When steroids, such as pregnenolone, progesterone and oestrogen, are synthesised de novo in neural tissues, they are more specifically referred to as neurosteroids. These neurosteroids bind specific ...receptors to promote essential brain functions. Pregnenolone supports cognition and protects mouse hippocampal cells against glutamate and amyloid peptide‐induced cell death. Progesterone promotes myelination, spinogenesis, synaptogenesis, neuronal survival and dendritic growth. Allopregnanolone increases hippocampal neurogenesis, neuronal survival and cognitive functions. Oestrogens, such as oestradiol, regulate synaptic plasticity, reproductive behaviour, aggressive behaviour and learning. In addition, neurosteroids are neuroprotective in animal models of Alzheimer's disease, Parkinson's disease, brain injury and ageing. Using in situ hybridisation and/or immunohistochemistry, steroidogenic enzymes, including cytochrome P450 side‐chain cleavage, 3β‐hydroxysteroid dehydrogenase/Δ5‐Δ4 isomerase, cytochrome P450arom, steroid 5α‐reductase and 3α‐hydroxysteroid dehydrogenase, have been detected in numerous brain regions, including the hippocampus, hypothalamus and cerebral cortex. In the present review, we summarise some of the studies related to the synthesis and function of oestrogens and progestagens in the central nervous system.
Post‐orogenic back‐arc magmatism is accompanied by hydrothermal ore deposits and mineralizations derived from mantle and crustal sources. We investigate Zannone Island (ZI), back‐arc Tyrrhenian ...basin, Italy, to define the source(s) of mineralizing hydrothermal fluids and their relationships with the regional petrological‐tectonic setting. On ZI, early Miocene thrusting was overprinted by late Miocene post‐orogenic extension and related hydrothermal alteration. Since active submarine hydrothermal outflow is reported close to the island, Zannone provides an ideal site to determine the P‐T‐X evolution of the long‐lived hydrothermal system. We combined field work with microstructural analyses on syn‐tectonic quartz veins and carbonate mineralizations, X‐ray diffraction analysis, microthermometry and element mapping of fluid inclusions (FIs), C, O, and clumped isotopes, and analyses of noble gases (He‐Ne‐Ar) and CO2 content in FIs. Our results document the evolution of a fluid system of magmatic origin with increasing mixing of meteoric fluids. Magmatic fluids were responsible for quartz veins precipitation at ∼125 to 150 MPa and ∼300°C–350°C. With the onset of extensional faulting, magmatic fluids progressively interacted with carbonate rocks and mixed with meteoric fluids, leading to (a) host rock alteration with associated carbonate and minor ore mineral precipitation, (b) progressive fluid neutralization, (c) cooling of the hydrothermal system (from ∼320°C to ∼86°C), and (d) embrittlement and fracturing of the host rocks. Both quartz and carbonate mineralizations show noble gases values lower than those from the adjacent active volcanic areas and submarine hydrothermal systems, indicating that the fossil‐to‐active hydrothermal history is associated with the emplacement of multiple magmatic intrusions.
Key Points
Deciphering the fossil‐to‐active hydrothermal system on Zannone Island in which magmatic and meteoric fluids mixed
Polyphase and long‐lived hydrothermal activity associated with mantle‐ and crustal‐derived magmas
Fluid mixing and fluid‐rock interaction led to fluid neutralization, cooling, embrittlements, alteration, and minor ore minerals
Thin hydrogel films based on an ABA triblock copolymer gelator where A is pH-sensitive poly(2-(diisopropylamino)ethyl methacrylate) (PDPA) and B is biocompatible poly(2-(methacryloyloxy)ethyl ...phosphorylcholine) (PMPC) were used as a stimulus-responsive substrate that allows fine adjustment of the mechanical environment experienced by mouse myoblast cells. The hydrogel film elasticity could be reversibly modulated by a factor of 40 via careful pH adjustment without adversely affecting cell viability. Myoblast cells exhibited pronounced stress fiber formation and flattening on increasing the hydrogel elasticity. As a new tool to evaluate the strength of cell adhesion, we combined a picosecond laser with an inverted microscope and utilized the strong shock wave created by the laser pulse to determine the critical pressure required for cell detachment. Furthermore, we demonstrate that an abrupt jump in the hydrogel elasticity can be utilized to monitor how cells adapt their morphology to changes in their mechanical environment.
Supported phospholipid bilayers (SPBs) are useful for studying cell adhesion, cell−cell interactions, protein−lipid interactions, protein crystallization, and applications in biosensor and ...biomaterial areas. We have recently reported that SPBs could be formed on titanium dioxide, an important biomaterial, from vesicles containing anionic phospholipid phosphatidyl serine (PS) in the presence of calcium. Here, we show that the mobility of the fluorescently labeled PS present in these bilayers is severely restricted, whereas that of the zwitterionic phosphatidyl choline is not affected. Removal of calcium alleviated the restriction on the mobility of PS. Both components were found to be mobile in SPBs of identical compositions prepared in the presence of calcium on silica. To explain these results, we propose that, on TiO2, PS is trapped in the proximal leaflet of the bilayers. This proposal is supported by the results of protein adsorption experiments carried out on bilayers containing various amounts of PS prepared on silica and titania.
The pharmaceutical utility of silk fibroin (SF) materials for drug delivery was investigated. SF films were prepared from aqueous solutions of the fibroin protein polymer and crystallinity was ...induced and controlled by methanol treatment. Dextrans of different molecular weights, as well as proteins, were physically entrapped into the drug delivery device during processing into films. Drug release kinetics were evaluated as a function of dextran molecular weight, and film crystallinity. Treatment with methanol resulted in an increase in β-sheet structure, an increase in crystallinity and an increase in film surface hydrophobicity determined by FTIR, X-ray and contact angle techniques, respectively. The increase in crystallinity resulted in the sustained release of dextrans of molecular weights ranging from 4 to 40 kDa, whereas for less crystalline films sustained release was confined to the 40 kDa dextran. Protein release from the films was studied with horseradish peroxidase (HRP) and lysozyme (Lys) as model compounds. Enzyme release from the less crystalline films resulted in a biphasic release pattern, characterized by an initial release within the first 36 h, followed by a lag phase and continuous release between days 3 and 11. No initial burst was observed for films with higher crystallinity and subsequent release patterns followed linear kinetics for HRP, or no substantial release for Lys. In conclusion, SF is an interesting polymer for drug delivery of polysaccharides and bioactive proteins due to the controllable level of crystallinity and the ability to process the biomaterial in biocompatible fashion under ambient conditions to avoid damage to labile compounds to be delivered.
Titanium is widely used in biomedical applications. Its mechanical properties and biocompatibility, conferred by a layer of oxide present on its surface, make titanium the material of choice for ...various implants (artificial hip and knee joints, dental prosthetics, vascular stents, heart valves). Furthermore, the high refractive index of titanium oxide is advantageous in biosensor applications based on optical detection methods. In both of the above fields of application, novel surface modification strategies leading to biointeractive interfaces (that trigger specific responses in biological systems) are continuously sought. In this report, we investigate the interactions between TiO2 and phosphatidyl serine-containing liposomes, present a novel approach for preparing supported phospholipid bilayers (SPBs) of various compositions on TiO2, and use the unique ability of liposomes to distinguish between different surfaces to create SPB corrals on SiO2/TiO2 structured substrates. These results represent an important first step toward the design of biointeractive interfaces on titanium oxide surfaces that are based on a cell membrane-like environment.
The western Mediterranean subduction zone (WMSZ) extends from the northern Apennine to southern Spain and turns around forming the narrow and tight Calabrian and Gibraltar Arcs. The evolution of the ...WMSZ is characterized by a first phase of orogenic wedging followed, from 30 Ma on, by trench retreat and back‐arc extension. Combining new and previous geological data, new tomographic images of the western Mediterranean mantle, and plate kinematics, we describe the evolution of the WMSZ during the last 35 Myr. Our reconstruction shows that the two arcs form by fragmentation of the 1500 km long WMSZ in small, narrow slabs. Once formed, these two narrow slabs retreat outward, producing back‐arc extension and large scale rotation of the flanks, shaping the arcs. The Gibraltar Arc first formed during the middle Miocene, while the Calabrian Arc formed later, during the late Miocene‐Pliocene. Despite the different paleogeographic settings, the mechanism of rupture and backward migration of the narrow slabs presents similarities on both sides of the western Mediterranean, suggesting that the slab deformation is also driven by lateral mantle flow that is particularly efficient in a restricted (upper mantle) style of mantle convection.
Ancient drainage systems are being increasingly documented in the Amazon basin and their characterization is crucial for reconstructing fluvial evolution in this area. Fluvial morphologies, including ...elongate belts, are well preserved along the Madeira River. Digital Elevation Model from the Shuttle Radar Topography Mission favored the detection of these features even where they are covered by dense rainforest. These paleomorphologies are attributed to the shifting position of past tributaries of the Madeira River through avulsions. These radial paleodrainage networks produced fan-shaped morphologies that resemble distributary megafans. Distinguishing avulsive tributary systems from distributary megafans in the sedimentary record is challenging. Madeira´s paleodrainage reveals the superposition of tributary channels formed by multiple avulsions within a given time period, rather than downstream bifurcation of coexisting channels. Channel avulsion in this Amazonian area during the late Quaternary is related to tectonics due to features as: (i) straight lineaments coincident with fault directions; (ii) northeastward tilting of the terrain with Quaternary strata; and (iii) several drainage anomalies, including frequent orthogonal drainage inflections. These characteristics altogether lead to propose that the radial paleodrainage present at the Madeira River margin results from successive avulsions of tributary channels over time due to tectonics.
The aim of this study was to evaluate the episodic-like memory (ELM) and the transcriptional regulation of the enzymes involved in hippocampal allopregnanolone synthesis in young adult and ...middle-aged male and female rats. Young adult males, but not middle-aged ones, showed a good performance in the ELM task. In contrast, neither young nor middle-aged females were able to discriminate the spatial order in which the objects were presented. In females, aging decreased the transcription of steroidogenic-related genes. In addition, the mRNA levels of 5α-reductase-1 were higher and the methylation of its promoter was lower in young adult females than in males, suggesting an epigenetic control. Further studies are needed to establish correlations between ELM and the transcriptional regulation of hippocampal steroidogenic enzymes. Our results contribute to the knowledge of sex differences in gene expression, methylation and memory during aging.
•Aging affected episodic-like memory functions in male rats.•Aging decreased the transcription of steroidogenic-related genes in female rats.•5α-reductase-1 transcription was higher in young female rats than in male rats.•5α-reductase-1 transcription was related to the methylation status of its promoter.
•The mRNA expression of hippocampal steroidogenic enzymes decreases during aging.•The promoter methylation of P450scc, 5α-reductase-1 and 3α-HSD increases in adults.•Aged enriched rats show enhanced ...mRNA expression of neurosteroidogenic enzymes.•An enriched environment reduces methylation of the 5α-reductase-1 gene.
We analyzed the effects of aging and environmental enrichment on the mRNA expression and DNA methylation state of steroidogenic enzymes in the hippocampus. The effects of aging were evaluated by comparing young adult (90-day-old) and middle-aged (450-day-old) female Wistar rats. To elucidate the effects of environmental enrichment, a subgroup of middle-aged rats exposed to sensory and social stimulation for 105 days was compared to rats housed under standard laboratory conditions. Aging decreased the transcription of neurosteroidogenic-related genes and increased the promoter methylation state of cytochrome P450 side chain cleavage, 3α-hydroxysteroid dehydrogenase (3α-HSD) and 5α-reductase-1. Exposure of middle-aged rats to environmental enrichment increased mRNA levels of 5α-reductase-1, 3α-HSD and cytochrome P450 17α-hydroxylase/c17,20-lyase and decreased the methylation state of the 5α-reductase-1 gene. Thus, sensory and social stimulation attenuate the age-related decline in the mRNA expression of hippocampal steroidogenic enzymes. Epigenetic mechanisms associated with differential promoter methylation could be involved.
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