New classification for bone type at dental implant sites: a dental computed tomography study.

OBJECTIVE: This study proposed a new classification method of bone quantity and quality at the dental implant site using cone-beam computed tomography (CBCT) image analysis, classifying cortical and cancellous bones separately and using CBCT for quantitative analysis. METHODS: Preoperative CBCT images were obtained from 128 implant patients (315 sites). First, measure the crestal cortical bone thickness (in mm) and the cancellous bone density [in grayscale values (GV) and bone mineral density (g/cm3)] at the implant sites. The new classification for bone quality at the implant site proposed in this study is a "nine-square division" bone classification system, where the cortical bone thickness is classified into A: > 1.1 mm, B:0.7-1.1 mm, and C: < 0.7 mm, and the cancellous bone density is classified into 1: > 600 GV (= 420 g/cm3), 2:300-600 GV (= 160 g/cm3-420 g/cm3), and 3: < 300 GV (= 160 g/cm3). RESULTS: The results of the nine bone type proportions based on the new jawbone classification were as follows: A1 (8.57%,27/315), A2 (13.02%), A3 (4.13%), B1 (17.78%), B2 (20.63%), B3 (8.57%) C1 (4.44%), C2 (14.29%), and C3 (8.57%). CONCLUSIONS: The proposed classification can complement the parts overlooked in previous bone classification methods (bone types A3 and C1). TRIAL REGISTRATION: The retrospective registration of this study was approved by the Institutional Review Board of China Medical University Hospital, No. CMUH 108-REC2-181.

The retromer complex in development and disease.

The retromer complex is a multimeric protein complex involved in recycling proteins from endosomes to the trans-Golgi network or plasma membrane. It thus regulates the abundance and subcellular distribution of its cargo within cells. Studies using model organisms show that the retromer complex is involved in specific developmental processes. Moreover, a number of recent studies implicate aberrant retromer function in photoreceptor degeneration, Alzheimer's disease and Parkinson's disease. Here, and in the accompanying poster, we provide an overview of the molecular and cellular mechanisms of retromer-mediated protein trafficking, highlighting key examples of retromer function in vivo.

Correction: the retromer complex is required for rhodopsin recycling and its loss leads to photoreceptor degeneration.

[This corrects the article DOI: 10.1371/journal.pbio.1001847.].

The retromer complex is required for rhodopsin recycling and its loss leads to photoreceptor degeneration.

Rhodopsin mistrafficking can cause photoreceptor (PR) degeneration. Upon light exposure, activated rhodopsin 1 (Rh1) in Drosophila PRs is internalized via endocytosis and degraded in lysosomes. Whether internalized Rh1 can be recycled is unknown. Here, we show that the retromer complex is expressed in PRs where it is required for recycling endocytosed Rh1 upon light stimulation. In the absence of subunits of the retromer, Rh1 is processed in the endolysosomal pathway, leading to a dramatic increase in late endosomes, lysosomes, and light-dependent PR degeneration. Reducing Rh1 endocytosis or Rh1 levels in retromer mutants alleviates PR degeneration. In addition, increasing retromer abundance suppresses degenerative phenotypes of mutations that affect the endolysosomal system. Finally, expressing human Vps26 suppresses PR degeneration in Vps26 mutant PRs. We propose that the retromer plays a conserved role in recycling rhodopsins to maintain PR function and integrity.

Genetic models of apoptosis-induced proliferation decipher activation of JNK and identify a requirement of EGFR signaling for tissue regenerative responses in Drosophila.

Recent work in several model organisms has revealed that apoptotic cells are able to stimulate neighboring surviving cells to undergo additional proliferation, a phenomenon termed apoptosis-induced proliferation. This process depends critically on apoptotic caspases such as Dronc, the Caspase-9 ortholog in Drosophila, and may have important implications for tumorigenesis. While it is known that Dronc can induce the activity of Jun N-terminal kinase (JNK) for apoptosis-induced proliferation, the mechanistic details of this activation are largely unknown. It is also controversial if JNK activity occurs in dying or in surviving cells. Signaling molecules of the Wnt and BMP families have been implicated in apoptosis-induced proliferation, but it is unclear if they are the only ones. To address these questions, we have developed an efficient assay for screening and identification of genes that regulate or mediate apoptosis-induced proliferation. We have identified a subset of genes acting upstream of JNK activity including Rho1. We also demonstrate that JNK activation occurs both in apoptotic cells as well as in neighboring surviving cells. In a genetic screen, we identified signaling by the EGFR pathway as important for apoptosis-induced proliferation acting downstream of JNK signaling. These data underscore the importance of genetic screening and promise an improved understanding of the mechanisms of apoptosis-induced proliferation.

Drosophila IAP1-mediated ubiquitylation controls activation of the initiator caspase DRONC independent of protein degradation.

Ubiquitylation targets proteins for proteasome-mediated degradation and plays important roles in many biological processes including apoptosis. However, non-proteolytic functions of ubiquitylation are also known. In Drosophila, the inhibitor of apoptosis protein 1 (DIAP1) is known to ubiquitylate the initiator caspase DRONC in vitro. Because DRONC protein accumulates in diap1 mutant cells that are kept alive by caspase inhibition ("undead" cells), it is thought that DIAP1-mediated ubiquitylation causes proteasomal degradation of DRONC, protecting cells from apoptosis. However, contrary to this model, we show here that DIAP1-mediated ubiquitylation does not trigger proteasomal degradation of full-length DRONC, but serves a non-proteolytic function. Our data suggest that DIAP1-mediated ubiquitylation blocks processing and activation of DRONC. Interestingly, while full-length DRONC is not subject to DIAP1-induced degradation, once it is processed and activated it has reduced protein stability. Finally, we show that DRONC protein accumulates in "undead" cells due to increased transcription of dronc in these cells. These data refine current models of caspase regulation by IAPs.

Preoperative assessment of bone density for dental implantation: a comparative study of three different ROI methods.

BACKGROUND: Dental cone beam computed tomography (CBCT) is commonly used to evaluate cancellous bone density before dental implant surgery. However, to our knowledge, no measurement approach has been standardized yet. This study aimed to evaluate the relationship between three different regions of interest (ROI) methods on cancellous bone density at the dental implant site using dental CBCT images. METHODS: Patients' dental CBCT images (n = 300) obtained before dental implant surgery were processed using Mimics (Materialise, Leuven, Belgium). At the potential implant sites, the rectangle, cylinder, and surrounding cylinder ROI methods were used to measure bone density. Repeated measures one-way analysis of variance was performed to compare the three ROI methods in terms of measurement results. Pearson correlation analysis was performed to identify the likely pair-wise correlations between the three ROI methods. RESULTS: The density value obtained using the surrounding cylinder approach (grayscale value [GV],523.56 ± 228.03) was significantly higher than the values obtained using the rectangle (GV, 497.04 ± 236.69) and cylinder (GV,493 ± 231.19) ROI methods in terms of results. Furthermore, significant correlations were noted between the ROI methods (r > 0.965; p < 0.001). CONCLUSIONS: The density measured using the surrounding cylinder method was the highest. The choice of method may not influence the trends of measurement results. TRIAL REGISTRATION: This study was approved by the Institutional Review Board of China Medical University Hospital, No. CMUH111-REC3-205. Informed consent was waived by the Institutional Review Board of China Medical University Hospital, CMUH111-REC3-205, owing to the retrospective nature of the study.

Can Male Patient's Age Affect the Cortical Bone Thickness of Jawbone for Dental Implant Placement? A Cohort Study.

Dental implants are among the most common treatments for missing teeth. The thickness of the crestal cortical bone at the potential dental implant site is a critical factor affecting the success rate of dental implant surgery. However, previous studies have predominantly focused on female patients, who are at a high risk of osteoporosis, for the discussion of bone quality and quantity at the dental implant site. This study aimed to investigate the effect of male patients' age on the crestal cortical bone of the jaw at the dental implant site by using dental cone-beam computed tomography (CBCT). This study performed dental CBCT on 84 male patients of various ages to obtain tomograms of 288 dental implant sites at the jawbone (41 sites in the anterior maxilla, 95 in the posterior maxilla, 59 in the anterior mandible, and 93 in the posterior mandible) for measuring the cortical bone thickness. A one-way analysis of variance and Scheffe's test were performed on the measurement results to compare the cortical bone thickness at implant sites in the four jaw areas. The correlation between male patient age and cortical bone thickness at the dental implant site was determined. The four jaw areas in order of the cortical bone thickness were as follows: posterior mandible (1.07 ± 0.44 mm), anterior mandible (0.99 ± 0.30 mm), anterior maxilla (0.82 ± 0.32 mm), and posterior maxilla (0.71 ± 0.27 mm). Apart from dental implant sites in the anterior and posterior mandibles, no significant correlation was observed between male patients' age and the cortical bone thickness at the dental implant site.

Relationship between Cortical Bone Thickness and Cancellous Bone Density at Dental Implant Sites in the Jawbone.

Dental implant surgery is a common treatment for missing teeth. Its survival rate is considerably affected by host bone quality and quantity, which is often assessed prior to surgery through dental cone-beam computed tomography (CBCT). Dental CBCT was used in this study to evaluate dental implant sites for (1) differences in and (2) correlations between cancellous bone density and cortical bone thickness among four regions of the jawbone. In total, 315 dental implant sites (39 in the anterior mandible, 42 in the anterior maxilla, 107 in the posterior mandible, and 127 in the posterior maxilla) were identified in dental CBCT images from 128 patients. All CBCT images were loaded into Mimics 15.0 to measure cancellous bone density (unit: grayscale value (GV) and cortical bone thickness (unit: mm)). Differences among the four regions of the jawbone were evaluated using one-way analysis of variance and Scheffe's posttest. Pearson coefficients for correlations between cancellous bone density and cortical bone thickness were also calculated for the four jawbone regions. The results revealed that the mean cancellous bone density was highest in the anterior mandible (722 ± 227 GV), followed by the anterior maxilla (542 ± 208 GV), posterior mandible (535 ± 206 GV), and posterior maxilla (388 ± 206 GV). Cortical bone thickness was highest in the posterior mandible (1.15 ± 0.42 mm), followed by the anterior mandible (1.01 ± 0.32 mm), anterior maxilla (0.89 ± 0.26 mm), and posterior maxilla (0.72 ± 0.19 mm). In the whole jawbone, a weak correlation (r = 0.133, p = 0.041) was detected between cancellous bone density and cortical bone thickness. Furthermore, except for the anterior maxilla (r = 0.306, p = 0.048), no correlation between the two bone parameters was observed (all p > 0.05). Cancellous bone density and cortical bone thickness varies by implant site in the four regions of the jawbone. The cortical and cancellous bone of a jawbone dental implant site should be evaluated individually before surgery.

Effects of velocity relaxation on the anomalous kinetics of a one-dimensional A+A-->Ø reaction.

A one-dimensional A+A-->slashed circle reaction with alternating dichotomic velocities is investigated to study the effects of velocity relaxation on the anomalous kinetics of this reaction. While we keep the magnitudes constant, the particle velocities are allowed to change from one moving direction to the other with a relaxation time, beta. The kinetics of the reaction is studied for various relaxation times. Although the anomalous slower reaction rate is anticipated for the reaction in one-dimension, compared to the classical rate law, the rate is found to speed up at intermediate times for intermediate values of beta . The time evolution for the spatial distribution of particles is also discussed to elucidate the effects of the velocity relaxation times on the kinetics of the reaction.

Plasma Membrane Localization of Apoptotic Caspases for Non-apoptotic Functions.

Caspases are best characterized for their function in apoptosis. However, they also have non-apoptotic functions such as apoptosis-induced proliferation (AiP), where caspases release mitogens for compensatory proliferation independently of their apoptotic role. Here, we report that the unconventional myosin, Myo1D, which is known for its involvement in left/right development, is an important mediator of AiP in Drosophila. Mechanistically, Myo1D translocates the initiator caspase Dronc to the basal side of the plasma membrane of epithelial cells where Dronc promotes the activation of the NADPH-oxidase Duox for reactive oxygen species generation and AiP in a non-apoptotic manner. We propose that the basal side of the plasma membrane constitutes a non-apoptotic compartment for caspases. Finally, Myo1D promotes tumor growth and invasiveness of the neoplastic scrib RasV12 model. Together, we identified a new function of Myo1D for AiP and tumorigenesis, and reveal a mechanism by which cells sequester apoptotic caspases in a non-apoptotic compartment at the plasma membrane.

Hyper-IgM syndrome: a case report.

Hyperimmunoglobulin M syndrome is a rare primary immunodeficiency disorder. We report a case of a 6-month-old boy who suffered from developmental delays, frequent respiratory tract infection, and unusual fungal and bacterial infection. X-linked hyperimmunoglobulin M syndrome was ultimately diagnosed with decreasing immunoglobulin-G, A, and E (immunoglobulin G = 51.3 mg/dL, immunoglobulin A = 8.32 mg/dL, immunoglobulin E <17.5 mg/dL), elevating immunoglobulin M (immunoglobulin M = 140 mg/dL), and decreasing T-cell expression of the CD40 ligand over flow cytometry. Seizure episodes and hypotonia developed with greater signal intensity at the putamen in a brain magnetic resonance imaging, which is compatible with hypoxic ischemic encephalopathy. This is the youngest proven case of hyper-IgM syndrome in Taiwan ever reported.

IL-6 trans-signaling in formation and progression of malignant ascites in ovarian cancer.

Classic signaling by the proinflammatory cytokine interleukin 6 (IL-6) involves its binding to target cells that express the membrane-bound IL-6 receptor α. However, an alternate signaling pathway exists in which soluble IL-6 receptor (sIL-6Rα) can bind IL-6 and activate target cells that lack mIL-6Rα, such as endothelial cells. This alternate pathway, also termed trans-signaling, serves as the major IL-6 signaling pathway in various pathologic proinflammatory conditions including cancer. Here we report that sIL-6Rα is elevated in malignant ascites from ovarian cancer patients, where it is associated with poor prognosis. IL-6 trans-signaling on endothelial cells prevented chemotherapy-induced apoptosis, induced endothelial hyperpermeability, and increased transendothelial migration of ovarian cancer cells. Selective blockade of the MAPK pathway with ERK inhibitor PD98059 reduced IL-6/sIL-6Rα-mediated endothelial hyperpermeability. ERK activation by the IL-6/sIL-6Rα complex increased endothelial integrity via Src kinase activation and Y685 phosphorylation of VE-cadherin. Selective targeting of IL-6 trans-signaling in vivo reduced ascites formation and enhanced the taxane sensitivity of intraperitoneal human ovarian tumor xenografts in mice. Collectively, our results show that increased levels of sIL-6Rα found in ovarian cancer ascites drive IL-6 trans-signaling on endothelial cells, thereby contributing to cancer progression. Selective blockade of IL-6 trans-signaling may offer a promising therapeutic strategy to improve the management of patients with advanced ovarian cancer.

Influences of apolipoprotein E polymorphism on the risk for breast cancer and HER2/neu status in Taiwan.

Apolipoprotein E (APOE) polymorphism plays an important role in lipid metabolism. Preliminary evidence suggests that APOE genotype appears to be a risk factor for not only cardiovascular disease, but also Alzheimer's disease and cancer. We screened the APOE genotype in 290 breast cancer patients and 232 non-cancer controls and determined the relationship between APOE gene polymorphism and breast cancer in Taiwan. We found risk for breast cancer was associated with the APOE genotype (xi(2) = 8.652, p = 0.013). Carriers of the epsilon4 allele were more common in breast cancer cases than carriers of epsilon3 allele (p = 0.004, OR = 1.786, 95% CI: 1.197-2.664). In addition, the epsilon4 allele is also associated with HER2/neu negative status in breast cancer patients (p = 0.006, OR = 0.277, 95% CI: 0.111-0.693). No significant associations between APOE genotype and tumor grade, TN classification, progesterone receptor, estrogen receptor, lymphatic invasion, or recurrence of breast cancer were in evidence. These results suggest that the APOE epsilon4 allele may be a risk factor for breast cancer and correlates with HER2/neu negative status.