Motivations for understanding the underlying mechanisms of alcohol toxicity range from economical to toxicological and clinical. On the one hand, acute alcohol toxicity limits biofuel yields, and on ...the other hand, acute alcohol toxicity provides a vital defense mechanism to prevent the spread of disease. Herein the role that stored curvature elastic energy (SCE) in biological membranes might play in alcohol toxicity is discussed, for both short and long-chain alcohols. Structure–toxicity relationships for alcohols ranging from methanol to hexadecanol are collated, and estimates of alcohol toxicity per alcohol molecule in the cell membrane are made. The latter reveal a minimum toxicity value per molecule around butanol before alcohol toxicity per molecule increases to a maximum around decanol and subsequently decreases again. The impact of alcohol molecules on the lamellar to inverse hexagonal phase transition temperature (T H ) is then presented and used as a metric to assess the impact of alcohol molecules on SCE. This approach suggests the nonmonotonic relationship between alcohol toxicity and chain length is consistent with SCE being a target of alcohol toxicity. Finally, in vivo evidence for SCE-driven adaptations to alcohol toxicity in the literature are discussed.
Memories are stored and retained through complex, coupled processes operating on multiple timescales. To understand the computational principles behind these intricate networks of interactions, we ...construct a broad class of synaptic models that efficiently harness biological complexity to preserve numerous memories by protecting them against the adverse effects of overwriting. The memory capacity scales almost linearly with the number of synapses, which is a substantial improvement over the square root scaling of previous models. This was achieved by combining multiple dynamical processes that initially store memories in fast variables and then progressively transfer them to slower variables. Notably, the interactions between fast and slow variables are bidirectional. The proposed models are robust to parameter perturbations and can explain several properties of biological memory, including delayed expression of synaptic modifications, metaplasticity, and spacing effects.
The observation of place cells has suggested that the hippocampus plays a special role in encoding spatial information. However, place cell responses are modulated by several nonspatial variables and ...reported to be rather unstable. Here, we propose a memory model of the hippocampus that provides an interpretation of place cells consistent with these observations. We hypothesize that the hippocampus is a memory device that takes advantage of the correlations between sensory experiences to generate compressed representations of the episodes that are stored in memory. A simple neural network model that can efficiently compress information naturally produces place cells that are similar to those observed in experiments. It predicts that the activity of these cells is variable and that the fluctuations of the place fields encode information about the recent history of sensory experiences. Place cells may simply be a consequence of a memory compression process implemented in the hippocampus.
•Review of lipid monolayer spontaneous curvatures.•Structural trends in lipid intrinsic curvatures.•Lipid Intrinsic curvatures collated; gaps identified.
Lipid monolayer spontaneous curvatures (or ...lipid intrinsic curvatures) are one of several material properties of lipids that enable the stored curvature elastic energy in a lipid aggregate to be determined. Stored curvature elastic energy is important since it can modulate the function of membrane proteins and plays a role in the regulatory pathways of phospholipid homeostasis. Due to the large number of different lipid molecules that might theoretically exist in nature, very few lipid spontaneous curvatures have been determined. Herein the values of lipid spontaneous curvatures that exist in the literature are collected, alongside key experimental details. Where possible, trends in the data are discussed and finally, obvious gaps in the knowledge are signposted.
In this study, we report nonmetal plasmonic MoS2@TiO2 heterostructures for highly efficient photocatalytic H2 generation. Large area laminated MoS2 in conjunction with TiO2 nanocavity arrays is ...achieved via carefully controlled anodization, physical vapor deposition, and chemical vapor deposition processes. The broad spectral response ranging from ultraviolet-visible (UV-vis) to near-infrared (NIR) wavelengths and finite element frequency-domain simulations suggest that this MoS2@TiO2 heterostructure enhances photocatalytic activity for H+ reduction. A high H2 yield rate of 181 μmol h−1 cm−2 (equal to 580 mmol h−1 g−1 based on the loading mass of MoS2) is achieved using a low catalyst loading mass. The spatially uniform heterostructure, correlated with plasmon-resonance through the conformal MoS2 coating that effectively regulates charge transfer pathways, is proven to be vitally important for the unique solar energy harvesting and photocatalytic H2 production. As an innovative exploration, our study demonstrates that the photocatalytic activities of nonmetal, earth-abundant materials can be enhanced with plasmonic effects, which may serve as an excellent catalytic agent for solar energy conversion to chemical fuels.
Abstract
Monoterpene indole alkaloids (MIAs) are a diverse family of complex plant secondary metabolites with many medicinal properties, including the essential anti-cancer therapeutics vinblastine ...and vincristine
1
. As MIAs are difficult to chemically synthesize, the world’s supply chain for vinblastine relies on low-yielding extraction and purification of the precursors vindoline and catharanthine from the plant
Catharanthus roseus
, which is then followed by simple in vitro chemical coupling and reduction to form vinblastine at an industrial scale
2,3
. Here, we demonstrate the de novo microbial biosynthesis of vindoline and catharanthine using a highly engineered yeast, and in vitro chemical coupling to vinblastine. The study showcases a very long biosynthetic pathway refactored into a microbial cell factory, including 30 enzymatic steps beyond the yeast native metabolites geranyl pyrophosphate and tryptophan to catharanthine and vindoline. In total, 56 genetic edits were performed, including expression of 34 heterologous genes from plants, as well as deletions, knock-downs and overexpression of ten yeast genes to improve precursor supplies towards de novo production of catharanthine and vindoline, from which semisynthesis to vinblastine occurs. As the vinblastine pathway is one of the longest MIA biosynthetic pathways, this study positions yeast as a scalable platform to produce more than 3,000 natural MIAs and a virtually infinite number of new-to-nature analogues.
The curse of dimensionality plagues models of reinforcement learning and decision making. The process of abstraction solves this by constructing variables describing features shared by different ...instances, reducing dimensionality and enabling generalization in novel situations. Here, we characterized neural representations in monkeys performing a task described by different hidden and explicit variables. Abstraction was defined operationally using the generalization performance of neural decoders across task conditions not used for training, which requires a particular geometry of neural representations. Neural ensembles in prefrontal cortex, hippocampus, and simulated neural networks simultaneously represented multiple variables in a geometry reflecting abstraction but that still allowed a linear classifier to decode a large number of other variables (high shattering dimensionality). Furthermore, this geometry changed in relation to task events and performance. These findings elucidate how the brain and artificial systems represent variables in an abstract format while preserving the advantages conferred by high shattering dimensionality.
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•The geometry of abstraction supports generalization•Hippocampal and PFC representations are simultaneously abstract and high dimensional•Multiple task-relevant variables are represented in an abstract format•Representations in simulated neural networks are similar to recorded ones
Different types of cognitive, emotional, and behavioral flexibility—generalization in novel situations and the ability to generate many different responses to complex patterns of inputs—place different demands on neural representations. This paper shows how the geometry of neural representations can be critical for elucidating how the brain supports these forms of flexible behavior.
The effects of oxidative stress on cells are associated with a wide range of pathologies. Oxidative stress is predominantly initiated by the action of reactive oxygen species and/or lipoxygenases on ...polyunsaturated fatty acid containing lipids. The downstream products are oxidised phospholipids, bioactive aldehydes and a range of Schiff base by-products between aldehydes and lipids, or other biomacromolecules. In this review we assess the impact of oxidative stress on lipid membranes, focusing on the changes that occur to the curvature preference (lipid spontaneous curvature) and elastic properties of membranes, since these biophysical properties modulate phospholipid homeostasis. Studies show that the lipid products of oxidative stress reduce stored curvature elastic energy in membranes. Based upon this observation, we hypothesize that the effects of oxidative stress on lipid membranes will be reduced by compounds that increase stored curvature elastic energy. We find a strong correlation appears across literature studies that we have reviewed, such that many compounds like vitamin E, Curcumin, Coenzyme Q10 and vitamin A show behaviour consistent with this hypothesis. Finally, we consider whether age-related changes in lipid composition represent the homeostatic response of cells to compensate for the accumulation of in vivo lipid oxidation products.
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•Oxidative stress in lipid membranes lowers membrane curvature elastic energy.•Antioxidants may ameliorate oxidative stress by raising curvature elastic energy.•Age-related lipid changes: evidence of the cell's effort to ameliorate oxidative stress.
Component studies compare standard treatments to treatments with added components or dismantled components. A previous meta-analysis (Ahn & Wampold, 2001) failed to find any differences in outcome ...between treatments with more components and those with fewer components, leading the authors to conclude that common factors and not specific ingredients account for therapeutic change.
The current random effects model meta-analysis of psychotherapy component studies conducted between 1980 and 2010 included more than 3 times as many studies as Ahn and Wampold's (2001) meta-analysis (k = 66). Unlike the previous meta-analysis, this study conducted separate meta-analyses for additive and dismantling studies and also examined treatment outcomes at follow-up.
For the dismantling studies, there were no significant differences between the full treatments and the dismantled treatments. For the additive studies, the treatment with the added component yielded a small, but significant, effect at completion (d = 0.14) and a slightly larger effect at follow-up (d = 0.28), but only for the specific problems that were targeted for treatment. Despite the diversity of populations studied, problems treated, and treatments examined, there was little heterogeneity among the results of these studies.
These findings suggest that added specific ingredients may contribute modestly to treatment outcomes.
Recent research on nanoparticles in a number of crops has evidenced for enhanced germination and seedling growth, physiological activities including photosynthetic activity and nitrogen metabolism, ...mRNA expression and protein level, and also positive changes in gene expression indicating their potential use in crop improvement. We used a medicinally rich vegetable crop, bitter melon, as a model to evaluate the effects of seed treatment with a carbon-based nanoparticle, fullerol C60(OH)20, on yield of plant biomass and fruit characters, and phytomedicine contents in fruits.
We confirmed the uptake, translocation and accumulation of fullerol through bright field imaging and Fourier transform infra-red spectroscopy. We observed varied effects of seed treatment at five concentrations, including non-consequential and positive, on plant biomass yield, fruit yield and its component characters, and content of five phytomedicines in fruits. Fullerol-treatment resulted in increases up to 54% in biomass yield and 24% in water content. Increases of up to 20% in fruit length, 59% in fruit number, and 70% in fruit weight led to an improvement up to 128% in fruit yield. Contents of two anticancer phytomedicines, cucurbitacin-B and lycopene, were enhanced up to 74% and 82%, respectively, and contents of two antidiabetic phytomedicines, charantin and insulin, were augmented up to 20% and 91%, respectively. Non-significant correlation inter se plant biomass, fruit yield, phytomedicine content and water content evidenced for separate genetic control and biosynthetic pathways for production of plant biomass, fruits, and phytomedicines in fruits, and also no impact of increased water uptake.
While our results indicated possibility of improving crop yield and quality by using proper concentrations of fullerol, extreme caution needs to be exercised given emerging knowledge about accumulation and toxicity of nanoparticles in bodily tissues.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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