153 research outputs found
Higgs Inflation as a Mirage
We discuss a simple unitarization of Higgs inflation that is genuinely weakly
coupled up to Planckian energies. A large non-minimal coupling between the
Higgs and the Ricci curvature is induced dynamically at intermediate energies,
as a simple ratio of mass scales. Despite not being dominated by the Higgs
field, inflationary dynamics simulates the `Higgs inflation' one would get by
blind extrapolation of the low-energy effective Lagrangian, at least
qualitatively. Hence, Higgs inflation arises as an approximate `mirage' picture
of the true dynamics. We further speculate on the generality of this phenomenon
and show that, if Higgs-inflation arises as an effective description, the
details of the UV completion are necessary to extract robust quantitative
predictions.Comment: 21 pages, 2 figure
Dicarbonyl stress and mitochondrial dysfunction in the aged heart
Aging; Cardiomyocytes; MitochondriaEnvejecimiento; Cardiomiocitos; MitocondriasEnvelliment; Cardiomiòcits; Mitocondri
TRPV4 Channels Promote Pathological, but Not Physiological, Cardiac Remodeling through the Activation of Calcineurin/NFAT and TRPC6
Calcium; Heart failure; Pathological remodelingCalci; Insuficiència cardÃaca; Remodelació patològicaCalcio; Insuficiencia cardiaca; Remodelación patológicaTRPV4 channels, which respond to mechanical activation by permeating Ca2+ into the cell, may play a pivotal role in cardiac remodeling during cardiac overload. Our study aimed to investigate TRPV4 involvement in pathological and physiological remodeling through Ca2+-dependent signaling. TRPV4 expression was assessed in heart failure (HF) models, induced by isoproterenol infusion or transverse aortic constriction, and in exercise-induced adaptive remodeling models. The impact of genetic TRPV4 inhibition on HF was studied by echocardiography, histology, gene and protein analysis, arrhythmia inducibility, Ca2+ dynamics, calcineurin (CN) activity, and NFAT nuclear translocation. TRPV4 expression exclusively increased in HF models, strongly correlating with fibrosis. Isoproterenol-administered transgenic TRPV4−/− mice did not exhibit HF features. Cardiac fibroblasts (CFb) from TRPV4+/+ animals, compared to TRPV4−/−, displayed significant TRPV4 overexpression, elevated Ca2+ influx, and enhanced CN/NFATc3 pathway activation. TRPC6 expression paralleled that of TRPV4 in all models, with no increase in TRPV4−/− mice. In cultured CFb, the activation of TRPV4 by GSK1016790A increased TRPC6 expression, which led to enhanced CN/NFATc3 activation through synergistic action of both channels. In conclusion, TRPV4 channels contribute to pathological remodeling by promoting fibrosis and inducing TRPC6 upregulation through the activation of Ca2+-dependent CN/NFATc3 signaling. These results pose TRPV4 as a primary mediator of the pathological response.This research was funded by the Instituto de Salud Carlos III—Fondo de Investigación Sanitaria [PI16/00619]; the Sociedad Española de CardiologÃa [SEC/FEC-INV-BAS 20/016]; and the Societat Catalana de Cardiologia 2021
Impact of massive neutrinos on the Higgs self-coupling and electroweak vacuum stability
The presence of right-handed neutrinos in the type I seesaw mechanism may
lead to significant corrections to the RG evolution of the Higgs self-coupling.
Compared to the Standard Model case, the Higgs mass window can become narrower,
and the cutoff scale become lower. Naively, these effects decrease with
decreasing right-handed neutrino mass. However, we point out that the unknown
Dirac Yukawa matrix may impact the vacuum stability constraints even in the low
scale seesaw case not far away from the electroweak scale, hence much below the
canonical seesaw scale of 10^15 GeV. This includes situations in which
production of right-handed neutrinos at colliders is possible. We illustrate
this within a particular parametrization of the Dirac Yukawas and with explicit
low scale seesaw models. We also note the effect of massive neutrinos on the
top quark Yukawa coupling, whose high energy value can be increased with
respect to the Standard Model case.Comment: 17 pages, 7 figures, minor revisions, version to appear in JHE
Higgs mass and vacuum stability in the Standard Model at NNLO
We present the first complete next-to-next-to-leading order analysis of the
Standard Model Higgs potential. We computed the two-loop QCD and Yukawa
corrections to the relation between the Higgs quartic coupling (lambda) and the
Higgs mass (Mh), reducing the theoretical uncertainty in the determination of
the critical value of Mh for vacuum stability to 1 GeV. While lambda at the
Planck scale is remarkably close to zero, absolute stability of the Higgs
potential is excluded at 98% C.L. for Mh < 126 GeV. Possible consequences of
the near vanishing of lambda at the Planck scale, including speculations about
the role of the Higgs field during inflation, are discussed.Comment: 35 pages, 8 figures. Final published version, misprints fixed,
figures update
Vacuum stability, neutrinos, and dark matter
Motivated by the discovery hint of the Standard Model (SM) Higgs mass around
125 GeV at the LHC, we study the vacuum stability and perturbativity bounds on
Higgs scalar of the SM extensions including neutrinos and dark matter (DM).
Guided by the SM gauge symmetry and the minimal changes in the SM Higgs
potential we consider two extensions of neutrino sector (Type-I and Type-III
seesaw mechanisms) and DM sector (a real scalar singlet (darkon) and minimal
dark matter (MDM)) respectively. The darkon contributes positively to the
function of the Higgs quartic coupling and can stabilize the
SM vacuum up to high scale. Similar to the top quark in the SM we find the
cause of instability is sensitive to the size of new Yukawa couplings between
heavy neutrinos and Higgs boson, namely, the scale of seesaw mechanism. MDM and
Type-III seesaw fermion triplet, two nontrivial representations of
group, will bring the additional positive contributions to the gauge coupling
renormalization group (RG) evolution and would also help to stabilize
the electroweak vacuum up to high scale.Comment: 18 pages, 15 figures; published versio
A Shift Symmetry in the Higgs Sector: Experimental Hints and Stringy Realizations
We interpret reported hints of a Standard Model Higgs boson at ~ 125 GeV in
terms of high-scale supersymmetry breaking with a shift symmetry in the Higgs
sector. More specifically, the Higgs mass range suggested by recent LHC data
extrapolates, within the (non-supersymmetric) Standard Model, to a vanishing
quartic Higgs coupling at a UV scale between 10^6 and 10^18 GeV. Such a small
value of lambda can be understood in terms of models with high-scale SUSY
breaking if the Kahler potential possesses a shift symmetry, i.e., if it
depends on H_u and H_d only in the combination (H_u+\bar{H}_d). This symmetry
is known to arise rather naturally in certain heterotic compactifications. We
suggest that such a structure of the Higgs Kahler potential is common in a
wider class of string constructions, including intersecting D7- and D6-brane
models and their extensions to F-theory or M-theory. The latest LHC data may
thus be interpreted as hinting to a particular class of compactifications which
possess this shift symmetry.Comment: v2: References added. v3: References added, published versio
Defective dimerization of FoF1-ATP synthase secondary to glycation favors mitochondrial energy deficiency in cardiomyocytes during aging
Aging; Dicarbonyl stress; MitochondriaEnvelliment; Estrès dicarbonÃlic; MitocondrisEnvejecimiento; Estrés dicarbonÃlico; MitocondriasAged cardiomyocytes develop a mismatch between energy demand and supply, the severity of which determines the onset of heart failure, and become prone to undergo cell death. The FoF1-ATP synthase is the molecular machine that provides >90% of the ATP consumed by healthy cardiomyocytes and is proposed to form the mitochondrial permeability transition pore (mPTP), an energy-dissipating channel involved in cell death. We investigated whether aging alters FoF1-ATP synthase self-assembly, a fundamental biological process involved in mitochondrial cristae morphology and energy efficiency, and the functional consequences this may have. Purified heart mitochondria and cardiomyocytes from aging mice displayed an impaired dimerization of FoF1-ATP synthase (blue native and proximity ligation assay), associated with abnormal mitochondrial cristae tip curvature (TEM). Defective dimerization did not modify the in vitro hydrolase activity of FoF1-ATP synthase but reduced the efficiency of oxidative phosphorylation in intact mitochondria (in which membrane architecture plays a fundamental role) and increased cardiomyocytes’ susceptibility to undergo energy collapse by mPTP. High throughput proteomics and fluorescence immunolabeling identified glycation of 5 subunits of FoF1-ATP synthase as the causative mechanism of the altered dimerization. In vitro induction of FoF1-ATP synthase glycation in H9c2 myoblasts recapitulated the age-related defective FoF1-ATP synthase assembly, reduced the relative contribution of oxidative phosphorylation to cell energy metabolism, and increased mPTP susceptibility. These results identify altered dimerization of FoF1-ATP synthase secondary to enzyme glycation as a novel pathophysiological mechanism involved in mitochondrial cristae remodeling, energy deficiency, and increased vulnerability of cardiomyocytes to undergo mitochondrial failure during aging.This work was supported by the Instituto de Salud Carlos III of the Spanish Ministry of Health (FIS-PI19-01196) and a grant from the Sociedad Española de CardiologÃa (SEC/FEC-INV-BAS 217003
New protein-protein interactions of mitochondrial connexin 43 in mouse heart
Connexin 43 (Cx43), the gap junction protein involved in cell-to-cell coupling in the heart, is also present in the subsarcolemmal fraction of cardiomyocyte mitochondria. It has been described to regulate mitochondrial potassium influx and respiration and to be important for ischaemic preconditioning protection, although the molecular effectors involved are not fully characterized. In this study, we looked for potential partners of mitochondrial Cx43 in an attempt to identify new molecular pathways for cardioprotection. Mass spectrometry analysis of native immunoprecipitated mitochondrial extracts showed that Cx43 interacts with several proteins related with mitochondrial function and metabolism. Among them, we selected for further analysis only those present in the subsarcolemmal mitochondrial fraction and known to be related with the respiratory chain. Apoptosis-inducing factor () and the beta-subunit of the electron-transfer protein (), two proteins unrelated to date with Cx43, fulfilled these conditions, and their interaction with Cx43 was proven by direct and reverse co-immunoprecipitation. Furthermore, a previously unknown molecular interaction between and was established, and protein content and sub-cellular localization appeared to be independent from the presence of Cx43. Our results identify new protein-protein interactions between -Cx43, -Cx43 and - as possible players in the regulation of the mitochondrial redox state
New perspectives on bioactivity of olive oil: evidence from animal models, human interventions and the use of urinary proteomic biomarkers
Olive oil (OO) is the primary source of fat in the Mediterranean diet and has been associated with longevity and a lower incidence of chronic diseases, particularly CHD. Cardioprotective effects of OO consumption have been widely related with improved lipoprotein profile, endothelial function and inflammation, linked to health claims of oleic acid and phenolic content of OO. With CVD being a leading cause of death worldwide, a review of the potential mechanisms underpinning the impact of OO in the prevention of disease is warranted. The current body of evidence relies on mechanistic studies involving animal and cell-based models, epidemiological studies of OO intake and risk factor, small- and large-scale human interventions, and the emerging use of novel biomarker techniques associated with disease risk. Although model systems are important for mechanistic research nutrition, methodologies and experimental designs with strong translational value are still lacking. The present review critically appraises the available evidence to date, with particular focus on emerging novel biomarkers for disease risk assessment. New perspectives on OO research are outlined, especially those with scope to clarify key mechanisms by which OO consumption exerts health benefits. The use of urinary proteomic biomarkers, as highly specific disease biomarkers, is highlighted towards a higher translational approach involving OO in nutritional recommendations
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