at high concentrations. Due to the historical difficulties with using multiplexed library plates, primary HTS often uses a one-compound–one-well approach. However, as compound collections grow, innovative strategies are required to increase the capacity of primary screening campaigns. Toward this goal, we have developed a novel compound pooling method that increases screening capacity without compromising data quality. This method circumvents issues related to the long-term storage of complex compound mixtures by using acoustic dispensing to enable “just-in-time” compound pooling directly in the assay well immediately prior to assay. Using this method, we can pool two compounds per well, effectively doubling the capacity of a primary screen. Here, we present data from pilot studies using just-in-time pooling, as well as data from a large >2-million-compound screen using this approach. These data suggest that, for many targets, this method can be used to vastly increase screening capacity without significant reduction in the ability to detect screening hits. [ABSTRACT FROM PUBLISHER]

Telomerase maintains chromosomal termini and is down-regulated during cellular differentiation leading to telomeric attrition and replicative senescence. We have found that undifferentiated human teratocarcinoma (HT) cells express high levels of hTERT, promoter is devoid of methylation in these cells. With retinoic acid treatment, methylation of the hTERT promoter increases as hTERT promoter activity decreases demonstrating a strong inverse association between methylation of the hTERT prooter and hTERT gene expression. We used two compounds to further distinguis the role of DNA methylation in control of the hTERT gene. Trichostatin A, a histone deacetylase inhibitor, was found to induce hTERT activity in early differentiation of HT cells but 5-azacytidine, a demethylating agent, induced hTERT later in differentiation. These studies indicate that histone deacetylation is involved in the early stages of hTERT gene down-regulation and the DNA methylation serves as an important locking mechanism that maintains the hTERT gene in a silenced state during differentiation of cancer cells. Understanding the contol of telomerase in cancer is important in facilitating potential gene therapy modalities in age-associated diseases of geriatric patients.

Background: Gastrointestinal tract (GIT) is the most common extranodal site for non-Hodgkin's lymphoma (NHL) and constitutes about 10%-15% of all NHL. This was a prospective study to evaluate the epidemiological, clinicopathological characteristics, and treatment outcome of primary GIT diffuse large B-cell lymphoma (PGIL). Materials and Methods: Newly diagnosed patients of PGIL with DLBCL histology were eligible. Lugano staging system was used. All patients were treated with prephase treatment (1 mg vincristine and 100 mg prednisolone) followed by CHOP-based chemotherapy (with or without rituximab) as definitive treatment. Results: A total of 21 patients of PGIL were diagnosed. The median age was 46 years (range: 27–69 years) with male:female ratio of 2:1. Dull aching abdominal pain was the most common presenting complaint. Stomach was the most common site involved (52.4%, n = 11) followed by the colon (23.8%, n = 5). The estimated median survival in patients with Stage IV disease was significantly lower as compared to patients with localized disease (Stage I and II) (6.23 months vs. 23.4 months; P = 0.04). Patients, who did not achieve complete response (CR), had 15.5 times higher risk of death, as compared to those who achieved CR (P = 0.01). Conclusions: Stomach was the most common site for PGIL. Localized disease and CR after first-line chemotherapy were associated with better survival. A higher cost of rituximab was the prohibitive factor for cure in these patients.