Competing endogenous rna networks as biomarkers in neurodegenerative diseases

Protein aggregation is classically considered the main cause of neuronal death in neurodegenerative diseases (NDDs). However, increasing evidence suggests that alteration of RNA metabolism is a key factor in the etiopathogenesis of these complex disorders. Non-coding RNAs are the major contributor to the human transcriptome and are particularly abundant in the central nervous system, where they have been proposed to be involved in the onset and development of NDDs. Interestingly, some ncRNAs (such as lncRNAs, circRNAs and pseudogenes) share a common functionality in their ability to regulate gene expression by modulating miRNAs in a phenomenon known as the competing endogenous RNA mechanism. Moreover, ncRNAs are found in body fluids where their presence and concentration could serve as potential non-invasive biomarkers of NDDs. In this review, we summarize the ceRNA networks described in Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis and spinocerebellar ataxia type 7, and discuss their potential as biomarkers of these NDDs. Although numerous studies have been carried out, further research is needed to validate these complex interactions between RNAs and the alterations in RNA editing that could provide specific ceRNET profiles for neurodegenerative disorders, paving the way to a better understanding of these diseases

Interaction between Calpain 5, Peroxisome proliferator-activated receptor-gamma and Peroxisome proliferator-activated receptor-delta genes: a polygenic approach to obesity

<p>Abstract</p> <p>Context</p> <p>Obesity is a multifactorial disorder, that is, a disease determined by the combined effect of genes and environment. In this context, polygenic approaches are needed.</p> <p>Objective</p> <p>To investigate the possibility of the existence of a crosstalk between the <it>CALPAIN 10 </it>homologue <it>CALPAIN 5 </it>and nuclear receptors of the peroxisome proliferator-activated receptors family.</p> <p>Design</p> <p>Cross-sectional, genetic association study and gene-gene interaction analysis.</p> <p>Subjects</p> <p>The study sample comprise 1953 individuals, 725 obese (defined as body mass index ≥ 30) and 1228 non obese subjects.</p> <p>Results</p> <p>In the monogenic analysis, only the peroxisome proliferator-activated receptor delta (<it>PPARD</it>) gene was associated with obesity (OR = 1.43 [1.04–1.97], p = 0.027). In addition, we have found a significant interaction between <it>CAPN5 </it>and <it>PPARD </it>genes (p = 0.038) that reduces the risk for obesity in a 55%.</p> <p>Conclusion</p> <p>Our results suggest that <it>CAPN5 </it>and <it>PPARD </it>gene products may also interact in vivo.</p

The Effective Electroweak Chiral Lagrangian: The Matter Sector

We parametrize in a model-independent way possible departures from the minimal Standard Model predictions in the matter sector. We only assume the symmetry breaking pattern of the Standard Model and that new particles are sufficiently heavy so that the symmetry is non-linearly realized. Models with dynamical symmetry breaking are generically of this type. We review in the effective theory language to what extent the simplest models of dynamical breaking are actually constrained and the assumptions going into the comparison with experiment. Dynamical symmetry breaking models can be approximated at intermediate energies by four-fermion operators. We present a complete classification of the latter when new particles appear in the usual representations of the $SU(2)_L\times SU(3)_c$ group as well as a partial classification in the general case. We discuss the accuracy of the four-fermion description by matching to a simple `fundamental' theory. The coefficients of the effective lagrangian in the matter sector for dynamical symmetry breaking models (expressed in terms of the coefficients of the four-quark operators) are then compared to those of models with elementary scalars (such as the minimal Standard Model). Contrary to a somewhat widespread belief, we see that the sign of the vertex corrections is not fixed in dynamical symmetry breaking models. This work provides the theoretical tools required to analyze, in a rather general setting, constraints on the matter sector of the Standard Model.Comment: Latex, 45 pages, 8 eps figures. Sections 5, 6 and 9 have been rewritten to clarify the contents. Some mistakes and typos have been corrected. Two references have been added. Figures 7 and 8 have been modifie

Epigenetic activation of a cryptic TBC1D16 transcript enhances melanoma progression by targeting EGFR

Metastasis is respoMetastasis is responsible for most cancer-related deaths, and, among common tumor types, melanoma is one with great potential to metastasize. Here we study the contribution of epigenetic changes to the dissemination process by analyzing the changes that occur at the DNA methylation level between primary cancer cells and metastases. We found a hypomethylation event that reactivates a cryptic transcript of the Rab GTPase activating protein TBC1D16 (TBC1D16-47 kDa; referred to hereafter as TBC1D16-47KD) to be a characteristic feature of the metastatic cascade. This short isoform of TBC1D16 exacerbates melanoma growth and metastasis both in vitro and in vivo. By combining immunoprecipitation and mass spectrometry, we identified RAB5C as a new TBC1D16 target and showed that it regulates EGFR in melanoma cells. We also found that epigenetic reactivation of TBC1D16-47KD is associated with poor clinical outcome in melanoma, while conferring greater sensitivity to BRAF and MEK inhibitors

From thermal rectifiers to thermoelectric devices

We discuss thermal rectification and thermoelectric energy conversion from the perspective of nonequilibrium statistical mechanics and dynamical systems theory. After preliminary considerations on the dynamical foundations of the phenomenological Fourier law in classical and quantum mechanics, we illustrate ways to control the phononic heat flow and design thermal diodes. Finally, we consider the coupled transport of heat and charge and discuss several general mechanisms for optimizing the figure of merit of thermoelectric efficiency.Comment: 42 pages, 22 figures, review paper, to appear in the Springer Lecture Notes in Physics volume "Thermal transport in low dimensions: from statistical physics to nanoscale heat transfer" (S. Lepri ed.

Constraints on the χ_(c1) versus χ_(c2) polarizations in proton-proton collisions at √s = 8 TeV

The polarizations of promptly produced χ_(c1) and χ_(c2) mesons are studied using data collected by the CMS experiment at the LHC, in proton-proton collisions at √s=8  TeV. The χ_c states are reconstructed via their radiative decays χ_c → J/ψγ, with the photons being measured through conversions to e⁺e⁻, which allows the two states to be well resolved. The polarizations are measured in the helicity frame, through the analysis of the χ_(c2) to χ_(c1) yield ratio as a function of the polar or azimuthal angle of the positive muon emitted in the J/ψ → μ⁺μ⁻ decay, in three bins of J/ψ transverse momentum. While no differences are seen between the two states in terms of azimuthal decay angle distributions, they are observed to have significantly different polar anisotropies. The measurement favors a scenario where at least one of the two states is strongly polarized along the helicity quantization axis, in agreement with nonrelativistic quantum chromodynamics predictions. This is the first measurement of significantly polarized quarkonia produced at high transverse momentum