Resveratrol induces mitochondrial biogenesis and protects against metabolic decline, but whether SIRT1 mediates these benefits is the subject of debate. To circumvent the developmental defects of ...germline SIRT1 knockouts, we have developed an inducible system that permits whole-body deletion of SIRT1 in adult mice. Mice treated with a moderate dose of resveratrol showed increased mitochondrial biogenesis and function, AMPK activation, and increased NAD+ levels in skeletal muscle, whereas SIRT1 knockouts displayed none of these benefits. A mouse overexpressing SIRT1 mimicked these effects. A high dose of resveratrol activated AMPK in a SIRT1-independent manner, demonstrating that resveratrol dosage is a critical factor. Importantly, at both doses of resveratrol no improvements in mitochondrial function were observed in animals lacking SIRT1. Together these data indicate that SIRT1 plays an essential role in the ability of moderate doses of resveratrol to stimulate AMPK and improve mitochondrial function both in vitro and in vivo.
Display omitted
► Resveratrol's ability to improve mitochondrial function requires SIRT1 in vivo ► Moderate doses of resveratrol activate AMPK and raise NAD+ in a SIRT1-dependent manner ► Activation of AMPK in the absence of SIRT1 does not improve mitochondrial function ► Overexpression of SIRT1 mimics resveratrol's effects on AMPK and mitochondria
3D woven composites reinforced with either S2 glass, carbon or a hybrid combination of both and containing either polyethylene or carbon z-yarns were tested under low-velocity impact. Different ...impact energies (in the range of 21–316J) were used and the mechanical response (in terms of the impact strength and energy dissipated) was compared with that measured in high-performance, albeit standard, 2D laminates. It was found that the impact strength in both 2D and 3D materials was mainly dependent on the in-plane fiber fracture. Conversely, the energy absorption capability was primarily influenced by the presence of z-yarns, having the 3D composites dissipated over twice the energy than the 2D laminates, irrespective of their individual characteristics (fiber type, compaction degree, porosity, etc.). X-ray microtomography revealed that this improvement was due to the z-yarns, which delayed delamination and maintained the structural integrity of the laminate, promoting energy dissipation by tow splitting, intensive fiber breakage under the tup and formation of a plug by out-of-plane shear.
The interaction between cement paste and sulfate-rich solutions or soils induces gypsum, ettringite or thaumasite precipitation. These expansive processes may be mitigated by using BaCO3 (witherite) ...as a setting regulator. The present study explored ettringite decomposition in the presence of witherite at different temperatures (25, 40 and 65°C) and reaction times (up to 90days) to further the understanding of this process as grounds for developing new sulfate-resistant cements (SR-PC).
According to the XRD, FTIR and DSC-TG findings, sulfoaluminate decomposition and barite formation begin in the first 24h of the reaction, even at ambient temperature (25°C), and progress rapidly for the first 30days. The reaction follows a different pathway at 65°C than at 25 and 40°C due to ettringite instability at high temperatures.
•Production of renewable liquid hydrocarbons through pomace oil hydrotreatment.•Hydrogenation at lower hydrogen pressure with catalysts commonly used in petrochemical industry.•Analysis of pyrolysis ...pre-treatment of pomace oil on the overall hydrotreatment process.•Comparison of the two-step process (pyrolysis+hydrotreatment) with single pyrolysis or hydrogenation.•Analysis of hydrogenated products applications as bio-chemicals.
Olive pomace oil is a by-product from the olive oil industry that is still being used in the food industry as a low value vegetable oil. Crude olive pomace oil needs to be refined and is blended with virgin olive oils before being used as edible oil. The detection of toxic compounds led to more restricted legislation and to the search of alternative valorisation processes, such as hydrotreating to obtain bio-hydrocarbons. Hydrotreating of olive pomace oil at moderate temperatures (from 300 to 430°C) and in presence of initial hydrogen pressure of 1.1MPa led to triglycerides destruction and to their conversion into a large range of organic compounds with predominance to hydrocarbons. Even without any catalyst, conversions into hydrocarbons were always higher than 90% (v/v). Catalyst presence, such as: CoMo/Al2O3, FCC (fluid catalytic cracking) or HZSM-5 changed hydrogenated liquids composition. The highest content of alkanes was obtained with CoMo catalyst, while FCC and HZSM-5 led to the highest contents of aromatic compounds. The results obtained showed that olive pomace oil can be efficiently converted into bio-hydrocarbons with a wide range of applications. It was also studied the effect of pyrolysing olive pomace oil prior to its hydrotreating. Pyrolysis pre-treatment seems to have favoured hydrotreating process by promoting initial cracking reactions. Thus, it was possible to increase the production of liquid compounds with a higher content of light molecules. However, the advantages of using a more complex two steps process still need to be proven.
In this work, the relationship between the composition of pore solution in alkali-activated slag cement (AAS) pastes activated with different alkaline activator, and the composition and structure of ...the main reaction products, has been studied. Pore solution was extracted from hardened AAS pastes. The analysis of the liquids was performed through different techniques: Na, Mg and Al by atomic absorption (AA), Ca ions by ionic chromatography (IC) and Si by colorimetry; pH was also determined. The solid phases were analysed by XRD, FTIR, solid-state
29Si and
27Al NMR and BSE/EDX.
The most significant changes in the ionic composition of the pore solution of the AAS pastes activated with waterglass take place between 3 and 24 h of reaction. These changes are due to the decrease of the Na content and mainly to the Si content. Results of
29Si MAS NMR and FTIR confirm that the activation process takes place with more intensity after 3 h (although at this age,
Q
2 units already exist). The pore solution of the AAS pastes activated with NaOH shows a different evolution to this of pastes activated with waterglass. The decrease of Na and Si contents progresses with time.
The nature of the alkaline activator influences the structure and composition of the calcium silicate hydrate formed as a consequence of the alkaline activation of the slag. The characteristic of calcium silicate hydrate in AAS pastes activated with waterglass is characterised by a low structural order with a low Ca/Si ratio. Besides, in this paste,
Q
3 units are detected. The calcium silicate hydrate formed in the pastes activated with NaOH has a higher structural order (higher crystallinity) and contains more Al in its structure and a higher Ca/Si ratio than those obtained with waterglass.
Pinus pinaster
(maritime pine) is widely planted in the Mediterranean Basin. Maritime pine forests’ carbon stocks are dynamic because of the effect of wildfires and timber activities. Management ...practices offer an opportunity to mitigate climate change via increasing carbon storage in various ecosystems. In this work, we quantified carbon pools in
P. pinaster
forests in relation to fire occurrence and different post-fire salvage logging techniques. For this, we studied an area in northern Portugal where different parts had burned zero, one and four times during the last three decades. Following the last fire in 2012, two salvage logging treatments were carried out: (1) typical logging where all logs and tree biomass were removed and (2) conservation logging where burned tree branches were left in piles and log extraction was restricted to specific extraction trails. We assessed the carbon stocks for the aboveground and belowground compartments, taking into account their different components (vegetation, litter, roots and soil organic carbon). Our main findings were, firstly, that recurrent fires can be catastrophic in terms of carbon sequestration if the overstory dominated by
P. pinaster
does not regenerate after fire (2.4 times less). Secondly, soil organic carbon constituted an important carbon pool, being the most important when pines are eliminated due to recurrent fires with short intervals (90–95 %). Finally, the conservation technique applied here, leaving piles of branches on the soil surface, would be a suitable measure to increase carbon storage, at least in the short term, but might interfere with the recruitment of the pine stand.
The alkali activation of metakaolin (MK) leads to the production of high‐mechanical‐performance network‐structure materials. Adding calcium hydroxide (Ca(OH)2) to the raw MK produces a somewhat ...different reaction: a network structure and C‐S‐H gel form. In the present study, MK and (MK + Ca(OH)2) mixes were activated with 5M and 12M NaOH solutions and cured at 45°C. A 5M concentration, in the absence of Ca(OH)2, did not produce MK activation within the test time. An activator concentration of 12M resulted in complete activation and the formation of a network structure. When Ca(OH)2 was present in the raw mix, a small amount of C‐S‐H gel formed.
Besides their role in lipid absorption, bile acids (BAs) can act as signalling molecules. Cholic acid was shown to counteract obesity and associated metabolic disorders in high-fat-diet (cHF)-fed ...mice while enhancing energy expenditure through induction of mitochondrial uncoupling protein 1 (UCP1) and activation of non-shivering thermogenesis in brown adipose tissue (BAT). In this study, the effects of another natural BA, chenodeoxycholic acid (CDCA), on dietary obesity, UCP1 in both interscapular BAT and in white adipose tissue (brite cells in WAT), were characterized in dietary-obese mice.
To induce obesity and associated metabolic disorders, male 2-month-old C57BL/6J mice were fed cHF (35% lipid wt wt(-1), mainly corn oil) for 4 months. Mice were then fed either (i) for 8 weeks with cHF or with cHF with two different doses (0.5%, 1%; wt wt(-1)) of CDCA (8-week reversion); or (ii) for 3 weeks with cHF or with cHF with 1% CDCA, or pair-fed (PF) to match calorie intake of the CDCA mice fed ad libitum; mice on standard chow diet were also used (3-week reversion).
In the 8-week reversion, the CDCA intervention resulted in a dose-dependent reduction of obesity, dyslipidaemia and glucose intolerance, which could be largely explained by a transient decrease in food intake. The 3-week reversion revealed mild CDCA-dependent and food intake-independent induction of UCP1-mediated thermogenesis in interscapular BAT, negligible increase of UCP1 in subcutaneous WAT and a shift from carbohydrate to lipid oxidation.
CDCA could reverse obesity in cHF-fed mice, mainly in response to the reduction in food intake, an effect probably occuring but neglected in previous studies using cholic acid. Nevertheless, CDCA-dependent and food intake-independent induction of UCP1 in BAT (but not in WAT) could contribute to the reduction in adiposity and to the stabilization of the lean phenotype.
The absence of effective chronic treatment, expansion to non-endemic countries and the significant burden in public health have stimulated the search for novel therapeutic options to treat Chagas ...disease, a protozoan disease caused by Trypanosoma cruzi. Despite current efforts, no new drug candidates were approved in clinical trials in the past five decades. Considering this, our group has focused on the expansion of a series (LINS03) with low micromolar activity against amastigotes, considering the optimization of pharmacokinetic properties through increasing drug-likeness and solubility. In this work, we report a new set of 13 compounds with modifications in both the arylpiperazine and the aromatic region linked by an amide group. Five analogues showed activity against intracellular amastigotes (IC50 17.8 to 35.9 µM) and no relevant cytotoxicity to mammalian cells (CC50 > 200 µM). Principal component analysis (PCA) was performed to identify structural features associated to improved activity. The data revealed that polarity, hydrogen bonding ability and flexibility were key properties that influenced the antiparasitic activity. In silico drug-likeness assessments indicated that compounds with the 4-methoxycinammyl (especially compound 2b) had the most prominent balance between properties and activity in the series, as confirmed by SAR analysis.
Fatty livers are more prone to damage caused by ischemia/reperfusion (I/R). Impaired microcirculation, Kupffer cell dysfunction, increased adhesion of leukocytes, impaired mitochondrial function and ...ATP depletion are probable causes for fatty liver susceptibility. Therefore, hepatic steatosis is a major risk factor for liver surgery and success of transplantation of fatty donor organs. The mechanisms involved in I/R injury are complex and there is no general consensus regarding the sources of ROS generation, nitric oxide (NO) action, the role of tumor necrosis factor-α (TNF-α), and transcription factors, such as nuclear factor kappa B (NFκB). Impairment of mitochondrial function is one of the most important alterations that occur in I/R injury, resulting in the alteration of energy metabolism. Ischemic preconditioning (IPC) and post conditioning (IPost) are adaptive mechanisms against I/R insults that induce intracellular protective responses associated with the preservation of mitochondrial function.There are several pharmacological drugs and natural derivatives presenting metabolic and/or antioxidant effects that can directly or indirectly protect the liver against I/R injury. While the precise targets and mechanisms are still not totally understood, the mitochondrion presents itself as a major player on mediating these protective events. As so, compounds that are able to improve mitochondrial function and hepatic energetic balance might prove viable candidates when developing new pharmacological approaches that can minimize injury to steatotic livers subjected to I/R events.
PDF
