Ydj1 governs fungal morphogenesis and stress response, and facilitates mitochondrial protein import via Mas1 and Mas2

We thank Zhen-Yuan Lin for help in the preparation of the AP-MS samples, and Cathy Collins for technical assistance. MDL is supported by a Sir Henry Wellcome Postdoctoral Fellowship (Wellcome Trust 096072), LEC is supported by a Canada Research Chair in Microbial Genomics and Infectious Disease and by Cana-dian Institutes of Health Research (CIHR) Grants MOP-119520 and MOP-86452. OK is supported by National Insti-tutes of Health grant 5R01GM108975. A-CG is supported by a CIHR Foundation Grant (FDN143301), Genome Cana-da Genomics Innovation Network (GIN) Node and Tech-nical Development Grants, and a Canada Research Chair in Functional Proteomics. J-PL was supported by a TD Bank Health Research Fellowship at the Lunenfeld-Tanenbaum Research Institute and by a Scholarship for the Next Gen-eration of Scientists from the Cancer Research Society. JLX is supported by a CIHR – Frederick Banting and Charles Best Canada Graduate Scholarship. The funding agencies had no role in the study design, data collection and inter-pretation, or the decision to submit the work for publication.Peer reviewedPublisher PD

Candida albicans Is Resistant to Polyglutamine Aggregation and Toxicity

Acknowledgments We thank the Donnelly Sequencing Centre for sequencing, and Jonathan Krieger at the SikKids Proteomics, Analytics, Robotics & Chemical Biology Centre at The Hospital for Sick Children for mass spectrometry analysis. M.D.L. is supported by a Sir Henry Wellcome Postdoctoral Fellowship (Wellcome Trust grant 096072), T.K. is supported by a Queen Elizabeth II Graduate Scholarship in Science and Technology (University of Toronto), M.L.D. is supported by a Canadian Institutes of Health Research (CIHR) Operating grant 325538, L.E.C. is supported by a Canada Research Chair in Microbial Genomics and Infectious Disease, by CIHR grants MOP-119520 and MOP-86452, and by the Natural Sciences and Engineering Research Council (NSERC) of Canada (grants 06261 and 462167).Peer reviewedPublisher PD

Hsp90 governs dispersion and drug resistance of fungal biofilms

Fungal biofilms are a major cause of human mortality and are recalcitrant to most treatments due to intrinsic drug resistance. These complex communities of multiple cell types form on indwelling medical devices and their eradication often requires surgical removal of infected devices. Here we implicate the molecular chaperone Hsp90 as a key regulator of biofilm dispersion and drug resistance. We previously established that in the leading human fungal pathogen, Candida albicans, Hsp90 enables the emergence and maintenance of drug resistance in planktonic conditions by stabilizing the protein phosphatase calcineurin and MAPK Mkc1. Hsp90 also regulates temperature-dependent C. albicans morphogenesis through repression of cAMP-PKA signalling. Here we demonstrate that genetic depletion of Hsp90 reduced C. albicans biofilm growth and maturation in vitro and impaired dispersal of biofilm cells. Further, compromising Hsp90 function in vitro abrogated resistance of C. albicans biofilms to the most widely deployed class of antifungal drugs, the azoles. Depletion of Hsp90 led to reduction of calcineurin and Mkc1 in planktonic but not biofilm conditions, suggesting that Hsp90 regulates drug resistance through different mechanisms in these distinct cellular states. Reduction of Hsp90 levels led to a marked decrease in matrix glucan levels, providing a compelling mechanism through which Hsp90 might regulate biofilm azole resistance. Impairment of Hsp90 function genetically or pharmacologically transformed fluconazole from ineffectual to highly effective in eradicating biofilms in a rat venous catheter infection model. Finally, inhibition of Hsp90 reduced resistance of biofilms of the most lethal mould, Aspergillus fumigatus, to the newest class of antifungals to reach the clinic, the echinocandins. Thus, we establish a novel mechanism regulating biofilm drug resistance and dispersion and that targeting Hsp90 provides a much-needed strategy for improving clinical outcome in the treatment of biofilm infections

A vision of the farming sector’s future: What is in there for farmers in the time of the second machine age?

Recent technological advances both on the farm and in the lab are boosting not only the efficiency of modern farming but have made it also more independent form nature than ever before. Increasingly affordable and accessible new technologies are helping us to better understand and ‘manage’ nature and thus, for first time in history farming is becoming as any other industry - susceptible to specialisation and economies of scale. This in turn, besides increases in productivity and the minimum efficient scale, leads to fundamental organisational change, away from traditional family farms and towards corporate forms with the associated implications for employment and rural livelihoods. Recent evidence from the digitalisation in agriculture suggest that new technologies require developing capabilities in abstract and analytical skills substituting skills in routine tasks. However, this is not the end game for farmers; new partnerships between technology providers and agribusiness players emerge as digitalisation and connectivity become a strategic issue. Thus, while the first Industrial Revolution led to machines replacing ‘muscles’ the new Digital Revolution is leading to machines replacing ‘brains and souls’, and it may eventually end family farming as we know it

Abstract basins of attraction

Abstract basins appear naturally in different areas of several complex variables. In this survey we want to describe three different topics in which they play an important role, leading to interesting open problems

Pharmacological targeting of cognitive impairment in depression: recent developments and challenges in human clinical research

Impaired cognition is often overlooked in the clinical management of depression, despite its association with poor psychosocial functioning and reduced clinical engagement. There is an outstanding need for new treatments to address this unmet clinical need, highlighted by our consultations with individuals with lived experience of depression. Here we consider the evidence to support different pharmacological approaches for the treatment of impaired cognition in individuals with depression, including treatments that influence primary neurotransmission directly as well as novel targets such as neurosteroid modulation. We also consider potential methodological challenges in establishing a strong evidence base in this area, including the need to disentangle direct effects of treatment on cognition from more generalised symptomatic improvement and the identification of sensitive, reliable and objective measures of cognition

Planning the Future of U.S. Particle Physics (Snowmass 2013): Chapter 4: Cosmic Frontier

These reports present the results of the 2013 Community Summer Study of the APS Division of Particles and Fields ("Snowmass 2013") on the future program of particle physics in the U.S. Chapter 4, on the Cosmic Frontier, discusses the program of research relevant to cosmology and the early universe. This area includes the study of dark matter and the search for its particle nature, the study of dark energy and inflation, and cosmic probes of fundamental symmetries.Comment: 61 page

The Schr\"oder functional equation and its relation to the invariant measures of chaotic maps

The aim of this paper is to show that the invariant measure for a class of one dimensional chaotic maps, $T(x)$, is an extended solution of the Schr\"oder functional equation, $q(T(x))=\lambda q(x)$, induced by them. Hence, we give an unified treatment of a collection of exactly solved examples worked out in the current literature. In particular, we show that these examples belongs to a class of functions introduced by Mira, (see text). Moreover, as a new example, we compute the invariant densities for a class of rational maps having the Weierstrass $\wp$ functions as an invariant one. Also, we study the relation between that equation and the well known Frobenius-Perron and Koopman's operators.Comment: 9 page

Wound-on-tension for two drum winders

The two drum winder remains to be a high productivity winder for rewinding some paper and nonwoven webs at very high speeds. Winding models of varied capabilities exist for center winders, center winders with rider rollers, and surface winders. Winding models for two drum winders however are still in the introductory stages. Two drum winders are somewhat more complex than other winders due to the number of rollers, driven and undriven, which impinge the surface of the winding roll. The objectives of this paper are to show the influence of various winder operating parameters and thread path on the wound-on-tension in the outer layer (WOT).Mechanical and Aerospace Engineerin