Formal total synthesis of (±)-conduramine E utilising the Bryce-Smith-Gilbert photoamination reaction

Utilising a Bryce-Smith-Gilbert photoamination of benzene as a key step, a synthesis of ()-conduramine E was carried out. A highly regioselective dihydroxylation of a cyclic diene was effected utilising Sharpless AD-mix-b

The Shackles of Peer Review: Unveiling the Flaws in the Ivory Tower

This essay delves into the ethical dilemmas encountered within the academic peer review process and investigates the prevailing deficiencies in this system. It highlights how established scholars often adhere to mainstream theories not out of genuine belief, but to safeguard their own reputations. This practice perpetuates intellectual conformity, fuels confirmation bias, and stifles dissenting voices. Furthermore, as the number of incorrect papers published by influential scientists increases, it inadvertently encourages more researchers to follow suit, tacitly endorsing incorrect viewpoints. By examining historical instances of suppressed ideas later proven valuable, this essay calls for a reevaluation of academia's commitment to genuine innovation and progress which is usually achieved by applications of fundamental principles in from textbooks.Comment: 10 pages, 0 figure

Factors Influencing Team Performance:What Can Support Teams in High-Performance Sport Learn from Other Industries? A Systematic Scoping Review

BACKGROUND: The primary aim of our systematic scoping review was to explore the factors influencing team function and performance across various industries and discuss findings in the context of the high-performance sport support team setting. These outcomes may also be used to inform future research into high-performance teamwork in sport. METHODS: A systematic scoping review of literature published in English since 2000 reporting team-based performance outcomes and included a performance metric that was ‘team outcome based’ was conducted using search of the Academic Search Ultimate, Medline, Business Source Ultimate, APA PsycInfo, CINAHL, SPORTDiscus, and Military database (ProQuest) using the terms: ‘team’, ‘function’ OR ‘dysfunction’, ‘Perform*’ OR ‘outcome’. RESULTS: Application of the search strategy identified a total of 11,735 articles for title and abstract review. Seventy-three articles were selected for full-text assessment with the aim to extract data for either quantitative or qualitative analysis. Forty-six of the 73 articles met our inclusion criteria; 27 articles were excluded as they did not report a performance metric. Eleven studies explored leadership roles and styles on team performance, three studies associated performance feedback to team performance, and 12 studies explored the relationship between supportive behaviour and performance. Team orientation and adaptability as key figures of team performance outcomes were explored in 20 studies. CONCLUSIONS: Our findings identified 4 key variables that were associated with team function and performance across a variety of industries; (i) leadership styles, (ii) supportive team behaviour, (iii) communication, and (iv) performance feedback. High-performance teams wishing to improve performance should examine these factors within their team and its environment. It is widely acknowledged that the dynamics of team function is important for outcomes in high-performance sport, yet there is little evidence to provide guidance. This inequality between real-world need and the available evidence should be addressed in future research. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40798-021-00406-7

Mitocans induce lipid flip-flop and permeabilize the membrane to signal apoptosis

Pancratistatin (PST) and narciclasine (NRC) are natural therapeutic agents that exhibit specificity toward the mitochondria of cancerous cells and initiate apoptosis. Unlike traditional cancer therapeutic agents, PST and NRC are effective, targeted, and have limited adverse effects on neighboring healthy, noncancerous cells. Currently, the mechanistic pathway of action for PST and NRC remains elusive, which in part inhibits PST and NRC from becoming efficacious therapeutic alternatives. Herein, we use neutron and x-ray scattering in combination with calcein leakage assays to characterize the effects of PST, NRC, and tamoxifen (TAM) on a biomimetic model membrane. We report an increase in lipid flip-flop half-times (t1/2) (≈12.0%, ≈35.1%, and a decrease of ≈45.7%) with 2 mol percent PST, NRC, and TAM respectively. An increase in bilayer thickness (≈6.3%, ≈7.8%, and ≈7.8%) with 2 mol percent PST, NRC, and TAM, respectively, was also observed. Lastly, increases in membrane leakage (≈31.7%, ≈37.0%, and ≈34.4%) with 2 mol percent PST, NRC, and TAM, respectively, were seen. Considering the maintenance of an asymmetric lipid composition across the outer mitochondrial membrane (OMM) is crucial to eukaryotic cellular homeostasis and survival, our results suggest PST and NRC may play a role in disrupting the native distribution of lipids within the OMM. A possible mechanism of action for PST- and NRC-induced mitochondrial apoptosis is proposed via the redistribution of the native OMM lipid organization and through OMM permeabilization

Near-Infrared Spectroscopy of McNeil's Nebula Object

We present 0.8-5.2 micron spectroscopy of the compact source at the base of a variable nebula (McNeil's Nebula Object) in the Lynds 1630 dark cloud that went into outburst in late 2003. The spectrum of this object reveals an extremely red continuum, CO bands at 2.3-2.5 microns in emission, a deep 3.0 micron ice absorption feature, and a solid state CO absorption feature at 4.7 microns. In addition, emission lines of H, Ca II, Mg I, and Na I are present. The Paschen lines exhibit P Cygni profiles, as do two lines of He I, although the emission features are very weak in the latter. The Brackett lines, however, are seen to be purely in emission. The P Cygni profiles clearly indicate that mass outflow is occurring in a wind with a velocity of ~400 km/s. The H line ratios do not yield consistent estimates of the reddening, nor do they agree with the extinction estimated from the ice feature (A_V ~ 11). We propose that these lines are optically thick and are produced in a dense, ionized wind. The near-infrared spectrum does not appear similar to any known FUor or EXor object. However, all evidence suggests that McNeil's Nebula Object is a heavily-embedded low-mass Class I protostar, surrounded by a disk, whose brightening is due to a recent accretion event.Comment: 11 pages, 2 ps figures, accepted for publication in ApJ Letter

Do Australian Football players have sensitive groins?:Players with current groin pain exhibit mechanical hyperalgesia of the adductor tendon

Objectives: This is the first study to evaluate the mechanical sensitivity, clinical classifications and prevalence of groin pain in Australian football players. Design Case-control. Methods: Professional (n = 66) and semi-professional (n = 9) Australian football players with and without current or previous groin injuries were recruited. Diagnoses were mapped to the Doha Agreement taxonomy. Point and career prevalence of groin pain was calculated. Pressure pain thresholds (PPTs) were assessed at regional and distant sites using handheld pressure algometry across four sites bilaterally (adductor longus tendon, pubic bone, rectus femoris, tibialis anterior muscle). To assess the relationship between current groin pain and fixed effects of hyperalgesia of each site and a history of groin pain, a mixed-effect logistic regression model was utilised. Receiver Operator Characteristic (ROC) curve were determined for the model. Results: Point prevalence of groin pain in the preseason was 21.9% with a career prevalence of 44.8%. Adductor-related groin pain was the most prevalent classification in the pre-season period. Hyperalgesia was observed in the adductor longus tendon site in athletes with current groin pain (OR = 16.27, 95% CI 1.86 to 142.02). The ROC area under the curve of the regression model was fair (AUC = 0.76, 95% CI 0.54 to 0.83). Conclusions: Prevalence data indicates that groin pain is a larger issue than published incidence rates imply. Adductor-related groin pain is the most common diagnosis in pre-season in this population. This study has shown that hyperalgesia exists in Australian football players experiencing groin pain indicating the value of assessing mechanical pain sensitivity as a component of the clinical assessment

Investigating the cut-off effect of n-alcohols on lipid movement: a biophysical study

Cellular membranes are responsible for absorbing the effects of external perturbants for the cell’s survival. Such perturbants include small ubiquitous molecules like n-alcohols which were observed to exhibit anesthetic capabilities, with this effect tapering off at a cut-off alcohol chain length. To explain this cut-off effect and complement prior biochemical studies, we investigated a series of nalcohols (with carbon lengths 2-18) and their impact on several bilayer properties, including lipid flip-flop, intervesicular exchange, diffusion, membrane bending rigidity and more. To this end, we employed an array of biophysical techniques such as time-resolved small angle neutron scattering (TRSANS), small angle X-ray scattering (SAXS), all atomistic and coarse-grained molecular dynamics (MD) simulations, and calcein leakage assays. At an alcohol concentration of 30 mol % of the overall lipid content, TR-SANS showed 1-hexanol (C6OH) increased transverse lipid diffusion, i.e. flip-flop. As alcohol chain length increased from C6 to C10 and longer, lipid flip-flop slowed by factors of 5.6 to 32.2. Intervesicular lipid exchange contrasted these results with only a slight cut-off at alcohol concentrations of 30 mol % but not 10 mol %. SAXS, MD simulations, and leakage assays revealed changes to key bilayer properties, such as bilayer thickness and fluidity, that correlate well with the effects on lipid flip-flop rates. Finally, we tie our results to a defect-mediated pathway for alcohol-induced lipid flip-flop

Vitamin e Does Not Disturb Polyunsaturated Fatty Acid Lipid Domains

The function of vitamin E in biomembranes remains a prominent topic of discussion. As its limitations as an antioxidant persist and novel functions are discovered, our understanding of the role of vitamin E becomes increasingly enigmatic. As a group of lipophilic molecules (tocopherols and tocotrienols), vitamin E has been shown to influence the properties of its host membrane, and a wealth of research has connected vitamin E to polyunsaturated fatty acid (PUFA) lipids. Here, we use contrast-matched small-angle neutron scattering and differential scanning calorimetry to integrate these fields by examining the influence of vitamin E on lipid domain stability in PUFA-based lipid mixtures. The influence of α-tocopherol, ?-tocopherol, and α-tocopherylquinone on the lateral organization of a 1:1 lipid mixture of saturated distearoylphosphatidylcholine (DSPC) and polyunsaturated palmitoyl-linoleoylphosphatidylcholine (PLiPC) with cholesterol provides a complement to our growing understanding of the influence of tocopherol on lipid phases. Characterization of domain melting suggests a slight depression in the transition temperature and a decrease in transition cooperativity. Tocopherol concentrations that are an order of magnitude higher than anticipated physiological concentrations (2 mol percent) do not significantly perturb lipid domains; however, addition of 10 mol percent is able to destabilize domains and promote lipid mixing. In contrast to this behavior, increasing concentrations of the oxidized product of α-tocopherol (α-tocopherylquinone) induces a proportional increase in domain stabilization. We speculate how the contrasting effect of the oxidized product may supplement the antioxidant response of vitamin E

Synthesis, structure and electrochemical properties of some thiosemicarbazone complexes of ruthenium

Reaction of salicylaldehyde thiosemicarbazone (L-1), 2-hydroxyacetophenone thiosemicarbazone (L-2) and 2-hydroxynapthaldehyde thiosemicarbazone (L-3) with [Ru(dmso)(4)Cl-2] affords a family of three dimeric complexes (1), (2) and (3) respectively. Crystal structure of the complex (3) has been determined. In these complexes, each monomeric unit consists of one ruthenium center and two thiosemicarbazone ligands, one of which is coordinated to ruthenium as O,N,S-donor and the other as N,S-donor forming a five-membered chelate ring. Two such monomeric units remain bridged by the sulfur atoms of the O,N,S-coordinated thiosemicarbazones. Due to this sulfur bridging, the two ruthenium centers become so close to each other, that a ruthenium-ruthenium single bond is also formed. All the complexes are diamagnetic in the solid state and in dimethylsulfoxide solution show intense absorptions in the visible and ultraviolet region. Origin of these spectral transitions has been established from DFT calculations. Cyclic voltammetry on the complexes shows two irreversible ligand oxidations on the positive side of SCE and two irreversible ligand reductions on the negative side

Methanol Accelerates DMPC Flip-Flop and Transfer: A SANS Study on Lipid Dynamics

© 2019 Biophysical Society Methanol is a common solubilizing agent used to study transmembrane proteins/peptides in biological and synthetic membranes. Using small angle neutron scattering and a strategic contrast-matching scheme, we show that methanol has a major impact on lipid dynamics. Under increasing methanol concentrations, isotopically distinct 1,2-dimyristoyl-sn-glycero-3-phosphocholine large unilamellar vesicle populations exhibit increased mixing. Specifically, 1,2-dimyristoyl-sn-glycero-3-phosphocholine transfer and flip-flop kinetics display linear and exponential rate enhancements, respectively. Ultimately, methanol is capable of influencing the structure-function relationship associated with bilayer composition (e.g., lipid asymmetry). The use of methanol as a carrier solvent, despite better simulating some biological conditions (e.g., antimicrobial attack), can help misconstrue lipid scrambling as the action of proteins or peptides, when in actuality it is a combination of solvent and biological agent. As bilayer compositional stability is crucial to cell survival and protein reconstitution, these results highlight the importance of methanol, and solvents in general, in biomembrane and proteolipid studies