Nutritional immunity describes the host-driven manipulation of essential micronutrients, including iron, zinc and manganese. To withstand nutritional immunity and proliferate within their hosts, ...pathogenic microbes must express efficient micronutrient uptake and homeostatic systems. Here we have elucidated the pathway of cellular zinc assimilation in the major human fungal pathogen Candida albicans. Bioinformatics analysis identified nine putative zinc transporters: four cytoplasmic-import Zip proteins (Zrt1, Zrt2, Zrt3 and orf19.5428) and five cytoplasmic-export ZnT proteins (orf19.1536/Zrc1, orf19.3874, orf19.3769, orf19.3132 and orf19.52). Only Zrt1 and Zrt2 are predicted to localise to the plasma membrane and here we demonstrate that Zrt2 is essential for C. albicans zinc uptake and growth at acidic pH. In contrast, ZRT1 expression was found to be highly pH-dependent and could support growth of the ZRT2-null strain at pH 7 and above. This regulatory paradigm is analogous to the distantly related pathogenic mould, Aspergillus fumigatus, suggesting that pH-adaptation of zinc transport may be conserved in fungi and we propose that environmental pH has shaped the evolution of zinc import systems in fungi. Deletion of C. albicans ZRT2 reduced kidney fungal burden in wild type, but not in mice lacking the zinc-chelating antimicrobial protein calprotectin. Inhibition of zrt2Δ growth by neutrophil extracellular traps was calprotectin-dependent. This suggests that, within the kidney, C. albicans growth is determined by pathogen-Zrt2 and host-calprotectin. As well as serving as an essential micronutrient, zinc can also be highly toxic and we show that C. albicans deals with this potential threat by rapidly compartmentalising zinc within vesicular stores called zincosomes. In order to understand mechanistically how this process occurs, we created deletion mutants of all five ZnT-type transporters in C. albicans. Here we show that, unlike in Saccharomyces cerevisiae, C. albicans Zrc1 mediates zinc tolerance via zincosomal zinc compartmentalisation. This novel transporter was also essential for virulence and liver colonisation in vivo. In summary, we show that zinc homeostasis in a major human fungal pathogen is a multi-stage process initiated by Zrt1/Zrt2-cellular import, followed by Zrc1-dependent intracellular compartmentalisation.
We combine Dark Energy Survey Year 1 clustering and weak lensing data with baryon acoustic oscillations and Big Bang nucleosynthesis experiments to constrain the Hubble constant. Assuming a flat ΛCDM ...model with minimal neutrino mass (∑m_ν = 0.06 eV), we find |$H_0=67.4^{+1.1}_{-1.2}\ \rm {km\,\rm s^{-1}\,\rm Mpc^{-1}}$| (68 per cent CL). This result is completely independent of Hubble constant measurements based on the distance ladder, cosmic microwave background anisotropies (both temperature and polarization), and strong lensing constraints. There are now five data sets that: (a) have no shared observational systematics; and (b) each constrains the Hubble constant with fractional uncertainty at the few-per cent level. We compare these five independent estimates, and find that, as a set, the differences between them are significant at the 2.5σ level (χ^2/dof = 24/11, probability to exceed = 1.1 per cent). Having set the threshold for consistency at 3σ, we combine all five data sets to arrive at |$H_0=69.3^{+0.4}_{-0.6}\ \rm {km\,\mathrm{ s}^{-1}\,\mathrm{ Mpc}^{-1}}$|.
The design of the n2EDM experiment Ayres, N. J.; Ban, G.; Bienstman, L. ...
The European physical journal. C, Particles and fields,
2021/6, Letnik:
81, Številka:
6
Journal Article
Recenzirano
Odprti dostop
We present the design of a next-generation experiment, n2EDM, currently under construction at the ultracold neutron source at the Paul Scherrer Institute (PSI) with the aim of carrying out a ...high-precision search for an electric dipole moment of the neutron. The project builds on experience gained with the previous apparatus operated at PSI until 2017, and is expected to deliver an order of magnitude better sensitivity with provision for further substantial improvements. An overview is of the experimental method and setup is given, the sensitivity requirements for the apparatus are derived, and its technical design is described.
Abstract
We report on a search for a new, short-range, spin-dependent interaction using a modified version of the experimental apparatus used to measure the permanent neutron electric dipole moment ...at the Paul Scherrer Institute. This interaction, which could be mediated by axion-like particles, concerned the unpolarized nucleons (protons and neutrons) near the material surfaces of the apparatus and polarized ultracold neutrons stored in vacuum. The dominant systematic uncertainty resulting from magnetic-field gradients was controlled to an unprecedented level of approximately 4 pT cm
−1
using an array of optically-pumped cesium vapor magnetometers and magnetic-field maps independently recorded using a dedicated measurement device. No signature of a theoretically predicted new interaction was found, and we set a new limit on the product of the scalar and the pseudoscalar couplings
g
s
g
p
λ
2
<
8.3
×
10
−
28
m
2
(95% C.L.) in a range of 5
µ
m
<
λ
<
25
mm for the monopole–dipole interaction. This new result confirms and improves our previous limit by a factor of 2.7 and provides the current tightest limit obtained with free neutrons.
We present a novel Active Magnetic Shield (AMS), designed and implemented for the n2EDM experiment at the Paul Scherrer Institute. The experiment will perform a high-sensitivity search for the ...electric dipole moment of the neutron. Magnetic-field stability and control is of key importance for n2EDM. A large, cubic, 5 m side length, magnetically shielded room (MSR) provides a passive, quasi-static shielding-factor of about 105 for its inner sensitive volume. The AMS consists of a system of eight complex, feedback-controlled compensation coils constructed on an irregular grid spanned on a volume of less than 1000 m3 around the MSR. The AMS is designed to provide a stable and uniform magnetic-field environment around the MSR, while being reasonably compact. The system can compensate static and variable magnetic fields up to ±50μT (homogeneous components) and ±5μT/m (first-order gradients), suppressing them to a few μT in the sub-Hertz frequency range. The presented design concept and implementation of the AMS fulfills the requirements of the n2EDM experiment and can be useful for other applications, where magnetically silent environments are important and spatial constraints inhibit simpler geometrical solutions.
We present a novel Active Magnetic Shield (AMS), designed and implemented for the n2EDM experiment at the Paul Scherrer Institute. The experiment will perform a high-sensitivity search for the ...electric dipole moment of the neutron. Magnetic-field stability and control is of key importance for n2EDM. A large, cubic, 5 m side length, magnetically shielded room (MSR) provides a passive, quasi-static shielding-factor of about
10
5
for its inner sensitive volume. The AMS consists of a system of eight complex, feedback-controlled compensation coils constructed on an irregular grid spanned on a volume of less than 1000 m
3
around the MSR. The AMS is designed to provide a stable and uniform magnetic-field environment around the MSR, while being reasonably compact. The system can compensate static and variable magnetic fields up to
±
50
μ
T
(homogeneous components) and
±
5
μ
T/m
(first-order gradients), suppressing them to a few
μ
T
in the sub-Hertz frequency range. The presented design concept and implementation of the AMS fulfills the requirements of the n2EDM experiment and can be useful for other applications, where magnetically silent environments are important and spatial constraints inhibit simpler geometrical solutions.
LGBTQ+ individuals experience disproportionately higher rates of mental health and substance use difficulties. Discrimination is a significant factor in explaining these disparities. Meyer’s (2003) ...minority stress theory (MST) indicates that proximal group-specific processes mediate the relationship between discrimination and health outcomes, with the effects moderated by other social factors. However, online discrimination has been understudied among LGBTQ+ people. Focusing on LGBTQ+ young adults experiencing online heterosexist discrimination (OHD), the current study aimed to investigate the effect of OHD on mental health outcomes and explore whether the effect was mediated by proximal factors of internalized heterosexism, online concealment, and acceptance concerns and moderated by social support. Path analysis was used to examine the effects. A total of 383 LGBTQ+ young adults (18–35) from an introductory psychology subject pool, two online crowdsourcing platforms, and the community completed a questionnaire assessing these constructs. OHD was associated with increased psychological distress and cannabis use. Two proximal stressors (acceptance concerns and sexual orientation concealment) mediated the relationship between OHD and psychological distress. Sexual orientation concealment also mediated the relationship between OHD and cannabis use. There was no evidence that online social support from LGBTQ+ peers moderated any of the relationships. MST is a viable guiding framework for exploring OHD. Acceptance concerns and online concealment are important constructs to consider and may be potential treatment targets for individuals experiencing psychological distress or engaging in cannabis use due to OHD.
PDF
