Axion-like particles and the 3.5 keV line in 4D string models

This work is focused on axions and axion like particles (ALPs) and their possible relation with the 3.55 keV photon line detected, in recent years, from galaxy clusters and other astrophysical objects. We focus on axions that come from string compactification and we study the vacuum structure of the resulting low energy 4D N=1 supergravity effective field theory. We then provide a model which might explain the 3.55 keV line through the following processes. A 7.1 keV dark matter axion decays in two light axions, which, in turn, are transformed into photons thanks to the Primakoff effect and the existence of a kinetic mixing between two U(1)s gauge symmetries belonging respectively to the hidden and the visible sector. We present two models, the first one gives an outcome inconsistent with experimental data, while the second can yield the desired result.

Examination of FGFRL1 as a candidate gene for diaphragmatic defects at chromosome 4p16.3 shows that Fgfrl1 null mice have reduced expression of Tpm3, sarcomere genes and Lrtm1 in the diaphragm

Fgfrl1 (also known as Fgfr5; OMIM 605830) homozygous null mice have thin, amuscular diaphragms and die at birth because of diaphragm hypoplasia. FGFRL1 is located at 4p16.3, and this chromosome region can be deleted in patients with congenital diaphragmatic hernia (CDH). We examined FGFRL1 as a candidate gene for the diaphragmatic defects associated with 4p16.3 deletions and re-sequenced this gene in 54 patients with CDH. We confirmed six known coding single nucleotide polymorphisms (SNPs): c.209G > A (p.Pro20Pro), c.977G > A (p.Pro276Pro), c.1040T > C (p.Asp297Asp), c.1234C > A (p.Pro362Gln), c.1420G > T (p.Arg424Leu), and c.1540C > T (p.Pro464Leu), but we did not identify any gene mutations. We genotyped additional CDH patients for four of these six SNPs, including the three non-synonymous SNPs, to make a total of 200 chromosomes, and found that the allele frequency for the four SNPs, did not differ significantly between patients and normal controls (p > or = 0.05). We then used Affymetrix Genechip Mouse Gene 1.0 ST arrays and found eight genes with significantly reduced expression levels in the diaphragms of Fgfrl1 homozygous null mice when compared with wildtype mice-Tpm3, Fgfrl1 (p = 0.004), Myl2, Lrtm1, Myh4, Myl3, Myh7 and Hephl1. Lrtm1 is closely related to Slit3, a protein associated with herniation of the central tendon of the diaphragm in mice. The Slit proteins are known to regulate axon branching and cell migration, and inhibition of Slit3 reduces cell motility and decreases the expression of Rac and Cdc42, two genes that are essential for myoblast fusion. Further studies to determine if Lrtm1 has a similar function to Slit3 and if reduced Fgfrl1 expression can cause diaphragm hypoplasia through a mechanism involving decreased myoblast motility and/or myoblast fusion, seem indicated.

Early loading at 21 days of non-submerged titanium implants with a chemically modified sandblasted and acid-etched surface: 3-year results of a prospective study in the posterior mandible

BACKGROUND: This study evaluates 3-year success rates of titanium screw-type implants with a chemically modified sandblasted and acid-etched surface (mod SLA), which were functionally loaded after 3 weeks of healing. METHODS: A total of 56 implants, inserted in the posterior mandibles of 39 partially edentulous patients, underwent undisturbed healing for 3 weeks. At day 21, the implants were fully loaded with provisional crowns. Definitive metal ceramic restorations were fabricated after 6 months of healing. Clinical measurements regarding soft tissue parameters and radiographs were obtained at different time points up to 36 months after implant placement. The soft tissue and radiographic parameters for the mod SLA implants after 3 years in function were compared to a historic control group of implants with an SLA surface using an early loading protocol after 6 weeks. RESULTS: None of the implants failed to integrate. However, two implants were considered "spinners" at day 21 and were left unloaded for an extended period. Therefore, 96.4% of the inserted implants were loaded according to the protocol tested. All 56 implants, including the "spinners," showed favorable clinical and radiographic findings at the 3-year follow-up examination. All 56 implants were considered successfully integrated, resulting in a 3-year survival and success rate of 100%. Dental implants with a mod SLA surface demonstrated statistically significant differences for probing depths and clinical attachment level values compared to the historic control group, with the mod SLA surface implants having overall lower probing depths and clinical attachment level scores. CONCLUSION: This prospective study using an early loading protocol demonstrates that titanium implants with the mod SLA surface can achieve and maintain successful tissue integration over a period of 3 years.

Stability of Contour Augmentation and Esthetic Outcomes of Implant Supported Single Crowns in the Esthetic Zone. 3-Year Results of a Prospective Study With Early Implant Placement Post Extraction

Early implant placement is one of the treatment options after tooth extraction. Implant surgery is performed after a healing period of 4 to 8 weeks and combined with a simultaneous contour augmentation using the guided bone regeneration technique to rebuild stable esthetic facial hard- and soft-tissue contours.

Comparison of actual surgical outcomes and 3-dimensional surgical simulations

PURPOSE: The advent of imaging software programs has proved to be useful for diagnosis, treatment planning, and outcome measurement, but precision of 3-dimensional (3D) surgical simulation still needs to be tested. This study was conducted to determine whether the virtual surgery performed on 3D models constructed from cone-beam computed tomography (CBCT) can correctly simulate the actual surgical outcome and to validate the ability of this emerging technology to recreate the orthognathic surgery hard tissue movements in 3 translational and 3 rotational planes of space. MATERIALS AND METHODS: Construction of pre- and postsurgery 3D models from CBCTs of 14 patients who had combined maxillary advancement and mandibular setback surgery and 6 patients who had 1-piece maxillary advancement surgery was performed. The postsurgery and virtually simulated surgery 3D models were registered at the cranial base to quantify differences between simulated and actual surgery models. Hotelling t tests were used to assess the differences between simulated and actual surgical outcomes. RESULTS: For all anatomic regions of interest, there was no statistically significant difference between the simulated and the actual surgical models. The right lateral ramus was the only region that showed a statistically significant, but small difference when comparing 2- and 1-jaw surgeries. CONCLUSIONS: Virtual surgical methods were reliably reproduced. Oral surgery residents could benefit from virtual surgical training. Computer simulation has the potential to increase predictability in the operating room.

Delayed gadolinium-enhanced MRI of cartilage in the ankle at 3 T: feasibility and preliminary results after matrix-associated autologous chondrocyte implantation

To demonstrate the feasibility of delayed gadolinium-enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC) in the ankle at 3 T and to obtain preliminary data on matrix associated autologous chondrocyte (MACI) repair tissue.

Identification of a fibronectin interaction site in the extracellular matrix protein ameloblastin

Mammalian teeth are composed of hydroxyapatite crystals that are embedded in a rich extracellular matrix. This matrix is produced by only two cell types, the mesenchymal odontoblasts and the ectodermal ameloblasts. Ameloblasts secrete the enamel proteins amelogenin, ameloblastin, enamelin and amelotin. Odontoblasts secrete collagen type I and several calcium-binding phosphoproteins including dentin sialophosphoprotein, dentin matrix protein, bone sialoprotein and osteopontin. The latter four proteins have recently been grouped in the family of the SIBLINGs (small integrin-binding ligand, N-linked glycoproteins) because they display similar gene structures and because they contain an RGD tripeptide sequence that binds to integrin receptors and thus mediates cell adhesion. We have prepared all the other tooth-specific proteins in recombinant form and examined whether they might also promote cell adhesion similar to the SIBLINGs. We found that only ameloblastin consistently mediated adhesion of osteoblastic and fibroblastic cells to plastic or titanium surfaces. The activity was dependent on the intact three-dimensional structure of ameloblastin and required de novo protein synthesis of the adhering cells. By deletion analysis and in vitro mutagenesis, the active site could be narrowed down to a sequence of 13 amino acid residues (VPIMDFADPQFPT) derived from exon 7 of the rat ameloblastin gene or exons 7-9 of the human gene. Kinetic studies and RNA interference experiments further demonstrated that this sequence does not directly bind to a cell surface receptor but that it interacts with cellular fibronectin, which in turn binds to integrin receptors. The identification of a fibronectin-binding domain in ameloblastin might permit interesting applications for dental implantology. Implants could be coated with peptides containing the active sequence, which in turn would recruit fibronectin from the patient's blood. The recruited fibronectin should then promote cell adhesion on the implant surface, thereby accelerating osseointegration of the implant.

Caspase-3-independent photoreceptor degeneration by N-methyl-N-nitrosourea (MNU) induces morphological and functional changes in the mouse retina

Retinal degeneration is followed by significant changes in the structure and function of photoreceptors in humans and several genetic animal models. However, it is not clear whether similar changes occur when the degeneration is induced pharmacologically. Therefore, our aim was to investigate the influence of retinotoxic N-methyl-N-nitrosourea (MNU) on the function, morphology and underlying molecular pathways of programmed cell death.

Elevated level of metabotropic glutamate receptor 2/3 in the prefrontal cortex in major depression

Clinical, postmortem and preclinical research strongly implicates dysregulation of glutamatergic neurotransmission in major depressive disorder (MDD). Recently, metabotropic glutamate receptors (mGluRs) have been proposed as attractive targets for the discovery of novel therapeutic approaches against depression. The aim of this study was to examine mGluR2/3 protein levels in the prefrontal cortex (PFC) from depressed subjects. In addition, to test whether antidepressants influence mGluR2/3 expression we also studied levels of mGluR2/3 in fluoxetine-treated monkeys. Postmortem human prefrontal samples containing Brodmann's area 10 (BA10) were obtained from 11 depressed and 11 psychiatrically healthy controls. Male rhesus monkeys were treated chronically with fluoxetine (dose escalated to 3mg/kg, p.o.; n=7) or placebo (n=6) for 39 weeks. The mGluR2/3 immunoreactivity was investigated using Western blot method. There was a robust (+67%) increase in the expression of the mGlu2/3 protein in the PFC of depressed subjects relative to healthy controls. The expression of mGlu2/3 was unchanged in the PFC of monkeys treated with fluoxetine. Our findings provide the first evidence that mGluR2/3 is elevated in the PFC in MDD. This observation is consistent with reports showing that mGluR2/3 antagonists exhibit antidepressant-like activity in animal models and demonstrates that these receptors are promising targets for the discovery of novel antidepressants.

The role of bone debris in early healing adjacent to hydrophilic and hydrophobic implant surfaces in man

To evaluate morphologically and morphometrically the sequential healing and osseointegration events at moderately rough implant surfaces with and without chemical modification. Particularly the role of bone debris in initiating bone formation was emphasized.

Use of the Supermolecule Approach To Model the Syn and Anti Conformations of Solvated Cyclic 3‘,5‘-Adenosine Monophosphate

The supermolecule approach has been used to model the hydration of cyclic 3‘,5‘-adenosine monophosphate, cAMP. Model building combined with PM3 optimizations predict that the anti conformer of cAMP is capable of hydrogen bonding to an additional solvent water molecule compared to the syn conformer. The addition of one water to the syn superstructure with concurrent rotation of the base about the glycosyl bond to form the anti superstructure leads to an additional enthalpy of stabilization of approximately −6 kcal/mol at the PM3 level. This specific solute−solvent interaction is an example of a large solvent effect, as the method predicts that cAMP has a conformational preference for the anti isomer in solution. This conformational preference results from a change in the number of specific solute−solvent interactions in this system. This prediction could be tested by NMR techniques. The number of waters predicted to be in the first hydration sphere around cAMP is in agreement with the results of hydration studies of nucleotides in DNA. In addition, the detailed picture of solvation about this cyclic nucleotide is in agreement with infrared experimental results.

miR-21 functionally interacts with the 3'UTR of chemokine CCL20 and down-regulates CCL20 expression in miR-21 transfected colorectal cancer cells

As deregulation of miRNAs and chemokine CCL20 was shown to play a role in colorectal cancer (CRC) pathogenesis, we analyzed the functional interactions of candidate miRNAs with CCL20 mRNA. After target prediction software programs indicated a role for miR-21 in CCL20 regulation, we applied the luciferase reporter assay system to demonstrate that miR-21 functionally interacts with the 3'UTR of CCL20 mRNA and down-regulates CCL20 in miR-21 mimic transfected CRC cell lines (Caco-2, SW480 and SW620). Thus, regulation of CCL20 expression by miR-21 might be a regulatory mechanism involved in progression of CRC.