LipidII:Just Another Brick in the Wall?

Nearly all bacteria contain a peptidoglycan cell wall. The peptidoglycan precursor molecule is LipidII, containing the basic peptidoglycan building block attached to a lipid. Although the suitability of LipidII as an antibacterial target has long been recognized, progress on elucidating the role(s) of LipidII in bacterial cell biology has been slow. The focus of this review is on exciting new developments, both with respect to antibacterials targeting LipidII as well as the emerging role of LipidII in organizing the membrane and cell wall synthesis. It appears that on both sides of the membrane, LipidII plays crucial roles in organizing cytoskeletal proteins and peptidoglycan synthesis machineries. Finally, the recent discovery of no less than three different categories of LipidII flippases will be discussed

In vivo cluster formation of nisin and Lipid II is correlated with membrane depolarization

Nisin and related lantibiotics kill bacteria by pore formation, or by sequestering Lipid II. Some lantibiotics sequester Lipid II into clusters, which were suggested to kill cells through delocalized peptidoglycan synthesis. Here, we show that cluster formation is always concomitant with (i) membrane pore formation and (ii) membrane depolarization. Nisin variants that cluster Lipid II kill L-form bacteria with similar efficiency, suggesting that delocalization of peptidoglycan synthesis is not the primary killing mechanism of these lantibiotics

The association between indoor temperature and body mass index in children:the PIAMA birth cohort study

Background: Several experimental studies showed consistent evidence for decreased energy expenditure at higher ambient temperatures. Based on this, an association between thermal exposure and body weight may be expected. However, the effect of thermal exposure on body weight has hardly been studied. Therefore, this study investigated the association between indoor temperature and body mass index (BMI) in children in real life. Methods: This longitudinal observational study included 3 963 children from the Dutch Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort that started in 1996. These children were followed from birth until the age of 11 years. Winter indoor temperature (living room and bedroom) was reported at baseline and BMI z-scores were available at 10 consecutive ages. Missing data were multiply imputed. Associations between indoor temperature and BMI were analyzed using generalized estimating equations (GEE), adjusted for confounders and stratified by gender. In a subgroup of 104 children, bedroom temperature was also measured with data loggers. Results: Mean reported living room and bedroom temperature were 20.3 degrees C and 17.4 degrees C, respectively. Reported and measured bedroom temperatures were positively correlated (r = 0.42, p = 0.001). Neither reported living room temperature (-0.03 = 0.04) and bedroom temperature (-0.01 = 0.02) nor measured bedroom temperature (-0.04 = 0.05) were associated with BMI z-score between the age of 3 months and 11 years. Conclusions: This study in children did not support the hypothesized association between indoor temperature and BMI in a real life setting

Psychomotor therapy targeting anger and aggressive behaviour in individuals with mild or borderline intellectual disabilities:A systematic review

Background: Poor anger regulation is considered a risk factor of aggression in individuals with mild or borderline intellectual disabilities. Psychomotor therapy (PMT) targets anger regulation through body- and movement-oriented interventions. This study aims to inform practitioners on efficacy and research-base of PMT in this population. Method: This systematic review evaluated nine studies which met inclusion criteria in terms of participants, intervention procedures, outcomes and certainty of evidence. Results: Seven studies revealed a substantial reduction of aggressive behaviour or anger. Certainty of evidence was rated inconclusive in most cases due to absence of experimental control. Conclusions: We can conclude that body-oriented PMT, involving progressive relaxation and meditation procedure "Soles of the Feet", is a promising approach. However, the paucity of studies and methodological limitations preclude classifying it as an evidence-based practice. This suggests stronger methodological research and research aimed at PMT's mechanisms of action (e.g., improved interoceptive awareness) is warranted.</p

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

Conservation planning in an uncertain climate: Identifying projects that remain valuable and feasible across future scenarios

Conservation actors face the challenge of allocating limited resources despite uncertainty about future climate conditions. In many cases, the potential value and feasibility of proposed projects vary across climate scenarios. A key goal is to identify areas where conservation outcomes can balance both environmental and human needs. We developed a conservation prioritization framework that jointly considers the value and feasibility of candidate projects across future climate scenarios. We then applied this framework to the challenge of meeting environmental flow targets across the Red River basin of the south‐central United States. To estimate the conservation feasibility of meeting environmental flow goals in a river reach in each climate scenario, we used a basin‐wide hydrologic planning tool to quantify the reduction in societal water usage needed to meet environmental flow targets. To estimate the biodiversity value of each river reach in each climate scenario, we used climate‐driven species distribution models and species’ conservation status. We found that river reaches in the east‐central portion of the basin may be good candidates for conservation investments, because they had high biodiversity value and high sociopolitical feasibility in all future climate scenarios. In contrast, sites in the arid western reaches of the basin had high biodiversity value, but low feasibility of achieving environmental flow goals. Our framework should have broad applicability given that the value and feasibility of conservation projects vary across climate scenarios in ecosystems around the world. It may serve as a coarse filter to identify sites for more detailed analyses and could be integrated with complementarity‐based approaches to conservation planning to balance species’ representation across projects.This research was supported by S.M.W.'s Science to Action Fellowship through the National Climate Adaptation Science Center at the US Geological Survey. U.S. Geological Survey. Grant Number: G17AP00120 Open Access fees paid for in whole or in part by the University of Oklahoma Libraries.Ye

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

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

Global maps of soil temperature

Research in global change ecology relies heavily on global climatic grids derived from estimates of air temperature in open areas at around 2 m above the ground. These climatic grids do not reflect conditions below vegetation canopies and near the ground surface, where critical ecosystem functions occur and most terrestrial species reside. Here, we provide global maps of soil temperature and bioclimatic variables at a 1-km(2) resolution for 0-5 and 5-15 cm soil depth. These maps were created by calculating the difference (i.e. offset) between in situ soil temperature measurements, based on time series from over 1200 1-km(2) pixels (summarized from 8519 unique temperature sensors) across all the world's major terrestrial biomes, and coarse-grained air temperature estimates from ERA5-Land (an atmospheric reanalysis by the European Centre for Medium-Range Weather Forecasts). We show that mean annual soil temperature differs markedly from the corresponding gridded air temperature, by up to 10 degrees C (mean = 3.0 +/- 2.1 degrees C), with substantial variation across biomes and seasons. Over the year, soils in cold and/or dry biomes are substantially warmer (+3.6 +/- 2.3 degrees C) than gridded air temperature, whereas soils in warm and humid environments are on average slightly cooler (-0.7 +/- 2.3 degrees C). The observed substantial and biome-specific offsets emphasize that the projected impacts of climate and climate change on near-surface biodiversity and ecosystem functioning are inaccurately assessed when air rather than soil temperature is used, especially in cold environments. The global soil-related bioclimatic variables provided here are an important step forward for any application in ecology and related disciplines. Nevertheless, we highlight the need to fill remaining geographic gaps by collecting more in situ measurements of microclimate conditions to further enhance the spatiotemporal resolution of global soil temperature products for ecological applications.Peer reviewe