O sítio de Habitat Pré-Histórico de Loureira (Alvaiázere – Leiria – Centro de Portugal)

Figueiredo, Alexandra; Tognoli, Anderson; Monteiro, Cláudio; Saraiva, Rui; Gonçalves, Rui; Figueiredo, Silvério

doi:10.19177/memorare.v1e3201452-67

Cited by 3 publications

(4 citation statements)

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“…When the cargo is negatively charged or hydrophobic, it is possible to achieve non-covalent complexation with CPPs, due to a large number of cooperative interactions between both molecules. 33 The main advantage of this strategy lies in the fact that the intermolecular interactions are reversible, so the biological activity of the cargo is not compromised by covalent connection with the CPP. This non-covalent strategy has been extensively used for the cellular delivery of nucleic acids.…”

Section: Approaches To Improve Cell Uptake Of Biological Macromoleculesmentioning

confidence: 99%

Cellular Uptake of Nanoparticles versus Small Molecules: A Matter of Size

2018

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The primary function of the cell membrane is to protect cells from their surroundings. This entails a strict regulation on controlling the exchange of matter between the cell and its environment. A key factor when considering potential biological applications of a particular chemical structure has to do with its ability to internalize into cells. Molecules that can readily cross cell membranes are frequently needed in biological research and medicine, since most therapeutic entities are designed to modulate intracellular components. However, the design of molecules that do not penetrate cells is also relevant toward, for example, extracellular contrast agents, which are most widely used in clinical diagnosis. Small molecules have occupied the forefront of biomedical research until recently, but the past few decades have seen an increasing use of larger chemical structures, such as proteins or nanoparticles, leading to unprecedented and often unexpectedly novel research. Great achievements have been made toward understanding the rules that govern cellular uptake, which show that cell internalization of molecules is largely affected by their size. For example, macromolecules such as proteins and nucleic acids are usually unable to internalize cells. Intriguingly, in the case of nanoparticles, larger sizes seem to facilitate internalization via endocytic pathways, through which the particles remain trapped in lysosomes and endosomes. In this Account, we aimed at presenting our personal view of how different chemical structures behave in terms of cell internalization due to their size, ranging from small drugs to large nanoparticles. We first introduce the properties of cell membranes and the main mechanisms involved in cellular uptake. We then discuss the cellular internalization of molecules, distinguishing between those with molecular weights below 1 kDa and biological macromolecules such as proteins and nucleic acids. In the last section, we review the biological behavior of nanoparticles, with a special emphasis on plasmonic nanoparticles, which feature a high potential in the biomedical field. For each group of chemical structures, we discuss the parameters affecting their cellular internalization but also strategies that can be applied to achieve the desired intracellular delivery. Particular attention is paid to approaches that allow conditional regulation of the cell internalization process using external triggers, such as activable cell penetrating peptides, due to the impact that these systems may have in drug delivery and sensing applications. The Account ends with a "Conclusions and Outlook" section, where general lessons and future directions toward further advancements are briefly presented.

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Section: Approaches To Improve Cell Uptake Of Biological Macromoleculesmentioning

confidence: 99%

Cellular Uptake of Nanoparticles versus Small Molecules: A Matter of Size

2018

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“…We have demonstrated how the single-fusion biosensor can be used to determine the distribution of function for a library of TIR1/AFB variants, and plan to perform comprehensive mutational scanning and directed evolution of these proteins in the future, to further refine the sequence function map of these multifaceted signaling proteins [120][121][122][123][124][125] and to engineer novel functions 126 . For mutational studies in Aux/IAAs the single-fusion ratiometric sensor, also provides a simple quantitative reporter of Aux/IAA degradation, which would prove useful in studying the numerous functional elements of these transcriptional regulators 21,[127][128][129][130][131][132] . While the ratiometric Venus-IAA17-2A-mScarlet-I construct would not be amenable to OrthoRep continuous mutagenesis, due to the included fluorescent protein reporters, we expect alternative means of creating specific IAA17 variant libraries cloned between Venus and the 2A sequence would yield similar results.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Genetically encoded, noise-tolerant, auxin biosensors in yeast facilitate metabolic engineering and directed evolution

Chaisupa

Rahman

Hildreth

et al. 2023

Preprint

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Auxins are important plant growth regulating compounds that are applied in vast quantities to crops across the globe to control weeds and improve crop quality and yield. Auxins are also produced by nearly every kingdom of life and control both organismal behavior as well as inter-kingdom interactions. Improving our understanding of auxin biosynthesis and signaling is critical to both improving crop plants and controlling symbiotic, commensal, and parasitic inter-kingdom relationships, many of which are critical to ecosystems from forests and oceans to the human microbiome. We present a suite of auxin biosensors that will advance our understanding of and ability to engineer auxin perception by plants and auxin production by fungi. We have developed genetically encoded, ratiometric auxin biosensors in the model yeast Saccharomyces cerevisiae, based on the mechanism plants use to perceive auxin. The ratiometric design of these biosensors improves measurements of auxin concentration by reducing clonal and growth phase variation. These biosensors are capable of measuring exogenous auxin in yeast cultures across five orders of magnitude, likely spanning the physiologically relevant range. We implement these biosensors to measure the production of auxin during different growth conditions and phases for S. cerevisiae. Finally, we demonstrate how these biosensors could be used to improve quantitative functional studies and directed evolution of plant auxin perception machinery. These genetically encoded auxin biosensors will enable future studies of auxin biosynthesis, transport, and signaling in a wide range of yeast species, as well as other fungi, and plants.

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“…However, according to previous experimental and FEM studies the effect of temperature rise can be considered negligible due to three main factors: the heat sink effect resulting from the large mass of the anvils compared to the sample discs, the small temperature increments, and the HPT parameters used in the tests. Firstly, the heat generated is dissipated by conduction from the sample to the anvil and by convection / emission from the HPT machine to the environment [53,54]. Secondly, plastic deformation as the main heating source, generates little heating and gives rise to temperatures far below any steel transformation temperature [53][54][55]56].…”

Section: Twes Formationmentioning

confidence: 99%

“…Firstly, the heat generated is dissipated by conduction from the sample to the anvil and by convection / emission from the HPT machine to the environment [53,54]. Secondly, plastic deformation as the main heating source, generates little heating and gives rise to temperatures far below any steel transformation temperature [53][54][55]56]. Thirdly, parameters such as the J o u r n a l P r e -p r o o f low rotational speed and short processing time (1 rpm and between 1 and 3 minutes), low final strain (up to 3 turns on 0.98 mm diameter samples) [56], and a soft material processed (180 ± 10 HV for the annealed AISI 51200) [55], would also limit greatly the temperature rise in the sample discs processed by HPT.…”

Section: Twes Formationmentioning

confidence: 99%