Loss of Mitochondrial Membrane Potential Triggers the Retrograde Response Extending Yeast Replicative Lifespan

In the budding yeast Saccharomyces cerevisiae, loss of mitochondrial DNA (rho0) can induce the retrograde response under appropriate conditions, resulting in increased replicative lifespan (RLS). Although the retrograde pathway has been extensively elaborated, the nature of the mitochondrial signal triggering this response has not been clear. Mitochondrial membrane potential (MMP) was severely reduced in rho0 compared to rho+ cells, and RLS was concomitantly extended. To examine the role of MMP in the retrograde response, MMP was increased in the rho0 strain by introducing a mutation in the ATP1 gene, and it was decreased in rho+ cells by deletion of COX4. The ATP1-111 mutation in rho0 cells partially restored the MMP and reduced mean RLS to that of rho+ cells. COX4 deletion decreased MMP in rho+ cells to a value intermediate between rho+ and rho0 cells and similarly increased RLS. The increase in expression of CIT2, the diagnostic gene for the retrograde response, seen in rho0 cells, was substantially suppressed in the presence of the ATP1-111 mutation. In contrast, CIT2 expression increased in rho+ cells on deletion of COX4. Activation of the retrograde response results in the translocation of the transcription factor Rtg3 from the cytoplasm to the nucleus. Rtg3–GFP translocation to the nucleus was directly observed in rho0 and rho+ cox4Δ cells, but it was blunted in rho0 cells with the ATP1-111 mutation. We conclude that a decrease in MMP is the signal that initiates the retrograde response and leads to increased RLS

Differential gene expression signatures for cell wall integrity found in chitin synthase II (chs2Δ) and myosin II (myo1Δ) deficient cytokinesis mutants of Saccharomyces cerevisiae

<p>Abstract</p> <p>Background</p> <p>Myosin II-dependent contraction of the cytokinetic ring and primary septum formation by chitin synthase II are interdependent processes during cytokinesis in <it>Saccharomyces cerevisiae</it>. Hence, null mutants of myosin II <it>(myo1</it>Δ<it>) </it>and chitin synthase II <it>(chs2</it>Δ<it>) </it>share multiple morphological and molecular phenotypes. To understand the nature of their interdependent functions, we will seek to identify genes undergoing transcriptional regulation in <it>chs2</it>Δ strains and to establish a transcription signature profile for comparison with <it>myo1</it>Δ strains.</p> <p>Results</p> <p>A total of 467 genes were commonly regulated between <it>myo1Δ </it>and <it>chs2Δ </it>mutant strains (p ≤ 0.01). Common regulated biological process categories identified by Gene Set Enrichment Analysis (GSEA) in both gene expression profiles were: protein biosynthesis, RNA processing, and stress response. Expression of 17/20 genes in the main transcriptional fingerprint for cell wall stress was confirmed in the <it>chs2Δ </it>strain versus 5/20 for the <it>myo1Δ </it>strain. One of these genes, <it>SLT2/MPK1</it>, was up-regulated in both strains and both strains accumulated the hyperphosphorylated form of Slt2p thereby confirming that the <it>PKC1 </it>cell wall integrity pathway (CWIP) was activated by both mutations. The <it>SLT2/MPK1 </it>gene, essential for <it>myo1Δ </it>strains, was not required in the <it>chs2Δ </it>strain.</p> <p>Conclusion</p> <p>Comparison of the <it>chs2Δ </it>and <it>myo1</it>Δ gene expression profiles revealed similarities in the biological process categories that respond to the <it>chs2Δ </it>and <it>myo1</it>Δ gene mutations. This supports the view that these mutations affect a common function in cytokinesis. Despite their similarities, these mutants exhibited significant differences in expression of the main transcriptional fingerprint for cell wall stress and their requirement of the CWIP for survival.</p

High-temperature performance of mortars and concretes based on alkali-activated slag/metakaolin blends

This paper assesses the performance of mortars and concretes based on alkali activated granulated blastfurnace slag (GBFS)/metakaolin (MK) blends when exposed to high temperatures. High stability of mortars with contents of MK up to 60 wt.% when exposed to 600 °C is identified, with residual strengths of 20 MPa following exposure to this temperature. On the other hand, exposure to higher temperatures leads to cracking of the concretes, as a consequence of the high shrinkage of the binder matrix and the restraining effects of the aggregate, especially in those specimens with binders containing high MK content. A significant difference is identified between the water absorption properties of mortars and concretes, and this is able to be correlated with divergences in their performance after exposure to high temperatures. This indicates that the performance at high temperatures of alkali-activated mortars is not completely transferable to concrete, because the systems differ in permeability. The differences in the thermal expansion coefficients between the binder matrix and the coarse aggregates contribute to the macrocracking of the material, and the consequent reduction of mechanical properties

Why early collective action pays off: evidence from setting Protected Geographical Indications

AbstractThe registration of Geographical Indications (GIs) under the European Union (EU) legislation requires collective action and considerable efforts borne by multiple actors such as producers, processors, public authorities and research centers. We analyze their efforts, risks and benefits by comparing two EU GI registration processes in Italy and Austria, namely the Sorana bean Protected Geographical Indication (PGI) and the Perry from Mostviertel PGI. Results from the institutional and transaction costs analysis suggest that intensive interaction for solving conflicting interests, negotiating quality standards and defining common rules might pay off in indirect benefits and reduced risks. In particular, an inclusion of diverse and heterogeneous interest groups and a high degree of direct enterprise participation along the GI application process (as observed in the Italian case) generate benefits such as trust and social cohesion, which then support the actual use of the GI label and a better implementation of associated quality standards. A supportive legal framework with assistance from public authorities can back up the community of producers not only in technical aspects, but also as mediators when conflicts seem to be difficult to solve. As there seems to be a positive relationship between the intensity and effectiveness of collective action and the likelihood of achieving broadly accepted standards and social cohesion needed for successful GI implementation, the question for future research would not be how to avoid collective efforts but how to effectively organize the interaction among heterogeneous producer groups

Método Computacional para la Medición Automática del área de Quistes del Parásito Toxoplasma Gondii

Toxoplasma gondii;, es un organismo intracelular que puede causar infecciones parasitarias, afectando al ser humano e invadiendo tejidos como el cerebro. En pacientes inmunocomprometidos entre ellos con VIHSIDA, T. gondii ;es capaz de reactivar la infección y causar encefalitis toxoplásmica. La infección crónica por T. gondii;, se caracteriza por la formación de un quiste que le permite al patógeno, mantenerse en el huésped por largos periodos e incluso por todo el tiempo de vida del mismo. En ocasiones el quiste sufre rupturas y libera bradizoitos, quienes tienen la capacidad de formar nuevos quistes, de ahí la variedad en el tamaño de los mismos. La medición del tamaño de un quiste contribuye con información sobre la relación del parásito y la respuesta immune del huésped, esto permitirá la búsqueda de sustancias que inhiban el proceso de formación quístico. Este trabajo tuvo como objetivo desarrollar un algoritmo para la determinación del área de quistes de T. gondii ;provenientes de material biológico de consumo humano, mediante el Toolbox Image Processing del software Matlab 2013. El algoritmo determinó el área de varios quistes del parásito, indicando la medida específica en pixeles y posteriormente la trazabilidad a una medida dimensional dada en nanometros cuadrados (nm2)

Follow-up of a new titanium-coated polyetheretherketone cage for the cervical spine

Poly-ether-ether-ketone (PEEK) cages have lower modulus of elasticity when compared with Titanium (TTN) cages. This suggests that PEEK-cages could show a lower rate of subsidence after anterior cervical discectomy-fusion (ACDF) and might lead to a lower loss of correction. We investigated the one to five year-results of standalone PEEK-TTN-porous coated cages in a patient cohort from 2014 to 2017. The patients underwent single-level ACDF for disc herniation and degenerative discopathy. Clinical and radiological outcome were assessed in 50 eligible patients after a mean of 27 months. Results: Solid arthrodesis was found in 84%. Neck disability index (NDI), and visual analogue scale (VAS) of neck and arm show comparable results to the literature. Conclusions: Clinical and radiological outcomes of ACDF with PEEK-body-cages with a porous coated surface show good bony integration. The modulus of elasticity, design, shape, size, cage surface architecture, as well as bone density, endplate preparation, radical microdiscectomy and distraction during surgery should be considered as important factors influencing the clinical results. One main advantage, over titanium cages, is the absence of MRI artifacts, allowing an excellent postoperative follow-up. inferior clinical outcome compared with bone grafts due to a higher elasticity modulus, which could result in cage subsidence.8 Nevertheless, due to structural properties, TTN implants are likely to provide a good osseo-integration9 and several clinical studies demonstrate successful results after implantation of TTN-cages.10-13 PEEKcages have a modulus of elasticity closely resembling that of cortical bone, which might lead to advantages in load sharing and stress distribution. This might reduce the subsidence rate with an improved segmental correction in the long term and a potentially higher fusion rate.14-16 A direct comparison of cervical TTNand PEEKcages in a clinical setting is very rarely found in the literature, 16, 17 and even less studies consequently compare the radiological results.16, 17 The latter studies showed the PEEK-implants being superior in maintaining cervical interspace height and achieving radiographic fusion, 16, 17 even suggesting to cease the application of TTN-cages in cervical spine surgery.16 A solution in-between are newer cages that combine the benefit of both materials: PEEK-body cages plasma-sprayed with a porous titanium surface which is tightly bonded to the PEEK surface.18, 19 On TTN alloy substrates, osteoblasts exhibit a more differentiated phenotype and increased bone morphogenetic protein production than on poly-ether-ether-ketone.20 A group of Japanese surgeons found that TTN-coated PEEK cages exhibit radiographic signs of bone on-growth, as represented by vertebral cancellous condensation around the cage, compared with that around the uncoated PEEK cage.21 Therefore, a TTN-coated PEEK cage may have the potential to promote solid fusion and to improve clinical outcomes in cervical interbody fusion surgery. This keeps the ideal elasticity modulus close to a bonelike elasticity modulus and offers a highly biocompatible surface that is well tolerated by bone and allows its ongrowth to the porous surface. The aim of the present study is to assess clinical and radiological results of CeSpace XP®, a titanium-coated PEEK cage

Clinical applications of pharmacogenomics

Indexación: Scopus.Pharmacogenomics is an emergent field aimed at tailoring pharmacological therapy. Genetic polymorphisms can modify the expression and function of enzymes and proteins involved in drug metabolism, affecting absorption, distribution, biotransformation and excretion as well as the drug-target interaction. Therefore, the presence of allelic variants will classify people as poor, extensive or rapid/ultra rapid metabolizers, modifying drug efficacy and safety. In this work, the state of art in relation to this discipline is presented and the genetic variants of enzymes that are involved in drug pharmacokinetics or pharmacodynamics are described. The effects of these variants on the therapeutic response to drugs used in our country are also discussed.http://ref.scielo.org/4y6n8