Acetylated α-Tubulin and α-Synuclein: Physiological Interplay and Contribution to α-Synuclein Oligomerization

Emerging evidence supports that altered α-tubulin acetylation occurs in Parkinson’s disease (PD), a neurodegenerative disorder characterized by the deposition of α-synuclein fibrillary aggregates within Lewy bodies and nigrostriatal neuron degeneration. Nevertheless, studies addressing the interplay between α-tubulin acetylation and α-synuclein are lacking. Here, we investigated the relationship between α-synuclein and microtubules in primary midbrain murine neurons and the substantia nigra of post-mortem human brains. Taking advantage of immunofluorescence and Proximity Ligation Assay (PLA), a method allowing us to visualize protein–protein interactions in situ, combined with confocal and super-resolution microscopy, we found that α-synuclein and acetylated α-tubulin colocalized and were in close proximity. Next, we employed an α-synuclein overexpressing cellular model and tested the role of α-tubulin acetylation in α-synuclein oligomer formation. We used the α-tubulin deacetylase HDAC6 inhibitor Tubacin to modulate α-tubulin acetylation, and we evaluated the presence of α-synuclein oligomers by PLA. We found that the increase in acetylated α-tubulin significantly induced α-synuclein oligomerization. In conclusion, we unraveled the link between acetylated α-tubulin and α-synuclein and demonstrated that α-tubulin acetylation could trigger the early step of α-synuclein aggregation. These data suggest that the proper regulation of α-tubulin acetylation might be considered a therapeutic strategy to take on PD

Crackling Noise, Power Spectra and Disorder Induced Critical Scaling

Crackling noise is observed in many disordered non-equilibrium systems in response to slowly changing external conditions. Examples range from Barkhausen noise in magnets to acoustic emission in martensites to earthquakes. Using the non-equilibrium random field Ising model, we derive universal scaling predictions for the dependence of the associated power spectra on the disorder and field sweep rate, near an underlying disorder-induced non-equilibrium critical point. Our theory applies to certain systems in which the crackling noise results from avalanche-like response to a (slowly) increasing external driving force, and is characterized by a broad power law scaling regime of the power spectra. We compute the critical exponents and discuss the relevance of the results to experiments.Comment: 27 Latex Pages, 14 eps figure

Electrical anisotropy in high-Tc granular superconductors in a magnetic field

We propose an analytical model devoted to explain the anisotropy of the electrical resistance observed below the critical temperature in granular high-Tc superconductors submitted to a magnetic field H. Reported experimental results obtained on a YBCO sample show that the superconducting transition occurs in two stages, with a steep drop of the resistance at Tc and a subsequent, smoother decrease. In this second stage, the resistance versus temperature curve is strongly dependent not only on the field intensity, but also on the angle between H and the macroscopic current density j. We start from the assumption that the resistance below Tc is mainly due to the weak links between grains. In the model, weak links are thought of as flat surface elements separating adjacent grains. We calculate the probability for a weak link to undergo the transition to the resistive state as a function of the angle it makes with the external magnetic field H and the macroscopic current density j. In doing this, an important role is given to the strong nonuniformity of the local magnetic field within the specimen, due to the effect of the screening supercurrents flowing on the surface of the grains. Finally, we calculate the electrical resistance of the sample in the two cases H⊥j and H∥j. The predictions of this simple model turn out to be in reasonable agreement with reported experimental results obtained on a YBCO granular specimen

Molecular investigation of isolates from a multistate polymicrobial outbreak associated with contaminated total parenteral nutrition in Brazil

Background: Between November 2013 and June 2014, 56 cases of bacteremia (15 deaths) associated with the use of Total Parenteral Nutrition (TPN) and/or calcium gluconate (CG) were reported in four Brazilian states. Methods: We analyzed 73 bacterial isolates from four states: 45 from blood, 25 from TPN and three from CG, originally identified as Acinetobacter baumannii, Rhizobium radiobacter, Pantoea sp. or Enterobacteriaceae using molecular methods. Results: The first two bacterial species were confirmed while the third group of species could not be identified using standard identification protocols. These isolates were subsequently identified by Multi-Locus Sequence Analysis as Phytobacter diazotrophicus, a species related to strains from similar outbreaks in the United States in the 1970’s. Within each species, TPN and blood isolates proved to be clonal, whereas the R. radiobacter isolates retrieved from CG were found to be unrelated. Conclusion: This is the first report of a three-species outbreak caused by TPN contaminated with A. baumannii, R. radiobacter and P. diazotrophicus. The concomitant presence of clonal A. baumannii and P. diazotrophicus isolates in several TPN and blood samples, as well as the case of one patient, where all three different species were isolated simultaneously, suggest that the outbreak may be ascribed to a discrete contamination of TPN. In addition, this study highlights the clinical relevance of P. diazotrophicus, which has been involved in outbreaks in the past, but was often misidentified as P. agglomerans

Demagnetization via Nucleation of the Nonequilibrium Metastable Phase in a Model of Disorder

We study both analytically and numerically metastability and nucleation in a two-dimensional nonequilibrium Ising ferromagnet. Canonical equilibrium is dynamically impeded by a weak random perturbation which models homogeneous disorder of undetermined source. We present a simple theoretical description, in perfect agreement with Monte Carlo simulations, assuming that the decay of the nonequilibrium metastable state is due, as in equilibrium, to the competition between the surface and the bulk. This suggests one to accept a nonequilibrium "free-energy" at a mesoscopic/cluster level, and it ensues a nonequilibrium "surface tension" with some peculiar low-T behavior. We illustrate the occurrence of intriguing nonequilibrium phenomena, including: (i) Noise-enhanced stabilization of nonequilibrium metastable states; (ii) reentrance of the limit of metastability under strong nonequilibrium conditions; and (iii) resonant propagation of domain walls. The cooperative behavior of our system may also be understood in terms of a Langevin equation with additive and multiplicative noises. We also studied metastability in the case of open boundaries as it may correspond to a magnetic nanoparticle. We then observe burst-like relaxation at low T, triggered by the additional surface randomness, with scale-free avalanches which closely resemble the type of relaxation reported for many complex systems. We show that this results from the superposition of many demagnetization events, each with a well- defined scale which is determined by the curvature of the domain wall at which it originates. This is an example of (apparent) scale invariance in a nonequilibrium setting which is not to be associated with any familiar kind of criticality.Comment: 26 pages, 22 figure

Molecular investigation of isolates from a multistate polymicrobial outbreak associated with contaminated total parenteral nutrition in Brazil

Background: Between November 2013 and June 2014, 56 cases of bacteremia (15 deaths) associated with the use of Total Parenteral Nutrition (TPN) and/or calcium gluconate (CG) were reported in four Brazilian states. Methods: We analyzed 73 bacterial isolates from four states: 45 from blood, 25 from TPN and three from CG, originally identified as Acinetobacter baumannii, Rhizobium radiobacter, Pantoea sp. or Enterobacteriaceae using molecular methods. Results: The first two bacterial species were confirmed while the third group of species could not be identified using standard identification protocols. These isolates were subsequently identified by Multi-Locus Sequence Analysis as Phytobacter diazotrophicus, a species related to strains from similar outbreaks in the United States in the 1970’s. Within each species, TPN and blood isolates proved to be clonal, whereas the R. radiobacter isolates retrieved from CG were found to be unrelated. Conclusion: This is the first report of a three-species outbreak caused by TPN contaminated with A. baumannii, R. radiobacter and P. diazotrophicus. The concomitant presence of clonal A. baumannii and P. diazotrophicus isolates in several TPN and blood samples, as well as the case of one patient, where all three different species were isolated simultaneously, suggest that the outbreak may be ascribed to a discrete contamination of TPN. In addition, this study highlights the clinical relevance of P. diazotrophicus, which has been involved in outbreaks in the past, but was often misidentified as P. agglomerans

Games people play with brands: An application of Transactional Analysis to marketplace relationships.

Relationships have been normalised in marketing theory as mutuality beneficial, long-term dyads. This obscures their emotional content, ignores critical conceptualisations of corporate exploitation, and fails to capture the range of possible marketplace relationship forms. In this paper we offer Berne’s (1964) Transactional Analysis (TA) as a way to uncover the biographical psychology that informs marketplace relationship structures and their accompanying emotions, and to provide a critique of such arrangements. We first explain TA, its origins, its relationship with psychoanalysis, its limitations, and contemporary extensions beyond therapy. We then present the structural basis of marketplace relationships from a TA perspective, before illustrating how TA Game Analysis can be applied through an analysis of the iPhone and related mobile phone contracts, and the Games If I didn’t Love Apple and Smallprint. Finally we discuss the implications of such an approach for transforming market practices based on recognition of Marketplace Games and their modification