Oleaginous yeasts have been seen as a feasible alternative to produce the precursors of biodiesel due to their capacity to accumulate lipids as triacylglycerol having profiles with high content of ...unsaturated fatty acids. The yeast Yarrowia lipolytica is a promising microorganism that can produce lipids under nitrogen depletion conditions and excess of the carbon source. However, under these conditions, this yeast also produces citric acid (overflow metabolism) decreasing lipid productivity. This work presents two mathematical models for lipid production by Y. lipolytica from glucose. The first model is based on Monod and inhibition kinetics, and the second one is based on the Droop quota model approach, which is extended to yeast. The two models showed good agreements with the experimental data used for calibration and validation. The quota based model presented a better description of the dynamics of nitrogen and glucose dynamics leading to a good management of N/C ratio which makes this model interesting for control purposes. Then, quota model was used to evaluate, by means of simulation, a scenario for optimizing lipid productivity and lipid content. For that, a control strategy was designed by approximating the flow rates of glucose and nitrogen with piecewise linear functions. Simulation results achieved productivity of 0.95 g L−1 hr−1 and lipid content fraction of 0.23 g g−1, which indicates that this strategy is a promising alternative for the optimization of lipid production.
Two mathematical models for lipid production by Yarrowia lipolytica are developed. The Droop model for microalgae is extended for yeast. The models are calibrated and validated with independent data sets. Multi objective optimization of lipid accumulation is studied with the quota model. A simple control strategy for critical quota is promising to optimize lipid productivity.
This work presents two mathematical models of the metabolism of Yarrowia lipolytica. The first model is based on Monod and inhibition kinetics, and the second one is based on the Droop quota model approach. The quota based model was used for maximizing lipid productivity and lipid content in simulation.
Diabetic nephropathy (DN) is the leading cause of renal failure worldwide and its complications have become a public health problem. Inflammation, oxidative stress and fibrosis play central roles in ...the progression of DN that lead to renal failure. Potential deleterious effect of inflammation in early evolution of DN is not fully disclosed. Therefore, it is relevant to explore therapies that might modulate this process in order to reduce DN progression. We explored the beneficial effect of all-trans retinoic acid (ATRA) in early inflammation in glomeruli, proximal and distal tubules in streptozotocin (STZ)-induced diabetes. ATRA was administered (1 mg/kg daily by gavage) on days 3 to 21 after STZ administration. It was found that 21 days after STZ injection, diabetic rats exhibited proteinuria, increased natriuresis and loss of body weight. Besides, diabetes induced an increase in interleukins IL-1β, IL-1α, IL-16, IL-13, IL-2; tumor necrosis factor alpha (TNF-α) and transforming growth factor-beta 1 (TGF-β1), chemokines (CCL2, CCL20, CXCL5 and CXCL7), adhesion molecules (ICAM-1 and L-selectin) and growth factors (GM-CSF, VEGF, PDGF) in glomeruli and proximal tubules, whereas ATRA treatment remarkably ameliorated these alterations. To further explore the mechanisms through which ATRA decreased inflammatory response, the NF-κB/p65 signaling mediated by TLR4 was studied. We found that ATRA administration attenuates the TLR4/NF-κB inflammatory signaling and prevents NF-κB nuclear translocation in glomeruli and proximal tubules.
Background
Inflammation is a common feature in chronic kidney disease (CKD) that appears specifically associated with cardiovascular derangements in CKD patients. Observational studies have revealed ...a link between low Mg levels and inflammation. In this study, we hypothesize that Mg might have a modulatory effect on the inflammation induced under the uraemic milieu.
Methods
In vivo studies were performed in a 5/6 nephrectomized rat model of CKD. Furthermore, a possible direct effect of Mg was addressed through in vitro studies with vascular smooth muscle cells (VSMCs).
Results
Uraemic rats fed a normal (0.1%) Mg diet showed a systemic inflammatory response evidenced by the elevation in plasma of the pro‐inflammatory cytokines TNF‐α, IL‐1β and IL‐6, and GPx activity, a marker of oxidative stress. Importantly, an increased expression of these cytokines in the aortic tissue was also observed. In contrast, a dietary Mg supplementation (0.6%) greatly prevented the oxidative stress and the pro‐inflammatory response. In vitro, in VSMCs cultured in a pro‐inflammatory high phosphate medium, incubation with Mg 1.6 mM inhibited the increase in the production of ROS, the rise in the expression of TNF‐α, IL‐1β, IL‐6 and IL‐8 and the activation of NF‐κB signalling that was observed in cells incubated with a normal (0.8 mM) Mg.
Conclusion
Mg supplementation reduced inflammation associated with CKD, exerting a direct effect on vascular cells. These findings support a possible beneficial effect of Mg supplementation along the clinical management of CKD patients.
Growth Arrest-Specific 1 (Gas1) is a pleiotropic protein with different functions, in the adult kidney Gas1 acts as an endogenous inhibitor of cell proliferation but it is also necessary for the ...maintenance and proliferation of Renal Progenitor Cells (RPC) during early development, thus it fulfills important functions in the adult kidney. However, it is not known whether or not Gas1 is expressed during postnatal development, a critical stage for renal maturation. For this reason, the main objective of this work was to characterize the expression pattern of Gas1 in the different regions of the kidney by immunofluorescence and Western blot analysis during the postnatal development of the rat. We found that Gas1 is present and has a differential expression pattern in the various regions of the nephron during postnatal development. We observed that the highest levels of expression of Gas1 occur in the adult, however, Gas1 is also expressed in RPC and interestingly, the expression of RPC markers such as the Neural cell adhesion molecule (NCAM) and Cluster of differentiation 24 (CD24) were found to have an inverse pattern of expression to Gas1 (decreases as the kidney matures) during postnatal renal maturation, this indicates a role for Gas1 in the regulation of renal cell proliferation at this stage of development.
Square markers are a widespread tool to find correspondences for camera localization because of their robustness, accuracy, and detection speed. Their identification is usually based on a binary ...encoding that accounts for the different rotations of the marker; however, most systems do not consider the possibility of observing reflected markers. This case is possible in environments containing mirrors or reflective surfaces, and its lack of consideration is a source of detection errors, which is contrary to the robustness expected from square markers. This is the first work in the literature that focuses on reflection-aware square marker dictionaries. We present the derivation of the inter-marker distance of a reflection-aware dictionary and propose new algorithms for generating and identifying such dictionaries. Additionally, part of the proposed method can be used to optimize preexisting dictionaries to take reflection into account. The experimentation carried out demonstrates how our proposal greatly outperforms the most popular predefined dictionaries in terms of inter-marker distance and how the optimization process significantly improves them.
Fingolimod is an immunomodulatory sphingosine-1-phosphate (S1P) analogue approved for the treatment of relapsing-remitting multiple sclerosis (RRMS). The identification of biomarkers of clinical ...responses to fingolimod is a major necessity in MS to identify optimal responders and avoid the risk of disease progression in non-responders. With this aim, we used RNA sequencing to study the transcriptomic changes induced by fingolimod in peripheral blood mononuclear cells of MS-treated patients and their association with clinical response. Samples were obtained from 10 RRMS patients (five responders and five non-responders) at baseline and at 12 months of fingolimod therapy. Fingolimod exerted a vast impact at the transcriptional level, identifying 7155 differentially expressed genes (DEGs) compared to baseline that affected the regulation of numerous signaling pathways. These DEGs were predominantly immune related, including genes associated with S1P metabolism, cytokines, lymphocyte trafficking, master transcription factors of lymphocyte functions and the NF-kB pathway. Responder and non-responder patients exhibited a differential transcriptomic regulation during treatment, with responders presenting a higher number of DEGs (6405) compared to non-responders (2653). The S1P, NF-kB and TCR signaling pathways were differentially modulated in responder and non-responder patients. These transcriptomic differences offer the potential of being exploited as biomarkers of a clinical response to fingolimod.
Cell recruitment is a process by which a differentiated cell induces neighboring cells to adopt its same cell fate. In Drosophila, cells expressing the protein encoded by the wing selector gene, ...vestigial (vg), drive a feed-forward recruitment signal that expands the Vg pattern as a wave front. However, previous studies on Vg pattern formation do not reveal these dynamics. Here, we use live imaging to show that multiple cells at the periphery of the wing disc simultaneously activate a fluorescent reporter of the recruitment signal, suggesting that cells may be recruited without the need for their contact neighbors be recruited in advance. In support of this observation, when Vg expression is inhibited either at the dorsal-ventral boundary or away from it, the activation of the recruitment signal still occurs at a distance, suggesting that Vg expression is not absolutely required to send or propagate the recruitment signal. However, the strength and extent of the recruitment signal is clearly compromised. We conclude that a feed-forward, contact-dependent cell recruitment process is not essential for Vg patterning, but it is necessary for robustness. Overall, our findings reveal a previously unidentified role of cell recruitment as a robustness-conferring cell differentiation mechanism.
Cytokinesis in plant cells begins with the fusion of vesicles that transport cell wall materials to the center of the cell division plane, where the cell plate forms and expands radially until it ...fuses with the parental cell wall. Vesicle fusion is facilitated by trans-SNARE complexes, with assistance from Sec1/Munc18 (SM) proteins. The SNARE protein KNOLLE and the SM protein KEULE are required for membrane fusion at the cell plate. Due to the crucial function of KEULE, all Arabidopsis (Arabidopsis thaliana) keule mutants identified to date are seedling lethal. Here, we identified the Arabidopsis serrata4-1 (sea4-1) and sea4-2 mutants, which carry recessive, hypomorphic alleles of KEULE. Homozygous sea4-1 and sea4-2 plants are viable and fertile but have smaller rosettes and fewer leaves at bolting than the wild type. Their leaves are serrated, small, and wavy, with a complex venation pattern. The mutant leaves also develop necrotic patches and undergo premature senescence. RNA-seq revealed transcriptome changes likely leading to reduced cell wall integrity and an increase in the unfolded protein response. These findings shed light on the roles of KEULE in postembryonic development, particularly in the patterning of rosette leaves and leaf margins.
Fibroblast Growth Factor 23 (FGF23) and Klotho play an essential role in the regulation of mineral metabolism, and both are altered as a consequence of renal failure. FGF23 increases to augment ...phosphaturia, which prevents phosphate accumulation at the early stages of chronic kidney disease (CKD). This effect of FGF23 requires the presence of Klotho in the renal tubules. However, Klotho expression is reduced as soon as renal function is starting to fail to generate a state of FGF23 resistance. Changes in these proteins directly affect to other mineral metabolism parameters; they may affect renal function and can produce damage in other organs such as bone, heart, or vessels. Some of the mechanisms responsible for the changes in FGF23 and Klotho levels are related to modifications in the Wnt signaling. This review examines the link between FGF23/Klotho and Wnt/β-catenin in different organs: kidney, heart, and bone. Activation of the canonical Wnt signaling produces changes in FGF23 and Klotho and vice versa; therefore, this pathway emerges as a potential therapeutic target that may help to prevent CKD-associated complications.
FGF23 Fails to Inhibit Uremic Parathyroid Glands CANALEJO, Rocío; CANALEJO, Antonio; MARTINEZ-MORENO, Julio Manuel ...
Journal of the American Society of Nephrology,
07/2010, Letnik:
21, Številka:
7
Journal Article
Recenzirano
Odprti dostop
Fibroblast growth factor 23 (FGF23) modulates mineral metabolism by promoting phosphaturia and decreasing the production of 1,25-dihydroxyvitamin D(3). FGF23 decreases parathyroid hormone (PTH) mRNA ...and secretion, but despite a marked elevation in FGF23 in uremia, PTH production increases. Here, we investigated the effect of FGF23 on parathyroid function in normal and uremic hyperplastic parathyroid glands in rats. In normal parathyroid glands, FGF23 decreased PTH production, increased expression of both the parathyroid calcium-sensing receptor and the vitamin D receptor, and reduced cell proliferation. Furthermore, FGF23 induced phosphorylation of extracellular signal-regulated kinase 1/2, which mediates the action of FGF23. In contrast, in hyperplastic parathyroid glands, FGF23 did not reduce PTH production, did not affect expression of the calcium-sensing receptor or vitamin D receptor, and did not affect cell proliferation. In addition, FGF23 failed to activate the extracellular signal-regulated kinase 1/2-mitogen-activated protein kinase pathway in hyperplastic parathyroid glands. We observed very low expression of the FGF23 receptor 1 and the co-receptor Klotho in uremic hyperplastic parathyroid glands, which may explain the lack of response to FGF23 in this tissue. In conclusion, in hyperparathyroidism secondary to renal failure, the parathyroid cells resist the inhibitory effects of FGF23, perhaps as a result of the low expression of FGF23 receptor 1 and Klotho in this condition.
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