Subelliptic Li-Yau estimates on three dimensional model spaces

We describe three elementary models in three dimensional subelliptic geometry which correspond to the three models of the Riemannian geometry (spheres, Euclidean spaces and Hyperbolic spaces) which are respectively the SU(2), Heisenberg and SL(2) groups. On those models, we prove parabolic Li-Yau inequalities on positive solutions of the heat equation. We use for that the $\Gamma_{2}$ techniques that we adapt to those elementary model spaces. The important feature developed here is that although the usual notion of Ricci curvature is meaningless (or more precisely leads to bounds of the form $-\infty$ for the Ricci curvature), we describe a parameter $\rho$ which plays the same role as the lower bound on the Ricci curvature, and from which one deduces the same kind of results as one does in Riemannian geometry, like heat kernel upper bounds, Sobolev inequalities and diameter estimates

The subelliptic heat kernel on SU(2): Representations, Asymptotics and Gradient bounds

The Lie group SU(2) endowed with its canonical subriemannian structure appears as a three-dimensional model of a positively curved subelliptic space. The goal of this work is to study the subelliptic heat kernel on it and some related functional inequalities.Comment: Update: Added section + Correction of typo

A constant and similar assembly defect of mitochondrial respiratory chain complex I allows rapid identification of NDUFS4 mutations in patients with Leigh syndrome

AbstractIsolated complex I deficiency is a frequent cause of respiratory chain defects in childhood. In this study, we report our systematic approach with blue native PAGE (BN-PAGE) to study mitochondrial respiratory chain assembly in skin fibroblasts from patients with Leigh syndrome and CI deficiency. We describe five new NDUFS4 patients with a similar and constant abnormal BN-PAGE profile and present a meta-analysis of the literature. All NDUFS4 mutations that have been tested with BN-PAGE result in a constant and similar abnormal assembly profile with a complete loss of the fully assembled complex I usually due to a truncated protein and the loss of its canonical cAMP dependent protein kinase phosphorylation consensus site. We also report the association of abnormal brain MRI images with this characteristic BN-PAGE profile as the hallmarks of NDUFS4 mutations and the first founder NDUFS4 mutations in the North-African population

Electrostatic and electrokinetic contributions to the elastic moduli of a driven membrane

We discuss the electrostatic contribution to the elastic moduli of a cell or artificial membrane placed in an electrolyte and driven by a DC electric field. The field drives ion currents across the membrane, through specific channels, pumps or natural pores. In steady state, charges accumulate in the Debye layers close to the membrane, modifying the membrane elastic moduli. We first study a model of a membrane of zero thickness, later generalizing this treatment to allow for a finite thickness and finite dielectric constant. Our results clarify and extend the results presented in [D. Lacoste, M. Cosentino Lagomarsino, and J. F. Joanny, Europhys. Lett., {\bf 77}, 18006 (2007)], by providing a physical explanation for a destabilizing term proportional to \kps^3 in the fluctuation spectrum, which we relate to a nonlinear ($E^2$) electro-kinetic effect called induced-charge electro-osmosis (ICEO). Recent studies of ICEO have focused on electrodes and polarizable particles, where an applied bulk field is perturbed by capacitive charging of the double layer and drives flow along the field axis toward surface protrusions; in contrast, we predict "reverse" ICEO flows around driven membranes, due to curvature-induced tangential fields within a non-equilibrium double layer, which hydrodynamically enhance protrusions. We also consider the effect of incorporating the dynamics of a spatially dependent concentration field for the ion channels.Comment: 22 pages, 10 figures. Under review for EPJ

Protective role of vitamin B6 (PLP) against DNA damage in Drosophila models of type 2 diabetes

Growing evidence shows that improper intake of vitamin B6 increases cancer risk and several studies indicate that diabetic patients have a higher risk of developing tumors. We previously demonstrated that in Drosophila the deficiency of Pyridoxal 5' phosphate (PLP), the active form of vitamin B6, causes chromosome aberrations (CABs), one of cancer prerequisites, and increases hemolymph glucose content. Starting from these data we asked if it was possible to provide a link between the aforementioned studies. Thus, we tested the effect of low PLP levels on DNA integrity in diabetic cells. To this aim we generated two Drosophila models of type 2 diabetes, the first by impairing insulin signaling and the second by rearing flies in high sugar diet. We showed that glucose treatment induced CABs in diabetic individuals but not in controls. More interestingly, PLP deficiency caused high frequencies of CABs in both diabetic models demonstrating that hyperglycemia, combined to reduced PLP level, impairs DNA integrity. PLP-depleted diabetic cells accumulated Advanced Glycation End products (AGEs) that largely contribute to CABs as α-lipoic acid, an AGE inhibitor, rescued not only AGEs but also CABs. These data, extrapolated to humans, indicate that low PLP levels, impacting on DNA integrity, may be considered one of the possible links between diabetes and cancer

Burden of liver disease progression in hospitalized patients with type 2 diabetes mellitus

BACKGROUND AND AIMS: There are uncertainties on the burden of liver disease in patients with type-2 diabetes (T2D). METHODS: We measured adjusted hazard ratios of liver disease progression to hepatocellular cancer and/or decompensated cirrhosis in a 2010-2020 retrospective, bicentric, longitudinal, cohort of 52,066 hospitalized patients with T2D. RESULTS: Mean age was 64±14 years and 58% were men. Alcohol use disorders accounted for 57% of liver-related complications and were associated with all liver-related risk factors. Non-metabolic liver-related risk factors accounted for 37% of the liver burden. T2D control was not associated with liver disease progression. The incidence (95% confidence interval) of liver-related complications and of competing mortality were 3.9 (3.5-4.3) and 27.8 (26.7-28.9) per 1000 person-years at risk, respectively. The cumulative incidence of liver disease progression exceeded the cumulative incidence of competing mortality only in the presence of a well-identified risk factors of liver disease progression, including alcohol use. The incidence of hepatocellular cancer was 0.3 (95% CI, 0.1-0.5) per 1000 person-year in patients with obesity and it increased with age. The adjusted hazard ratios of liver disease progression were 55.7 (40.5-76.6), 3.5 (2.3-5.2), 8.9 (6.9-11.5), and 1.5 (1.1-2.1), for alcoholic liver disease, alcohol use disorders without alcoholic liver disease, non-metabolic liver-related risk factors, and obesity, respectively. The attributable fractions of alcohol use disorders, non-metabolic liver risk-related risk factors, and obesity to the liver burden were 55%, 14%, and 7%, respectively. CONCLUSIONS: In this analysis of data from two hospital-based cohorts of patients with T2D, alcohol use disorders, rather than obesity, contributed to most of the liver burden. These results suggest that patients with T2D should be advised to drink minimal amounts of alcohol. LAY SUMMARY: • There is uncertainty on the burden of liver-related complications in patients with type-2 diabetes • We studied the risks of liver cancer and complications of liver disease in over 50,000 patients with type-2 diabetes • We found that alcohol was the main factor associated with complications of liver disease • This finding has major implications on the alcohol advice given to patients with type-2 diabetes

The Comparison between Circadian Oscillators in Mouse Liver and Pituitary Gland Reveals Different Integration of Feeding and Light Schedules

The mammalian circadian system is composed of multiple peripheral clocks that are synchronized by a central pacemaker in the suprachiasmatic nuclei of the hypothalamus. This system keeps track of the external world rhythms through entrainment by various time cues, such as the light-dark cycle and the feeding schedule. Alterations of photoperiod and meal time modulate the phase coupling between central and peripheral oscillators. In this study, we used real-time quantitative PCR to assess circadian clock gene expression in the liver and pituitary gland from mice raised under various photoperiods, or under a temporal restricted feeding protocol. Our results revealed unexpected differences between both organs. Whereas the liver oscillator always tracked meal time, the pituitary circadian clockwork showed an intermediate response, in between entrainment by the light regimen and the feeding-fasting rhythm. The same composite response was also observed in the pituitary gland from adrenalectomized mice under daytime restricted feeding, suggesting that circulating glucocorticoids do not inhibit full entrainment of the pituitary clockwork by meal time. Altogether our results reveal further aspects in the complexity of phase entrainment in the circadian system, and suggest that the pituitary may host oscillators able to integrate multiple time cues

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The human OPA1delTTAG mutation induces premature age-related systemic neurodegeneration in mouse

Dominant optic atrophy is a rare inherited optic nerve degeneration caused by mutations in the mitochondrial fusion gene OPA1. Recently, the clinical spectrum of dominant optic atrophy has been extended to frequent syndromic forms, exhibiting various degrees of neurological and muscle impairments frequently found in mitochondrial diseases. Although characterized by a specific loss of retinal ganglion cells, the pathophysiology of dominant optic atrophy is still poorly understood. We generated an Opa1 mouse model carrying the recurrent Opa1(delTTAG) mutation, which is found in 30% of all patients with dominant optic atrophy. We show that this mouse displays a multi-systemic poly-degenerative phenotype, with a presentation associating signs of visual failure, deafness, encephalomyopathy, peripheral neuropathy, ataxia and cardiomyopathy. Moreover, we found premature age-related axonal and myelin degenerations, increased autophagy and mitophagy and mitochondrial supercomplex instability preceding degeneration and cell death. Thus, these results support the concept that Opa1 protects against neuronal degeneration and opens new perspectives for the exploration and the treatment of mitochondrial diseases

Intertwining relations for one-dimensional diffusions and application to functional inequalities

International audienceFollowing the recent work [13] fulfilled in the discrete case, we pro- vide in this paper new intertwining relations for semigroups of one-dimensional diffusions. Various applications of these results are investigated, among them the famous variational formula of the spectral gap derived by Chen and Wang [15] together with a new criterion ensuring that the logarithmic Sobolev inequality holds. We complete this work by revisiting some classical examples, for which new estimates on the optimal constants are derived