The Ubiquitin Ligase RPM-1 and the p38 MAPK PMK-3 Regulate AMPA Receptor Trafficking

Ubiquitination occurs at synapses, yet its role remains unclear. Previous studies demonstrated that the RPM-1 ubiquitin ligase organizes presynaptic boutons at neuromuscular junctions in C. elegans motorneurons. Here we find that RPM-1 has a novel postsynaptic role in interneurons, where it regulates the trafficking of the AMPA-type glutamate receptor GLR-1 from synapses into endosomes. Mutations in rpm-1 cause the aberrant accumulation of GLR-1 in neurites. Moreover, rpm-1 mutations enhance the endosomal accumulation of GLR-1 observed in mutants for lin-10, a Mint2 ortholog that promotes GLR-1 recycling from Syntaxin-13 containing endosomes. As in motorneurons, RPM-1 negatively regulates the pmk-3/p38 MAPK pathway in interneurons by repressing the protein levels of the MAPKKK DLK-1. This regulation of PMK-3 signaling is critical for RPM-1 function with respect to GLR-1 trafficking, as pmk-3 mutations suppress both lin-10 and rpm-1 mutations. Positive or negative changes in endocytosis mimic the effects of rpm-1 or pmk-3 mutations, respectively, on GLR-1 trafficking. Specifically, RAB-5(GDP), an inactive mutant of RAB-5 that reduces endocytosis, mimics the effect of pmk-3 mutations when introduced into wild-type animals, and occludes the effect of pmk-3 mutations when introduced into pmk-3 mutants. By contrast, RAB-5(GTP), which increases endocytosis, suppresses the effect of pmk-3 mutations, mimics the effect of rpm-1 mutations, and occludes the effect of rpm-1 mutations. Our findings indicate a novel specialized role for RPM-1 and PMK-3/p38 MAPK in regulating the endosomal trafficking of AMPARs at central synapses

Class II functional orthopaedic treatment: a systematic review of systematic reviews

This Systematic Review (SR) aims to assess the quality of SRs and Meta-Analyses (MAs) on functional orthopaedic treatment of Class II malocclusion and to summarise and rate the reported effects. Electronic and manual searches were conducted until June 2014. SRs and MAs focusing on the effects of functional orthopaedic treatment of Class II malocclusion in growing patients were included. The methodological quality of the included papers was assessed using the AMSTAR (Assessment of Multiple Systematic Reviews). The design of the primary studies included in each SR was assessed with Level of Research Design scoring. The evidence of the main outcomes was summarised and rated according to a scale of statements. 14 SRs fulfilled the inclusion criteria. The appliances evaluated were as follows: Activator (2 studies), Twin Block (4 studies), headgear (3 studies), Herbst (2 studies), Jasper Jumper (1 study), Bionator (1 study) and Fränkel-2 (1 study). Four studies reviewed several functional appliances, as a group. The mean AMSTAR score was 6 (ranged 2-10). Six SRs included only controlled clinical trials (CCTs), three SRs included only randomised controlled trials (RCTs), four SRs included both CCTs and RCTs and one SR included also expert opinions. There was some evidence of reduction of the overjet, with different appliances except from headgear; there was some evidence of small maxillary growth restrain with Twin Block and headgear; there was some evidence of elongation of mandibular length, but the clinical relevance of this results is still questionable; there was insufficient evidence to determine an effect on soft tissues

The Psychological Impact of Dental Aesthetics in Patients with Juvenile Idiopathic Arthritis Compared with Healthy Peers: A Cross-Sectional Study.

This study aimed to assess whether dental aesthetics had a different impact on the psychosocial domains of adolescents with juvenile idiopathic arthritis (JIA) as compared with healthy peers. Fifty JIA patients and eighty controls aged between 13 and 17 years were enrolled. The Psychosocial Impact of Dental Aesthetics Questionnaire (PIDAQ) was administered along with tools for the self-assessment of malocclusion and self-esteem. An objective evaluation of malocclusion severity was performed through a clinical evaluation with the Dental Aesthetic Index (DAI). The sample was divided according to the DAI stages of malocclusion severity; a two-way analysis of variance (ANOVA) was performed to assess whether there was a difference in the studied variables according to the malocclusion and the presence of JIA. The results showed no interaction between the malocclusion severity and the presence of JIA in all analyzed variables (all p > 0.05). According to the DAI stages, the Dental Self-Confidence domain of the PIDAQ and the Perception of Occlusion Scale showed statistically significant differences only within the controls (p = 0.027 and p = 0.014, respectively). Therefore, JIA adolescents seem to be less concerned about their dental aesthetics compared with healthy peers, and clinicians should take particular care when proposing orthodontic treatments aiming only to improve dental aesthetic

Parallel Genetic Algorithms for calibrating Cellular Automata models: Application to lava flows

Cellular Automata are highly nonlinear dynamical systems which are suitable for simulating natural phenomena whose behaviour may be specified in terms of local interactions. The Cellular Automata model SCIARA, developed for the simulation of lava flows, demonstrated to be able to reproduce the behaviour of Etnean events. However, in order to apply the model for the prediction of future scenarios, a thorough calibrating phase is required. This work presents the application of Genetic Algorithms, general-purpose search algorithms inspired to natural selection and genetics, for the parameters optimisation of the modelSCIARA. Difficulties due to the elevated computational time suggested the adoption a Master-Slave Parallel Genetic Algorithm for the calibration of the model with respect to the 2001 Mt. Etna eruption. Results demonstrated the usefulness of the approach, both in terms of computing time and quality of performed simulations

Effect of orthopedic and functional orthodontic treatment in children with obstructive sleep apnea: A systematic review and meta-analysis

Orthodontic treatment is suggested in growing individuals to correct transverse maxillary deficiency and mandibular retrusion. Since, as a secondary effect, these orthodontic procedures may improve pediatric obstructive sleep apnea (OSA), this systematic review assessed their effects on apnea-hypopnea index (AHI) and oxygen saturation (SaO2). Twenty-five (25) manuscripts were included for qualitative synthesis, 19 were selected for quantitative synthesis. Five interventions were analyzed: rapid maxillary expansion (RME, 15 studies), mandibular advancement (MAA, five studies), myofunctional therapy (MT, four studies), and RME combined with MAA (one study). RME produced a significant AHI reduction and minimum SaO2 increase immediately after active treatment, at six and 12 months from baseline. A significant AHI reduction was also observed six and 12 months after the beginning of MAA treatment. MT showed positive effects, with different protocols. In this systematic review and meta-analysis of data from mainly uncontrolled studies, interceptive orthodontic treatments showed overall favorable effects on respiratory outcomes in pediatric OSA. However, due to the low to very low level of the body evidence, this treatment cannot be suggested as elective for OSA treatment. An orthodontic indication is needed to support this therapy and a careful monitoring is required to ensure positive improvement in OSA parameters

The Catania 1669 lava eruptive crisis: simulation of a new possible eruption

SCIARA (Smart Cellular Interactive Automata for modeling the Rheology of Aetnean lava flows, to be read as “shea’rah”), our first two-dimensional Cellular Automata model for the simulation of lava flows, was tested and validated with success on several lava events like the 1986/87 Etnean eruption and the last phase of the 1991/93 Etnean one. Real and simulated events are satisfying within limits to forecast the surface covered by the lava flow. Moreover, improved versions have been adopted in testing other real lava flows of Mount Etna and of Reunion Island (Indian Ocean). The model has been applied with success in the determination of risk zones in the inhabited areas of Nicolosi, Pedara, S. Alfio and Zafferana (Sicily). The main goal of the present work has been the verification of the effects, in volcanic risk terms, in the Etnean area from Nicolosi to Catania, of a eruptive crisis similar to the event that occurred in 1669, as if the episode would happen nowadays. Catania has been severely interested in some major Etnean events in history, the most famous one being, namely, the 1669 eruption, involving 1 km3 of lava during 130 days. The simulation of lava tubes and the usage of different histories within the experiments have been crucial in the determination of a new risk area for Catania. In fact, simulations carried out without the introduction of lava tubes, never involved the city, proving the fact that lava tubes, played a fundamental role in the 1669 Catania lava crisis

Predicting the impact of lava flows at Mount Etna (Italy)

Forecasting the time, nature and impact of future eruptions is difficult at volcanoes such as Mount Etna, in Italy, where eruptions occur from the summit and on the flanks, affecting areas distant from each other. Nonetheless, the identification and quantification of areas at risk from new eruptions is fundamental for mitigating potential human casualties and material damage. Here, we present new results from the application of a methodology to define flexible high-resolution lava invasion susceptibility maps based on a reliable computational model for simulating lava flows at Etna and on a validation procedure for assessing the correctness of susceptibility mapping in the study area. Furthermore, specific scenarios can be extracted at any time from the simulation database, for land-use and civil defence planning in the long-term, to quantify, in real-time, the impact of an imminent eruption, and to assess the efficiency of protective measures

Evaluation of the relationship between obesity, dental caries and periodontal disease in adolescents

AIM: To assess the prevalence of caries, oral hygiene quality and periodontal disease in a cohort of obese adolescents compared to a control group. MATERIALS AND METHODS: Study Design: cross-sectional study conducted on 204 subjects (age range 10-16 years). Ninety obese subjects (BMI >90) and 114 normal-weight subjects (BMI <75) were visited at the Bambino Gesù Children's Hospital and in a junior high school in Rome, respectively. An ad hoc questionnaire (investigating demographic and oral health behaviour data) was filled in by patients and their caregivers. Accurate oral examinations were conducted. The Decayed-Missing-Filled Teeth/Surfaces Index in both permanent (DMFT/DMFS) and primary dentition (dmft/dmfs), Gingival Bleeding Index (GBI), Visible Plaque Index (VPI), and Probing Depth (PD) were recorded. STATISTICS: data analysis was carried out using the Statistical Package for the Social Sciences (SPSS 21.0; SPSS IBM, New York, NY). The data of the two groups were compared by means of Student's t Test or the Mann-Whitney test for numerical data and the Chi-square test for categorical data. RESULTS: Patients affected by obesity, compared with controls, presented less compromised teeth in the primary dentition (dmft obese: 0.30 &#177;± 1.12; normal-weight: 1.00 &#177; 1.90; P<0.001) and less compromised dental surfaces (dmfs obese: 0.51 &#177; 2.14; normal-weight: 1.61 &#177; 3.10; P<0.001). Furthermore obese patients showed minor gingival inflammation with less bleeding on probing (GBI) (obese: 23.95 &#177; 21.43; normal-weight: 38.17&#177; 24.37; P<0.001), and less probing depth in a greater number of sites (PPD &#8804; 3) (obese: 101.92 &#177; 9.27; normal-weight: 97.28 &#177; 12.13; P<0.001). Moreover, the obese group showed a better oral hygiene (VPI) (obese: 25.69 &#177;25.83; normal-weight: 37.72 &#177;24.34; P<0.001). CONCLUSION: In our study, obese adolescents showed a better oral hygiene, fewer compromised teeth and better periodontal health when compared with normal-weight patients

UEV-1 Is an Ubiquitin-Conjugating Enzyme Variant That Regulates Glutamate Receptor Trafficking in C. elegans Neurons

The regulation of AMPA-type glutamate receptor (AMPAR) membrane trafficking is a key mechanism by which neurons regulate synaptic strength and plasticity. AMPAR trafficking is modulated through a combination of receptor phosphorylation, ubiquitination, endocytosis, and recycling, yet the factors that mediate these processes are just beginning to be uncovered. Here we identify the ubiquitin-conjugating enzyme variant UEV-1 as a regulator of AMPAR trafficking in vivo. We identified mutations in uev-1 in a genetic screen for mutants with altered trafficking of the AMPAR subunit GLR-1 in C. elegans interneurons. Loss of uev-1 activity results in the accumulation of GLR-1 in elongated accretions in neuron cell bodies and along the ventral cord neurites. Mutants also have a corresponding behavioral defect—a decrease in spontaneous reversals in locomotion—consistent with diminished GLR-1 function. The localization of other synaptic proteins in uev-1-mutant interneurons appears normal, indicating that the GLR-1 trafficking defects are not due to gross deficiencies in synapse formation or overall protein trafficking. We provide evidence that GLR-1 accumulates at RAB-10-containing endosomes in uev-1 mutants, and that receptors arrive at these endosomes independent of clathrin-mediated endocytosis. UEV-1 homologs in other species bind to the ubiquitin-conjugating enzyme Ubc13 to create K63-linked polyubiquitin chains on substrate proteins. We find that whereas UEV-1 can interact with C. elegans UBC-13, global levels of K63-linked ubiquitination throughout nematodes appear to be unaffected in uev-1 mutants, even though UEV-1 is broadly expressed in most tissues. Nevertheless, ubc-13 mutants are similar in phenotype to uev-1 mutants, suggesting that the two proteins do work together to regulate GLR-1 trafficking. Our results suggest that UEV-1 could regulate a small subset of K63-linked ubiquitination events in nematodes, at least one of which is critical in regulating GLR-1 trafficking