Strict adherence to a diet is an essential pillar of long-term treatment for many inborn errors of metabolism (IEMs). Tools that educate patients about dietary management can positively condition ...adherence and prevent morbidity. We designed a free online dietary calculation program (Odimet
, version 2.1.) for IEMs patients in 2008, updated in 2022, that provides detailed information on the content of amino acids, protein, lipids, carbohydrates, vitamins and minerals in >3000 food products, including specific medical foods for IEM. We analyzed the statistics on visits to Odimet
to evaluate its usefulness for long-term dietary management during a 5-year period focusing on three periods: pre-pandemic (15 March 2018-14 March 2020); pandemic 1 (15 March 2020-14 March 2021); and pandemic 2 period (15 March 2021-15 March 2023), in 120 patients with the following distribution: 84 patients with phenylketonuria (PKU); 12 with maple syrup urine disease (MSUD); 11 with urea cycle disorders (UCDs); and 13 with classical galactosemia. The evolutionary levels of their specific metabolic markers were evaluated, showing that globally, both pediatric and adult patients maintain a good metabolic control, even during a pandemic (median levels of phenylalanine in pediatric PKU patients 213.4 µmol/L and 482.3 µmol/L in adults; of leucine in MSUD patients: 144.2 µmol/L; of glutamine in UCDs: 726.8 µmol/L; and of galactose 1-phosphate levels in galactosemia: 0.08 µmol/L). The proportion of patients using Odimet
ranges from 78-100%. An increase in the number of diets being calculated was observed during COVID-19 pandemic. Currently, 14,825 products have been introduced (3094 from the general database, and 11,731 added by users to their own profiles). In 2023 63 emergency dietary adjustments in the studied intoxication-type pathologies were calculated in Odimet
. Our results suggest that its regular use contributes to maintaining metabolic stability in IEMs patients, allowing them to adapt their menus to their lifestyle, and represents a powerful complementary tele-health tool which can be used to perform remote real-time dietary follow-up.
Departamento de Biología Molecular Centro de Biología Molecular "Severo Ochoa" UAM-CSIC, Facultad de Ciencias, Universidad Autónoma, Madrid; and Área de Bioquímica, Centro Regional de Investigaciones ...Biomédicas (CRIB), Facultad de Ciencias del Medio Ambiente, Universidad de Castilla-La Mancha, Toledo, Spain
Ca 2+ signaling in mitochondria is important to tune mitochondrial function to a variety of extracellular stimuli. The main mechanism is Ca 2+ entry in mitochondria via the Ca 2+ uniporter followed by Ca 2+ activation of three dehydrogenases in the mitochondrial matrix. This results in increases in mitochondrial NADH/NAD ratios and ATP levels and increased substrate uptake by mitochondria. We review evidence gathered more than 20 years ago and recent work indicating that substrate uptake, mitochondrial NADH/NAD ratios, and ATP levels may be also activated in response to cytosolic Ca 2+ signals via a mechanism that does not require the entry of Ca 2+ in mitochondria, a mechanism depending on the activity of Ca 2+ -dependent mitochondrial carriers (CaMC). CaMCs fall into two groups, the aspartate-glutamate carriers (AGC) and the ATP-Mg/P i carriers, also named SCaMC (for short CaMC). The two mammalian AGCs, aralar and citrin, are members of the malate-aspartate NADH shuttle, and citrin, the liver AGC, is also a member of the urea cycle. Both types of CaMCs are activated by Ca 2+ in the intermembrane space and function together with the Ca 2+ uniporter in decoding the Ca 2+ signal into a mitochondrial response.
The microlocalisation of Cu was examined in the leaves of white lupin and soybean grown hydroponically in the presence of 1.6 (control) or 192 μM (excess) Cu, along with its effect on leaf ...morphology, (ultra)structure and the antioxidative response. The 192 μM dose led to a reduction in the total leaf area and leaf thickness in both species, although more strongly so in white lupin. In the latter species it was also associated with smaller spongy parenchyma cells, and smaller spaces between them, while in the soybean it more strongly reduced the size of the palisade parenchyma and epidermal cells. Energy-dispersive X-ray microanalysis showed that under Cu excess the metal was mainly localised inside the spongy parenchyma cells of the white lupin leaves, and in the lower epidermis cell walls in those of the soybean. Cu excess also promoted ultrastructural chloroplast alterations, reducing the photosynthetic capacity index and the green area of the leaves, especially in the soybean. Despite this, soybean appeared to be more tolerant to Cu excess than white lupin, because soybean displayed (1) lower accumulation of Cu in the leaves, (2) enhanced microlocalisation of Cu in the cell walls and (3) greater levels of induced total –SH content and superoxide dismutase and catalase activities that are expected for better antioxidative responses.
The effect of Bradyrhizobium–legume symbiosis on plant growth, toxicological variables and Cu bioaccumulation was studied in white lupin and soybean plants treated with 1.6, 48, 96 and 192μM Cu. In ...both species, those plants grown in the presence of root nodule-forming symbiotic Bradyrhizobium showed less root and shoot growth reduction, plus greater translocation of Cu to the shoot, than those grown without symbiotic Bradyrhizobium. The effective added concentrations of Cu that reduced shoot and root dry weight by 50% (EC50), and the critical toxic concentration that caused a 10% reduction in plant growth (CTC10%), were higher in plants grown with symbiotic Bradyrhizobium, and were in general higher in the roots whether the plants were grown with or without these bacteria. The production of malondialdehyde and total thiols was stimulated by Cu excess in the shoots and roots of white lupin grown with or without symbiotic Bradyrhizobium, but mainly in those without the symbionts. In contrast, in soybean, the increases in malondialdehyde and total thiols associated with rising Cu concentration were a little higher (1.2–5.0 and 1.0–1.6 times respectively) in plants grown with symbiotic Bradyrhizobium than without. Finally, the organ most sensitive to Cu excess was generally the shoot, both in white lupin and soybean grown with or without symbiotic Bradyrhizobium. Further, Bradyrhizobium–legume symbiosis appears to increase the tolerance to Cu excess in both legumes, but mainly in white lupin; plant growth was less reduced and CTC10% and EC50 values increased compared to plants grown without symbiotic Bradyrhizobium. Bradyrhizobium N2 fixation in both legumes would therefore seem to increase the phytoremediation potential of these plants when growing on Cu-contaminated sites.
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•Cu toxicity was studied in white lupin and soybean grown with/without Bradyrhizobium.•Bradyrhizobium–legume symbiosis mitigates Cu toxicity in these legumes.•N2 fixation protects more against Cu toxicity in white lupin than in soybean plants.•N2 fixation increases the phytoextraction of Cu, especially by white lupin plants.
AGC1/Aralar/Slc25a12 is the mitochondrial carrier of aspartate-glutamate, the regulatory component of the NADH malate-aspartate shuttle (MAS) that transfers cytosolic redox power to neuronal ...mitochondria. The deficiency in AGC1/Aralar leads to the human rare disease named "early infantile epileptic encephalopathy 39" (EIEE 39, OMIM # 612949) characterized by epilepsy, hypotonia, arrested psychomotor neurodevelopment, hypo myelination and a drastic drop in brain aspartate (Asp) and
-acetylaspartate (NAA). Current evidence suggest that neurons are the main brain cell type expressing Aralar. However, paradoxically, glial functions such as myelin and Glutamine (Gln) synthesis are markedly impaired in AGC1 deficiency. Herein, we discuss the role of the AGC1/Aralar-MAS pathway in neuronal functions such as Asp and NAA synthesis, lactate use, respiration on glucose, glutamate (Glu) oxidation and other neurometabolic aspects. The possible mechanism triggering the pathophysiological findings in AGC1 deficiency, such as epilepsy and postnatal hypomyelination observed in humans and mice, are also included. Many of these mechanisms arise from findings in the
-KO mice model that extensively recapitulate the human disease including the astroglial failure to synthesize Gln and the dopamine (DA) mishandling in the nigrostriatal system. Epilepsy and DA mishandling are a direct consequence of the metabolic defect in neurons due to AGC1/Aralar deficiency. However, the deficits in myelin and Gln synthesis may be a consequence of neuronal affectation or a direct effect of AGC1/Aralar deficiency in glial cells. Further research is needed to clarify this question and delineate the transcellular metabolic fluxes that control brain functions. Finally, we discuss therapeutic approaches successfully used in AGC1-deficient patients and mice.
•As toxicity was studied in cardoon plants grown with/without 5μM Cd.•Cd reduces plant growth, CTC10% and EC50.•Cd increases As phytoextraction capacity but reduces As tolerance.•Cardoons may act as ...As-accumulators, or As-excluders under As+Cd contamination conditions.
The effect of As (0–80μM) and of As+Cd (0–80μM+5μM) combinations on plant growth, toxicological variables and As and Cd bioaccumulation was studied in cardoon plants under controlled conditions. Plants grown in the presence of As alone showed less reduction in overall root and shoot development than those exposed to As+Cd, although the main root was shorter than in the latter plants. The effective added concentrations of As that reduced shoot or root dry weight by 50% (EC50) and the critical toxic concentration that caused a 10% reduction in plant growth (CTC10%) were higher in plants grown with As alone. In both treatments (As and As+Cd), the CTC10% was higher in the roots, but the root EC50 was lower than the shoot EC50. The presence of Cd increased the accumulation of As in the shoot, but ≥20μM As reduced the shoot bioaccumulation of Cd. Thus, the presence of 5μM Cd with As appears to reduce the tolerance of cardoon plants to the latter element, but it increases their As phytoextraction capacity. Cardoon plants could be used as excluders in As-contaminated sites and as accumulators in those co-contaminated with As and Cd.
The extracellular matrix of white adipose tissue (AT) is a very promising biomaterial for tissue engineering, due to its abundance, easy accessibility, malleability, and proven biological activity. ...Decellularised AT (DAT) can be processed by freeze-drying in acetic acid solutions, and changing the DAT concentration in the solution gives rise to three-dimensional (3D) scaffolds of different stiffness and porosity. In a previous report, we demonstrated that human Dental Pulp Stem Cells (hDPSCs) could differentiate to osteoblasts and generate mineralised bone on 3D solid foams of porcine Decellularised Adipose Tissue (pDAT) at a concentration of 0.5 % (w/v). In this research work, we assessed whether and how osteogenesis by hDPSCs would be regulated by testing pDAT solid foams formulated at three different concentrations: 0.25 % (w/v), 0.5 % (w/v), and 1 % (w/v), which showed different stiffness, porosity and water retention properties. As a control condition we tested solid foams formulated with 0.5 % bovine Collagen-I. Thus, we performed Alkaline Phosphatase and Alizarin Red staining, together with Transmission Electron Microscopy and the detection of osteoblastic differentiation markers Osterix and Osteocalcin at both protein and transcript level, to compare the osteogenesis mediated by hDPSCs grown on all these 3D scaffolds, in the presence or absence of osteoblastic induction media. Our results demonstrate that pDAT at 0.25 % supported osteogenesis better than the rest of tested scaffolds, including bovine Collagen-I, in 3D hDPSC cultures. This enhanced osteogenesis could be attributed to the formulation of 0.25 % pDAT solid foams, which presented a higher porosity.
Este texto responde a la invitación a pensar desde el concepto de inclinación que la filósofa Adriana Cavarero pone en el centro de la reflexión contemporánea, en diálogo con autores de ...extraordinaria significación como Judith Butler. El objetivo central del artículo es indagar en las dimensiones sociológicas del arte contemporáneo a través del análisis de las figuras de la mediación y del cuidado, a partir de un despliegue de posibles canalizaciones de la sociología del arte en la actualidad, preocupadas por las formas de hacer y producir, difundir y sostener, arte y conocimiento. En la actualidad, la noción de mediación ha adquirido centralidad en el mundo del arte, diagnosticándose una saturación de sus usos y una polisemia en sus significados, por ser una de las más relevantes en la teoría social contemporánea. El cuidado también se ha tornado central a la hora de abordar distintas formas de hacer, en el mundo del arte y en las prácticas de conocimiento. Así, este artículo postula un análisis sociológico del arte contemporáneo que aporta un despliegue de los cuidados en el arte a través de la mediación.
► Cu excess causes (ultra)structural changes in white lupin and soybean root nodules. ► White lupin root nodules show a less effective anti-oxidative response against Cu. ► White lupin root nodules ...are more sensitive to Cu excess than those of soybean.
Copper (Cu) is a heavy metal which, at high concentrations, is toxic to organisms. Some plants, however, possess systems for dealing with excess Cu, such as its cell localisation, and have antioxidant enzymes that help to reduce the oxidative stress. The present work examines the microlocalisation of Cu and the antioxidant enzyme activity present in the nodules of white lupin and soybean plants grown hydroponically for 35 days in the presence of 1.6μM (control) or 192μM (excess) Cu. The effect of these conditions on nodule (ultra)structure was also examined. Energy-dispersive X-ray microanalysis showed the cell walls to be the main area of Cu binding in the inner and outer cortex and infected zone of white lupin nodules grown under the excess Cu conditions, while in soybean a high Cu signal was detected inside cells (cytoplasm or vacuoles) both in the inner cortex and infected zone. At the tissue level, an increasing Cu gradient was seen from the outer towards the inner nodule cortex in white lupin nodules, while the opposite was seen in soybean. Cu excess also induced oxidative stress and promoted damage to the ultrastructure of nodules. In the white lupin infected cells, a breakdown of the peribacteroidal membrane was seen, along with an increased number of vesicles in the cytosol of these cells. In the infected cells of the soybean nodules, the bacteroidal membrane became degraded and precipitation was seen within the vacuoles of the infected and uninfected cells. Finally, the white lupin nodules seemed to be more sensitive to Cu excess than those of soybean, with the nodulation process, N2 fixation, and the ultrastructure of bacteroids more strongly affected. A less effective antioxidative stress response against Cu was also seen in white lupin than in soybean nodules: the excess copper treatment induced a smaller increase in the total thiol content and ascorbate peroxidase activity in white lupin nodules than in soybean nodules, and promoted a greater reduction in catalase activity.
Parkinson’s disease (PD) is a neurological disorder characterized by motor dysfunction, dopaminergic neuron loss, and alpha-synuclein (αSyn) inclusions. Many PD risk factors are known, but those ...affecting disease progression are not. Lifestyle and microbial dysbiosis are candidates in this context. Diet-driven gut dysbiosis and reduced barrier function may increase exposure of enteric neurons to toxins. Here, we study whether fiber deprivation and exposure to bacterial curli, a protein cross-seeding with αSyn, individually or together, exacerbate disease in the enteric and central nervous systems of a transgenic PD mouse model. We analyze the gut microbiome, motor behavior, and gastrointestinal and brain pathologies. We find that diet and bacterial curli alter the microbiome and exacerbate motor performance, as well as intestinal and brain pathologies, but to different extents. Our results shed important insights on how diet and microbiome-borne insults modulate PD progression via the gut-brain axis and have implications for lifestyle management of PD.
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•Fiber deprivation shifts microbiome structure and affects gut barrier•Curli accelerates alpha-synuclein pathology in colon and brain•Combining challenges replicates and accelerates Parkinsonian features
Schmit et al. investigate how dietary fiber deprivation in combination with a bacterial toxin affect PD progression. They point to a translational PD-relevant sequence of events exacerbating disease progression in a disease mouse model and put forth the idea of lifestyle adaptations to mitigate the disease.
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