Alternative polyadenylation determines the functional landscape of inverted Alu repeats.

Inverted Alu repeats (IRAlus) are abundantly found in the transcriptome, especially in introns and 3' untranslated regions (UTRs). Yet, the biological significance of IRAlus embedded in 3' UTRs remains largely unknown. Here, we find that 3' UTR IRAlus silences genes involved in essential signaling pathways. We utilize J2 antibody to directly capture and map the double-stranded RNA structure of 3' UTR IRAlus in the transcriptome. Bioinformatic analysis reveals alternative polyadenylation as a major axis of IRAlus-mediated gene regulation. Notably, the expression of mouse double minute 2 (MDM2), an inhibitor of p53, is upregulated by the exclusion of IRAlus during UTR shortening, which is exploited to silence p53 during tumorigenesis. Moreover, the transcriptome-wide UTR lengthening in neural progenitor cells results in the global downregulation of genes associated with neurodegenerative diseases, including amyotrophic lateral sclerosis, via IRAlus inclusion. Our study establishes the functional landscape of 3' UTR IRAlus and its role in human pathophysiology.

The Ralstonia pseudosolanacearum Type III Effector RipL Delays Flowering and Promotes Susceptibility to Pseudomonas syringae in Arabidopsis thaliana.

The plant defense responses to microbial infection are tightly regulated and integrated with the developmental program for optimal resources allocation. Notably, the defense- associated hormone salicylic acid (SA) acts as a promoter of flowering while several plant pathogens actively target the flowering signaling pathway to promote their virulence or dissemination. Ralstonia pseudosolanacearum inject tens of effectors in the host cells that collectively promote bacterial proliferation in plant tissues. Here, we characterized the function of the broadly conserved R. pseudosolanacearum effector RipL, through heterologous expression in Arabidopsis thaliana . RipL-expressing transgenic lines presented a delayed flowering, which correlated with a low expression of flowering regulator genes. Delayed flowering was also observed in Nicotiana benthamiana plants transiently expressing RipL. In parallel, RipL promoted plant susceptibility to virulent strains of Pseudomonas syringae in the effector-expressing lines or when delivered by the type III secretion system. Unexpectedly, SA accumulation and SA-dependent immune signaling were not significantly affected by RipL expression. Rather, the RNA-seq analysis of infected RipL-expressing lines revealed that the overall amplitude of the transcriptional response was dampened, suggesting that RipL could promote plant susceptibility in an SA-independent manner. Further elucidation of the molecular mechanisms underpinning RipL effect on flowering and immunity may reveal novel effector functions in host cells.

Diversified host target families mediate convergently evolved effector recognition across plant species.

Recognition of pathogen effectors is a crucial step for triggering plant immunity. Resistance (R) genes often encode for nucleotide-binding leucine-rich repeat receptors (NLRs), and NLRs detect effectors from pathogens to trigger effector-triggered immunity (ETI). NLR recognition of effectors is observed in diverse forms where NLRs directly interact with effectors or indirectly detect effectors by monitoring host guardees/decoys (HGDs). HGDs undergo different biochemical modifications by diverse effectors and expand the effector recognition spectrum of NLRs, contributing robustness to plant immunity. Interestingly, in many cases of the indirect recognition of effectors, HGD families targeted by effectors are conserved across the plant species while NLRs are not. Notably, a family of diversified HGDs can activate multiple non-orthologous NLRs across plant species. Further investigation on HGDs would reveal the mechanistic basis of how the diversification of HGDs confers novel effector recognition by NLRs.

Direct acetylation of a conserved threonine of RIN4 by the bacterial effector HopZ5 or AvrBsT activates RPM1-dependent immunity in Arabidopsis.

Plant pathogenic bacteria deliver effectors into plant cells to suppress immunity and promote pathogen survival; however, these effectors can be recognized by plant disease resistance proteins to activate innate immunity. The bacterial acetyltransferase effectors HopZ5 and AvrBsT trigger immunity in Arabidopsis thaliana genotypes lacking SUPPRESSOR OF AVRBST-ELICITED RESISTANCE 1 (SOBER1). Using an Arabidopsis accession, Tscha-1, that naturally lacks functional SOBER1 but is unable to recognize HopZ5, we demonstrated that RESISTANCE TO P. SYRINGAE PV MACULICOLA 1 (RPM1) and RPM1-INTERACTING PROTEIN 4 (RIN4) are indispensable for HopZ5- or AvrBsT-triggered immunity. Remarkably, T166 of RIN4, the phosphorylation of which is induced by AvrB and AvrRpm1, is directly acetylated by HopZ5 and AvrBsT. Furthermore, we demonstrated that the acetylation of RIN4 T166 is required and sufficient for HopZ5- or AvrBsT-triggered RPM1-dependent defense activation. Finally, we showed that SOBER1 interferes with HopZ5- or AvrBsT-triggered immunity by deacetylating RIN4 T166. Collectively, our study elucidates detailed molecular mechanisms underlying the activation and suppression of plant innate immunity triggered by two bacterial acetyltransferases, HopZ5 and AvrBsT, from different bacterial pathogens.

Effect of bite force on orthodontic mini-implants in the molar region: Finite element analysis.

OBJECTIVE: To examine the effect of bite force on the displacement and stress distribution of orthodontic mini-implants (OMIs) in the molar region according to placement site, insertion angle, and loading direction. METHODS: Five finite element models were created using micro-computed tomography (microCT) images of the maxilla and mandible. OMIs were placed at one maxillary and two mandibular positions: between the maxillary second premolar and first molar, between the mandibular second premolar and first molar, and between the mandibular first and second molars. The OMIs were inserted at angles of 45° and 90° to the buccal surface of the cortical bone. A bite force of 25 kg was applied to the 10 occlusal contact points of the second premolar, first molar, and second molar. The loading directions were 0°, 5°, and 10° to the long axis of the tooth. RESULTS: With regard to placement site, the displacement and stress were greatest for the OMI placed between the mandibular first molar and second molar, and smallest for the OMI placed between the maxillary second premolar and first molar. In the mandibular molar region, the angled OMI showed slightly less displacement than the OMI placed at 90°. The maximum Von Mises stress increased with the inclination of the loading direction. CONCLUSIONS: These results suggest that placement of OMIs between the second premolar and first molar at 45° to the cortical bone reduces the effect of bite force on OMIs.

Availability of a 5% lidocaine patch used prophylactically for venipuncture- or injection-related pain in children.

PURPOSE: Venipuncture- or injection-related pain is still major problem during anesthetic induction in children. This study was designed to determine the availability of a 5% lidocaine patch used prophylactically for venipuncture- or injection-related pain during the induction of anesthesia. METHODS: In a randomized, double-blind study, 72 pediatric patients were allocated to one of two groups: pretreatment with a 5% lidocaine patch (Lidoderm(®), Endo Pharmaceuticals, Chadds Ford, PA, USA) (group A) or pretreatment with a placebo patch (group B). Pain severity was evaluated on the Faces, Legs, Activity, Cry, and Consolability Scale (FLACC) during venipuncture, and a 4-point scale during the injection of rocuronium. RESULTS: The FLACC score during venipuncture was significantly lower for group A than group B (p < 0.001). There was no significant difference in the grades of the 4-point scale observed during the injection of rocuronium between groups A and B. No significant adverse effect was noted for the groups. CONCLUSION: Although pretreatment with a 5% lidocaine patch was found to be a safe, effective, and simple method of preventing venipuncture pain in children, this method did not reduce drug injection pain during the induction of anesthesia.

Hypothermic cardiopulmonary bypass for minimally invasive mitral valve plasty in adult moyamoya disease.

A 43-year-old man underwent minimally invasive mitral valve plasty of a flail mitral valve. Four years previously, he had been diagnosed with moyamoya disease (MMD) by cerebral magnetic resonance imaging/angiography findings. In MMD, risk factors for cerebral stroke include changes in arterial carbon dioxide partial pressure, blood pressure, and body temperature. And during cardiopulmonary bypass (CPB), these hemodynamic changes can be challenging. However, hypothermia during CPB can decrease cerebral oxygen consumption and have a cerebral protective effect. We performed a minimally invasive mitral valve plasty, using hypothermic CPB, in a patient with MMD, without any neurological deficits.

Accidental epidural injection of rocuronium.

Epidural administration of local anesthetics or opioid during general anesthesia is a widespread method for postoperative analgesia. Despite the availability of this technique, inadvertent administration of nonepidural medications into the epidural space can be associated with serious neurological complications. We report a case of accidental epidural rocuronium injection.

Vertical alveolar ridge augmentation using autogenous bone grafts and platelet-enriched fibrin glue with simultaneous implant placement.

OBJECTIVE: The aim of this study was to evaluate the combined use of autogenous bone and platelet-enriched fibrin glue as grafting material for vertical alveolar ridge augmentation with simultaneous implant placement in a canine alveolar ridge defect model. STUDY DESIGN: In 6 mongrel dogs, bilateral vertical alveolar ridge defects were created in the mandible. After 3 months of healing, 2 dental implants were placed in each defect of the mandible, creating 6-mm supra-alveolar peri-implant defects. The 2 implants per defect were subjected to surgical treatments involving either a combination of autogenous bone grafts and platelet-enriched fibrin glue, or a conventional flap procedure only (control). After a healing period of 6 months, the dogs were humanely killed for histological and histometric analyses. RESULTS: Implant placement alone produced limited vertical alveolar height (0.6 +/- 0.4 mm). However, alveolar augmentation including a combination of autogenous bone grafts and platelet-enriched fibrin glue with simultaneous implant placement resulted in alveolar ridge augmentation amounting to 4.2 +/- 1.0 mm, comprising 63% of the defect height. New bone-implant contact was 40.5% in the defects treated with combined autogenous bone grafts and platelet-enriched fibrin glue, and was 48.4% in the resident bone; this difference was not statistically significant. CONCLUSION: The present study demonstrates that vertical alveolar ridge augmentation using autogenous bone grafts and platelet-enriched fibrin glue with simultaneous implant placement might effectively increase vertical alveolar ridge height and allow for an acceptable level of osseointegration.

Flapless implant surgery: an experimental study.

OBJECTIVE: The purpose of this study was to examine the effect of flapless implant surgery on crestal bone loss and osseointegration in a canine mandible model. STUDY DESIGN: In 6 mongrel dogs, bilateral, edentulated, flat alveolar ridges were created in the mandible. After 3 months of healing, 2 implants in each side were placed by either flap or flapless procedures. After a healing period of 8 weeks, microcomputerized tomography at the implantation site was performed. Osseointegration was calculated as percentage of implant surface in contact with bone. Additionally, bone height was measured in the peri-implant bone. RESULTS: The mean osseointegration was greater at flapless sites (70.4%) than at sites with flaps (59.5%) (P < .05). The mean peri-implant bone height was greater at flapless sites (10.1 mm) than at sites with flaps (9.0 mm) (P < .05). CONCLUSION: Flapless surgery can achieve results superior to surgery with reflected flaps. The specific improvements of this technique include enhanced osseointegration of dental implants and increased bone height.

The effect of platelet-rich plasma on bone healing around implants placed in bone defects treated with Bio-Oss: a pilot study in the dog tibia.

OBJECTIVE: The aim of this study was to examine the influence of platelet-rich plasma (PRP) used as an adjunct to Bio-Oss for the repair of bone defects adjacent to titanium dental implants. STUDY DESIGN: In 6 mongrel dogs, 12 screw-shaped titanium dental implants were inserted into the osteotomy sites in the dogs' tibias. Before implantation, a standardized gap (2.0 mm) was created between the implant surface and the surrounding bony walls. The gaps were filled with either Bio-Oss cancellous granules alone or Bio-Oss cancellous granules mixed with PRP. RESULTS: After 4 months, the Bio-Oss-treated defects revealed a significantly higher percentage of bone-implant contact than the defects treated with Bio-Oss and PRP (60.1% vs. 30.8%; P < .05). CONCLUSION: The results indicate that when PRP is used as an adjunct to Bio-Oss in the repair of bone defects adjacent to titanium dental implants, PRP may decrease periimplant bone healing.

Maxillary sinus floor augmentation using autogenous bone grafts and platelet-enriched fibrin glue with simultaneous implant placement.

OBJECTIVE: The aim of this study was to evaluate the use of autogenous bone in combination with platelet-enriched fibrin glue as a grafting material for maxillary sinus augmentation with simultaneous implant placement in dogs. STUDY DESIGN: The mucous membranes of 12 sinuses in 6 dogs were elevated bilaterally. In the right sinus, autogenous bone mixed with platelet-enriched fibrin glue was grafted into the space between the membrane and the sinus wall. In the left sinus, autogenous bone alone was grafted as a control. At the same time, 2 dental implants were inserted into the grafting material through the maxillary sinus floor. The animals were killed 6 months after surgery. RESULTS: The mean bone-implant contact was 40.5% on the fibrin glue side and 32.3% on the control side (P < .05). The mean height of newly formed bone in the augmented area was 12.2 mm on the fibrin glue side and 10.7 mm on the control side (P < .05). CONCLUSION: The results indicate that the use of autogenous bone mixed with platelet-enriched fibrin glue can achieve results superior to those for grafts of autogenous bone alone. The specific improvements of this technique include enhanced osseointegration of dental implants and increased height of new bone.

A retrospective study of the effects on sinus complications of exposing dental implants to the maxillary sinus cavity.

OBJECTIVE: The aim of this study was to investigate whether dental implant exposure to the maxillary sinus cavity increased the risk of maxillary sinus complications. STUDY DESIGN: Nine patients with 23 implants that had been inserted into the maxillary sinus more than 4 mm without lifting the sinus mucous membranes were evaluated for sinus complications 6 to 10 months after implant insertion, using a questionnaire and computerized tomography (CT). RESULTS: There were no clinical signs of sinusitis in any patient. However, CT scans showed postoperative sinus mucous thickening around 14 of the 23 implants. CONCLUSION: This study showed that implant exposure to the maxillary sinus cavity can cause sinus mucous thickening around the implants.

The effects of exposing dental implants to the maxillary sinus cavity on sinus complications.

OBJECTIVE: The aim of this study was to investigate whether dental implant exposure to the maxillary sinus cavity increases the risk of maxillary sinus complications. STUDY DESIGN: An implant was placed bilaterally in the maxillary sinus of 8 adult female mongrel dogs in a way that it penetrated the bone and mucous membrane of the maxillary sinus floor to the extent of 2 mm, 4 mm, or 8 mm. The implants were left in place for 6 months. RESULTS: Radiographic and histologic examinations did not show any signs of pathologic findings in the maxillary sinus of the 8 dogs. CONCLUSION: This study indicates that implant protrusion into the maxillary sinus cavity is not related to the development of sinus complications in canines.