Improved spatial separation of neutral molecules

We have developed and experimentally demonstrated an improved electrostatic deflector for the spatial separation of molecules according to their dipole-moment-to-mass ratio. The device features a very open structure that allows for significantly stronger electric fields as well as for stronger deflection without molecules crashing into the device itself. We have demonstrated its performance using the prototypical OCS molecule and we discuss opportunities regarding improved quantum-state-selectivity for complex molecules and the deflection of unpolar molecules.Comment: 6 figure

A 12-week lifestyle intervention: effects on fatigue, fear, and nutritional status in children with a Fontan circulation

IntroductionChildren and adolescents with a Fontan circulation are less physically active compared to healthy peers. In the current study, effects of a 12-week lifestyle intervention on fatigue, fears regarding exercise, caloric intake, rest energy expenditure (REE), and body composition were measured in children with a Fontan circulation.MethodsThis study was a semi-cross-over randomized controlled trial. The lifestyle intervention consisted of a 12-week high-weight resistance training (three supervised training sessions a week) supported by high-protein diet (>2 g/kg) and tailored recommended caloric intake. Fatigue (measured by the validated PedsQol Multidimensional Fatigue Scale), fears regarding exercise (measured on a fear thermometer), REE (measured using indirect calorimetry), caloric intake and body composition using air displacement plethysmography, and four-skinfold method were measured before and after the intervention and control period.ResultsTwenty-seven pediatric Fontan patients, median age 12.9 years (IQR: 10.5–16.2), of the included 28 patients successfully completed the program. Before training, both child- and parent-reported levels of fatigue were significantly worse on all domains (general, sleep/rest, and cognitive fatigue) compared to healthy peers. After training, parent-reported fatigue significantly improved on the general and cognitive fatigue domains [effect size +16 points (7–25), p < 0.001, and +10 points (2–17), p = 0.015, compared to the control period]. Before training, fear regarding exercise scored on the fear thermometer was low for both children and parents (median score 1 and 2, respectively, on a scale of 0–8). After training, child-reported fear decreased further compared to the control period [effect size −1.4 points (−2.3 to −0.6), p = 0.001]. At baseline, children had increased REE +12% compared to reference values, which did not change after exercise. Children ate an average of 637 calories below recommended intake based on REE, caloric deficit became smaller after the intervention, and protein intake increased compared to the control period [−388 calories (−674 to −102), p = 0.008, and +15 g (0.4–30), p = 0.044]. Body fat percentage did not change significantly.ConclusionA 12-week lifestyle intervention improved parent-reported fatigue symptoms in the children, further decreased child-reported fears, and increased caloric and protein intake

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

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

Australian Sphingidae – DNA Barcodes Challenge Current Species Boundaries and Distributions

© 2014 Rougerie et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The attached file is the published version of the article

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

Kinetic Modeling of the Assembly, Dynamic Steady State, and Contraction of the FtsZ Ring in Prokaryotic Cytokinesis

Cytokinesis in prokaryotes involves the assembly of a polymeric ring composed of FtsZ protein monomeric units. The Z ring forms at the division plane and is attached to the membrane. After assembly, it maintains a stable yet dynamic steady state. Once induced, the ring contracts and the membrane constricts. In this work, we present a computational deterministic biochemical model exhibiting this behavior. The model is based on biochemical features of FtsZ known from in vitro studies, and it quantitatively reproduces relevant in vitro data. An essential part of the model is a consideration of interfacial reactions involving the cytosol volume, where monomeric FtsZ is dispersed, and the membrane surface in the cell's mid-zone where the ring is assembled. This approach allows the same chemical model to simulate either in vitro or in vivo conditions by adjusting only two geometrical parameters. The model includes minimal reactions, components, and assumptions, yet is able to reproduce sought-after in vivo behavior, including the rapid assembly of the ring via FtsZ-polymerization, the formation of a dynamic steady state in which GTP hydrolysis leads to the exchange of monomeric subunits between cytoplasm and the ring, and finally the induced contraction of the ring. The model gives a quantitative estimate for coupling between the rate of GTP hydrolysis and of FtsZ subunit turnover between the assembled ring and the cytoplasmic pool as observed. Membrane constriction is chemically driven by the strong tendency of GTP-bound FtsZ to self-assembly. The model suggests a possible mechanism of membrane contraction without a motor protein. The portion of the free energy of GTP hydrolysis released in cyclization is indirectly used in this energetically unfavorable process. The model provides a limit to the mechanistic complexity required to mimic ring behavior, and it highlights the importance of parallel in vitro and in vivo modeling

Challenges in body composition assessment using air-displacement plethysmography by BOD POD in pediatric and young adult patients

Background &amp; aims: Air-Displacement-Plethysmography (ADP) by BOD POD is widely used for body fat assessment in children. Although validated in healthy subjects, studies about use in pediatric patients are lacking. We evaluated user experience and usability of ADP measurements with the BOD POD system in healthy children and pediatric and young adult patients. Methods: Using the experiences of seven cohort studies, which included healthy children and patients aged 2–22 years, we retrospectively evaluated the user experience with the User Experience Questionnaire (UEQ) (n = 13) and interviews (n = 7). Technical performance was studied using the quality control data collected by the ADP-system. Results: From 2016 to 2022, 1606 measurements were scheduled. BOD POD was mostly rated ‘user-friendly’, with a generally neutral evaluation on all scales of the UEQ. However, questionable reliability and validity of the results were frequently (86%) reported. We found a high technical failure-rate of the device, predominantly in stability (17%) and accuracy of the measurement (12%), especially in the ‘pediatric option’ for children aged &lt;6 years. Measurement failure-rate was 38%, mostly due to subject's fear or device failure, especially in young and lean children, and in children with physical and/or intellectual disabilities. Conclusion: We conclude that ADP by BOD POD in children and young adults is non-invasive and user-friendly. However, in specific pediatric populations, BOD POD has several limitations and high (technical) failure-rates, especially in young children with aberrant body composition. We recommend caution when interpreting body composition results of pediatric patients as assessed with BOD POD using the current default settings.</p