The AAA+ ATPase RavA-ViaA complex sensitizes Escherichia coli to aminoglycosides under anaerobic low energy conservation conditions

Aminoglycosides have been used against Gram-negative bacteria for decades. Yet, uncertainties remain about various aspects of their uptake mechanism. Moreover their killing efficiency is well known to vary as a function of growth conditions and types of metabolism used by the targeted bacterium. Here we show that RavA, an AAA+ ATPase from the MoxR subfamily, associated with its VWA-containing partner, ViaA sensitize E. coli to lethal concentrations of AG, including gentamycin (Gm) and tobramycin, but not of antibiotics of other classes. We show this sensitizing effect to be due to enhanced Gm uptake in a proton motive force dependent manner. We evaluated the influence of RavA ViaA throughout a series of growth conditions, including aerobiosis and anaerobiosis. This led us to observe that the sensitizing effect of RavA ViaA varies with the respiratory chain used, i.e. RavA ViaA influence was prominent in the absence of exogenous electron acceptor or with fumarate, i.e. in poor energy conservation conditions, and dispensable in the presence of nitrate or oxygen, i.e. in high level of energy conservation. We propose RavA ViaA to be able to sense energetic state of the cell and to be used under low energy conditions for facilitating uptake of chemicals across the membrane, including Gm.

Stationary Lactococcus cremoris: Energetic State, Protein Synthesis Without Nitrogen and Their Effect on Survival

During storage and ripening of fermented foods, Lactococcus cremoris is predominantly in a non-growing state. L. cremoris can become stationary due to starvation or acidification, and its metabolism in these non-growing states affects the fermented product. Available studies on the response of L. cremoris to acid and starvation stress are based on population level data. We here characterized the energetic state and the protein synthesis capacity of stationary L. cremoris cultures at the single cell level. We show that glucose starved stationary cells are energy-depleted, while acid-induced stationary cells are energized and can maintain a pH gradient over their membrane. In the absence of glucose and arginine, a small pH gradient can still be maintained. Subpopulations of stationary cells can synthesize protein without a nitrogen source, and the subpopulation size decreases with increasing stationary phase length. Protein synthesis capacity during starvation only benefits culturability after 6 days. These results highlight significant differences between glucose starved stationary and acid-induced stationary cells. Furthermore, they show that the physiology of stationary phase L. cremoris cells is multi-facetted and heterogeneous, and the presence of an energy source during stationary phase impacts the cells capacity to adapt to their environment.

Embodied Instruction: An Exploration and Qualitative Comparison of Expression and Performance of Yoga Instruction

Background: An inclusive, whole-child model of education is shifting the paradigm into an integrative mind-body approach. Toward contextualizing learning at the close of the cartesian era, the current work explores embodied instruction through the lens of a teacher whose primary focus is the integration of mind and body. Perhaps the longest standing curriculum aimed at embodied learning, yoga provides a unique perspective on techniques and experiences of embodied teaching.Method: This case study employed an in-depth explorative participatory design to observe instructor intentions in and performance of instruction. Consecutive interviews (5) in conjunction with participatory observation of weekly classes (8) were audio recorded, transcribed verbatim, and triangulated with researcher memos. A grounded and comparative methodology was used to analyze expressed understanding of embodied learning and performed instruction.Results: In-depth interviews revealed four themes of expressed understanding of embodied instruction: energetic state, personality of instruction, inviting experience and student vulnerability. Participatory observations revealed four themes of performance of embodied instruction: scoping, cadence, silence, and inviting practice. Overlap in expressed understanding and observed instruction were found in each theme. An example of the expressed understanding of a thematic concept is inviting experience: “If someone comes in the very first time and the teacher is very invasive and says, “Do this, do this, do this.” And the next pose the teacher is hovering over them, you are not going to go back. You are going to hate it so much [I] let people be really all over the place at the beginning as long as they are safe. [I] allow them that kind of freedom, initially”. This was further supported in the observed instruction; an example of this is: “We’re going to play with [a posture]. that firmness in your abs, engage the core so a foot might lift. Maybe both feet.” And “with the arms firm, maybe the legs straighten”.Conclusion: The current study yields preliminary insight into yoga instruction strategies to support further development of embodied teaching and learning.

Age-Dependent Honey Bee Appetite Regulation Is Mediated by Trehalose and Octopamine Baseline Levels

There are multiple feedback mechanisms involved in appetite regulation, which is an integral part of maintaining energetic homeostasis. Older forager honey bees, in comparison to newly emerged bees and nurse bees, are known to have highly fluctuating hemolymph trehalose levels, higher appetite changes due to starvation, and higher octopamine levels in the brain. What remains unknown is if the hemolymph trehalose and octopamine levels interact with one another and how this varies as the bee ages. We manipulated trehalose and octopamine levels across age using physiological injections and found that nurse and forager bees increase their appetite levels due to increased octopamine levels in the brain. This is further enhanced by lower trehalose levels in the hemolymph. Moreover, nurse bees with high octopamine levels in the brain and low trehalose levels had the same appetite levels as untreated forager bees. Our findings suggest that the naturally higher levels of octopamine as the bee ages may result in higher sensitivity to fluctuating trehalose levels in the hemolymph that results in a more direct way of assessing the energetic state of the individual. Consequently, forager bees have a mechanism for more precise regulation of appetite in comparison to newly emerged and nurse bees.

Genetic variants of the EGFR ligand-binding domain and their association with structural alterations in Arab cancer patients

Objective This study aimed to identify novel genetic variants in the CR2 extracellular domain of the epidermal growth factor receptor (EGFR) in healthy individuals and patients with six different types of adenocarcinoma, in Arabian peninsula populations. It also aimed to investigate the effects of these variants on the EGFR structure and their eventual relevance to tumorigenesis. Results We detected seven new EGFR genetic variants in 168 cancer patients and 114 controls. A SNP rs374670788 was more frequent in bladder cancer but not significantly associated to. However, a missense mutation (V550M) was significantly associated to colon, ovary, lung, bladder and thyroid cancer samples (p < 0.05). Three mutations (H590R, E602K and T605T) were found in the heterozygous form only in colon cancer patients. Genomic analysis of the synonymous mutation (G632G) showed that the T/A genotype could be associated to thyroid cancer in Arab patients (p < 0.05). An additional novel SNP rs571064657 was observed in control individuals. Computational analysis of the genetic variants revealed a reduction in the stabilization of the EGFR tethered form for both V550M and the common R521K variant with low energetic state (− ∆∆G). Molecular interactions analysis suggested that these mutations might affect the receptor’s function and promote tumorigenesis.

Energetic state and the continuum of migratory tactics in brown trout (Salmo trutta)

Alternative migratory tactics, like partial migration, are common in many taxa. The proximate and ultimate drivers underpinning these strategies are unclear, though factors like condition and energetic status have been posited as important predictors. We sampled and PIT tagged 1882 wild brown trout prior to the first so-called decision window, and explored the links between migratory tactics (residency, autumn or spring migration) and body metrics (length and condition), lipids (triglycerides and cholesterol), and sex, in 150 randomly selected individuals. We found that more females adopted the autumn and spring migration tactic than males, while more males adopted the residency tactic than females, likely reflecting sex-biased benefits in anadromy. We also found that autumn migrants were in poorer condition prior to the presumed first decision window than spring migrants and residents. Lastly, we found that both condition and cholesterol were positively correlated to the timing of migration, such that individuals in poorer condition and/or with lower cholesterol migrated earlier. Collectively, these results suggest that energy depletion is an important factor in determining migratory strategy, including timing.

Medicinal Plants in Physical Exercise: A Review

Background: The use of medicinal plants may have an effective action on the performance of athletes. Aims: This review aimed to evaluate the effects of the use of medicinal plants and some phytocompounds on physical performance. Methodology: MEDLINE/PUBMED and EMBASE were consulted following the PRISMA guidelines. Results: Panax ginseng increases the anti-fatigue effect, decreases the stress promoted by the physical exercise, and improves muscular function through gene expression enhancement. Arnica montana has a crucial anti-inflammatory action showing relief of muscular pain a. Zingiber officinale has an anti-inflammatory and analgesic role on muscular pain, and it can be used to speed up the recovery of muscular strength after intense activity. Ephedra sinica is related to thermogenic and sympathomimetic effects, being able to increase the energetic state. Capsaicin increases the energetic expenditure due to fat oxidation, promotes the anti-fatigue effect, and enhances the athlete’s resistance. Caffeine has ergogenic importance related to its antioxidant capacity, and it improves mental alertness condition. Conclusion: The nutritional supplementation with products derived from medicinal plants may be an efficient alternative to improve the athlete’s performance, being a natural substitute for synthetic supplements, which usually are forbidden in competitions.

Molecular Dynamics Study on SiO2 Interfaces of Nonfiring Solids

As a sustainable ecosystem, the general firing process for ceramics emits large amounts of CO2 gas; thus in ceramics production, the focus is the nonfiring process; however, the solidification and strengthen mechanism of this nonfiring system, which essentially reacts between surface-activated ceramic particles and a solvent, has not been elucidated to date. The nonfiring process had three steps, i.e., particle surface activate process by grinding process, maintaining the active state until starting nonfiring solidification begins, and nonfiring solidification process. Thus, in this study, the reaction of silica and water was simulated by adapting molecular dynamics based on LAMMPS with ReaxFF potentials. Reproducing the activated silica surface state, three ended models called O model, Si model, and OH model were prepared which indicated ended molecules of each surface. These models and a water molecule as a solvent were bonded in the atomic scale, and the energetic state and mechanical properties were evaluated. A reacted or structured O-H-O bond was reproduced in the nonfiring process in the O-ended model. The bond was a hydrogen bond. A Si-O-Si bond was produced when a Si atom was ended on the interface. The bonded interface was able to tensile. However, the tensile strength was weaker than that of the solid silica model. The nonbonded OH model did not have tensile strength.

The Implications of PDK1–4 on Tumor Energy Metabolism, Aggressiveness and Therapy Resistance

A metabolic shift from oxidative phosphorylation (OXPHOS) to glycolysis—known as the Warburg effect—is characteristic for many cancers. It gives the cancer cells a survival advantage in the hypoxic tumor microenvironment and protects them from cytotoxic effects of oxidative damage and apoptosis. The main regulators of this metabolic shift are the pyruvate dehydrogenase complex and pyruvate dehydrogenase kinase (PDK) isoforms 1–4. PDK is known to be overexpressed in several cancers and is associated with bad prognosis and therapy resistance. Whereas the expression of PDK1–3 is tissue specific, PDK4 expression is dependent on the energetic state of the whole organism. In contrast to other PDK isoforms, not only oncogenic, but also tumor suppressive functions of PDK4 have been reported. In tumors that profit from high OXPHOS and high de novo fatty acid synthesis, PDK4 can have a protective effect. This is the case for prostate cancer, the most common cancer in men, and makes PDK4 an interesting therapeutic target. While most work is focused on PDK in tumors characterized by high glycolytic activity, little research is devoted to those cases where PDK4 acts protective and is therefore highly needed.