FAM5C Contributes to Aggressive Periodontitis

Aggressive periodontitis is characterized by a rapid and severe periodontal destruction in young systemically healthy subjects. A greater prevalence is reported in Africans and African descendent groups than in Caucasians and Hispanics. We first fine mapped the interval 1q24.2 to 1q31.3 suggested as containing an aggressive periodontitis locus. Three hundred and eighty-nine subjects from 55 pedigrees were studied. Saliva samples were collected from all subjects, and DNA was extracted. Twenty-one single nucleotide polymorphisms were selected and analyzed by standard polymerase chain reaction using TaqMan chemistry. Non-parametric linkage and transmission distortion analyses were performed. Although linkage results were negative, statistically significant association between two markers, rs1935881 and rs1342913, in the FAM5C gene and aggressive periodontitis (p = 0.03) was found. Haplotype analysis showed an association between aggressive periodontitis and the haplotype A-G (rs1935881-rs1342913; p = 0.009). Sequence analysis of FAM5C coding regions did not disclose any mutations, but two variants in conserved intronic regions of FAM5C, rs57694932 and rs10494634, were found. However, these two variants are not associated with aggressive periodontitis. Secondly, we investigated the pattern of FAM5C expression in aggressive periodontitis lesions and its possible correlations with inflammatory/immunological factors and pathogens commonly associated with periodontal diseases. FAM5C mRNA expression was significantly higher in diseased versus healthy sites, and was found to be correlated to the IL-1 beta, IL-17A, IL-4 and RANKL mRNA levels. No correlations were found between FAM5C levels and the presence and load of red complex periodontopathogens or Aggregatibacter actinomycetemcomitans. This study provides evidence that FAM5C contributes to aggressive periodontitis.

Management of Bell's Palsy: A Report of 2 Cases

Bell's palsy is a neuropathy of the peripheral seventh cranial nerve, resulting from traumatic, compressive, infective, inflammatory or metabolic abnormalities or it can be idiopathic. HIV, Epstein-Barr virus and hepatitis B virus have been suspected as initiating organisms, but herpes simplex virus is the most frequently implicated. This report describes 2 cases of Bell's palsy in children that were managed with antiviral agents. Both patients experienced complete recovery within 28 days; after 1 year follow-up, no recurrence was observed and both patients have normal facial movement. Differential diagnosis is essential to guide the treatment plan in Bell's palsy. Special attention should be given to children with respect to prescription of medications that can cause important side effects.

Application of Low-Level Laser Irradiation (LLLI) and rhBMP-2 in Critical Bone Defect of Ovariectomized Rats: Histomorphometric Evaluation

Objectives: The aim of this study was to evaluate the osteogenic potential of recombinant human bone morphogenetic protein-2 (rhBMP-2) and low-level laser irradiation (LLLI), isolated or combined in critical bone defects (5mm) in parietal bone using ovariectomized female rats as an experimental animal model. Materials and Methods: Forty-nine female Wistar rats, bilaterally ovariectomized (OVX), were divided into seven treatment groups of seven animals each: (I) laser in a single application, (II) 7 mu g of pure rhBMP-2, (III) laser and 7 mu g of pure rhBMP-2, (IV) 7 mu g of rhBMP-2/monoolein gel, (V) laser and 7 mu g of rhBMP-2/monoolein gel, (VI) laser and pure monoolein gel, and (VII) critical bone defect controls. The low-level laser source used was a gallium aluminum arsenide semiconductor diode laser device (lambda = 780 nm, D = 120 J/cm(2)). Results: Groups II and III presented higher levels of newly formed bone than all other groups with levels of 40.57% and 40.39%, respectively (p < 0.05). The levels of newly formed bone of groups I, IV, V, and VI were similar with levels of 29.67%, 25.75%, 27.75%, and 30.64%, respectively (p > 0.05). The area of new bone formation in group VII was 20.96%, which is significantly lower than groups I, II, III, and VI. Conclusions: It was concluded that pure rhBMP-2 and a single dose of laser application stimulated new bone formation, but the new bone formation area was significantly increased when only rhBMP-2 was used. Additionally, the laser application in combination with other treatments did not influence the bone formation area.

Ultra-Structural Changes at the Apical Stop Irradiated with CO(2) Laser

Objective: This study evaluated ultra-structural dentine changes at the apical stop after CO(2) laser irradiation used during biomechanical preparation. Background: Most studies evaluating the sealing efficiency of CO(2) lasers have been carried out after apical root canal resections and retro-filling procedures. Methods: Sixty human canines were prepared with #1 to #6 Largo burs. The apical stops were established at 1 mm (n = 30) and 2 mm (n = 30) from the apex. Final irrigation was performed with 1% NaOCl and 15% EDTA followed by 20 ml of distilled and deionized water. Specimens were subdivided into three subgroups (n = 10 for each stop distance): GI-no radiation (n = 20); GII-3W potency (n = 20), GIII-5W potency (n = 20). After preparation, specimens were evaluated by scanning electron microscopy, with ultra-structural changes classified according to a scoring system based on six qualitatively different outcomes. Results: Statistical analysis using the Mann-Whitney test confirmed more intense results for the specimens irradiated at 5 W potency than at 3 W (p<0.0001). The Kruskal-Wallis test indicated that when using the same potencies (3 or 5 W) at 1 and 2 mm from the apex, there were no statistically significant differences in ultra-structural changes. Conclusions: Our results showed that ultra-structural changes ranged from smear layer removal to dentine fusion. As laser potency was increased from 3 to 5 W, ultra-structural changes included extensive fused lava-like areas sealing the apical foramen.

A Genome-Wide Association Study of Upper Aerodigestive Tract Cancers Conducted within the INHANCE Consortium

Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p <= 5 x 10(-7)). Two novel variants were identified, a 4q21 variant (rs1494961, p = 1 x 10(-8)) located near DNA repair related genes HEL308 and FAM175A (or Abraxas) and a 12q24 variant (rs4767364, p = 2 x 10(-8)) located in an extended linkage disequilibrium region that contains multiple genes including the aldehyde dehydrogenase 2 (ALDH2) gene. Three remaining variants are located in the ADH gene cluster and were identified previously in a candidate gene study involving some of these samples. The association between these three variants and UADT cancers was independently replicated in 5,092 UADT cancer cases and 6,794 controls non-overlapping samples presented here (rs1573496-ADH7, p = 5 x 10(-8); rs1229984-ADH1B, p = 7 x 10(-9); and rs698-ADH1C, p = 0.02). These results implicate two variants at 4q21 and 12q24 and further highlight three ADH variants in UADT cancer susceptibility.

H(2) infrared line emission from the ionized region of planetary nebulae

Context. The analysis and interpretation of the H(2) line emission from planetary nebulae have been done in the literature by assuming that the molecule survives only in regions where the hydrogen is neutral, as in photodissociation, neutral clumps, or shocked regions. However, there is strong observational and theoretical evidence that at least part of the H(2) emission is produced inside the ionized region of these objects. Aims. The aim of the present work is to calculate and analyze the infrared line emission of H(2) produced inside the ionized region of planetary nebulae using a one-dimensional photoionization code. Methods. The photoionization code Aangaba was improved in order to calculate the statistical population of the H(2) energy levels, as well as the intensity of the H(2) infrared emission lines in the physical conditions typical of planetary nebulae. A grid of models was obtained and the results then analyzed and compared with the observational data. Results. We show that the contribution of the ionized region to the H(2) line emission can be important, particularly in the case of nebulae with high-temperature central stars. This result explains why H(2) emission is more frequently observed in bipolar planetary nebulae (Gatley's rule), since this kind of object typically has hotter stars. Collisional excitation plays an important role in populating the rovibrational levels of the electronic ground state of H(2) molecules. Radiative mechanisms are also important, particularly for the upper vibrational levels. Formation pumping can have minor effects on the line intensities produced by de-excitation from very high rotational levels, especially in dense and dusty environments. We included the effect of the H(2) molecule on the thermal equilibrium of the gas, concluding that, in the ionized region, H(2) only contributes to the thermal equilibrium in the case of a very high temperature of the central star or a high dust-to-gas ratio, mainly through collisional de-excitation.

PFLEIDERER 2: IDENTIFICATION OF A NEW GLOBULAR CLUSTER IN THE GALAXY

We provide evidence that indicates the star cluster Pfleiderer 2, which is projected in a rich field, as a newly identified Galactic globular cluster. Since it is located in a crowded field, core extraction and decontamination tools were applied to reveal the cluster sequences in B, V, and I color-magnitude diagrams (CMDs). The main CMD features of Pfleiderer 2 are a tilted red giant branch and a red horizontal branch, indicating a high metallicity around solar. The reddening is E(B - V) = 1.01. The globular cluster is located at a distance of d(circle dot) = 16 +/- 2 kpc from the Sun. The cluster is located 2.7 kpc above the Galactic plane and at a distance of R(GC) = 9.7 kpc from the Galactic center, which is unusual for a metal-rich globular cluster.

Cluster and cluster galaxy evolution history from IR to X-ray observations of the young cluster RX J1257.2+4738 at z=0.866

Context. The cosmic time around the z similar to 1 redshift range appears crucial in the cluster and galaxy evolution, since it is probably the epoch of the first mature galaxy clusters. Our knowledge of the properties of the galaxy populations in these clusters is limited because only a handful of z similar to 1 clusters are presently known. Aims. In this framework, we report the discovery of a z similar to 0.87 cluster and study its properties at various wavelengths. Methods. We gathered X-ray and optical data (imaging and spectroscopy), and near and far infrared data (imaging) in order to confirm the cluster nature of our candidate, to determine its dynamical state, and to give insight on its galaxy population evolution. Results. Our candidate structure appears to be a massive z similar to 0.87 dynamically young cluster with an atypically high X-ray temperature as compared to its X-ray luminosity. It exhibits a significant percentage (similar to 90%) of galaxies that are also detected in the 24 mu m band. Conclusions. The cluster RXJ1257.2+4738 appears to be still in the process of collapsing. Its relatively high temperature is probably the consequence of significant energy input into the intracluster medium besides the regular gravitational infall contribution. A significant part of its galaxies are red objects that are probably dusty with on-going star formation.

Populations III.1 and III.2 gamma-ray bursts: constraints on the event rate for future radio and X-ray surveys

Aims. We calculate the theoretical event rate of gamma-ray bursts (GRBs) from the collapse of massive first-generation (Population III; Pop III) stars. The Pop III GRBs could be super-energetic with the isotropic energy up to E(iso) greater than or similar to 10(55-57) erg, providing a unique probe of the high-redshift Universe. Methods. We consider both the so-called Pop III.1 stars (primordial) and Pop III.2 stars (primordial but affected by radiation from other stars). We employ a semi-analytical approach that considers inhomogeneous hydrogen reionization and chemical evolution of the intergalactic medium. Results. We show that Pop III.2 GRBs occur more than 100 times more frequently than Pop III.1 GRBs, and thus should be suitable targets for future GRB missions. Interestingly, our optimistic model predicts an event rate that is already constrained by the current radio transient searches. We expect similar to 10-10(4) radio afterglows above similar to 0.3 mJy on the sky with similar to 1 year variability and mostly without GRBs (orphans), which are detectable by ALMA, EVLA, LOFAR, and SKA, while we expect to observe maximum of N < 20 GRBs per year integrated over at z > 6 for Pop III.2 and N < 0.08 per year integrated over at z > 10 for Pop III.1 with EXIST, and N < 0.2 for Pop III.2 GRBs per year integrated over at z > 6 with Swift.

THE SLOAN BRIGHT ARCS SURVEY: DISCOVERY OF SEVEN NEW STRONGLY LENSED GALAXIES FROM z=0.66-2.94

We report the discovery of seven new, very bright gravitational lens systems from our ongoing gravitational lens search, the Sloan Bright Arcs Survey (SBAS). Two of the systems are confirmed to have high source redshifts z = 2.19 and z = 2.94. Three other systems lie at intermediate redshift with z = 1.33, 1.82, 1.93 and two systems are at low redshift z = 0.66, 0.86. The lensed source galaxies in all of these systems are bright, with i-band magnitudes ranging from 19.73 to 22.06. We present the spectrum of each of the source galaxies in these systems along with estimates of the Einstein radius for each system. The foreground lens in most systems is identified by a red sequence based cluster finder as a galaxy group; one system is identified as a moderately rich cluster. In total, SBAS has now discovered 19 strong lens systems in the SDSS imaging data, 8 of which are among the highest surface brightness z similar or equal to 2-3 galaxies known.

The gene transformer-2 of Anastrepha fruit flies (Diptera, Tephritidae) and its evolution in insects

Background: In the tephritids Ceratitis, Bactrocera and Anastrepha, the gene transformer provides the memory device for sex determination via its auto-regulation; only in females is functional Tra protein produced. To date, the isolation and characterisation of the gene transformer-2 in the tephritids has only been undertaken in Ceratitis, and it has been shown that its function is required for the female-specific splicing of doublesex and transformer pre-mRNA. It therefore participates in transformer auto-regulatory function. In this work, the characterisation of this gene in eleven tephritid species belonging to the less extensively analysed genus Anastrepha was undertaken in order to throw light on the evolution of transformer-2. Results: The gene transformer-2 produces a protein of 249 amino acids in both sexes, which shows the features of the SR protein family. No significant partially spliced mRNA isoform specific to the male germ line was detected, unlike in Drosophila. It is transcribed in both sexes during development and in adult life, in both the soma and germ line. The injection of Anastrepha transformer-2 dsRNA into Anastrepha embryos caused a change in the splicing pattern of the endogenous transformer and doublesex pre-mRNA of XX females from the female to the male mode. Consequently, these XX females were transformed into pseudomales. The comparison of the eleven Anastrepha Transformer-2 proteins among themselves, and with the Transformer-2 proteins of other insects, suggests the existence of negative selection acting at the protein level to maintain Transformer-2 structural features. Conclusions: These results indicate that transformer-2 is required for sex determination in Anastrepha through its participation in the female-specific splicing of transformer and doublesex pre-mRNAs. It is therefore needed for the auto-regulation of the gene transformer. Thus, the transformer/transfomer-2 > doublesex elements at the bottom of the cascade, and their relationships, probably represent the ancestral state ( which still exists in the Tephritidae, Calliphoridae and Muscidae lineages) of the extant cascade found in the Drosophilidae lineage ( in which tra is just another component of the sex determination gene cascade regulated by Sex-lethal). In the phylogenetic lineage that gave rise to the drosophilids, evolution co-opted for Sex-lethal, modified it, and converted it into the key gene controlling sex determination.

Alternative splicing enriched cDNA libraries identify breast cancer-associated transcripts

Background: Alternative splicing (AS) is a central mechanism in the generation of genomic complexity and is a major contributor to transcriptome and proteome diversity. Alterations of the splicing process can lead to deregulation of crucial cellular processes and have been associated with a large spectrum of human diseases. Cancer-associated transcripts are potential molecular markers and may contribute to the development of more accurate diagnostic and prognostic methods and also serve as therapeutic targets. Alternative splicing-enriched cDNA libraries have been used to explore the variability generated by alternative splicing. In this study, by combining the use of trapping heteroduplexes and RNA amplification, we developed a powerful approach that enables transcriptome-wide exploration of the AS repertoire for identifying AS variants associated with breast tumor cells modulated by ERBB2 (HER-2/neu) oncogene expression. Results: The human breast cell line (C5.2) and a pool of 5 ERBB2 over-expressing breast tumor samples were used independently for the construction of two AS-enriched libraries. In total, 2,048 partial cDNA sequences were obtained, revealing 214 alternative splicing sequence-enriched tags (ASSETs). A subset with 79 multiple exon ASSETs was compared to public databases and reported 138 different AS events. A high success rate of RT-PCR validation (94.5%) was obtained, and 2 novel AS events were identified. The influence of ERBB2-mediated expression on AS regulation was evaluated by capillary electrophoresis and probe-ligation approaches in two mammary cell lines (Hb4a and C5.2) expressing different levels of ERBB2. The relative expression balance between AS variants from 3 genes was differentially modulated by ERBB2 in this model system. Conclusions: In this study, we presented a method for exploring AS from any RNA source in a transcriptome-wide format, which can be directly easily adapted to next generation sequencers. We identified AS transcripts that were differently modulated by ERBB2-mediated expression and that can be tested as molecular markers for breast cancer. Such a methodology will be useful for completely deciphering the cancer cell transcriptome diversity resulting from AS and for finding more precise molecular markers.

Effects of protein deprivation and re-feeding on P2X(2) receptors in enteric neurons

AIM: To investigate the effects of malnutrition and refeeding on the P2X(2) receptor, nitric oxide synthase (NOS), calretinin, calbindin and choline acetyltransferase (ChAT) in neurons of the rat ileum. METHODS: We analyzed the co-localization, numbers and sizes of P2X(2)-expressing neurons in relation to NOS-IR (immunoreactive), calbindin-IR, ChAT-IR, and calretinin-IR neurons of the myenteric and submucosal plexus. The experimental groups consisted of: (1) rats maintained on normal feed throughout pregnancy until 42 d post-parturition (N); (2) rats deprived of protein throughout pregnancy and 42 d post-parturition (D); and (3) rats undernourished for 21 d post-parturition and then given a protein diet from days 22 to 42 (DR). The myenteric and submucosal plexuses were evaluated by double labeling by immunohistochemical methods for P2X(2) receptor, NOS, ChAT, calbindin and calretinin. RESULTS: We found similar P2X(2) receptor immunoreactivity in the cytoplasm and surface membranes of myenteric and submucosal neurons from the N, D and DR groups. Double labeling of the myenteric plexus demonstrated that approximately 100% of NOS-IR, calbindin-IR, calretinin-IR and ChAT-IR neurons in all groups also expressed the P2X(2) receptor. In the submucosal plexus, the calretinin-IR, ChAT-IR and calbindinIR neurons were nearly all immunoreactive for the P2X(2) receptor. In the myenteric plexus, there was a 19% increase in numbers per cm(2) for P2X(2) receptor-IR neurons, 64% for NOS-IR, 84% for calretinin-IR and 26% for ChAT-IR neurons in the D group. The spatial density of calbindin-IR neurons, however, did not differ among the three groups. The submucosal neuronal density increased for calbindin-IR, calretinin-IR and ChAT-IR neurons. The average size of neurons in the myenteric plexus neurons in the D group was less than that in the controls and, in the re-fed rats; there was a 34% reduction in size only for the calretinin-IR neurons. CONCLUSION: This work demonstrates that expression of the P2X(2) receptor is present in inhibitory, intrinsic primary afferent, cholinergic secretomotor and vasomotor neurons. Undernutrition affected P2X(2) receptor expression in the submucosal plexus, and neuronal and size. These changes were rescued in the re-fed rats. (C) 2010 Baishideng. All rights reserved.

Thyroid Hormone Increases TGF-beta 1 in Cardiomyocytes Cultures Independently of Angiotensin II Type 1 and Type 2 Receptors

TH-induced cardiac hypertrophy in vivo is accompanied by increased cardiac Transforming Growth Factor-beta 1 (TGF-beta 1) levels, which is mediated by Angiotensin II type 1 receptors (AT1R) and type 2 receptors (AT2R). However, the possible involvement of this factor in TH-induced cardiac hypertrophy is unknown. In this study we evaluated whether TH is able to modulate TGF-beta 1 in isolated cardiac, as well as the possible contribution of AT1R and AT2R in this response. The cardiac fibroblasts treated with T(3) did not show alteration on TGF-beta 1 expression. However, cardiomyocytes treated with T(3) presented an increase in TGF-beta 1 expression, as well as an increase in protein synthesis. The AT1R blockade prevented the T(3)-induced cardiomyocyte hypertrophy, while the AT2R blockage attenuated this response. The T(3)-induced increase on TGF-beta 1 expression in cardiomyocytes was not changed by the use of AT1R and AT2R blockers. These results indicate that Angiotensin II receptors are not implicated in T(3)-induced increase on TGF-beta expression and suggest that the trophic effects exerted by T(3) on cardiomyocytes are not dependent on the higher TGF-beta 1 levels, since the AT1R and AT2R blockers were able to attenuate the T(3)-induced cardiomyocyte hypertrophy but were not able to attenuate the increase on TGF-beta 1 levels promoted by T(3).

The Monocarboxylate Transporter 8 and L-Type Amino Acid Transporters 1 and 2 Are Expressed in Mouse Skeletons and in Osteoblastic MC3T3-E1 Cells

Background: Several plasma membrane transporters have been shown to mediate the cellular influx and/or efflux of iodothyronines, including the sodium-independent organic anion co-transporting polypeptide 1 (OATP1), the sodium taurocholate co-transporting polypeptide (NTCP), the L-type amino acid transporter 1 (LAT1) and 2 (LAT2), and the monocarboxylate transporter 8 (MCT8). The aim of this study was to investigate if the mRNAs of these transporters were expressed and regulated by thyroid hormone (TH) in mouse calvaria-derived osteoblastic MC3T3-E1 cells and in the fetal and postnatal bones of mice. Methods: The mRNA expression of the iodothyronine transporters was investigated with real-time polymerase chain reaction analysis in euthyroid and hypothyroid fetuses and litters of mice and in MC3T3-E1 cells treated with increasing doses of triiodothyronine (T(3); 10(-10) to 10(-6) M) or with 10(-8) M T(3) for 1-9 days. Results: MCT8, LAT1, and LAT2 mRNAs were detected in fetal and postnatal femurs and in MC3T3-E1 cells, while OATP1 and NTCP mRNAs were not. LAT1 and LAT2 mRNAs were not affected by TH status in vivo or in vitro or by the stage of bone development or osteoblast maturation (analyzed by the expression of osteocalcin and alkaline phosphatase, which are key markers of osteoblastic differentiation). In contrast, the femoral mRNA expression of MCT8 decreased significantly during post-natal development, whereas MCT8 mRNA expression increased as MC3T3-E1 cells differentiated. We also showed that MCT8 mRNA was up-regulated in the femur of hypothyroid animals, and that it was down-regulated by treatment with T(3) in MC3T3-E1 cells. Conclusions: This is the first study to demonstrate the mRNA expression of LAT1, LAT2, and MCT8 in the bone tissue of mice and in osteoblast-like cells. In addition, the pattern of MCT8 expression observed in vivo and in vitro suggests that MCT8 may be important to modulate TH effects on osteoblast differentiation and on bone development and metabolism.