Disruption of γ-glutamylcysteine synthetase results in absolute glutathione auxotrophy and apoptosis in Candida albicans

AbstractGlutathione is the most abundant non-protein thiol and a major source of reducing equivalents in eukaryotes. We examined the role of glutathione in Candida albicans by the disruption of γ-glutamylcysteine synthetase (GCS1), an essential enzyme in glutathione biosynthesis. The gcs1/gcs1 null mutants exhibited glutathione auxotrophy, which could be rescued by supplementing with reduced and oxidized glutathione and γ-glutamylcysteine. When the mutants were depleted of glutathione, they showed typical markers of apoptosis. These results suggest that glutathione itself is an essential metabolite and C. albicans lacking GCS1 undergoes apoptosis

Algebraic charge liquids

High temperature superconductivity emerges in the cuprate compounds upon changing the electron density of an insulator in which the electron spins are antiferromagnetically ordered. A key characteristic of the superconductor is that electrons can be extracted from them at zero energy only if their momenta take one of four specific values (the `nodal points'). A central enigma has been the evolution of the zero energy electrons in the metallic state between the antiferromagnet and the superconductor, and recent experiments yield apparently contradictory results. The oscillation of the resistance in this metal as a function of magnetic field indicate that the zero energy electrons carry momenta which lie on elliptical `Fermi pockets', while ejection of electrons by high intensity light indicates that the zero energy electrons have momenta only along arc-like regions. We present a theory of new states of matter, which we call `algebraic charge liquids', which arise naturally between the antiferromagnet and the superconductor, and reconcile these observations. Our theory also explains a puzzling dependence of the density of superconducting electrons on the total electron density, and makes a number of unique predictions for future experiments.Comment: 6+8 pages, 2 figures; (v2) Rewritten for broader accessibility; (v3) corrected numerical error in Eq. (5

Tunable Emergent Heterostructures in a Prototypical Correlated Metal

At the interface between two distinct materials desirable properties, such as superconductivity, can be greatly enhanced, or entirely new functionalities may emerge. Similar to in artificially engineered heterostructures, clean functional interfaces alternatively exist in electronically textured bulk materials. Electronic textures emerge spontaneously due to competing atomic-scale interactions, the control of which, would enable a top-down approach for designing tunable intrinsic heterostructures. This is particularly attractive for correlated electron materials, where spontaneous heterostructures strongly affect the interplay between charge and spin degrees of freedom. Here we report high-resolution neutron spectroscopy on the prototypical strongly-correlated metal CeRhIn5, revealing competition between magnetic frustration and easy-axis anisotropy -- a well-established mechanism for generating spontaneous superstructures. Because the observed easy-axis anisotropy is field-induced and anomalously large, it can be controlled efficiently with small magnetic fields. The resulting field-controlled magnetic superstructure is closely tied to the formation of superconducting and electronic nematic textures in CeRhIn5, suggesting that in-situ tunable heterostructures can be realized in correlated electron materials

Enhancement drugs: are there limits to what we should enhance and why?

Substances, such as alcohol, opiates and cannabis, have been used by humans for millennia. Today, a much wider range of substances are used for a range of purposes, including the enhancement of performance during university studies, sexual experiences, sports, exercise, at celebrations, socializing and the experience of art and music. Substance use is also associated with a range of harmful effects to the individual and society as a whole. Prohibitions, regulation, prevention and treatment have all been used to protect against this harm. In this commentary, it is argued that public health interventions should target relevant harms and not to evaluate which aspects of human endeavors and experiences should be enhanced and which should not. It is argued that interventions should directly target the harmful effects, using the best available evidence. Two examples are given of substances that may be altered to prevent serious harm - one for alcohol and one for cannabis. In the case of alcohol, the addition of dissolved oxygen could reduce both the risk of accidents and the risk of liver damage associated with alcohol consumption. In the case of cannabis, there is strong indication that the reduction of content Δ-tetrahydrocannabinol and the increase of cannabidiol could reduce the risk of psychoses and the addiction associated with its use. The aim of this article is to show that responsible regulation should not necessarily be restricted to preventing the use and/or (in the case of alcohol) a reduction in the amounts and frequency of its use, but should also aim to include a range of other strategies that could reduce the burden of illness associated with illicit substance use

Open Problems on Central Simple Algebras

We provide a survey of past research and a list of open problems regarding central simple algebras and the Brauer group over a field, intended both for experts and for beginners.Comment: v2 has some small revisions to the text. Some items are re-numbered, compared to v

Ubiquitin transfer by a RING E3 ligase occurs from a closed E2~ubiquitin conformation

Funding: Investigator Award from the Wellcome Trust (098391/Z/12/Z) and (217196/Z/19/Z) and a Programme grant from Cancer Research UK (C434/A21747) to R.T.H.; J.C.P. thanks the University of St Andrews for financial support.Based on extensive structural analysis it was proposed that RING E3 ligases prime the E2~ubiquitin conjugate (E2~Ub) for catalysis by locking it into a closed conformation, where ubiquitin is folded back onto the E2 exposing the restrained thioester bond to attack by substrate nucleophile. However the proposal that the RING dependent closed conformation of E2~Ub represents the active form that mediates ubiquitin transfer has yet to be experimentally tested. To test this hypothesis we use single molecule Förster Resonance Energy Transfer (smFRET) to measure the conformation of a FRET labelled E2~Ub conjugate, which distinguishes between closed and alternative conformations. We describe a real-time FRET assay with a thioester linked E2~Ub conjugate to monitor single ubiquitination events and demonstrate that ubiquitin is transferred to substrate from the closed conformation. These findings are likely to be relevant to all RING E3 catalysed reactions ligating ubiquitin and other ubiquitin-like proteins (Ubls) to substrates.Publisher PDFPeer reviewe

Ultraviolet Laser Action in Ferromagnetic Zn1−xFexO Nanoneedles

Fe-doped ZnO nanoneedles (NDs) were fabricated by an Ar+ ion sputtering technique operated at room temperature. The as-grown samples show both ferromagnetic and lasing properties. The saturated magnetization moment was measured from 0.307 to 0.659 emu cm−3 at the field of 10 kOe with various Fe concentrations. Intense ultraviolet random lasing emission was observed from Zn1 − xFexO NDs at room temperature. The X-ray photoelectron spectroscopy result reveals that the doped Fe atoms occupy the Zn sites and lead to a decrease in oxygen deficiency

Less-simplified models of dark matter for direct detection and the LHC

We construct models of dark matter with suppressed spin-independent scattering cross section utilizing the existing simplified model framework. Even simple combinations of simplified models can exhibit interference effects that cause the tree level contribution to the scattering cross section to vanish, thus demonstrating that direct detection limits on simplified models are not robust when embedded in a more complicated and realistic framework. In general for fermionic WIMP masses ≳ 10 GeV direct detection limits on the spin-independent scattering cross section are much stronger than those coming from the LHC. However these model combinations, which we call less-simplified models, represent situations where LHC searches become more competitive than direct detection experiments even for moderate dark matter mass. We show that a complementary use of several searches at the LHC can strongly constrain the direct detection blind spots by setting limits on the coupling constants and mediators’ mass. We derive the strongest limits for combinations of vector + scalar, vector + “squark”, and “squark” + scalar mediator, and present the corresponding projections for the LHC 14 TeV for a number of searches: mono-jet, jets + missing energy, and searches for heavy vector resonances