Cooperative Gating and Spatial Organization of Membrane Proteins through Elastic Interactions

Biological membranes are elastic media in which the presence of a transmembrane protein leads to local bilayer deformation. The energetics of deformation allow two membrane proteins in close proximity to influence each other's equilibrium conformation via their local deformations, and spatially organize the proteins based on their geometry. We use the mechanosensitive channel of large conductance (MscL) as a case study to examine the implications of bilayer-mediated elastic interactions on protein conformational statistics and clustering. The deformations around MscL cost energy on the order of 10 kT and extend ~3nm from the protein edge, as such elastic forces induce cooperative gating and we propose experiments to measure these effects. Additionally, since elastic interactions are coupled to protein conformation, we find that conformational changes can severely alter the average separation between two proteins. This has important implications for how conformational changes organize membrane proteins into functional groups within membranes.Comment: 12 pages, 6 figures, 63 references, submitted to PLoS Computational Biolog

Conformal cosmology with a positive effective gravitational constant

The conformal cosmological model presented by Mannheim predicts a negative value for the effective gravitational constant, G. It also involves a scalar field, S, which is treated classically. In this paper we point out that a classical treatment of S is inappropriate, because the Hamiltonian is non-Hermitean, and the theory must be developed in the way pioneered by Bender and others. When this is done, we arrive at a Hamiltonian with an energy spectrum that is bounded below, and also a G that is positive. The resulting theory closely resembles the conventional cosmology based on Einstein relativity

Specialist alcohol inpatient treatment admissions and non-specialist hospital admissions for alcohol withdrawal in England: an inverse relationship

© The Author(s) 2020. Medical Council on Alcohol and Oxford University Press. AIMS: We assessed the relationship between specialist and non-specialist admissions for alcohol withdrawal since the introduction of the UK government Health and Social Care Act in 2012. METHODS: Using publicly available national data sets from 2009 to 2019, we compared the number of alcohol withdrawal admissions and estimated costs in specialist and non-specialist treatment settings. RESULTS: A significant negative correlation providing strong evidence of an association was observed between the fall in specialist and rise in non-specialist admissions. Significant cost reductions within specialist services were displaced to non-specialist settings. CONCLUSIONS: The shift in demand from specialist to non-specialist alcohol admissions due to policy changes in England should be reversed by specialist workforce investment to improve outcomes. In the meantime, non-specialist services and staff must be resourced and equipped to meet the complex needs of these service users

Weight bias 2.0: the effect of perceived weight change on performance evaluation and the moderating role of anti-fat bias

Overweight employees are viewed as lazy, slow, inactive, and even incapable. Even if such attributes are false, this perspective can seriously undermine others' evaluation of their work performance. The current study explores a broader phenomenon of weight bias that has an effect on weight change. In a longitudinal study with a time lag of 6 months, we surveyed 226 supervisor-employee dyads. We found supervisor perceptions of employee weight change notably altered their evaluation of the employee performance from Time 1, especially following low vs. high Time-1 performance evaluation. Meanwhile, the moderating effects among different levels of supervisor anti-fat bias functioned as boundary conditions for such performance evaluation alteration. In particular, the interaction between the Time-1 performance evaluation and the impact of supervisor perception of employee weight change on the Time-2 performance evaluation was significant only if supervisors held a stronger anti-fat bias

Thermodynamics of an Exactly Solvable Model for Superconductivity in a Doped Mott Insulator

Computing superconducting properties starting from an exactly solvable model for a doped Mott insulator stands as a grand challenge. We have recently shown that this can be done starting from the Hatsugai-Kohmoto (HK) model which can be understood generally as the minimal model that breaks the non-local $\mathbb Z_2$ symmetry of a Fermi liquid, thereby constituting a new quartic fixed point for Mott physics [Phillips et al., Nature Physics 16, 1175 (2020); Huang et al., Nature Physics (2022)]. In the current work, we compute the thermodynamics, condensation energy, and electronic properties such as the NMR relaxation rate $1/T_1$ and ultrasonic attenuation rate. Key differences arise with the standard BCS analysis from a Fermi liquid: 1) the free energy exhibits a local minimum at $T_p$ where the pairing gap turns on discontinuously above a critical value of the repulsive HK interaction, thereby indicating a first-order transition, 2) a tri-critical point emerges, thereby demarcating the boundary between the standard second-order superconducting transition and the novel first-order regime, 3) Mottness changes the sign of the quartic coefficient in the Landau-Ginzburg free-energy fuctional relative to that in BCS, 4) as this obtains in the strongly interacting regime, it is Mott physics that underlies the generic first-order transition, 5) the condensation energy exceeds that in BCS theory suggesting that multiple Mott bands might be a way of enhancing superconducting, 6) the heat-capacity jump is non-universal and increases with the Mott scale, 7) Mottness destroys the Hebel-Slichter peak in NMR, and 8) Mottness enhances the fall-off of the ultrasonic attenuation at the pairing temperature $T_p$. As several of these properties are observed in the cuprates, our analysis here points a way forward in computing superconducting properties of strongly correlated electron matter.Comment: accepted in PR

Chronic behavioral and cognitive deficits in a rat survival model of paraoxon toxicity

Organophosphate (OP) compounds, including paraoxon (POX), are similar to nerve agents such as sarin. There is a growing concern that OP agents could be weaponized to cause mass civilian causalities. We have developed a rodent survival model of POX toxicity that is being used to evaluate chronic morbidity and to screen for medical countermeasures against severe OP exposure. It is well known that the survivors of nerve gas and chronic OP exposure exhibit neurobehavioral deficits such as mood changes, depression, and memory impairments. In this study we investigated whether animals surviving severe POX exposure exhibited long-term neurological impairments. POX exposure produced overt signs of cholinergic toxicity. Rats were rescued using an optimized atropine, 2-PAM and diazepam therapy. Surviving rats were studied using established behavioral assays for identifying symptoms of depression and memory impairment 3-months after POX exposure. In the forced swim test, POX rats exhibited increased immobility time indicative of a despair-like state. In the sucrose preference test, POX rats consumed significantly less sucrose water indicating anhedonia-like condition. POX rats also displayed increased anxiety as characterized by significantly lower performance in the open arm of the elevated plus maze. Further, when tested with a novel object recognition paradigm, POX rats exhibited a negative discrimination ratio indicative of impaired recognition memory. The results indicate that this model of survival from severe POX exposure can be employed to study some of the molecular bases for OP-induced chronic behavioral and cognitive comorbidities and develop therapies for their treatment

Analytic models for mechanotransduction: gating a mechanosensitive channel

Analytic estimates for the forces and free energy generated by bilayer deformation reveal a compelling and intuitive model for MscL channel gating analogous to the nucleation of a second phase. We argue that the competition between hydrophobic mismatch and tension results in a surprisingly rich story which can provide both a quantitative comparison to measurements of opening tension for MscL when reconstituted in bilayers of different thickness and qualitative insights into the function of the MscL channel and other transmembrane proteins

Ascospore release and survival in Sclerotinia sclerotiorum

The release and survival of ascospores of a UK Sclerotinia sclerotiorum isolate were studied. Apothecia placed in a spore clock apparatus with different lighting regimes at 15 °C released ascospores continuously with an increasing rate for the duration of experiments (72–84 h). Spore release was not confined to light or dark periods in alternating regimes and occurred in continuous dark or light. Ascospores were released in both saturated air (90–95% rh) and at 65–75% rh. High temperature and rh were detrimental to ascospore survival but spore viability was maintained for longer periods than previously reported. The significance of these results in relation to disease control is discussed