Quantum-classical transition in Scale Relativity

The theory of scale relativity provides a new insight into the origin of fundamental laws in physics. Its application to microphysics allows us to recover quantum mechanics as mechanics on a non-differentiable (fractal) spacetime. The Schrodinger and Klein-Gordon equations are demonstrated as geodesic equations in this framework. A development of the intrinsic properties of this theory, using the mathematical tool of Hamilton's bi-quaternions, leads us to a derivation of the Dirac equation within the scale-relativity paradigm. The complex form of the wavefunction in the Schrodinger and Klein-Gordon equations follows from the non-differentiability of the geometry, since it involves a breaking of the invariance under the reflection symmetry on the (proper) time differential element (ds - ds). This mechanism is generalized for obtaining the bi-quaternionic nature of the Dirac spinor by adding a further symmetry breaking due to non-differentiability, namely the differential coordinate reflection symmetry (dx^mu - dx^mu) and by requiring invariance under parity and time inversion. The Pauli equation is recovered as a non-relativistic-motion approximation of the Dirac equation.Comment: 28 pages, no figur

Detecting and correcting partial errors: Evidence for efficient control without conscious access

Appropriate reactions to erroneous actions are essential to keeping behavior adaptive. Erring, however, is not an all-or-none process: electromyographic (EMG) recordings of the responding muscles have revealed that covert incorrect response activations (termed "partial errors") occur on a proportion of overtly correct trials. The occurrence of such "partial errors" shows that incorrect response activations could be corrected online, before turning into overt errors. In the present study, we showed that, unlike overt errors, such "partial errors" are poorly consciously detected by participants, who could report only one third of their partial errors. Two parameters of the partial errors were found to predict detection: the surface of the incorrect EMG burst (larger for detected) and the correction time (between the incorrect and correct EMG onsets; longer for detected). These two parameters provided independent information. The correct(ive) responses associated with detected partial errors were larger than the "pure-correct" ones, and this increase was likely a consequence, rather than a cause, of the detection. The respective impacts of the two parameters predicting detection (incorrect surface and correction time), along with the underlying physiological processes subtending partial-error detection, are discussed

Performance breakdown effects dissociate from error detection effects in typing

Mistakes in skilled performance are often observed to be slower than correct actions. This error slowing has been associated with cognitive control processes involved in performance monitoring and error detection. A limited literature on skilled actions, however, suggests that preerror actions may also be slower than accurate actions. This contrasts with findings from unskilled, discrete trial tasks, where preerror performance is usually faster than accurate performance. We tested 3 predictions about error-related behavioural changes in continuous typing performance. We asked participants to type 100 sentences without visual feedback. We found that (a) performance before errors was no different in speed than that before correct key-presses, (b) error and posterror key-presses were slower than matched correct key-presses, and (c) errors were preceded by greater variability in speed than were matched correct key-presses. Our results suggest that errors are preceded by a behavioural signature, which may indicate breakdown of fluid cognition, and that the effects of error detection on performance (error and posterror slowing) can be dissociated from breakdown effects (preerror increase in variability). © 2013 © 2013 The Experimental Psychology Society

Staphylococcus aureus Survives with a Minimal Peptidoglycan Synthesis Machine but Sacrifices Virulence and Antibiotic Resistance

Many important cellular processes are performed by molecular machines, composed of multiple proteins that physically interact to execute biological functions. An example is the bacterial peptidoglycan (PG) synthesis machine, responsible for the synthesis of the main component of the cell wall and the target of many contemporary antibiotics. One approach for the identification of essential components of a cellular machine involves the determination of its minimal protein composition. Staphylococcus aureus is a Gram-positive pathogen, renowned for its resistance to many commonly used antibiotics and prevalence in hospitals. Its genome encodes a low number of proteins with PG synthesis activity (9 proteins), when compared to other model organisms, and is therefore a good model for the study of a minimal PG synthesis machine. We deleted seven of the nine genes encoding PG synthesis enzymes from the S. aureus genome without affecting normal growth or cell morphology, generating a strain capable of PG biosynthesis catalyzed only by two penicillin-binding proteins, PBP1 and the bi-functional PBP2. However, multiple PBPs are important in clinically relevant environments, as bacteria with a minimal PG synthesis machinery became highly susceptible to cell wall-targeting antibiotics, host lytic enzymes and displayed impaired virulence in a Drosophila infection model which is dependent on the presence of specific peptidoglycan receptor proteins, namely PGRP-SA. The fact that S. aureus can grow and divide with only two active PG synthesizing enzymes shows that most of these enzymes are redundant in vitro and identifies the minimal PG synthesis machinery of S. aureus. However a complex molecular machine is important in environments other than in vitro growth as the expendable PG synthesis enzymes play an important role in the pathogenicity and antibiotic resistance of S. aureus

A simplified curcumin targets the membrane of Bacillus subtilis

Abstract Curcumin is the main constituent of turmeric, a seasoning popularized around the world with Indian cuisine. Among the benefits attributed to curcumin are anti‐inflammatory, antimicrobial, antitumoral, and chemopreventive effects. Besides, curcumin inhibits the growth of the gram‐positive bacterium Bacillus subtilis. The anti‐B. subtilis action happens by interference with the division protein FtsZ, an ancestral tubulin widespread in Bacteria. FtsZ forms protofilaments in a GTP‐dependent manner, with the concomitant recruitment of essential factors to operate cell division. By stimulating the GTPase activity of FtsZ, curcumin destabilizes its function. Recently, curcumin was shown to promote membrane permeabilization in B. subtilis. Here, we used molecular simplification to dissect the functionalities of curcumin. A simplified form, in which a monocarbonyl group substituted the β‐diketone moiety, showed antibacterial action against gram‐positive and gram‐negative bacteria of clinical interest. The simplified curcumin also disrupted the divisional septum of B. subtilis; however, subsequent biochemical analysis did not support a direct action on FtsZ. Our results suggest that the simplified curcumin exerted its function mainly through membrane permeabilization, with disruption of the membrane potential necessary for FtsZ intra‐cellular localization. Finally, we show here experimental evidence for the requirement of the β‐diketone group of curcumin for its interaction with FtsZ

Stress imaging in patients with a Fontan circulation: A systematic review

INTRODUCTION: The aims of this study were to provide an overview of the cardiac stress response in Fontan patients and of the use, safety and clinical value of stress imaging in Fontan patients. METHODS: Studies evaluating cardiac function using stress imaging in Fontan patients published up until 12 December 2021 were included in this review. RESULTS: From 1603 potential studies, 32 studies met the inclusion criteria. In total, stress imaging tests of 728 Fontan patients were included. Cardiac function was most often measured using physical stress (61%), all other studies used dobutamine-induced stress. Stroke volume (SV) increased in most studies (71%), mean SV at rest ranged from 27 mL/m 2 to 60 mL/m 2 versus 27 mL/m 2 to 101 mL/m 2 during stress, and increased with an average of 4%. Ejection fraction increased in almost all studies, whereas both end-systolic volume and end-diastolic volume decreased during stress. Higher heart rates were obtained with physical stress (82-180) compared to dobutamine induced stress (73-128). Compared to controls, increases in heartrate and SV were lower and end-diastolic volume decreased abnormally in 75% of reporting studies. No major adverse events were reported. Poorer cardiac stress response was related to decreased exercise capacity and higher risk for long-term (adverse) outcomes in Fontan patients. DISCUSSION: Cardiac stress response in Fontan patients differs from healthy subjects, reflected by lower increases in heart rate, diminished preload and decreased cardiac output, especially during higher levels of exercise. Stress imaging is safe, however the added clinical value needs to be investigated in more detail

Antibacterial activity of a new monocarbonyl analog of curcumin MAC 4 is associated with divisome disruption

Curcumin (CUR) is a symmetrical dicarbonyl compound with antibacterial activity. On the other hand, pharmacokinetic and chemical stability limitations hinder its therapeutic application. Monocarbonyl analogs of curcumin (MACs) have been shown to overcome these barriers. We synthesized and investigated the antibacterial activity of a series of unsymmetrical MACs derived from acetone against Mycobacterium tuberculosis and Gram-negative and Gram-positive species. Phenolic MACs 4, 6 and 8 showed a broad spectrum and potent activity, mainly against M. tuberculosis, Acinetobacter baumannii and methicillin-resistant Staphylococcus aureus (MRSA), with MIC (minimum inhibitory concentration) values ranging from 0.9 to 15.6 µg/mL. The investigation regarding toxicity on human lung cells (MRC-5 and A549 lines) revealed MAC 4 was more selective than MACs 6 and 8, with SI (selectivity index) values ranging from 5.4 to 15.6. In addition, MAC 4 did not demonstrate genotoxic effects on A549 cells and it was more stable than CUR in phosphate buffer (pH 7.4) for 24 h at 37 °C. Fluorescence and phase contrast microscopies indicated that MAC 4 has the ability to disrupt the divisome of Bacillus subtilis without damaging its cytoplasmic membrane. However, biochemical investigations demonstrated that MAC 4 did not affect the GTPase activity of B. subtilis FtsZ, which is the main constituent of the bacterial divisome. These results corroborated that MAC 4 is a promising antitubercular and antibacterial agent

Interaction and Modulation of Two Antagonistic Cell Wall Enzymes of Mycobacteria

Bacterial cell growth and division require coordinated cell wall hydrolysis and synthesis, allowing for the removal and expansion of cell wall material. Without proper coordination, unchecked hydrolysis can result in cell lysis. How these opposing activities are simultaneously regulated is poorly understood. In Mycobacterium tuberculosis, the resuscitation-promoting factor B (RpfB), a lytic transglycosylase, interacts and synergizes with Rpf-interacting protein A (RipA), an endopeptidase, to hydrolyze peptidoglycan. However, it remains unclear what governs this synergy and how it is coordinated with cell wall synthesis. Here we identify the bifunctional peptidoglycan-synthesizing enzyme, penicillin binding protein 1 (PBP1), as a RipA-interacting protein. PBP1, like RipA, localizes both at the poles and septa of dividing cells. Depletion of the ponA1 gene, encoding PBP1 in M. smegmatis, results in a severe growth defect and abnormally shaped cells, indicating that PBP1 is necessary for viability and cell wall stability. Finally, PBP1 inhibits the synergistic hydrolysis of peptidoglycan by the RipA-RpfB complex in vitro. These data reveal a post-translational mechanism for regulating cell wall hydrolysis and synthesis through protein–protein interactions between enzymes with antagonistic functions

Carotid Baroreflex Activation: Past, Present, and Future

Electrical activation of the carotid baroreceptor system is an attractive therapy for the treatment of resistant hypertension. In the past, several attempts were made to directly activate the baroreceptor system in humans, but the method had to be restricted to a few selected patients. Adverse effects, the need for better electrical devices and better surgical techniques, and the lack of knowledge about long-term effects has greatly hampered developments in this area for many years. Recently, a new and promising device was evaluated in a multicenter feasibility trial, which showed a clinically and statistically significant reduction in office systolic blood pressure (>20 mm Hg). This reduction could be sustained for at least 2 years with an acceptable safety profile. In the future, this new device may stimulate further application of electrical activation of the carotid baroreflex in treatment-resistant hypertension