Polymorphic toxin systems: Comprehensive characterization of trafficking modes, processing, mechanisms of action, immunity and ecology using comparative genomics

Background: Proteinaceous toxins are observed across all levels of inter-organismal and intra-genomic conflicts. These include recently discovered prokaryotic polymorphic toxin systems implicated in intra-specific conflicts. They are characterized by a remarkable diversity of C-terminal toxin domains generated by recombination with standalone toxin-coding cassettes. Prior analysis revealed a striking diversity of nuclease and deaminase domains among the toxin modules. We systematically investigated polymorphic toxin systems using comparative genomics, sequence and structure analysis. Results: Polymorphic toxin systems are distributed across all major bacterial lineages and are delivered by at least eight distinct secretory systems. In addition to type-II, these include type-V, VI, VII (ESX), and the poorly characterized "Photorhabdus virulence cassettes (PVC)", PrsW-dependent and MuF phage-capsid-like systems. We present evidence that trafficking of these toxins is often accompanied by autoproteolytic processing catalyzed by HINT, ZU5, PrsW, caspase-like, papain-like, and a novel metallopeptidase associated with the PVC system. We identified over 150 distinct toxin domains in these systems. These span an extraordinary catalytic spectrum to include 23 distinct clades of peptidases, numerous previously unrecognized versions of nucleases and deaminases, ADP-ribosyltransferases, ADP ribosyl cyclases, RelA/SpoT-like nucleotidyltransferases, glycosyltranferases and other enzymes predicted to modify lipids and carbohydrates, and a pore-forming toxin domain. Several of these toxin domains are shared with host-directed effectors of pathogenic bacteria. Over 90 families of immunity proteins might neutralize anywhere between a single to at least 27 distinct types of toxin domains. In some organisms multiple tandem immunity genes or immunity protein domains are organized into polyimmunity loci or polyimmunity proteins. Gene-neighborhood-analysis of polymorphic toxin systems predicts the presence of novel trafficking-related components, and also the organizational logic that allows toxin diversification through recombination. Domain architecture and protein-length analysis revealed that these toxins might be deployed as secreted factors, through directed injection, or via inter-cellular contact facilitated by filamentous structures formed by RHS/YD, filamentous hemagglutinin and other repeats. Phyletic pattern and life-style analysis indicate that polymorphic toxins and polyimmunity loci participate in cooperative behavior and facultative 'cheating' in several ecosystems such as the human oral cavity and soil. Multiple domains from these systems have also been repeatedly transferred to eukaryotes and their viruses, such as the nucleo-cytoplasmic large DNA viruses. Conclusions: Along with a comprehensive inventory of toxins and immunity proteins, we present several testable predictions regarding active sites and catalytic mechanisms of toxins, their processing and trafficking and their role in intra-specific and inter-specific interactions between bacteria. These systems provide insights regarding the emergence of key systems at different points in eukaryotic evolution, such as ADP ribosylation, interaction of myosin VI with cargo proteins, mediation of apoptosis, hyphal heteroincompatibility, hedgehog signaling, arthropod toxins, cell-cell interaction molecules like teneurins and different signaling messengers.

Complications of misdiagnosis of maxillary canine ectopic eruption

Ectopic eruption of maxillary canines can be associated with root resorption of adjacent teeth. This case report describes and discusses an interesting case of a 15-year-old girl with a Class III malocclusion and an impacted maxillary canine. Because of the unfavorable position of the ectopic canine and the severe root resorption of the maxillary left central and lateral incisors, the treatment options included extraction of the maxillary permanent canines. The mandibular first premolars were extracted to compensate for the Class III malocclusion. A panoramic radiograph taken earlier in the mixed dentition already indicated a possible eruption disturbance of the maxillary left permanent canine. The importance of early diagnosis of maxillary canine ectopic eruption is highlighted in this case report. The early identification of radiographic signs of an ectopic pathway of eruption should be followed by deciduous canine extraction to prevent canine retention and maxillary incisor root resorption. (Am J Orthod Dentofacial Orthop 2012;142:256-63)

Survival Analysis of Patients with Heart Failure: Implications of Time-Varying Regression Effects in Modeling Mortality

Background: Several models have been designed to predict survival of patients with heart failure. These, while available and widely used for both stratifying and deciding upon different treatment options on the individual level, have several limitations. Specifically, some clinical variables that may influence prognosis may have an influence that change over time. Statistical models that include such characteristic may help in evaluating prognosis. The aim of the present study was to analyze and quantify the impact of modeling heart failure survival allowing for covariates with time-varying effects known to be independent predictors of overall mortality in this clinical setting. Methodology: Survival data from an inception cohort of five hundred patients diagnosed with heart failure functional class III and IV between 2002 and 2004 and followed-up to 2006 were analyzed by using the proportional hazards Cox model and variations of the Cox's model and also of the Aalen's additive model. Principal Findings: One-hundred and eighty eight (188) patients died during follow-up. For patients under study, age, serum sodium, hemoglobin, serum creatinine, and left ventricular ejection fraction were significantly associated with mortality. Evidence of time-varying effect was suggested for the last three. Both high hemoglobin and high LV ejection fraction were associated with a reduced risk of dying with a stronger initial effect. High creatinine, associated with an increased risk of dying, also presented an initial stronger effect. The impact of age and sodium were constant over time. Conclusions: The current study points to the importance of evaluating covariates with time-varying effects in heart failure models. The analysis performed suggests that variations of Cox and Aalen models constitute a valuable tool for identifying these variables. The implementation of covariates with time-varying effects into heart failure prognostication models may reduce bias and increase the specificity of such models.

Long-Term Follow-Up of Implantable Cardioverter-Defibrillator for Secondary Prevention in Chagas' Heart Disease

Assessing the efficacy of implantable cardioverter-defibrillators (ICD) in patients with Chagas' heart disease (ChHD) and identifying the clinical predictors of mortality and ICD shock during long-term follow-up. ChHD is associated with ventricular tachyarrhythmias and an increased risk of sudden cardiac death. Although ChHD is a common form of cardiomyopathy in Latin American ICD users, little is known about its efficacy in the treatment of this population. The study cohort included 116 consecutive patients with ChHD and an ICD implanted for secondary prevention. Of the 116 patients, 83 (72%) were men; the mean age was 54 +/- 10.7 years. Several clinical variables were tested in a multivariate Cox model for predicting long-term mortality. The average follow-up was 45 +/- 32 months. New York Heart Association class I-II developed in 83% of patients. The mean left ventricular ejection fraction was 42 +/- 16% at implantation. Of the 116 patients, 58 (50%) had appropriate shocks and 13 (11%) had inappropriate therapy. A total of 31 patients died (7.1% annual mortality rate). New York Heart Association class III (hazard ratio [HR] 3.09, 95% confidence interval 1.37 to 6.96, p = 0.0064) was a predictor of a worse prognosis. The left ventricular ejection fraction (HR 0.972, 95% confidence interval 0.94 to 0.99, p = 0.0442) and low cumulative right ventricular pacing (HR 0.23, 95% confidence interval 0.11 to 0.49, p = 0.0001) were predictors of better survival. The left ventricular diastolic diameter was an independent predictor of appropriate shock (I-ER 1.032, 95% confidence interval 1.004 to 1.060, p = 0.025). In conclusion, in a long-term follow-up, ICD efficacy for secondary sudden cardiac death prevention in patients with ChHD was marked by a favorable annual rate of all-cause mortality (7.1%); 50% of the cohort received appropriate shock therapy. New York Heart Association class III and left ventricular ejection fraction were independent predictors of worse prognosis, and low cumulative right ventricular pacing defined better survival. (C) 2012 Elsevier Inc. All rights reserved. (Am J Cardiol 2012;110:1040-1045)

New Equation for Prediction of Reverse Remodeling after Cardiac Resynchronization Therapy

Objectives: To integrate data from two-dimensional echocardiography (2D ECHO), three-dimensional echocardiography (3D ECHO), and tissue Doppler imaging (TDI) for prediction of left ventricular (LV) reverse remodeling (LVRR) after cardiac resynchronization therapy (CRT). It was also compared the evaluation of cardiac dyssynchrony by TDI and 3D ECHO. Methods: Twenty-four consecutive patients with heart failure, sinus rhythm, QRS = 120 msec, functional class III or IV and LV ejection fraction (LVEF) = 0.35 underwent CRT. 2D ECHO, 3D ECHO with systolic dyssynchrony index (SDI) analysis, and TDI were performed before, 3 and 6 months after CRT. Cardiac dyssynchrony analyses by TDI and SDI were compared with the Pearson's correlation test. Before CRT, a univariate analysis of baseline characteristics was performed for the construction of a logistic regression model to identify the best predictors of LVRR. Results: After 3 months of CRT, there was a moderate correlation between TDI and SDI (r = 0.52). At other time points, there was no strong correlation. Nine of twenty-four (38%) patients presented with LVRR 6 months after CRT. After logistic regression analysis, SDI (SDI > 11%) was the only independent factor in the prediction of LVRR 6 months of CRT (sensitivity = 0.89 and specificity = 0.73). After construction of receiver operator characteristic (ROC) curves, an equation was established to predict LVRR: LVRR =-0.4LVDD (mm) + 0.5LVEF (%) + 1.1SDI (%), with responders presenting values >0 (sensitivity = 0.67 and specificity = 0.87). Conclusions: In this study, there was no strong correlation between TDI and SDI. An equation is proposed for the prediction of LVRR after CRT. Although larger trials are needed to validate these findings, this equation may be useful to candidates for CRT. (Echocardiography 2012;29:678-687)

Perception of the esthetic impact of mandibular incisor extraction treatment on laypersons, dental professionals, and dental students

Objective: To evaluate the degree of perception of laypersons, dental professionals, and dental students regarding dental esthetics in cases with mandibular central incisor extraction. Materials and Methods: Using a smile photograph of a person with normal occlusion and all teeth, modifications were made to reflect the extraction of a mandibular incisor of various compositions and sizes. For this purpose a program specifically for image manipulation (Adobe Photoshop CS3, Adobe Systems Inc) was used. After manipulation the images were printed on photographic paper, attached to a questionnaire and distributed to laypersons, dental professionals, and dental students (n = 90) to evaluate the degree of perception and esthetic using a scale of attractiveness, where 0 = hardly attractive, 5 = attractive, and 10 = very attractive. The differences between examiners were checked by the Mann-Whitney test. All the statistics were performed with a confidence level of 95%. Results: The results demonstrated the skill of the dental professionals and dental students in perceiving the difference between cases of normal occlusion and cases where an incisor was lacking (P < .05). The photograph in which the lateral incisors were shown to be larger than the central incisor was the one that obtained the highest value among the cases of extraction in all groups of evaluators. Conclusions: It can be concluded that dental professionals and dental students are more skillful at identifying deviation from normality. In addition, central incisor extraction should always be discarded when there are other treatment options available. (Angle Orthod. 2012;82:732-738.)

Effect of varicocele on sperm function and semen oxidative stress

OBJECTIVE To assess the effect of varicocele on sperm DNA integrity, mitochondrial activity, lipid peroxidation and acrosome integrity. PATIENTS AND METHODS In all, 30 patients with a clinically diagnosed varicocele of grade II or III and 32 men without a varicocele were evaluated for sperm DNA fragmentation (comet assay), mitochondrial activity (3,3'-diaminobenzidine assay), lipid peroxidation (malondialdehyde) and acrosome integrity (fluorescent probe labelled peanut agglutinin). RESULTS The varicocele group showed fewer spermatozoa with intact DNA (grade II, P = 0.040), more cells with inactive mitochondria (class III, P = 0.001), fewer cells with active mitochondria (class I, P = 0.005) and fewer spermatozoa with intact acrosomes (P < 0.001). Finally, no significant differences were observed in lipid peroxidation levels. CONCLUSION Men with varicocele showed an increase in sperm DNA fragmentation and a reduction in mitochondrial activity and acrosome integrity. However, lipid peroxidation levels remained unchanged.

Influence of intentional ankylosis of deciduous canines to reinforce the anchorage for maxillary protraction

Introduction: This retrospective cephalometric study analyzed the influence of intentional ankylosis of deciduous canines in patients with Class III malocclusion and anterior crossbite, in the deciduous and early mixed dentition stages, treated by orthopedic maxillary expansion followed by maxillary protraction. Methods: Lateral cephalograms of 40 patients were used, divided in 2 groups paired for age and gender. The Ankylosis Group was composed of 20 patients (10 boys and 10 girls) treated with induced ankylosis and presenting initial and final mean ages of 7 years 4 months and 8 years 3 months, respectively, with a mean period of maxillary protraction of 11 months. The Control Group comprised 20 patients (10 boys and 10 girls) treated without induced ankylosis, with initial and final mean ages of 7 years 8 months and 8 years 7 months, respectively, with a mean period of maxillary protraction of 11 months. Two-way analysis of variance and covariance analysis were applied to compare the initial and final cephalometric variables and the treatment changes between groups. Results: According to the results, the variables evidencing the significant treatment changes between groups confirmed that the intentional ankylosis enhanced the sagittal response of the apical bases (Pg-NPerp) and increased the facial convexity angles (NAP and ANB). Conclusions: The protocol involving intentional ankylosis of deciduous canines enhanced the sagittal response of the apical bases.

Influence of palatoplasty on occlusion of patients with isolated cleft palate

OBJECTIVE: This study compared the dental arch morphology of adult patients with isolated cleft palate in order to verify the influence of palatoplasty on occlusion. METHODS: Cast models of 77 patients, 30 males and 47 females, with an average age of 21 years and no syndromes were taken. They were in the permanent dentition and had not undergone orthodontic treatment. The sample was divided into non-operated and operated patients, the latter having been submitted to palatoplasty at a mean age of 2.2 years. RESULTS: Almost 80% of the sample exhibited sagittal discrepancies in the inter-arch relationship, with a Class II malocclusion prevailing (59.74%) followed by Class III (20,78%), regardless of palatoplasty. Transverse analysis showed a 23% incidence of posterior crossbite also not influenced by palatoplasty. Intra-arch relationship indicated that constriction and crowding on the upper arch were more frequent in the operated group (p=0.0238 and p=0.0002, respectively), showing an influence of palatoplasty on its morphology. The predominant morphological characteristics in patients with isolated cleft palate were a Class II malocclusion, upper dental arch constriction and upper and lower anterior crowding. CONCLUSION: The influence of palatoplasty was restricted to constriction and crowding of the upper dental arch, with no interference from the extension of the cleft, except for the upper crowding, which occurred more in patients with complete cleft palates.

Chewing time and chewing strokes in different dentofacial deformities

PURPOSE: To verify whether the number of chewing strokes and the chewing time are influenced by dentofacial deformities in habitual free mastication. METHODS: Participants were 15 patients with diagnosis of class II dentofacial deformity (GII), 15 with class III (GIII), and 15 healthy control individuals with no deformity (CG). Free habitual mastication of a cornstarch cookie was analyzed, considering the number of chewing strokes and the time needed to complete two mastications. Strokes were counted by considering the opening and closing movements of the mandible. The time needed to consume each bite was determined using a digital chronometer, started after the placement of the food in the oral cavity and stopped when each portion was swallowed. RESULTS: There were no differences between groups regarding both the number of strokes and the chewing time. However, with regards to the number of strokes, CG and GII presented a significant concordance between the first and the second chewing situation, which was not observed in GIII. The analysis of time showed significant concordance between the first and second chewing situation in CG, reasonable concordance in GII, and discordance in GIII. CONCLUSION: Dentofacial deformities do not influence the number of chewing strokes or the chewing time. However, class III individuals do not show uniformity regarding these aspects.

Riabilitazione protesica ed implanto-protesica di pazienti in età evolutiva affetti da Displasia Ectodermica

Introduction. Ectodermal Dysplasias are a heterogeneous group of inherited disorders characterized by dysplasia of tissues of ectodermal origin (hair, nails, teeth, skins and glands). Clinically, it may be divided into two broad categories: the X-linked hypoidrotic form and the hidrotic form. Hypohidrotic Ectodermal Dysplasia (H.E.D) is characterized by the triad oligo-anodontia, hypotricosis, hypo-anhydrosis (Christ-Siemens-Tourane syndrome). The incidence of HED is about 1/100,000. Mutation in the actodysplasin-A (EDA) and ectodysplasin-A receptor (EDAR) genes are responsible for X-linked and autosomal HED. The clinical features include sparse, fine hair, missing or conical-shaped teeth, decreased sweat and mucous glands, hypoplastic skin, and heat intolerance with exercise or increased ambient temperature. Complete or partial anodontia and malformation of teeth are the most frequent dental findings. Incisors and canines are often conical-shaped while primarily second molars, if present, are mostly affected by taurodontism. Treatment is supportive and includes protection from heat exposure, early prosthetic rehabilitation, skin, hair ear, nose and nail care, and genetic counseling for family planning. The diagnosis of HED in the neonatal and early infancy period may be difficult since sparse hair and absent teeth are normal finding at this age. In childhood the diagnosis is more easily made on the basis of history and clinical examination. Dental abnormalities are the most common complaint. Prosthetic rehabilitation has been recommended as an essential part of the management of HED because is important from functional, esthetic, and psychological standpoint. A team approach that includes input from a pediatric dentist, an orthodontist, a prosthodontist, and an oral and maxillofacial surgeon is necessary for a successful outcome. Conventional prosthodontic rehabilitation in young patient is often difficult because of the anatomical abnormalities of existing teeth and alveolar ridges. The conical shaped teeth and “knife-edge” alveolar ridges result in poor retention and instability of dentures. Moreover, denture must permit jaws expansion and a correct pattern of growth. Materials and Methods. Complete removable dentures were provided to allow for normal physiological development and a corrected masticatory function. Initial maxillary and mandibular impressions were made with smallest stock trays and irreversible hydrocolloid and then final impressions ware made with light-bodied polysulfide rubber base impression material. A base of autopolymerizing resin was constructed and a wax rim was added to the base. The patient’s vertical dimension of occlusion was established by assessing phonetic and esthetic criteria. Preliminary occlusal relations were recorded, and the mandibular cast was mounted on the articulator. Acrylic resin teeth specific for children dentures were selected and mounted. The dentures were tried in and, after proper adjustments, were inserted. The patients were monitored clinically every month to fit prostheses. Cephalometric radiographs were taken every 6 month with the prostheses in place in order to evaluate correct pattern of growth. Cephalometric measurements were realized and used to evaluate the effect of rehabilitation on craniofacial growth. Cephalometric measurements of sound patients were compared with ED patients. After two month expander screws (three-way screw in the upper denture and two-way the lower one)were inserted in each denture in order to permit the expansion of the denture and the jaws growth. Where conical teeth were present, composite crown were realized and luted to improve the esthetic and phonesis. In order to improve retention the placement of endosseous implants was carried out. TC 3D Accuitomo was performed and a resin model of mandibular bone of the patient was realized. At the age of 11 years two implants were inserted into anterior mandible in a child with anodontia. Despite a remarkable multi-dimensional atrophy of the mandibular alveolar process, the insertion of two tapered screw implants (SAMO Smiler, diameter 3.8, length 10 mm). After a submerged healing period of two-three month, the implants were exposed. Implants were connected with an expansion guide that permits mandibular growth and prosthetic retention. The amount of mandibular growth was also evaluate dusing the expansion guide. Results. Early oral rehabilitation improve oral function, phonesis and esthetic, reducing social impairment. Treated patients showed normal cephalometric measurement. Early rehabilitation is able to prevent the prognatissm of the mandibula . The number of teeth was significantly related to several changes in craniofacial morphology. Discussion. In the present study the 5,3% of ED patients showed hypodontia, the l’89,4% di oligodontia, and the 5,3% di anodontia. The cephalometric analysis supports that ED patients showed midface hypoplasia. ED groups showed an increased pogonion to nasion measurement than sound patients, indicative of class III tendency. The present study demonstrated that number of teeth was significantly correlated with deviation of cephalometric measurements from normality. Oligoanodontia is responsible for changing of cephalometric measuraments also on sagittal plane with a class III tendency. Maxillary jaw showed a retrused position related to the presence of hypodontia.

Analyse der Mechanismen zur Regulation der Zellzyklus-abhängigen Stabilität der MARCKS-mRNA

Die Expression des PKC-Hauptsubstrates MARCKS (myristoylated alanine-rich C kinase substrate) wird in Swiss 3T3-Fibroblasten in Abhängigkeit des Zellzyklus durch Variation der mRNA-Stabilität reguliert. In der vorliegenden Arbeit wurde die Beteiligung der 3' nichttranslatierten Region (3'UTR) der MARCKS-mRNA an der Stabilitätskontrolle analysiert. Durch Einsatz der RNase/EMSA-Technik konnten zwei cis-Elemente der MARCKS 3'UTR identifiziert und lokalisiert werden, die mit RNA-bindenden Swiss 3T3-Proteinen (trans-Faktoren) interagieren. Diese neu identifizierten cis-Elemente sind AU-reiche Elemente (ARE) der Klasse III, da sie sehr große Sequenzhomologie zu ARE dieser Klasse aufweisen und der MARCKS 3'UTR, wie für ARE typisch, Instabilität vermitteln.Durch UV-crosslinking wurden vier Proteine mit Molekülmassen von 55, 40, 36 und 30 kDa nachgewiesen, die spezifisch an das 52nt lange Haupt-ARE (MARCKS 52nt) mit unterschiedlicher Affinität binden konnten. Mit Hilfe von rekombinant hergestellten ELAV/Hu-Proteinen und einem ELAV/Hu-spezifischen, affinitätsgereinigten Antiserum konnte eines der vier Proteine (p36) als das ELAV/Hu-Protein HuR identifiziert werden. Die Funktion der ELAV/Hu-Proteine für die Stabilitätskontrolle der MARCKS-mRNA ließ sich durch transiente und stabile Transfektion von HuR und neuronenspezifischem HuD mit dem Tetracyclin induzierbaren Expressionssystem (Tetoff) in Swiss 3T3- bzw. MEF/3T3-Tetoff-Zellen verdeutlichen: Durch Überexpression von HuR und HuD wurde die wachstumsinduzierte Destabilisierung der MARCKS-mRNA bei Wiedereintritt der Zellen in den Zellzyklus unterbunden.

Mathematical Modeling to Investigate Antiarrhythmic Drug Side Effects: Rate-Dependence Role in Ionic Currents and Action Potentials Shape in the O’Hara Model

Sudden cardiac death due to ventricular arrhythmia is one of the leading causes of mortality in the world. In the last decades, it has proven that anti-arrhythmic drugs, which prolong the refractory period by means of prolongation of the cardiac action potential duration (APD), play a good role in preventing of relevant human arrhythmias. However, it has long been observed that the “class III antiarrhythmic effect” diminish at faster heart rates and that this phenomenon represent a big weakness, since it is the precise situation when arrhythmias are most prone to occur. It is well known that mathematical modeling is a useful tool for investigating cardiac cell behavior. In the last 60 years, a multitude of cardiac models has been created; from the pioneering work of Hodgkin and Huxley (1952), who first described the ionic currents of the squid giant axon quantitatively, mathematical modeling has made great strides. The O’Hara model, that I employed in this research work, is one of the modern computational models of ventricular myocyte, a new generation began in 1991 with ventricular cell model by Noble et al. Successful of these models is that you can generate novel predictions, suggest experiments and provide a quantitative understanding of underlying mechanism. Obviously, the drawback is that they remain simple models, they don’t represent the real system. The overall goal of this research is to give an additional tool, through mathematical modeling, to understand the behavior of the main ionic currents involved during the action potential (AP), especially underlining the differences between slower and faster heart rates. In particular to evaluate the rate-dependence role on the action potential duration, to implement a new method for interpreting ionic currents behavior after a perturbation effect and to verify the validity of the work proposed by Antonio Zaza using an injected current as a perturbing effect.

Characterization of the structure and iron uptake mechanisms of the Staphylococcus aureus ferric hydroxamate-binding lipoprotein FhuD2

The Reverse Vaccinology (RV) approach allows using genomic information for the delineation of new protein-based vaccines starting from an in silico analysis. The first powerful example of the application of the RV approach is given by the development of a protein-based vaccine against serogroup B Meningococcus. A similar approach was also used to identify new Staphylococcus aureus vaccine candidates, including the ferric hydroxamate-binding lipoprotein FhuD2. S. aureus is a widespread human pathogen, which employs various different strategies for iron uptake, including: (i) siderophore-mediated iron acquisition using the endogenous siderophores staphyloferrin A and B, (ii) siderophore-mediated iron acquisition using xeno-siderophores (the pathway exploited by FhuD2) and (iii) heme-mediated iron acquisition. In this work the high resolution crystal structure of FhuD2 in the iron (III)-siderophore-bound form was determined. FhuD2 belongs to the Periplasmic Binding Protein family (PBP ) class III, and is principally formed by two globular domains, at the N- and C-termini of the protein, that make up a cleft where ferrichrome-iron (III) is bound. The N- and C-terminal domains, connected by a single long α-helix, present Rossmann-like folds, showing a β-stranded core and an α-helical periphery, which do not undergo extensive structural rearrangement when they interact with the ligand, typical of class III PBP members. The structure shows that ferrichrome-bound iron does not come directly into contact with the protein; rather, the metal ion is fully coordinated by six oxygen donors of the hydroxamate groups of three ornithine residues, which, with the three glycine residues, make up the peptide backbone of ferrichrome. Furthermore, it was found that iron-free ferrichrome is able to subtract iron from transferrin. This study shows for the first time the structure of FhuD2, which was found to bind to siderophores ,and that the protein plays an important role in S. aureus colonization and infection phases.

Valutazione dello spostamento tridimensionale degli impianti in giovani pazienti affetti da EDs riabilitati con overdenture implanto-supportati

Ectodermal Dysplasias syndrome (EDs) are a heterogeneous group of inherited disorders characterized by dysplasia of tissues of ectodermal origin. Complete or partial anodontia are the most frequent dental findings. Prosthetic rehabilitation is recommended from functional, esthetic, and psychological points of view. Because of the anatomical abnormalities of existing teeth and alveolar ridges, conventional prosthetic rehabilitation in young patient is often difficult. Five growing patients (age 9 to 11 years) with oligo- or anodontia were prosthetically rehabilitated. Panoramic film and Cone Bean Computerized Tomography were performed and a resin model of mandibular bone was made. Despite a remarkable multi-dimensional atrophy of the alveolar bone, the insertion of two tapered implants was possible. After a submerged healing period of 2 month, the implants were exposed and abutment connection was performed. Implants were connected with an expansion bar that permits mandibular growth and prosthetic retention. A removable prosthesis was constructed with ball attachments. Mandibular growth was followed and evaluated using the expansion guide and cephalometric radiographs. Mandibular growth in sagittal and transverse direction had no adverse effects on implant position. The expansion bar permitted the undisturbed growth of the mandible. After 4.5 years of follow-up, this study showed that Implant-supported overdenture may improve oral function, phonesis and esthetics. The mandibular rotation accompanying growth had not caused a significant problem relative to the angulation and migration of the implants. Implants can be successfully placed, restored and loaded in growing EDs patients. The cephalometric analysis supported that EDs patients show midface hypoplasia with a class III tendency, which can be avoided by early rehabilitation. Thanks to the good stability and retention of the implant-supported overdenture, patients considered the prostheses as comparable to natural teeth.