Editorial

Metabolic disorders, particularly Diabetes Mellitus (DM), are major causes of death worldwide. In fact, the world statistics for DM are alarming: this epidemic disease kills one person every six seconds, being the fourth cause of death. Besides the health issues, the costs associated with DM, and its co-morbidities, are massive and the pressure in National Health Care Systems is dramatically increasing. Patients with DM, particularly those with type 2 diabetes (T2D), are primarily advised to change their dietary habits and exercise regime. However, as the disease progresses and becomes more severe, conventional drugs are prescribed. Most of these patients need polypharmacological therapy and though progresses have been made, efforts are mandatory in a search for a “perfect” antidiabetic drug. [...]info:eu-repo/semantics/publishedVersio

Mitochondrial dynamics and quality control in Huntington's disease

Huntington's disease (HD) is an inherited neurodegenerative disorder caused by polyglutamine expansion mutations in the huntingtin protein. Despite its ubiquitous distribution, expression of mutant huntingtin (mHtt) is particularly detrimental to medium spiny neurons within the striatum. Mitochondrial dysfunction has been associated with HD pathogenesis. Here we review the current evidence for mHtt-induced abnormalities in mitochondrial dynamics and quality control, with a particular focus on brain and neuronal data pertaining to striatal vulnerability. We address mHtt effects on mitochondrial biogenesis, protein import, complex assembly, fission and fusion, mitochondrial transport, and on the degradation of damaged mitochondria via autophagy (mitophagy). For an integrated perspective on potentially converging pathogenic mechanisms, we also address impaired autophagosomal transport and abnormal mHtt proteostasis in HD

Ulva rigida valorization into poly(3-hydroxybutyrate), organic acids and functional ingredients

Halomonas elongata 1H9T is a moderate halophilic strain able to produce poly(3-hydroxybutyrate) (P(3HB)), a biodegradable plastic, and gluconic acid, a valuable organic acid with wide industrial applications. In this work, the green alga Ulva rigida was used as platform to produce cultivation substrates for microbial conversion as well as functional ingredients, targeting its full valorization. The liquor obtained by autohydrolysis presented the highest concentration of oligosaccharides and protein, being an interesting feedstock to produce functional ingredients. The acid and/or enzymatic hydrolysis liquors are adequate as substrates for microbial processes. Shake flask assays with H. elongata revealed that the N-rich liquor produced after acidic treatment was the best suited for cell growth while the N-poor liquor produced by the enzymatic treatment of acid-pretreated algae residues produced the highest P(3HB) titers of 4.4 g/L. These hydrolysates were used in fed-batch cultivations as carbon and protein sources for the co-production of gluconic acid and polymer achieving titers of 123.2 g/L and 7.2 g/L, respectively. Besides gluconic acid, the Krebs cycle intermediate 2-oxoglutaric acid, also called alpha-ketoglutaric acid (KGA), was produced. Therefore, the co-production of P(3HB) and acids may be of considerable interest as an algal biorefinery valorization strategy.This research was funded by Fundação para a Ciência e Tecnologia (FCT) project number (PTDC/BII-BIO/29242/2017). Funding received from FCT—Fundação para a Ciência e Tecnologia, I.P., in the scope of the project UIDB/04565/2020 and UIDP/04565/2020 of the Research Unit Institute for Bioengineering and Biosciences—iBB and the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy—i4HB is acknowledged. Funding received from FCT under the scope of the strategic funding of UID/BIO/04469/2020 unit and LABBELS—Associate Laboratory in Biotechnology, Bioengineering and Microelectromechanical Systems, LA/P/0029/2020 project is also acknowledged.info:eu-repo/semantics/publishedVersio

Implications of epigallocatechin-3-gallate in cultured human Sertoli cells glycolytic and oxidative profile

Sertoli cells are crucial for the success of spermatogenesis, which is the biological process that ensures male fertility. These cells present high metabolic rates, being often subjected to high oxidative stress levels that, if uncontrolled, may compromise male fertility. Since the most abundant tea catechin, epigallocatechin-3-gallate (EGCG), has demonstrated a potent preventive activity against oxidative stress, we have evaluated its effect at concentrations of 5 and 50μM, on the metabolism, mitochondrial functionality and oxidative profile of human Sertoli cells (hSCs). While, the highest concentration of EGCG (50μM) increased glucose and pyruvate consumption, it decreased the conversion of pyruvate to alanine to sustain a regular lactate production. However, despite maintaining Krebs cycle functionality, EGCG (50μM) decreased mitochondrial membrane potential of hSCs, which could compromise the normal rates of ATP production. Interestingly, oxidative damages to proteins and lipids decreased in this experimental group, which may be valuable for the nutritional support of spermatogenesis.info:eu-repo/semantics/publishedVersio

Knockout of insulin-degrading enzyme leads to mice testicular morphological changes and impaired sperm quality

Insulin-degrading enzyme (IDE) is a zinc metalloprotease responsible for degrading and inactivating several bioactive peptides, including insulin. Individuals without this enzyme or with a loss-of-function mutation in the gene that codifies it, present hyperinsulinemia. In addition, impairment of IDE-mediated insulin clearance is associated with the development of metabolic diseases, namely prediabetes. Although insulin regulates male fertility, the role of IDE on male reproductive function remains unknown. We proposed to study the influence of IDE in the reproductive potential of males. As insulin mediates key events for the normal occurrence of spermatogenesis, we hypothesized that IDE functioning might be linked with sperm quality. We used C57BL/6N mice that were divided in three groups according to its genotype: wild type (WT), heterozygous and knockout (KO) male mice for Ide. Spermatozoa were collected from the cauda of epididymis and sperm parameters were evaluated. Testicular tissue morphology was assessed through hematoxylin and eosin stain. Mitochondrial complex protein levels and lipid peroxidation were also evaluated in the testicular tissue. Our results show that KO mice present a 50% decrease in testes weight compared to WT mice as well as a decrease in seminiferous tubules diameter. Moreover, KO mice present impaired sperm quality, namely a decrease in both sperm viability and morphology. These results provide evidence that IDE plays an important role in determining the reproductive potential of males.publishe

Uncovering the Use of Fucoxanthin and Phycobiliproteins into Solid Matrices to Increase Their Emission Quantum Yield and Photostability

In the search for a better and brighter future, the use of natural luminescent renewable materials as substitutes for synthetic ones in the energy field is of prime importance. The incorporation of natural pigments (e.g., xanthophylls and phycobiliproteins) is a fundamental step in a broad spectrum of applications that are presently marred by their limited stability. The incorporation of bio-based luminescent molecules into solid matrices allows the fabrication of thin films, which may dramatically increase the range of applications, including sustainable photovoltaic systems, such as luminescent solar concentrators or downshifting layers. In this work, we incorporated R-phycoerythrin (R-PE), C-phycocyanin (C-PC), and fucoxanthin (FX) into poly(vinyl alcohol) (PVA) and studied their optical properties. It was found that the emission and excitation spectra of the phycobiliproteins and FX were not modified by incorporation into the PVA matrix. Moreover, in the case of FX, the emission quantum yield (η) values also remained unaltered after incorporation, showing the suitability of the PVA as a host matrix. A preliminary photostability study was performed by exposing the solid samples to continuous AM1.5G solar radiation, which evidenced the potential of these materials for future photovoltaics.publishe

8-(3-phenylpropyl)-1,3,7-triethylxanthine is a synthetic caffeine substitute with stronger metabolic modulator activity

Caffeine is one of the most worldwide consumed methylxanthines. It is well-known for its thermogenic and cell metabolism modulating effects. Based on methylxanthines' chemical structure, 8-(3-phenylpropyl)-1,3,7-triethylxanthine (PTX) is a novel adenosine antagonist with higher receptor affinity than caffeine. Therefore, we hypothesized that PTX metabolic effects could be stronger than those of caffeine. For that purpose, murine 3T3-L1 cells were cultured in the presence of increasing doses of PTX or caffeine (0.1, 1, 10 and 100 μM) for 24 h. Cytotoxicity was evaluated by reduction of tetrazolium salt (MTT) and lactate dehydrogenase (LDH) release. Cell metabolites released to the culture medium were identified and quantified by proton nuclear magnetic resonance (1H NMR). Cellular oxidative profile was also evaluated. Our results showed that PTX displayed no signs of cytotoxicity at all studied concentrations. When compared with caffeine, PTX increased glucose, pyruvate, and glutamine consumption, as well as lactate, alanine, and acetate production. Additionally, PTX decreased protein oxidation, thus protecting against oxidative stress-induced damage. These results illustrate that PTX is a stronger and less cytotoxic caffeine substitute with potential applications as metabolic modulator and a good candidate for novel drug design.info:eu-repo/semantics/publishedVersio

HDAC6 inhibition induces mitochondrial fusion, autophagic flux and reduces diffuse mutant huntingtin in striatal neurons

Striatal neurons are vulnerable to Huntington's disease (HD). Decreased levels of acetylated alpha-tubulin and impaired mitochondrial dynamics, such as reduced motility and excessive fission, are associated with HD; however, it remains unclear whether and how these factors might contribute to the preferential degeneration of striatal neurons. Inhibition of the alpha-tubulin deacetylase HDAC6 has been proposed as a therapeutic strategy for HD, but remains controversial - studies in neurons show improved intracellular transport, whereas studies in cell-lines suggest it may impair autophagosome-lysosome fusion, and reduce clearance of mutant huntingtin (mHtt) and damaged mitochondria (mitophagy). Using primary cultures of rat striatal and cortical neurons, we show that mitochondria are intrinsically less motile and more balanced towards fission in striatal than in cortical neurons. Pharmacological inhibition of the HDAC6 deacetylase activity with tubastatin A (TBA) increased acetylated alpha-tubulin levels, and induced mitochondrial motility and fusion in striatal neurons to levels observed in cortical neurons. Importantly, TBA did not block neuronal autophagosome-lysosome fusion, and did not change mitochondrial DNA levels, suggesting no impairment in autophagy or mitochondrial clearance. Instead, TBA increased autophagic flux and reduced diffuse mHtt in striatal neurons, possibly by promoting transport of initiation factors to sites of autophagosomal biogenesis. This study identifies the pharmacological inhibition of HDAC6 deacetylase activity as a potential strategy to reduce the vulnerability of striatal neurons to HD

Data on metabolic profile of insulin-degrading enzyme knockout mice

Insulin-degrading enzyme (IDE) degrades and inactivates bioactive peptides such as insulin. As insulin is a master regulator of glucose homeostasis, lack of IDE is expected to have a profound impact on both insulin and glucose levels. This article shares data on glucose and insulin homeostasis of control, heterozygous and knockout mice for Ide after 18 weeks of a normal chow diet. This data article is related to a research article entitled “Knockout of insulin-degrading enzyme leads to mice testicular morphological changes and impaired sperm quality” (Meneses et al., 2019).publishersversionpublishe

Phytoplankton dynamics in relation to seasonal variability and upwelling and relaxation patterns at the mouth of Ria de Aveiro (West Iberian Margin) over a four-year period

From June 2004 to December 2007, samples were weekly collected at a fixed station located at the mouth of Ria de Aveiro (West Iberian Margin). We examined the seasonal and inter-annual fluctuations in composition and community structure of the phytoplankton in relation to the main environmental drivers and assessed the influence of the oceano-graphic regime, namely changes in frequency and intensity of upwelling events, over the dynamics of the phytoplankton assemblage. The samples were consistently handled and a final subset of 136 OTUs (taxa with relative abundance > 0.01%) was subsequently submitted to various multivariate analyses. The phytoplankton assemblage showed significant changes at all temporal scales but with an overriding importance of seasonality over longer-(inter-annual) or shorter-term fluctuations (upwelling-related). Sea-surface temperature, salinity and maximum upwelling index were retrieved as the main driver of seasonal change. Seasonal signal was most evident in the fluctuations of chlorophyll a concentration and in the high turnover from the winter to spring phytoplankton assemblage. The seasonal cycle of production and succession was disturbed by upwelling events known to disrupt thermal stratification and induce changes in the phytoplankton assemblage. Our results indicate that both the frequency and intensity of physical forcing were important drivers of such variability, but the outcome in terms of species composition was highly dependent on the available local pool of species and the timing of those events in relation to the seasonal cycle. We conclude that duration, frequency and intensity of upwelling events, which vary seasonally and inter-annually, are paramount for maintaining long-term phytoplankton diversity likely by allowing unstable coexistence and incorporating species turnover at different scales. Our results contribute to the understanding of the complex mechanisms of coastal phytoplankton dynamics in relation to changing physical forcing which is fundamental to improve predictability of future prospects under climate change.Portuguese Foundation for Science and Technology (FCT, Portugal) [SFRH/BPD/ 94562/2013]; FEDER funds; national funds; CESAM [UID/AMB/50017]; FCT/MEC through national funds; FEDERinfo:eu-repo/semantics/publishedVersio