Force Majeure: How Lessees Can Save Their Leases While the War on Fracking Rages on.

Abstract Forthcoming

Force Majeure: How Lessees Can Save Their Leases While the War on Fracking Rages on.

Abstract Forthcoming

Quasi-homogeneous associative functions

A triangular norm is a special kind of associative function on the closed unit interval [0,1]. Triangular norms (or t-norms) were introduced in the context of probabilistic metric space theory, and they have found applications also in other areas, such as fuzzy set theory. We determine the explicit forms of all t-norms which satisfy a generalized homogeneity property called quasi-homogeneity

In silico comparative analysis of LRRK2 interactomes from brain, kidney and lung

Mutations in LRRK2 are the most frequent cause of familial Parkinson’s disease (PD), with common LRRK2 non-coding variants also acting as risk factors for idiopathic PD. Currently, therapeutic agents targeting LRRK2 are undergoing advanced clinical trials in humans, however, it is important to understand the wider implications of LRRK2 targeted treatments given that LRRK2 is expressed in diverse tissues including the brain, kidney and lungs. This presents challenges to treatment in terms of effects on peripheral organ functioning, thus, protein interactors of LRRK2 could be targeted in lieu to optimize therapeutic effects. Herein an in-silico analysis of LRRK2 direct interactors in brain tissue from various brain regions was conducted along with a comparative analysis of the LRRK2 interactome in the brain, kidney, and lung tissues. This was carried out based on curated protein–protein interaction (PPI) data from protein interaction databases such as HIPPIE, human gene/protein expression databases and Gene ontology (GO) enrichment analysis using Bingo. Seven targets (MAP2K6, MATK, MAPT, PAK6, SH3GL2, CDC42EP3 and CHGB) were found to be viable objectives for LRRK2 based investigations for PD that would have minimal impact on optimal functioning within peripheral organs. Specifically, MAPT, CHGB, PAK6, and SH3GL2 interacted with LRRK2 in the brain and kidney but not in lung tissue whilst LRRK2-MAP2K6 interacted only in the cerebellum and MATK-LRRK2 interaction was absent in kidney tissues. CDC42EP3 expression levels were low in brain tissues compared to kidney/lung. The results of this computational analysis suggest new avenues for experimental investigations towards LRRK2-targeted therapeutics

Acute imidacloprid exposure alters mitochondrial function in bumblebee flight muscle and brain - Correction / Corrigendum

This article is a correction to: http://dx.doi.org/10.3389/finsc.2021.765179 Acute Imidacloprid Exposure Alters Mitochondrial Function in Bumblebee Flight Muscle and Brai

The dysregulated Pink1- drosophila mitochondrial proteome is partially corrected with exercise

One of the genes which has been linked to the onset of juvenile/early onset Parkinson’s disease (PD) is PINK1. There is evidence that supports the therapeutic potential of exercise in the alleviation of PD symptoms. It is possible that exercise may enhance synaptic plasticity, protect against neuro-inflammation and modulate L-Dopa regulated signalling pathways. We explored the effects of exercise on Pink1 deficient Drosophila melanogaster which undergo neurodegeneration and muscle degeneration. We used a ‘power-tower’ type exercise platform to deliver exercise activity to Pink1- and age matched wild-type Drosophila. Mitochondrial proteomic profiles responding to exercise were obtained. Of the 516 proteins identified, 105 proteins had different levels between Pink1- and wild-type non-exercised Drosophila. Gene ontology enrichment analysis and STRING network analysis highlighted proteins and pathways with altered expression within the mitochondrial proteome. Comparison of the Pink1- exercised proteome to wild-type proteomes showed that exercising the Pink1- Drosophila caused their proteomic profile to return towards wild-type levels

Acquisition of Ca2+ and HCO3−/CO32− for shell formation in embryos of the common pond snail Lymnaea stagnalis

Embryos of the freshwater common pond snail Lymnaea stagnalis develop to hatch within 10 days under control conditions (22°C, Miami-Dade tap water) and this development is impaired by removal of ambient calcium. In contrast, embryos did not exhibit dependence upon an ambient HCO3−/CO32− source, developing and hatching in HCO3−/CO32−-free water at rates comparable to controls. Post-metamorphic, shell-laying embryos exhibited a significant saturation-type calcium uptake as a function of increasing ambient calcium concentration. However, changes in ambient bicarbonate concentration did not influence calcium or apparent titratable alkalinity uptake. There was a distinct shift from no significant flux in pre-metamorphic embryos to net uptake of calcium in post-metamorphic stages as indicated by an increased uptake from the micro-environment surrounding the egg mass and increased net uptake in 24-h, whole egg mass flux measurements. Furthermore, HCO3−/CO32− acquisition as measured by titratable alkalinity flux is at least partially attributable to an endogenous carbonate source that is associated with acid extrusion. Thus, calcium requirements for embryonic shell formation are met via uptake but HCO3−/CO32−, which is also necessary for shell formation is acquired in part from endogenous sources with no detectable correlation to ambient HCO3−/CO32− availability

Experience of an NIHR Clinical Lectureship (medical/dental) and the determining factors for a clinical academic career post lectureship:a mixed-method evaluation

Objectives: The objective of this study is to investigate early-to-late postdoctoral clinical academic progression and the experiences of NIHR Clinical Lectureship (CL) fellows, considering enablers and barriers to success, and identifying the factors associated with immediate progression to a clinical academic role following completion of the award. Setting: Datasets of CL awardees across the UK. Participants: For semistructured interviews, n=40 CL awardees that had finished their award within the previous 5 years. For quantitative analysis, n=1226 completed or currently active CL awardees. Outcome measures: The responses from the semistructured interviews to the defined questions on experiences during the award, postaward progression, and enablers and barriers to academic progression. Other primary outcome measures were quantitative data on first destinations postaward, demographic data, and whether an awardee had previously held an NIHR Academic Clinical Fellowship (ACF) or was a recipient of the Academy of Medical Sciences (AMS) Starter Grant. Results: CL awardees identified numerous benefits to the award, with the majority achieving their aims. Most awardees progressed to a clinical academic role; however, some returned to a clinical only position, citing concerns around the time pressure associated with balancing clinical and academic responsibilities, and the competition to attain further postdoctoral awards. The region of the award partnership, year of award end and success in applying for an AMS Starter Grant were associated with progression to a clinical academic role. Gender, holding an ACF and having a craft or non-craft specialty had no independent statistical association with clinical academic progression. Conclusions: The CL is a valued element of the Integrated Academic Pathway. By addressing issues around later postdoctoral progression opportunities, responding to challenges experienced by CLs, and by understanding the factors identified in this study associated with clinical academic progression, it should be possible to increase the proportion of CLs that become fully independent clinical academic research leaders. Participants: 1226 NIHR CLs active or completed on the award between 2006 and 2020

Revisiting the exercise heart rate-music tempo preference relationship

In the present study, we investigated a hypothesized quartic relationship (meaning three inflection points) between exercise heart rate (HR) and preferred music tempo. Initial theoretical predictions suggested a positive linear relationship (Iwanaga, 1995a, 1995b); however, recent experimental work has shown that as exercise HR increases, step changes and plateaus that punctuate the profile of music tempo preference may occur (Karageorghis, Jones, & Stuart, 2008). Tempi bands consisted of slow (95–100 bpm), medium (115–120 bpm), fast (135–140 bpm), and very fast (155–160 bpm) music. Twenty-eight active undergraduate students cycled at exercise intensities representing 40, 50, 60, 70, 80, and 90% of their maximal HR reserve while their music preference was assessed using a 10-point scale. The Exercise Intensity x Music Tempo interaction was significant, F(6.16, 160.05) = 7.08, p < .001, ηp 2 =.21, as was the test for both cubic and quartic trajectories in the exercise HR–preferred-music-tempo relationship (p < .001). Whereas slow tempo music was not preferred at any exercise intensity, preference for fast tempo increased, relative to medium and very fast tempo music, as exercise intensity increased. The implications for the prescription of music in exercise and physical activity contexts are discussed

Structural Basis for the Function of Complement Component C4 within the Classical and Lectin Pathways of Complement

Complement component C4 is a central protein in the classical and lectin pathways within the complement system. During activation of complement, its major fragment C4b becomes covalently attached to the surface of pathogens and altered self-tissue, where it acts as an opsonin marking the surface for removal. Moreover, C4b provides a platform for assembly of the proteolytically active convertases that mediate downstream complement activation by cleavage of C3 and C5. In this article, we present the crystal and solution structures of the 195-kDa C4b. Our results provide the molecular details of the rearrangement accompanying C4 cleavage and suggest intramolecular flexibility of C4b. The conformations of C4b and its paralogue C3b are shown to be remarkably conserved, suggesting that the convertases from the classical and alternative pathways are likely to share their overall architecture and mode of substrate recognition. We propose an overall molecular model for the classical pathway C5 convertase in complex with C5, suggesting that C3b increases the affinity for the substrate by inducing conformational changes in C4b rather than a direct interaction with C5. C4b-specific features revealed by our structural studies are probably involved in the assembly of the classical pathway C3/C5 convertases and C4b binding to regulators