Gene therapy for periodontal bioengineering

Although significant advancements have been achieved in periodontal therapy over the last decade, predictable regeneration of the tooth-supporting tissues is a challenge in periodontology and oral implantology. Recently, gene therapy, a new therapeutic approach for genetic and acquired diseases, has been applied for tissue bioengineering in multiple clinical situations, including the craniofacial complex, among them defects resulting from periodontal disease. The use of gene therapy vectors has enhanced the bioavailability and targeting of multiple growth and host immune factors to repair alveolar bone defects. Early pre-clinical studies utilizing both ex vivo and in vivo gene transfer strategies demonstrate the feasibility of using gene therapy for periodontal tissue engineering. This review highlights the current progress made in the field of periodontal regenerative medicine via gene targeting approaches

Evidence Linking PPARG Genetic Variants with Periodontitis and Type 2 Diabetes Mellitus in a Brazilian Population

The peroxisome proliferator-activated receptor gamma (PPARG) gene encodes a transcription factor involved in the regulation of complex metabolic and inflammatory diseases. We investigated whether single nucleotide polymorphisms (SNPs) and haplotypes of the PPARG gene could contribute with susceptibility to develop periodontitis alone or together with type 2 diabetes mellitus (T2DM). Moreover, we evaluated the gene–phenotype association by assessing the subjects’ biochemical and periodontal parameters, and the expression of PPARG and other immune response–related genes. We examined 345 subjects with a healthy periodontium and without T2DM, 349 subjects with moderate or severe periodontitis but without T2DM, and 202 subjects with moderate or severe periodontitis and T2DM. PPARG SNPs rs12495364, rs1801282, rs1373640, and rs1151999 were investigated. Multiple logistic regressions adjusted for age, sex, and smoking status showed that individuals carrying rs1151999-GG had a 64% lower chance of developing periodontitis together with T2DM. The CCGT haplotype increased the risk of developing periodontitis together with T2DM. The rs1151999-GG and rs12495364-TC were associated with reduced risk of obesity, periodontitis, elevated triglycerides, and elevated glycated hemoglobin, but there was no association with gene expression. Polymorphisms of the PPARG gene were associated with developing periodontitis together with T2DM, and with obesity, lipid, glycemic, and periodontal characteristics

Implications of the Fermi-LAT diffuse gamma-ray measurements on annihilating or decaying Dark Matter

We analyze the recently published Fermi-LAT diffuse gamma-ray measurements in the context of leptonically annihilating or decaying dark matter (DM) with the aim to explain simultaneously the isotropic diffuse gamma-ray and the PAMELA, Fermi and HESS (PFH) anomalous $e^\pm$ data. Five different DM annihilation/decay channels $2e$, $2\mu$, $2\tau$, $4e$, or $4\mu$ (the latter two via an intermediate light particle $\phi$) are generated with PYTHIA. We calculate both the Galactic and extragalactic prompt and inverse Compton (IC) contributions to the resulting gamma-ray spectra. To find the Galactic IC spectra we use the interstellar radiation field model from the latest release of GALPROP. For the extragalactic signal we show that the amplitude of the prompt gamma-emission is very sensitive to the assumed model for the extragalactic background light. For our Galaxy we use the Einasto, NFW and Isothermal DM density profiles and include the effects of DM substructure assuming a simple subhalo model. Our calculations show that for the annihilating DM the extragalactic gamma-ray signal can dominate only if rather extreme power-law concentration-mass relation $C(M)$ is used, while more realistic $C(M)$ relations make the extragalactic component comparable or subdominant to the Galactic signal. For the decaying DM the Galactic signal always exceeds the extragalactic one. In the case of annihilating DM the PFH favored parameters can be ruled out only if power-law $C(M)$ relation is assumed. For DM decaying into $2\mu$ or $4\mu$ the PFH favored DM parameters are not in conflict with the Fermi gamma-ray data. We find that, due to the (almost) featureless Galactic IC spectrum and the DM halo substructure, annihilating DM may give a good simultaneous fit to the isotropic diffuse gamma-ray and to the PFH $e^\pm$ data without being in clear conflict with the other Fermi-LAT gamma-ray measurements.Comment: Accepted for publication in JCAP, added missing references, new Figs. 9 \& 10, 35 page

PDGF-B gene therapy accelerates bone engineering and oral implant osseointegration

Platelet-derived growth factor-BB (PDGF-BB) stimulates repair of healing-impaired chronic wounds such as diabetic ulcers and periodontal lesions. However, limitations in predictability of tissue regeneration occur due, in part, to transient growth factor bioavailability in vivo. Here, we report that gene delivery of PDGF-B stimulates repair of oral implant extraction socket defects. Alveolar ridge defects were created in rats and were treated at the time of titanium implant installation with a collagen matrix containing an adenoviral (Ad) vector encoding PDGF-B (5.5 x 10(8) or 5.5 x 10(9) pfu ml(-1)), Ad encoding luciferase (Ad-Luc; 5.5 x 10(9) pfu ml(-1); control) or recombinant human PDGF-BB protein (rhPDGF-BB, 0.3 mg ml(-1)). Bone repair and osseointegration were measured through backscattered scanning electron microscopy, histomorphometry, micro-computed tomography and biomechanical assessments. Furthermore, a panel of local and systemic safety assessments was performed. Results indicated that bone repair was accelerated by Ad-PDGF-B and rhPDGF-BB delivery compared with Ad-Luc, with the high dose of Ad-PDGF-B more effective than the low dose. No significant dissemination of the vector construct or alteration of systemic parameters was noted. In summary, gene delivery of Ad-PDGF-B shows regenerative and safety capabilities for bone tissue engineering and osseointegration in alveolar bone defects comparable with rhPDGF-BB protein delivery in vivo

Dark Energy and Neutrino CPT Violation

In this paper we study the dynamical CPT violation in the neutrino sector induced by the dark energy of the Universe. Specifically we consider a dark energy model where the dark energy scalar derivatively interacts with the right-handed neutrinos. This type of derivative coupling leads to a cosmological CPT violation during the evolution of the background field of the dark energy. We calculate the induced CPT violation of left-handed neutrinos and find the CPT violation produced in this way is consistent with the present experimental limit and sensitive to the future neutrino oscillation experiments, such as the neutrino factory.Comment: 10 pages, 2 figures. Typos corrected and references added. To be published in EPJ

Physics with the KLOE-2 experiment at the upgraded DAϕ\phiNE

Investigation at a $\phi$--factory can shed light on several debated issues in particle physics. We discuss: i) recent theoretical development and experimental progress in kaon physics relevant for the Standard Model tests in the flavor sector, ii) the sensitivity we can reach in probing CPT and Quantum Mechanics from time evolution of entangled kaon states, iii) the interest for improving on the present measurements of non-leptonic and radiative decays of kaons and eta/eta$^\prime$ mesons, iv) the contribution to understand the nature of light scalar mesons, and v) the opportunity to search for narrow di-lepton resonances suggested by recent models proposing a hidden dark-matter sector. We also report on the $e^+ e^-$ physics in the continuum with the measurements of (multi)hadronic cross sections and the study of gamma gamma processes.Comment: 60 pages, 41 figures; added affiliation for one of the authors; added reference to section

Search for Tensor, Vector, and Scalar Polarizations in the Stochastic Gravitational-Wave Background

The detection of gravitational waves with Advanced LIGO and Advanced Virgo has enabled novel tests of general relativity, including direct study of the polarization of gravitational waves. While general relativity allows for only two tensor gravitational-wave polarizations, general metric theories can additionally predict two vector and two scalar polarizations. The polarization of gravitational waves is encoded in the spectral shape of the stochastic gravitational-wave background, formed by the superposition of cosmological and individually unresolved astrophysical sources. Using data recorded by Advanced LIGO during its first observing run, we search for a stochastic background of generically polarized gravitational waves. We find no evidence for a background of any polarization, and place the first direct bounds on the contributions of vector and scalar polarizations to the stochastic background. Under log-uniform priors for the energy in each polarization, we limit the energy densities of tensor, vector, and scalar modes at 95% credibility to Ω0T<5.58×10-8, Ω0V<6.35×10-8, and Ω0S<1.08×10-7 at a reference frequency f0=25 Hz. © 2018 American Physical Society