Characterization of the Structural Requirements for the NADase Activity of Bacterial Toll/IL-1R domains in a Course-based Undergraduate Research Experience.

TLRs initiate innate immune signaling pathways via Toll/IL-1R (TIR) domains on their cytoplasmic tails. Various bacterial species also express TIR domain-containing proteins that contribute to bacterial evasion of the innate immune system. Bacterial TIR domains, along with the mammalian sterile α and TIR motif-containing protein 1 and TIRs from plants, also have been found to exhibit NADase activity. Initial X-ray crystallographic studies of the bacterial TIR from Acinetobacter baumannii provided insight into bacterial TIR structure but were unsuccessful in cocrystallization with the NAD+ ligand, leading to further questions about the TIR NAD binding site. In this study, we designed a Course-Based Undergraduate Research Experience (CURE) involving 16-20 students per year to identify amino acids crucial for NADase activity of A. baumannii TIR domain protein and the TIR from Escherichia coli (TIR domain-containing protein C). Students used structural data to identify amino acids that they hypothesized would play a role in TIR NADase activity, and created plasmids to express mutated TIRs through site-directed mutagenesis. Mutant TIRs were expressed, purified, and tested for NADase activity. The results from these studies provide evidence for a conformational change upon NAD binding, as was predicted by recent cryogenic electron microscopy and hydrogen-deuterium exchange mass spectrometry studies. Along with corroborating recent characterization of TIR NADases that could contribute to drug development for diseases associated with dysregulated TIR activity, this work also highlights the value of CURE-based projects for inclusion of a diverse group of students in authentic research experiences.

Tooth loss among Nigerians treated in teaching hospitals: a national pilot study.

AIM: The aim of this study was to identify the causes and patterns of tooth loss among Nigerian adults. BACKGROUND: Tooth loss continues to be a major problem in clinical dentistry and has received significant attention in everyday dental practice. In Nigeria there is a discernible lack of current data that would explain the reasons and patterns of tooth loss from its different geopolitical zones. METHODS AND MATERIALS: The reasons for tooth extractions during a period of 12 months were obtained from the hospital records of teaching and specialist hospitals in Nigeria's six geopolitical zones and the Federal Capital Territory (FCT). Data were analyzed using Statistical Package for the Social Sciences for Windows (SPSS) version 9.0. RESULTS: A total of 4,204 teeth were extracted from 3,431 patients. Of these teeth 52.4 percent were lost due to dental caries while 30.2 percent were removed because of periodontal disease, 5.0 percent were missing as a result of trauma, and 3.9 percent were impacted and required extraction. The remaining 8.5 percent were extracted for a variety of reasons such as orthodontic treatment, overeruption, neoplasms, supernumerary teeth, attrition, a cystic lesion, and hypoplasia. Dental caries was the most common diagnosis given for tooth loss in the South-South (79 percent), South-East (68 percent), North-East (47 percent), North-West (69 percent), and North-Central (35 percent) zones followed by periodontal disease. In contrast, periodontal disease was the most common cause of tooth loss in the South-West zone (65 percent) and in the FCT (55 percent), followed by dental caries at 22 percent and 33 percent, respectively. CONCLUSION: Although teeth were extracted based on a variety of diagnoses, dental caries was identified as the common reason cited for tooth loss in Nigeria and to a lesser extent periodontal disease. Also different reasons were given for tooth loss among the various geographical zones. CLINICAL SIGNIFICANCE: Tooth loss among Nigerians was attributed largely to dental caries and secondarily to periodontal disease. Both conditions can be prevented if diagnosed early enough and treatment is instituted in a timely manner.