Candida albicans Hyphal Extracellular Vesicles Are Different from Yeast Ones, Carrying an Active Proteasome Complex and Showing a Different Role in Host Immune Response.

Candida albicans is the principal causative agent of lethal fungal infections, predominantly in immunocompromised hosts. Extracellular vesicles (EVs) have been described as crucial in the interaction of microorganisms with their host. Since the yeast-to-hypha transition is an important virulence trait with great impact in invasive candidiasis (IC), we have addressed the characterization of EVs secreted by hyphal cells (HEVs) from C. albicans, comparing them to yeast EVs (YEVs). YEVs comprised a larger population of bigger EVs with mainly cell wall proteins, while HEVs were smaller, in general, and had a much higher protein diversity. YEVs were able to rescue the sensitivity of a cell wall mutant against calcofluor white, presumably due to the larger amount of cell wall proteins they contained. On the other hand, HEVs also contained many cytoplasmic proteins related to protein metabolism and intracellular protein transport and the endosomal sorting complexes required for transport (ESCRT) pathway related to exosome biogenesis, pointing to an intracellular origin of HEVs. Interestingly, an active 20S proteasome complex was secreted exclusively in HEVs. Moreover, HEVs contained a greater number of virulence-related proteins. As for their immunogenic role, both types of EV presented immune reactivity with human sera from patients suffering invasive candidiasis; however, under our conditions, only HEVs showed a cytotoxic effect on human macrophages and could elicit the release of tumor necrosis factor alpha (TNF-α) by these macrophages. IMPORTANCE This first analysis of HEVs of C. albicans has shown clear differences between them and the YEVs of C. albicans, showing their relevance and possible use in the discovery of new diagnostic markers and treatment targets against C. albicans infections. The data obtained point to different mechanisms of biogenesis of YEVs and HEVs, as well as different involvements in cell biology and host interaction. YEVs played a more relevant role in cell wall maintenance, while HEVs were more closely related to virulence, as they had greater effects on human immune cells. Importantly, an active 20S proteosome complex was described as a fungal-EV cargo. A deeper study of its role and those of many other proteins exclusively detected in HEVs and involved in different relevant biological processes of this fungus could open up interesting new areas of research in the battle against C. albicans

News, intelligence and 'little lies' : rumours between the Cherokees and the British 1740-1785

Rumour and information are one of the most fundamental ways in which people engage with one another. Rumours can change the way that individuals and groups see each other and the actions that they take. Sociologists and anthropologists have long used rumour as a way to explore the experiences of their subjects. Historians of early America have, in recent years, begun to make use of rumour as a way of examining the, often hidden, world of interactions between American Indians and white Europeans. This thesis will expand upon this work by exploring the changing role of rumour within an intercultural relationship over several decades. This thesis will focus on rumour in the relationship between the Cherokee Nation and the colonists of the British Empire. It will explore the ways that rumour influenced these interactions and the impact of the rapidly changing backcountry environment of the latter eighteenth century, both on rumour and on the wider Cherokee- British relationship. This thesis will argue that rumour shifted in the course of the eighteenth century from being a diplomatic tool which could be used- either to create further panic and confusion or to calm and smooth over problems- to an uncontrollable force which would deepen and exacerbate the divisions between Cherokees and the British. Rumour played an important role in politics and society in the eighteenth century backcountry and its changing function offers a way to better understand the shifting currents of life in early America

Aspects of the planetary Birkhoff normal form

The discovery in [G. Pinzari. PhD thesis. Univ. Roma Tre. 2009], [L. Chierchia and G. Pinzari, Invent. Math. 2011] of the Birkhoff normal form for the planetary many--body problem opened new insights and hopes for the comprehension of the dynamics of this problem. Remarkably, it allowed to give a {\sl direct} proof of the celebrated Arnold's Theorem [V. I. Arnold. Uspehi Math. Nauk. 1963] on the stability of planetary motions. In this paper, using a "ad hoc" set of symplectic variables, we develop an asymptotic formula for this normal form that may turn to be useful in applications. As an example, we provide two very simple applications to the three-body problem: we prove a conjecture by [V. I. Arnold. cit] on the "Kolmogorov set"of this problem and, using Nehoro{\v{s}}ev Theory [Nehoro{\v{s}}ev. Uspehi Math. Nauk. 1977], we prove, in the planar case, stability of all planetary actions over exponentially-long times, provided mean--motion resonances are excluded. We also briefly discuss perspectives and problems for full generalization of the results in the paper.Comment: 44 pages. Keywords: Averaging Theory, Birkhoff normal form, Nehoro{\v{s}}ev Theory, Planetary many--body problem, Arnold's Theorem on the stability of planetary motions, Properly--degenerate kam Theory, steepness. Revised version, including Reviewer's comments. Typos correcte

Integral quantification accuracy estimation for reporter ion-based quantitative proteomics (iQuARI)

With the increasing popularity of comparative studies of complex proteomes, reporter ion-based quantification methods such as iTRAQ and TMT have become common-place in biological studies. Their appeal derives from simple multiplexing and quantification of several samples at reasonable cost. This advantage yet comes with a known shortcoming: precursors of different species can interfere, thus reducing the quantification accuracy. Recently, two methods were brought to the community alleviating the amount of interference via novel experimental design. Before considering setting up a new workflow, tuning the system, optimizing identification and quantification rates, etc. one legitimately asks: is it really worth the effort, time and money? The question is actually not easy to answer since the interference is heavily sample and system dependent. Moreover, there was to date no method allowing the inline estimation of error rates for reporter quantification. We therefore introduce a method called iQuARI to compute false discovery rates for reporter ion based quantification experiments as easily as Target/Decoy FDR for identification. With it, the scientist can accurately estimate the amount of interference in his sample on his system and eventually consider removing shadows subsequently, a task for which reporter ion quantification might not be the solution of choice