Mitochondria Retrograde Signaling and the UPR mt: Where Are We in Mammals?

Mitochondrial unfolded protein response is a form of retrograde signaling that contributes to ensuring the maintenance of quality control of mitochondria, allowing functional integrity of the mitochondrial proteome. When misfolded proteins or unassembled complexes accumulate beyond the folding capacity, it leads to alteration of proteostasis, damages, and organelle/cell dysfunction. Extensively studied for the ER, it was recently reported that this kind of signaling for mitochondrion would also be able to communicate with the nucleus in response to impaired proteostasis. The mitochondrial unfolded protein response (UPR(mt)) is activated in response to different types and levels of stress, especially in conditions where unfolded or misfolded mitochondrial proteins accumulate and aggregate. A specific UPR(mt) could thus be initiated to boost folding and degradation capacity in response to unfolded and aggregated protein accumulation. Although first described in mammals, the UPR(mt) was mainly studied in Caenorhabditis elegans, and accumulating evidence suggests that mechanisms triggered in response to a UPR(mt) might be different in C. elegans and mammals. In this review, we discuss and integrate recent data from the literature to address whether the UPR(mt) is relevant to mitochondrial homeostasis in mammals and to analyze the putative role of integrated stress response (ISR) activation in response to the inhibition of mtDNA expression and/or accumulation of mitochondrial mis/unfolded proteins

Mechanical characterisation of the developing cell wall layers of tension wood fibres by Atomic Force Microscopy

Abstract Trees can generate large mechanical stresses at the stem periphery to control the orientation of their axes. This key factor in the biomechanical design of trees, named “maturation stress”, occurs in wood fibres during cellular maturation when their secondary cell wall thickens. In this study, the spatial and temporal stiffening kinetics of the different cell wall layers were recorded during fibre maturation on a sample of poplar tension wood using atomic force microscopy. The thickening of the different layers was also recorded. The stiffening of the CML, S 1 and S 2 -layers was initially synchronous with the thickening of the S 2 layer and continued a little after the S 2 -layer reached its final thickness as the G-layer begins to develop. In contrast, the global stiffness of the G-layer, which initially increased with its thickening, was almost stable long before it reached its final maximum thickness. A limited radial gradient of stiffness was observed in the G-layer, but it decreased sharply on the lumen side, where the new sub-layers are deposited during cell wall thickening. Although very similar at the ultrastructural and biochemical levels, the stiffening kinetics of the poplar G-layer appears to be very different from that described in maturing bast fibres. Highlight New insights into the changes in mechanical properties within the cell wall of poplar tension wood fibres during maturation have been obtained using atomic force microscopy

alpha-nucleus potentials for the neutron-deficient p nuclei

alpha-nucleus potentials are one important ingredient for the understanding of the nucleosynthesis of heavy neutron-deficient p nuclei in the astrophysical gamma-process where these p nuclei are produced by a series of (gamma,n), (gamma,p), and (gamma,alpha) reactions. I present an improved alpha-nucleus potential at the astrophysically relevant sub-Coulomb energies which is derived from the analysis of alpha decay data and from a previously established systematic behavior of double-folding potentials.Comment: 6 pages, 3 figures, accepted for publication in Phys. Rev.

Constraints on the Variations of the Fundamental Couplings

We reconsider several current bounds on the variation of the fine-structure constant in models where all gauge and Yukawa couplings vary in an interdependent manner, as would be expected in unified theories. In particular, we re-examine the bounds established by the Oklo reactor from the resonant neutron capture cross-section of 149Sm. By imposing variations in \Lambda_{QCD} and the quark masses, as dictated by unified theories, the corresponding bound on the variation of the fine-structure constant can be improved by about 2 orders of magnitude in such theories. In addition, we consider possible bounds on variations due to their effect on long lived \alpha- and \beta-decay isotopes, particularly 147Sm and 187Re. We obtain a strong constraint on \Delta \alpha / \alpha, comparable to that of Oklo but extending to a higher redshift corresponding to the age of the solar system, from the radioactive life-time of 187Re derived from meteoritic studies. We also analyze the astrophysical consequences of perturbing the decay Q values on bound state \beta-decays operating in the s-process.Comment: 25 pages, latex, 5 eps figure

Le diagnostic anténatal modifie-t-il la prise en charge néonatale et le devenir à 1 an des enfants suivis pour atrésie de l’œsophage de type III ?

OBJECTIVE: Evaluate neonatal management and outcome of neonates with either a prenatal or a post-natal diagnosis of EA type III. STUDY DESIGN: Population-based study using data from the French National Register for EA from 2008 to 2010. We compared children with prenatal versus post-natal diagnosis in regards to prenatal, maternal and neonatal characteristics. We define a composite variable of morbidity (anastomotic esophageal leaks, recurrent fistula, stenosis) and mortality at 1 year. RESULTS: Four hundred and eight live births with EA type III were recorded with a prenatal diagnosis rate of 18.1%. Transfer after birth was lower in prenatal subset (32.4% versus 81.5%, P<0.001). Delay between birth and first intervention was not significantly different. Defect size (2cm vs 1.4cm, P<0.001), gastrostomy (21.6% versus 8.7%, P<0.001) and length in neonatal unit care were higher in prenatal subset (47.9 days versus 33.6 days, P<0.001). The composite variables were higher in prenatal diagnosis subset (38.7% vs 26.1%, P=0.044). CONCLUSION: Despite the excellent survival rate of EA, cases with antenatal detection have a higher morbidity related to the EA type (longer gap). Even if it does not modify neonatal management and 1-year outcome, prenatal diagnosis allows antenatal parental counseling and avoids post-natal transfer

Both “illness and temptation of the enemy”: melancholy, the medieval patient and the writings of King Duarte of Portugal (r. 1433–38)

Recent historians have rehabilitated King Duarte of Portugal, previously maligned and neglected, as an astute ruler and philosopher. There is still a tendency, however, to view Duarte as a depressive or a hypochondriac, due to his own description of his melancholy in his advice book, the Loyal Counselor. This paper reassesses Duarte's writings, drawing on key approaches in the history of medicine, such as narrative medicine and the history of the patient. It is important to take Duarte's views on his condition seriously, placing them in the medical and theological contexts of his time and avoiding modern retrospective diagnosis. Duarte's writings can be used to explore the impact of plague, doubt and death on the life of a well-educated and conscientious late-medieval ruler