Mitochondrial fatty acid β-oxidation disorders: from disease to lipidomic studies—a critical review

Fatty acid oxidation disorders (FAODs) are inborn errors of metabolism (IEMs) caused by defects in the fatty acid (FA) mitochondrial β-oxidation. The most common FAODs are characterized by the accumulation of medium-chain FAs and long-chain (3-hydroxy) FAs (and their carnitine derivatives), respectively. These deregulations are associated with lipotoxicity which affects several organs and potentially leads to life-threatening complications and comorbidities. Changes in the lipidome have been associated with several diseases, including some IEMs. In FAODs, the alteration of acylcarnitines (CARs) and FA profiles have been reported in patients and animal models, but changes in polar and neutral lipid profile are still scarcely studied. In this review, we present the main findings on FA and CAR profile changes associated with FAOD pathogenesis, their correlation with oxidative damage, and the consequent disturbance of mitochondrial homeostasis. Moreover, alterations in polar and neutral lipid classes and lipid species identified so far and their possible role in FAODs are discussed. We highlight the need of mass-spectrometry-based lipidomic studies to understand (epi)lipidome remodelling in FAODs, thus allowing to elucidate the pathophysiology and the identification of possible biomarkers for disease prognosis and an evaluation of therapeutic efficacyinfo:eu-repo/semantics/publishedVersio

Lipids and phenylketonuria: current evidences pointed the need for lipidomics studies

Phenylketonuria (PKU) is the most prevalent inborn error of amino acid metabolism. The disease is due to the deficiency of phenylalanine (Phe) hydroxylase activity, which causes the accumulation of Phe. Early diagnosis through neonatal screening is essential for early treatment implementation, avoiding cognitive impairment and other irreversible sequelae. Treatment is based on Phe restriction in the diet that should be maintained throughout life. High dietary restrictions can lead to imbalances in specific nutrients, notably lipids. Previous studies in PKU patients revealed changes in levels of plasma/serum lipoprotein lipids, as well as in fatty acid profile of plasma and red blood cells. Most studies showed a decrease in important polyunsaturated fatty acids, namely DHA (22:6n-3), AA (20:4n-6) and EPA (20:5n-6). Increased oxidative stress and subsequent lipid peroxidation have also been observed in PKU. Despite the evidences that the lipid profile is changed in PKU patients, more studies are needed to understand in detail how lipidome is affected. As highlighted in this review, mass spectrometry-based lipidomics is a promising approach to evaluate the effect of the diet restrictions on lipid metabolism in PKU patients, monitor their outcome, namely concerning the risk for other chronic diseases, and find possible prognosis biomarkers.publishe

Repeatability and temporal consistency of lower limb biomechanical variables expressing interlimb coordination during the double-support phase in people with and without stroke sequelae

Reliable biomechanical methods to assess interlimb coordination during the double-support phase in post-stroke subjects are needed for assessing movement dysfunction and related variability. The data obtained could provide a significant contribution for designing rehabilitation programs and for their monitorisation. The present study aimed to determine the minimum number of gait cycles needed to obtain adequate values of repeatability and temporal consistency of lower limb kinematic, kinetic, and electromyographic parameters during the double support of walking in people with and without stroke sequelae. Eleven post-stroke and thirteen healthy participants performed 20 gait trials at self-selected speed in two separate moments with an interval between 72 h and 7 days. The joint position, the external mechanical work on the centre of mass, and the surface electromyographic activity of the tibialis anterior, soleus, gastrocnemius medialis, rectus femoris, vastus medialis, biceps femoris, and gluteus maximus muscles were extracted for analysis. Both the contralesional and ipsilesional and dominant and non-dominant limbs of participants with and without stroke sequelae, respectively, were evaluated either in trailing or leading positions. The intraclass correlation coefficient was used for assessing intra-session and inter-session consistency analysis. For most of the kinematic and the kinetic variables studied in each session, two to three trials were required for both groups, limbs, and positions. The electromyographic variables presented higher variability, requiring, therefore, a number of trials ranging from 2 to >10. Globally, the number of trials required inter-session ranged from 1 to >10 for kinematic, from 1 to 9 for kinetic, and 1 to >10 for electromyographic variables. Thus, for the double support analysis, three gait trials were required in order to assess the kinematic and kinetic variables in cross-sectional studies, while for longitudinal studies, a higher number of trials (>10) were required for kinematic, kinetic, and electromyographic variables.info:eu-repo/semantics/publishedVersio

Insights into milk-clotting activity of latex peptidases from <i>Calotropis procera</i> and <i>Cryptostegia grandiflora</i>

Latex fractions from Calotropis procera, Cryptostegia grandiflora, Plumeria rubra, and Himatanthus drasticus were assayed in order to prospect for new plant peptidases with milk-clotting activities, for use as rennet alternatives. Only C. procera and C. grandiflora latex fractions exhibited proteolytic and milk-clotting activities, which were not affected by high concentrations of NaCl and CaCl2. However, pre-incubation of both samples at 75 °C for 10 min eliminated completely their activities. Both proteolytic fractions were able to hydrolyze k-casein and to produce peptides of 16 kDa, a similar SDS-PAGE profile to commercial chymosin. RP-HPLC and mass spectrometry analyses of the k-casein peptides showed that the peptidases from C. procera or C. grandiflora hydrolyzed k-casein similar to commercial chymosin. The cheeses made with both latex peptidases exhibited yields, dry masses, and soluble proteins similar to cheeses prepared with commercial chymosin. In conclusion, C. procera and C. grandiflora latex peptidases with the ability to coagulate milk can be used as alternatives to commercial animal chymosin in the cheese manufacturing process.Centro de Investigación de Proteínas Vegetale

Insights into milk-clotting activity of latex peptidases from <i>Calotropis procera</i> and <i>Cryptostegia grandiflora</i>

Latex fractions from Calotropis procera, Cryptostegia grandiflora, Plumeria rubra, and Himatanthus drasticus were assayed in order to prospect for new plant peptidases with milk-clotting activities, for use as rennet alternatives. Only C. procera and C. grandiflora latex fractions exhibited proteolytic and milk-clotting activities, which were not affected by high concentrations of NaCl and CaCl2. However, pre-incubation of both samples at 75 °C for 10 min eliminated completely their activities. Both proteolytic fractions were able to hydrolyze k-casein and to produce peptides of 16 kDa, a similar SDS-PAGE profile to commercial chymosin. RP-HPLC and mass spectrometry analyses of the k-casein peptides showed that the peptidases from C. procera or C. grandiflora hydrolyzed k-casein similar to commercial chymosin. The cheeses made with both latex peptidases exhibited yields, dry masses, and soluble proteins similar to cheeses prepared with commercial chymosin. In conclusion, C. procera and C. grandiflora latex peptidases with the ability to coagulate milk can be used as alternatives to commercial animal chymosin in the cheese manufacturing process.Centro de Investigación de Proteínas Vegetale

Insights into milk-clotting activity of latex peptidases from <i>Calotropis procera</i> and <i>Cryptostegia grandiflora</i>

Latex fractions from Calotropis procera, Cryptostegia grandiflora, Plumeria rubra, and Himatanthus drasticus were assayed in order to prospect for new plant peptidases with milk-clotting activities, for use as rennet alternatives. Only C. procera and C. grandiflora latex fractions exhibited proteolytic and milk-clotting activities, which were not affected by high concentrations of NaCl and CaCl2. However, pre-incubation of both samples at 75 °C for 10 min eliminated completely their activities. Both proteolytic fractions were able to hydrolyze k-casein and to produce peptides of 16 kDa, a similar SDS-PAGE profile to commercial chymosin. RP-HPLC and mass spectrometry analyses of the k-casein peptides showed that the peptidases from C. procera or C. grandiflora hydrolyzed k-casein similar to commercial chymosin. The cheeses made with both latex peptidases exhibited yields, dry masses, and soluble proteins similar to cheeses prepared with commercial chymosin. In conclusion, C. procera and C. grandiflora latex peptidases with the ability to coagulate milk can be used as alternatives to commercial animal chymosin in the cheese manufacturing process.Centro de Investigación de Proteínas Vegetale

Pool boiling of nanofluids on biphilic surfaces: An experimental and numerical study

This study addresses the combination of customized surface modification with the use of nanofluids, to infer on its potential to enhance pool-boiling heat transfer. Hydrophilic surfaces patterned with superhydrophobic regions were developed and used as surface interfaces with different nanofluids (water with gold, silver, aluminum and alumina nanoparticles), in order to evaluate the effect of the nature and concentration of the nanoparticles in bubble dynamics and consequently in heat transfer processes. The main qualitative and quantitative analysis was based on extensive post-processing of synchronized high-speed and thermographic images. To study the nucleation of a single bubble in pool boiling condition, a numerical model was also implemented. The results show an evident benefit of using biphilic patterns with well-established distances between the superhydrophobic regions. This can be observed in the resulting plot of the dissipated heat flux for a biphilic pattern with seven superhydrophobic spots, δ = 1/d and an imposed heat flux of 2132 w/m2. In this case, the dissipated heat flux is almost constant (except in the instant t* ≈ 0.9 when it reaches a peak of 2400 W/m2), whilst when using only a single superhydrophobic spot, where the heat flux dissipation reaches the maximum shortly after the detachment of the bubble, dropping continuously until a new necking phase starts. The biphilic patterns also allow a controlled bubble coalescence, which promotes fluid convection at the hydrophilic spacing between the superhydrophobic regions, which clearly contributes to cool down the surface. This effect is noticeable in the case of employing the Ag 1 wt% nanofluid, with an imposed heat flux of 2132 W/m2, where the coalescence of the drops promotes a surface cooling, identified by a temperature drop of 0.7 °C in the hydrophilic areas. Those areas have an average temperature of 101.8 °C, whilst the average temperature of the superhydrophobic spots at coalescence time is of 102.9 °C. For low concentrations as the ones used in this work, the effect of the nanofluids was observed to play a minor role. This can be observed on the slight discrepancy of the heat dissipation decay that occurred in the necking stage of the bubbles for nanofluids with the same kind of nanoparticles and different concentration. For the Au 0.1 wt% nanofluid, a heat dissipation decay of 350 W/m2 was reported, whilst for the Au 0.5 wt% nanofluid, the same decay was only of 280 W/m2. The results of the numerical model concerning velocity fields indicated a sudden acceleration at the bubble detachment, as can be qualitatively analyzed in the thermographic images obtained in this work. Additionally, the temperature fields of the analyzed region present the same tendency as the experimental results.This work was funded by Portuguese national funds of FCT/MCTES (PIDDAC) through the base funding from the following research units: UIDB/00532/2020 (Transport Phenomena Research Center, CEFT), UIDB/04077/2020 (MEtRICs) and UIDP/04436/2020. The authors are also grateful for the funding of FCT through the projects LISBOA-01-0145-FEDER-030171/NORTE-01-0145-FEDER-030171 (PTDC/EME-SIS/30171/2017), funded by COMPETE2020, NORTE2020, PORTUGAL2020 and FEDER. The authors also acknowledge FCT for partially financing the research under the framework of the project UTAP-EXPL/CTE/0064/2017, financiado no ambito do Projeto 5665-Parcerias Internacionais de Ciencia e Tecnologia, UT Austin Programme. Mr Pedro Pontes also acknowledgesFCT for his fellowship ref. SFRH/BD/149286/2019

Continuous production of melamine-formaldehyde microcapsules using a mesostructured reactor

A mesostructured NETmix reactor was adapted to develop a continuous process to produce microcapsules, focusing on the steps commonly used in batch formulation: the emulsion and cure. Microcapsules were formed through a polycondensation process by coating Miglyol, a skin-hydrating emollient, with melamine-formaldehyde, which is a resistant shell material with surface smoothness. Different recirculation times were tested for the cure step. Microcapsules show a spherical shape and smooth membrane. Efficiencies of encapsulation of 75%, core contents of 70%, and diameters around 20 μm, ideal range for textile impregnation, were obtained. Scanning electron microscopy shows the integrity of microcapsules on textiles after impregnation and their flexible behavior. The thermogravimetric analysis confirmed the thermal stability of microcapsules up to 210 °C. With the NETmix reactor, it is possible to reduce the cure time of traditional batch formulation in 80%, producing microcapsules with similar characteristics in a continuous process.This work was supported by Associate Laboratory LSRE-LCM UID/EQU/50020/2019 funded by national funds through FCT/MCTES (PIDDAC) and Project TexBioPro, POCI-01- 0247-FEDER-003472, funded by FEDER, through COMPETE 2020, under PT2020.info:eu-repo/semantics/publishedVersio

Portuguese propolis: a source of valuable bioactivities

To FEDER/COMPETE/POCI– Operational Competitiveness and Internationalization Programme, under Project POCI-01-0145-FEDER-006958 and FCT - Portuguese Foundation for Science and Technology, under the project UID/AGR/04033/2013

The compound Poisson limit ruling periodic extreme behaviour of non-uniformly hyperbolic dynamics

We prove that the distributional limit of the normalised number of returns to small neighbourhoods of periodic points of non-uniformly hyperbolic dynamical systems is compound Poisson. The returns to small balls around a fixed point in the phase space correspond to the occurrence of rare events, or exceedances of high thresholds, so that there is a connection between the laws of Return Times Statistics and Extreme Value Laws. The fact that the fixed point in the phase space is a repelling periodic point implies that there is a tendency for the exceedances to appear in clusters whose average sizes is given by the Extremal Index, which depends on the expansion of the system at the periodic point. We recall that for generic points, the exceedances, in the limit, are singular and occur at Poisson times. However, around periodic points, the picture is different: the respective point processes of exceedances converge to a compound Poisson process, so instead of single exceedances, we have entire clusters of exceedances occurring at Poisson times with a geometric distribution ruling its multiplicity. The systems to which our results apply include: general piecewise expanding maps of the interval (Rychlik maps), maps with indifferent fixed points (Manneville-Pomeau maps) and Benedicks-Carleson quadratic maps.Comment: To appear in Communications in Mathematical Physic