In this work, the influences of heat generation/absorption and nanofluid volume fraction on the entropy generation and MHD combined convection heat transfer in a porous enclosure filled with a ...Cu–water nanofluid are studied numerically with of partial slip effect. The finite volume technique is utilized to solve the dimensionless equations governing the problem. A comparison with already published studies is conducted, and the data are found to be in an excellent agreement. The minimization of entropy generation and the local heat transfer according to various values of the controlling parameters are reported in detail. The outcome indicates that an augmentation in the heat generation/absorption parameter decreases the Nusselt number. Also, when the volume fraction is raised, the Nusselt number and entropy generation are reduced. The impact of Hartmann number on heat transfer and the Richardson number on the entropy generation and the thermal rendering criteria are also presented and discussed.
Recent advances in lipidomics and metabolomics have unveiled the complexity of fatty acid metabolism and the fatty acid lipidome in health and disease. A growing body of evidence indicates that ...imbalances in the metabolism and level of fatty acids drive the initiation and progression of central nervous system (CNS) disorders such as multiple sclerosis, Alzheimer’s disease, and Parkinson’s disease. Here, we provide an in-depth overview on the impact of the β-oxidation, synthesis, desaturation, elongation, and peroxidation of fatty acids on the pathophysiology of these and other neurological disorders. Furthermore, we discuss the impact of individual fatty acids species, acquired through the diet or endogenously synthesized in mammals, on neuroinflammation, neurodegeneration, and CNS repair. The findings discussed in this review highlight the therapeutic potential of modulators of fatty acid metabolism and the fatty acid lipidome in CNS disorders, and underscore the diagnostic value of lipidome signatures in these diseases.
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Matrix-assisted laser desorption/ionisation-mass spectrometry imaging (MALDI-MSI) is a powerful technique for visualising the spatial locations of lipids in biological tissues. However, a major ...challenge in interpreting the biological significance of local lipid compositions and distributions detected using MALDI-MSI is the difficulty in associating spectra with cellular lipid metabolism within the tissue. By-and-large this is due to the typically limited spatial resolution of MALDI-MSI (30–100 μm) meaning individual spectra represent the average spectrum acquired from multiple adjacent cells, each potentially possessing a unique lipid composition and biological function. The use of oversampling is one promising approach to decrease the sampling area and improve the spatial resolution in MALDI-MSI, but it can suffer from a dramatically decreased sensitivity. In this work we overcome these challenges through the coupling of oversampling MALDI-MSI with laser post-ionisation (MALDI-2). We demonstrate the ability to acquire rich lipid spectra from pixels as small as 6 μm, equivalent to or smaller than the size of typical mammalian cells. Coupled with an approach for automated lipid identification, it is shown that MALDI-2 combined with oversampling at 6 μm pixel size can detect up to three times more lipids and many more lipid classes than even conventional MALDI at 20 μm resolution in the positive-ion mode. Applying this to mouse kidney and human brain tissue containing active multiple sclerosis lesions, where 74 and 147 unique lipids are identified, respectively, the localisation of lipid signals to individual tubuli within the kidney and lipid droplets with lesion-specific macrophages is demonstrated.
Graphical abstract
It is widely acknowledged that waterbodies are becoming increasingly affected by a wide range of drivers of change arising from human activity. To illustrate how this can be quantified a linked ...modelling approach was applied in the Thames river basin in southern UK. Changes to river flows, water temperature, river and reservoir quality were predicted under three contrasting future “storylines”; one an extension of present day rates of economic development, the others representing more extreme and less sustainable visions. Modelling revealed that lower baseflow conditions will arise under all storylines. For the less extreme storyline river water quality is likely to deteriorate but reservoir quality will improve slightly. The two more extreme futures could not be supported by current management strategies to meet water demand. To satisfy these scenarios, transfer of river water from outside the Thames river basin would be necessary. Consequently, some improvement over present day water quality in the river may be seen, and for most indicators conditions would be better than in the less extreme storyline. However, because phosphorus concentrations will rise, the invoked changes in water demand management would not be of a form suitable to prevent a marked deterioration in reservoir water quality.
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•Future climate and human activity threaten water resources in the Thames Basin UK.•A linked model approach was used and included groundwater, river and lake domains.•Flow and quality modelled for three future policy and management scenarios.•Continuation of current economic development reduces flow and impairs river quality.•Water imports needed in less sustainable futures partly preserve freshwater status.
Abstract
Background
The presence of foamy macrophages and microglia containing intracellular myelin remnants is a pathological hallmark of neurodegenerative disorders such as multiple sclerosis (MS). ...Despite the importance of myelin internalization in affecting both central nervous system repair and neuroinflammation, the receptors involved in myelin clearance and their impact on the phagocyte phenotype and lesion progression remain to be clarified.
Methods
Flow cytometry, quantitative PCR, and immunohistochemistry were used to define the mRNA and protein abundance of CD36 in myelin-containing phagocytes. The impact of CD36 and nuclear factor erythroid 2–related factor 2 (NRF2) on the phagocytic and inflammatory features of macrophages and microglia was assessed using a pharmacological CD36 inhibitor (sulfo-N-succinimidyl oleate) and
Nrf2
−/−
bone marrow-derived macrophages. Finally, the experimental autoimmune encephalomyelitis (EAE) model was used to establish the impact of CD36 inhibition on neuroinflammation and myelin phagocytosis in vivo.
Results
Here, we show that the fatty acid translocase CD36 is required for the uptake of myelin debris by macrophages and microglia, and that myelin internalization increased CD36 expression through NRF2. Pharmacological inhibition of CD36 promoted the inflammatory properties of myelin-containing macrophages and microglia in vitro, which was paralleled by a reduced activity of the anti-inflammatory lipid-sensing liver X receptors and peroxisome proliferator-activated receptors. By using the EAE model, we provide evidence that CD36 is essential for myelin debris clearance in vivo. Importantly, CD36 inhibition markedly increased the neuroinflammatory burden and disease severity in the EAE model.
Conclusion
Altogether, we show for the first time that CD36 is crucial for clearing myelin debris and suppressing neuroinflammation in demyelinating disorders such as MS.
We report on the synthesis of new dinucleating phenol-based "end-off" compartmental ligands HLMeH and HLMe2 bearing two different binding sites, one bis(2-methylpyridyl)aminomethyl (BPA) and one ...thiosemicarbazone (TSC) site, and their corresponding copper(ii) complexes 1t and 2d. With the ligand HLMeH, a tetranuclear entity (1t) has been isolated in the solid state, whereas with HLMe2, which differs from HLMeH by a methyl substituent on the N-terminal amino group of the TSC arm, a dinuclear form (2d) is obtained. X-ray crystallography analysis shows that the nuclearity di vs. tetra is modulated by interactions between copper atoms and hydroxido bridges along with the sulphur atoms of TSC arms. From a magnetic point of view, 1t can be considered as an association of two dinuclear forms leading for both complexes to overall antiferromagnetic coupling. Analysis in acetonitrile solution of structure-property relationships has been carried out by comparing their UV/Vis, electrochemistry, ESI-MS, and NMR (variable temperature and DOSY = diffusion ordered spectroscopy) properties with trends from computational calculations (DFT). HRMAS-DOSY (High Resolution Magic Angle Spinning) NMR spectroscopy has been performed to evaluate the presence of different species in solution at room temperature.
ABSTRACT
We aim to determine the distribution of basaltic asteroids (classified as V-types) based on the spectrophotometric data reported in the MOVIS-C catalogue. A total of 782 asteroids were ...identified. The observations with all four filters (Y, J, H, Ks), available for 297 of these candidates, allow a reliable comparison with the laboratory data of howardite, eucrite, and diogenite meteorites. We found that the majority of the basaltic candidates (≈95${{\ \rm per\ cent}}$) are located in the inner main belt, while only 29 (≈4${{\ \rm per\ cent}}$) and 8 (≈1${{\ \rm per\ cent}}$) are located in the middle (MMB) and outer main belt (OMB), respectively. A fraction of ≈33${{\ \rm per\ cent}}$ from the V-type candidates is associated with the Vesta family (with respect to AstDyS). We also identified four MMB V-type candidates belonging to (15) Eunomia family, and another four low inclination ones corresponding to (135) Hertha. We report differences between the colour indices and albedo distributions of the V-type candidates located in the inner main belt compared to those from the MMB and OMB. These results support the hypothesis of a different origin for the basaltic asteroids with a semimajor axis beyond 2.5 au. Furthermore, lithological differences are present between the vestoids and the inner low inclination basaltic asteroids. The data allow us to estimate the unbiased distribution of basaltic asteroids across the main asteroid belt. We highlight that at least 80${{\ \rm per\ cent}}$ of the ejected basaltic material from (4) Vesta is missing or is not yet detected because it is fragmented in sizes smaller than 1 km.
Failure of remyelination underlies the progressive nature of demyelinating diseases such as multiple sclerosis. Macrophages and microglia are crucially involved in the formation and repair of ...demyelinated lesions. Here we show that myelin uptake temporarily skewed these phagocytes toward a disease-resolving phenotype, while sustained intracellular accumulation of myelin induced a lesion-promoting phenotype. This phenotypic shift was controlled by stearoyl-CoA desaturase-1 (SCD1), an enzyme responsible for the desaturation of saturated fatty acids. Monounsaturated fatty acids generated by SCD1 reduced the surface abundance of the cholesterol efflux transporter ABCA1, which in turn promoted lipid accumulation and induced an inflammatory phagocyte phenotype. Pharmacological inhibition or phagocyte-specific deficiency of Scd1 accelerated remyelination ex vivo and in vivo. These findings identify SCD1 as a novel therapeutic target to promote remyelination.
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