Mutations and changes in a protein's environment are well known for their potential to induce misfolding and aggregation, including amyloid formation. Alternatively, such perturbations can trigger ...new interactions that lead to the polymerization of folded proteins. In contrast to aggregation, this process does not require misfolding and, to highlight this difference, we refer to it as agglomeration. This term encompasses the amorphous assembly of folded proteins as well as the polymerization in one, two, or three dimensions. We stress the remarkable potential of symmetric homo‐oligomers to agglomerate even by single surface point mutations, and we review the double‐edged nature of this potential: how aberrant assemblies resulting from agglomeration can lead to disease, but also how agglomeration can serve in cellular adaptation and be exploited for the rational design of novel biomaterials.
The term agglomeration encompasses the amorphous assembly of folded proteins as well as their 1D, 2D, or 3D polymerization. Symmetric homo‐oligomers are prone to agglomerate, even through single surface point mutations. This Review summarizes how agglomeration can lead to aberrant assemblies and cause disease, how it can serve in cellular adaptation, and how it can be exploited for the rational design of novel biomaterials.
Background: Major depressive disorder is a common, chronic condition that imposes a substantial burden of disability globally. As current treatments are estimated to address only one-third of the ...disease burden of depressive disorders, there is a need for new approaches to prevent depression or to delay its progression. While in its early stages, converging evidence from laboratory, population research, and clinical trials now suggests that dietary patterns and specific dietary factors may influence the risk for depression. However, largely as a result of the recency of the nutritional psychiatry field, there are currently no dietary recommendations for depression.
Aim: The aim of this paper is to provide a set of practical dietary recommendations for the prevention of depression, based on the best available current evidence, in order to inform public health and clinical recommendations.
Results: Five key dietary recommendations for the prevention of depression emerged from current published evidence. These comprise: (1) follow 'traditional' dietary patterns, such as the Mediterranean, Norwegian, or Japanese diet; (2) increase consumption of fruits, vegetables, legumes, wholegrain cereals, nuts, and seeds; (3) include a high consumption of foods rich in omega-3 polyunsaturated fatty acids; (4) replace unhealthy foods with wholesome nutritious foods; (5) limit your intake of processed-foods, 'fast' foods, commercial bakery goods, and sweets.
Conclusion: Although there are a number of gaps in the scientific literature to date, existing evidence suggests that a combination of healthful dietary practices may reduce the risk of developing depression. It is imperative to remain mindful of any protective effects that are likely to come from the cumulative and synergic effect of nutrients that comprise the whole-diet, rather than from the effects of individual nutrients or single foods. As the body of evidence grows from controlled intervention studies on dietary patterns and depression, these recommendations should be modified accordingly.
Celotno besedilo
Dostopno za:
DOBA, FSPLJ, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Dermal exposure to metal(loid)s from contaminated soils has received less attention than oral and inhalation exposure. Still, it can be a relevant pathway for some contaminants. Comparison of ...synthetic sweats (donor solutions), the influence of sebum, and the characterization of diffusion parameters through a synthetic membrane (acting as skin surrogate) in the permeation of metal(loid)s (As, Cr, Cu, Ni, Pb, and, Zn) from polluted soils is missing. The dermal bioaccessibility tests were performed using two sweat compositions EN 1811, pH 6.5 (sweat A) and NIHS 96–10, pH 4.7 (sweat B). Diffusion parameters of soluble metal(loid)s using the Franz cell methodology were calculated using the Strat-M membrane. The influence of synthetic sebum in the permeation of metal(loid)s was also investigated. The metal(loid) bioaccessibility percentage was higher for sweat B (pH 4.7) compared to sweat A (pH 6.5), attributed to lower pH of sweat B. Among the six elements tested, only chromium and copper permeated the membrane. Permeation coefficient (K p) was higher for chromium in sweat A (0.05–0.11 cm h–1) than sweat B (0.0007–0.0037 cm h–1) likely due to a higher pH and thus more permeable Cr species. The presence of sebum increased lag times for copper permeation. Additional studies regarding speciation of metal(loid)s following extractions in synthetic sweat and comparison of synthetic membrane Strat-M and human skin in the permeation of metal(loid)s are recommended.
Scope
The aim of this study is to assess whether the long‐term addition of genistein to a high‐fat diet can ameliorate the metabolic and the cognitive alterations and whether the changes can be ...associated with modifications to the gut microbiota.
Methods and results
C57/BL6 mice were fed either a control (C) diet, a high‐fat (HF) diet, or a high‐fat diet containing genistein (HFG) for 6 months. During the study, indirect calorimetry, IP glucose tolerance tests, and behavioral analyses were performed. At the end of the study, plasma, liver, brain, and fecal samples were collected. The results showed that mice fed the HFG diet gained less weight, had lower serum triglycerides, and an improvement in glucose tolerance than those fed an HF diet. Mice fed the HFG diet also modified the gut microbiota that was associated with lower circulating levels of lipopolysaccharide (LPS) and reduced expression of pro‐inflammatory cytokines in the liver compared to those fed HF diet. The reduction in LPS by the consumption of genistein was accompanied by an improvement of the cognitive function.
Conclusions
Genistein is able to regulate the gut microbiota, reducing metabolic endotoxemia and decreasing the neuroinflammatory response despite the consumption of a HF diet.
Genistein is a dietary bioactive compound present in soy that has several health benefits. The present study reveals that genistein in mice fed a high‐fat diet is able to modify the gut microbiota by increasing the genus Prevotella and Akkermansia. This is accompanied by a decrease in circulating levels of lipopolysaccharide, reducing metabolic endotoxemia. As a consequence, there is a reduction in neuroinflammation, improving the cognitive function.
A sufficiently large perpendicular magnetic field quenches the kinetic (Fermi) energy of an interacting two-dimensional (2D) system of fermions, making them susceptible to the formation of a Wigner ...solid (WS) phase in which the charged carriers organize themselves in a periodic array in order to minimize their Coulomb repulsion energy. In low-disorder 2D electron systems confined to modulation-doped GaAs heterostructures, signatures of a magnetic-field-induced WS appear at low temperatures and very small Landau level filling factors ( ν ≃ 1 / 5 ). In dilute GaAs 2D hole systems, on the other hand, thanks to the larger hole effective mass and the ensuing Landau level mixing, the WS forms at relatively higher fillings ( ν ≃ 1 / 3 ). Here we report our measurements of the fundamental temperature vs filling phase diagram for the 2D holes' WS-liquid thermal melting. Moreover, via changing the 2D hole density, we also probe their Landau level mixing vs filling WS-liquid quantum melting phase diagram. We find our data to be in good agreement with the results of very recent calculations, although intriguing subtleties remain.
Biomolecular condensate formation has been implicated in a host of biological processes and has found relevance in biology and disease. Understanding the physical principles and underlying ...characteristics of how these macromolecular assemblies form and are regulated has become a central focus of the field. In this Review, we introduce features of phase-separating biomolecules from a general physical viewpoint and highlight how molecular features, including affinity, valence and a competition between inter- and intramolecular contacts, affect phase separation. We then discuss sequence properties of proteins that serve to mediate intermolecular interactions. Finally, we review how the intracellular environment can affect structural and sequence determinants of proteins and modulate physical parameters of their phase transitions. The works reviewed highlight that a complex interplay exists between structure, sequence and environmental determinants in the formation of biomolecular condensates.
Remodelling of energy storing white fat into energy expending beige fat could be a promising strategy to reduce adiposity. Here, we show that the bile acid-responsive membrane receptor TGR5 mediates ...beiging of the subcutaneous white adipose tissue (scWAT) under multiple environmental cues including cold exposure and prolonged high-fat diet feeding. Moreover, administration of TGR5-selective bile acid mimetics to thermoneutral housed mice leads to the appearance of beige adipocyte markers and increases mitochondrial content in the scWAT of Tgr5
mice but not in their Tgr5
littermates. This phenotype is recapitulated in vitro in differentiated adipocytes, in which TGR5 activation increases free fatty acid availability through lipolysis, hence fuelling β-oxidation and thermogenic activity. TGR5 signalling also induces mitochondrial fission through the ERK/DRP1 pathway, further improving mitochondrial respiration. Taken together, these data identify TGR5 as a druggable target to promote beiging with potential applications in the management of metabolic disorders.
We propose a new type of optical transistor for a broadband amplification of terahertz radiation. It is made of a graphene-superconductor hybrid, where electrons and Cooper pairs couple by Coulomb ...forces. The transistor operates via the propagation of surface plasmons in both layers, and the origin of amplification is the quantum capacitance of graphene. It leads to terahertz waves amplification, the negative power absorption, and as a result, the system yields positive gain, and the hybrid acts like an optical transistor, operating with the terahertz light. It can, in principle, amplify even a whole spectrum of chaotic signals (or noise), which is required for numerous biological applications.
Membraneless organelles are cellular compartments that form by liquid–liquid phase separation of one or more components. Other molecules, such as proteins and nucleic acids, will distribute between ...the cytoplasm and the liquid compartment in accordance with the thermodynamic drive to lower the free energy of the system. The resulting distribution colocalizes molecular species to carry out a diversity of functions. Two factors could drive this partitioning: the difference in solvation between the dilute versus dense phase and intermolecular interactions between the client and scaffold proteins. Here, we develop a set of knowledge‐based potentials that allow for the direct comparison between stickiness, which is dominated by desolvation energy, and pairwise residue contact propensity terms. We use these scales to examine experimental data from two systems: protein cargo dissolving within phase‐separated droplets made from FG repeat proteins of the nuclear pore complex and client proteins dissolving within phase‐separated FUS droplets. These analyses reveal a close agreement between the stickiness of the client proteins and the experimentally determined values of the partition coefficients (R > 0.9), while pairwise residue contact propensities between client and scaffold show weaker correlations. Hence, the stickiness of client proteins is sufficient to explain their differential partitioning within these two phase‐separated systems without taking into account the composition of the condensate. This result implies that selective trafficking of client proteins to distinct membraneless organelles requires recognition elements beyond the client sequence composition.
Statement
Empirical potentials for amino acid stickiness and pairwise residue contact propensities are derived. These scales are unique in that they enable direct comparison of desolvation versus contact terms. We find that partitioning of a client protein to a condensate is best explained by amino acid stickiness.
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