Trehalose is required for the acquisition of tolerance to a variety of stresses in the filamentous fungus Aspergillus nidulans

Trehalose is a non-reducing disaccharide found at high concentrations in Aspergillus nidulans conidia and rapidly degraded upon induction of conidial germination. Furthermore, trehalose is accumulated in response to a heat shock or to an oxidative shock. The authors have characterized the A. nidulans tpsA gene encoding trehalose-6-phosphate synthase, which catalyses the first step in trehalose biosynthesis. Expression of tpsA in a Saccharomyces cerevisiae tps1 mutant revealed that the tpsA gene product is a functional equivalent of the yeast Tps1 trehalose-6-phosphate synthase. The A. nidulans tpsA-null mutant does not produce trehalose during conidiation or in response to various stress conditions. While germlings of the tpsA mutant show an increased sensitivity to moderate stress conditions (growth at 45 °C or in the presence of 2 mM H2O2), they display a response to severe stress (60 min at 50 °C or in the presence of 100 mM H2O2) similar to that of wild-type germlings. Furthermore, conidia of the tpsA mutant show a rapid loss of viability upon storage. These results are consistent with a role of trehalose in the acquisition of stress tolerance. Inactivation of the tpsA gene also results in increased steady-state levels of sugar phosphates but does not prevent growth on rapidly metabolizable carbon sources (glucose, fructose) as seen in Saccharomyces cerevisiae. This suggests that trehalose 6-phosphate is a physiological inhibitor of hexokinase but that this control is not essential for proper glycolytic flux in A. nidulans. Interestingly, tpsA transcription is not induced in response to heat shock or during conidiation, indicating that trehalose accumulation is probably due to a post-translational activation process of the trehalose 6-phosphate synthase

Adapting to survive: How Candida overcomes host-imposed constraints during human colonization

Successful human colonizers such as Candida pathogens have evolved distinct strategies to survive and proliferate within the human host. These include sophisticated mechanisms to evade immune surveillance and adapt to constantly changing host microenvironments where nutrient limitation, pH fluctuations, oxygen deprivation, changes in temperature, or exposure to oxidative, nitrosative, and cationic stresses may occur. Here, we review the current knowledge and recent findings highlighting the remarkable ability of medically important Candida species to overcome a broad range of host-imposed constraints and how this directly affects their physiology and pathogenicity. We also consider the impact of these adaptation mechanisms on immune recognition, biofilm formation, and antifungal drug resistance, as these pathogens often exploit specific host constraints to establish a successful infection. Recent studies of adaptive responses to physiological niches have improved our understanding of the mechanisms established by fungal pathogens to evade the immune system and colonize the host, which may facilitate the design of innovative diagnostic tests and therapeutic approaches for Candida infections.Work at CBMA is supported by the Contrato-Programa UIBD/04050/2020 funded by Portuguese national funds through the FCT I.P. RA and CBA are recipients of FCT PhD fellowships (PD/BD/113813/2015 and PD/BD/135208/2017, respectively). Research stay of RA at KU Leuven was supported by Boehringer Ingelheim Fonds. Work at KU Leuven is supported by grants from the Fund for Scientific Research Flanders (FWO grant nr: G0F8519N) and by the Research Council of the KU Leuven (grant nr: C14/17/063). Work at the University of Exeter is funded by a programme grant from the UK Medical Research Council (MRC) [www.mrc.ac.uk: MR/M026663/1], by the MRC Centre for Medical Mycology, University of Exeter [MR/N006364/1], and by the Wellcome Trust [www.wellcome.ac.uk: 097377]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Adapting to survive: how Candida spp. respond to environmental physiological constraints

Candida species are important human pathogens and have emerged as a leading cause of nosocomial fungal infections. In order to survive and proliferate within the human host, these species have to adapt to the different niches and assimilate the available nutrients. For instance, during infection, they can encounter glucose-poor microenvironments and some studies have suggested that the ability to use non-fermentable carbon sources affects the virulence of these pathogens. Our studies have demonstrated that the presence of alternative carbon sources such as lactate and acetate influence Candida biofilm formation, antifungal drug resistance and immune recognition. Additionally, there is evidence that carboxylate transporters have a role on these processes. An overview of the most significant results will be presented.Our data support the view that the different carbon sources present in the host niches affect directly the physiology of Candida cells, with implications on how these pathogens respond to antifungal treatment

The popular music heritage of the Dutch pirates: illegal radio and cultural identity

This article explores how cultural identities are negotiated in relation to the heritage of illegal radio in the Netherlands. The term ‘pirate radio’ commonly refers to the offshore radio stations that were broadcasting during the 1960s. These stations introduced commercial radio and popular music genres like beat music, which were not played by public broadcasters at the time. In their wake, land-based pirates began broadcasting for local audiences. This study examines the identities that are constituted by the narrative of pirate radio. Drawing on in-depth interviews with archivists, fans and broadcasters, this article explores the connection between pirate radio, popular music heritage and cultural identity. Moreover, it considers how new technologies such as internet radio provide platforms to engage with this heritage and thus to maintain these local identities. To examine how the memories of pirate radio live on in the present a narrative approach to identity will be used

First Test of Lorentz Invariance in the Weak Decay of Polarized Nuclei

A new test of Lorentz invariance in the weak interactions has been made by searching for variations in the decay rate of spin-polarized 20Na nuclei. This test is unique to Gamow-Teller transitions, as was shown in the framework of a recently developed theory that assumes a Lorentz symmetry breaking background field of tensor nature. The nuclear spins were polarized in the up and down direction, putting a limit on the amplitude of sidereal variations of the form |(\Gamma_{up} - \Gamma_{down})| / (\Gamma_{up} + \Gamma_{down}) < 3 * 10^{-3}. This measurement shows a possible route toward a more detailed testing of Lorentz symmetry in weak interactions.Comment: 11 pages, 6 figure

Influence of daily 10-85 mu g vitamin D supplements during pregnancy and lactation on maternal vitamin D status and mature milk antirachitic activity

Pregnant and lactating women and breastfed infants are at risk of vitamin D deficiency. The supplemental vitamin D dose that optimises maternal vitamin D status and breast milk antirachitic activity (ARA) is unclear. Healthy pregnant women were randomised to 10 (n 10), 35 (n 11), 60 (n 11) and 85 (n 11) mu g vitamin D-3/d from 20 gestational weeks (GW) to 4 weeks postpartum (PP). The participants also received increasing dosages of fish oil supplements and a multivitamin. Treatment allocation was not blinded. Parent vitamin D and 25-hydroxyvitamin D (25(OH)D) were measured in maternal plasma at 20 GW, 36 GW and 4 weeks PP, and in milk at 4 weeks PP. Median 25(OH)D and parent vitamin D at 20 GW were 85 (range 25-131) nmol/l and 'not detectable (nd)' (range nd-40) nmol/l. Both increased, seemingly dose dependent, from 20 to 36 GW and decreased from 36 GW to 4 weeks PP. In all, 35 mu g vitamin D/d was needed to increase 25(OH)D to adequacy (80-249 nmol/l) in >97 center dot 5 % of participants at 36 GW, while >85 mu g/d was needed to reach this criterion at 4 weeks PP. The 25(OH)D increments from 20 to 36 GW and from 20 GW to 4 weeks PP diminished with supplemental dose and related inversely to 25(OH)D at 20 GW. Milk ARA related to vitamin D-3 dose, but the infant adequate intake of 513 IU/l was not reached. Vitamin D-3 dosages of 35 and >85 mu g/d were needed to reach adequate maternal vitamin D status at 36 GW and 4 weeks PP, respectively

Informed consent procedures in patients with an acute inability to provide informed consent : Policy and practice in the CENTER-TBI study

Purpose: Enrolling traumatic brain injury (731) patients with an inability to provide informed consent in research is challenging. Alternatives to patient consent are not sufficiently embedded in European and national legislation, which allows procedural variation and bias. We aimed to quantify variations in informed consent policy and practice. Methods: Variation was explored in the CENTER-TBI study. Policies were reported by using a questionnaire and national legislation. Data on used informed consent procedures were available for 4498 patients from 57 centres across 17 European countries. Results: Variation in the use of informed consent procedures was found between and within EU member states. Proxy informed consent (N = 1377;64%) was the most frequently used type of consent in the ICU, followed by patient informed consent (N 426;20%) and deferred consent (N 334;16%). Deferred consent was only actively used in 15 centres (26%), although it was considered valid in 47 centres (82%). Conclusions: Alternatives to patient consent are essential for TBI research. While there seems to be concordance amongst national legislations, there is regional variability in institutional practices with respect to the use of different informed consent procedures. Variation could be caused by several reasons, including inconsistencies in clear legislation or knowledge of such legislation amongst researchers. (C) 2020 Published by Elsevier Inc.Peer reviewe

Oscillatory activity in the medial prefrontal cortex and nucleus accumbens correlates with impulsivity and reward outcome.

Actions expressed prematurely without regard for their consequences are considered impulsive. Such behaviour is governed by a network of brain regions including the prefrontal cortex (PFC) and nucleus accumbens (NAcb) and is prevalent in disorders including attention deficit hyperactivity disorder (ADHD) and drug addiction. However, little is known of the relationship between neural activity in these regions and specific forms of impulsive behaviour. In the present study we investigated local field potential (LFP) oscillations in distinct sub-regions of the PFC and NAcb on a 5-choice serial reaction time task (5-CSRTT), which measures sustained, spatially-divided visual attention and action restraint. The main findings show that power in gamma frequency (50-60 Hz) LFP oscillations transiently increases in the PFC and NAcb during both the anticipation of a cue signalling the spatial location of a nose-poke response and again following correct responses. Gamma oscillations were coupled to low-frequency delta oscillations in both regions; this coupling strengthened specifically when an error response was made. Theta (7-9 Hz) LFP power in the PFC and NAcb increased during the waiting period and was also related to response outcome. Additionally, both gamma and theta power were significantly affected by upcoming premature responses as rats waited for the visual cue to respond. In a subgroup of rats showing persistently high levels of impulsivity we found that impulsivity was associated with increased error signals following a nose-poke response, as well as reduced signals of previous trial outcome during the waiting period. Collectively, these in-vivo neurophysiological findings further implicate the PFC and NAcb in anticipatory impulsive responses and provide evidence that abnormalities in the encoding of rewarding outcomes may underlie trait-like impulsive behaviour.RCUK, Wellcome, OtherThis is the final version of the article. It first appeared at http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0111300