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71.
Glycans are one of the four fundamental macromolecular components of living matter, and they are highly regulated in the cell. Their functions are metabolic, structural and modulatory. In particular, ER resident N-glycans participate with the Glc3Man9GlcNAc2 highly conserved sequence, in protein folding process, where the physiological balance between glycosylation/deglycosylation on the innermost glucose residue takes place, according GANAB/UGGT concentration ratio. However, under abnormal conditions, the cell adapts to the glucose availability by adopting an aerobic or anaerobic regimen of glycolysis, or to external stimuli through internal or external recognition patterns, so it responds to pathogenic noxa with unfolded protein response (UPR). UPR can affect Multiple Sclerosis (MS) and several neurological and metabolic diseases via the BiP stress sensor, resulting in ATF6, PERK and IRE1 activation. Furthermore, the abnormal GANAB expression has been observed in MS, systemic lupus erythematous, male germinal epithelium and predisposed highly replicating cells of the kidney tubules and bile ducts. The latter is the case of Polycystic Liver Disease (PCLD) and Polycystic Kidney Disease (PCKD), where genetically induced GANAB loss affects polycystin-1 (PC1) and polycystin-2 (PC2), resulting in altered protein quality control and cyst formation phenomenon. Our topics resume the role of glycans in cell physiology, highlighting the N-glycans one, as a substrate of GANAB, which is an emerging key molecule in MS and other human pathologies. 相似文献
72.
73.
Elisa Boschetti Leonardo Caporali Roberto DAngelo Carolina Malagelada Anna Accarino Maria Teresa Dotti Roberta Costa Giovanna Cenacchi Loris Pironi Rita Rinaldi Vincenzo Stanghellini Stefano Ratti Lucia Manzoli Valerio Carelli Roberto De Giorgio 《International journal of molecular sciences》2022,23(15)
mitochondrial neuro-gastrointestinal encephalomyopathy (MNGIE) is a rare genetic disorder characterized by thymidine phosphorylase (TP) enzyme defect. The absence of TP activity induces the imbalance of mitochondrial nucleotide pool, leading to impaired mitochondrial DNA (mtDNA) replication and depletion. Since mtDNA is required to ensure oxidative phosphorylation, metabolically active tissues may not achieve sufficient energy production. The only effective life-saving approach in MNGIE has been the permanent replacement of TP via allogeneic hematopoietic stem cell or liver transplantation. However, the follow-up of transplanted patients showed that gut tissue changes do not revert and fatal complications, such as massive gastrointestinal bleeding, can occur. The purpose of this study was to clarify whether the reintroduction of TP after transplant can recover mtDNA copy number in a normal range. Using laser capture microdissection and droplet-digital-PCR, we assessed the mtDNA copy number in each layer of full-thickness ileal samples of a naive MNGIE cohort vs. controls and in a patient pre- and post-TP replacement. The treatment led to a significant recovery of gut tissue mtDNA amount, thus showing its efficacy. Our results indicate that a timely TP replacement is needed to maximize therapeutic success before irreversible degenerative tissue changes occur in MNGIE. 相似文献
74.
Antoine Rozenknop Roberto Wolfler Calvo Laurent Alfandari Daniel Chemla Lucas Létocart 《Journal of Scheduling》2013,16(6):585-604
This paper presents a heuristic method based on column generation for the EDF (Electricité De France) long-term electricity production planning problem proposed as subject of the ROADEF/EURO 2010 Challenge. This is to our knowledge the first-ranked method among those methods based on mathematical programming, and was ranked fourth overall. The problem consists in determining a production plan over the whole time horizon for each thermal power plant of the French electricity company, and for nuclear plants, a schedule of plant outages which are necessary for refueling and maintenance operations. The average cost of the overall outage and production planning, computed over a set of demand scenarios, is to be minimized. The method proceeds in two stages. In the first stage, dates for outages are fixed once for all for each nuclear plant. Data are aggregated with a single average scenario and reduced time steps, and a set-partitioning reformulation of this aggregated problem is solved for fixing outage dates with a heuristic based on column generation. The pricing problem associated with each nuclear plant is a shortest path problem in an appropriately constructed graph. In the second stage, the reload level is determined at each date of an outage, considering now all scenarios. Finally, the production quantities between two outages are optimized for each plant and each scenario by solving independent linear programming problems. 相似文献
75.
Iván Cores Gabriel Rodríguez Mará J. martín Patricia González Roberto R. Osorio 《New Generation Computing》2013,31(3):163-185
The execution times of large-scale parallel applications on nowadays multi/many-core systems are usually longer than the mean time between failures. Therefore, parallel applications must tolerate hardware failures to ensure that not all computation done is lost on machine failures. Checkpointing and rollback recovery is one of the most popular techniques to implement fault-tolerant applications. However, checkpointing parallel applications is expensive in terms of computing time, network utilization and storage resources. Thus, current checkpoint-recovery techniques should minimize these costs in order to be useful for large scale systems. In this paper three different and complementary techniques to reduce the size of the checkpoints generated by application-level checkpointing are proposed and implemented. Detailed experimental results obtained on a multicore cluster show the effectiveness of the proposed methods to reduce checkpointing cost. 相似文献
76.
Claudio Rocchini Paolo Cignoni Fabio Ganovelli Claudio Montani Paolo Pingi Roberto Scopigno 《The Visual computer》2004,20(2-3):149-164
A new algorithm for the integration of partially overlapping range images into a triangular mesh is presented. The algorithm consists of three main steps: it locates the intersections between the range surfaces and a reference grid chosen by the user, then merges all nearly coincident and redundant intersections according to a proximity criterion, and, finally, reconstructs the merged surface(s) from the filtered intersection set.
Compared with previous methods, which adopt a volumetric approach, our algorithm shows lower computational costs and improves the accuracy of the surfaces produced. It takes into account the quality of the input measurements and is able to patch small holes corresponding to the parts of the 3D scanned object that were not observed by the acquisition device.
The algorithm has been tested on several datasets of range maps; graphical and numeric results are reported. 相似文献
77.
Antonino B. DAssoro Roberto Leon-Ferre Eike-Benjamin Braune Urban Lendahl 《International journal of molecular sciences》2022,23(11)
The Notch signaling pathway is an architecturally simple signaling mechanism, well known for its role in cell fate regulation during organ development and in tissue homeostasis. In keeping with its importance for normal development, dysregulation of Notch signaling is increasingly associated with different types of tumors, and proteins in the Notch signaling pathway can act as oncogenes or tumor suppressors, depending on the cellular context and tumor type. In addition to a role as a driver of tumor initiation and progression in the tumor cells carrying oncogenic mutations, it is an emerging realization that Notch signaling also plays a role in non-mutated cells in the tumor microenvironment. In this review, we discuss how aberrant Notch signaling can affect three types of cells in the tumor stroma—cancer-associated fibroblasts, immune cells and vascular cells—and how this influences their interactions with the tumor cells. Insights into the roles of Notch in cells of the tumor environment and the impact on tumor-stroma interactions will lead to a deeper understanding of Notch signaling in cancer and inspire new strategies for Notch-based tumor therapy. 相似文献
78.
Silvio Borrelli Ida Matarazzo Eugenio Lembo Laura Peccarino Claudia Annoiato Maria Rosaria Scognamiglio Andrea Foderini Chiara Ruotolo Aldo Franculli Federica Capozzi Pavlo Yavorskiy Fatme Merheb Michele Provenzano Gaetano La Manna Luca De Nicola Roberto Minutolo Carlo Garofalo 《International journal of molecular sciences》2022,23(12)
Increasing potassium intake ameliorates blood pressure (BP) and cardiovascular (CV) prognoses in the general population; therefore the World Health Organization recommends a high-potassium diet (90–120 mEq/day). Hyperkalaemia is a rare condition in healthy individuals due to the ability of the kidneys to effectively excrete dietary potassium load in urine, while an increase in serum K+ is prevalent in patients with chronic kidney disease (CKD). Hyperkalaemia prevalence increases in more advanced CKD stages, and is associated with a poor prognosis. This scenario generates controversy on the correct nutritional approach to hyperkalaemia in CKD patients, considering the unproven link between potassium intake and serum K+ levels. Another concern is that drug-induced hyperkalaemia leads to the down-titration or withdrawal of renin-angiotensin system inhibitors (RASI) and mineralocorticoids receptors antagonists (MRA) in patients with CKD, depriving these patients of central therapeutic interventions aimed at delaying CKD progression and decreasing CV mortality. The new K+-binder drugs (Patiromer and Sodium-Zirconium Cyclosilicate) have proven to be adequate and safe therapeutic options to control serum K+ in CKD patients, enabling RASI and MRA therapy, and possibly, a more liberal intake of fruit and vegetables. 相似文献
79.
Marianna Barbalinardo Marta Giannelli Ludovica Forcini Barbara Luppi Anna Donnadio Maria Luisa Navacchia Giampiero Ruani Giovanna Sotgiu Annalisa Aluigi Roberto Zamboni Tamara Posati 《International journal of molecular sciences》2022,23(12)
Skin disorders are widespread around the world, affecting people of all ages, and oxidative stress represents one of the main causes of alteration in the normal physiological parameters of skin cells. In this work, we combined a natural protein, fibroin, with antioxidant compounds extracted in water from pomegranate waste. We demonstrate the effective and facile fabrication of bioactive and eco-sustainable films of potential interest for skin repair. The blended films are visually transparent (around 90%); flexible; stable in physiological conditions and in the presence of trypsin for 12 days; able to release the bioactive compounds in a controlled manner; based on Fickian diffusion; and biocompatible towards the main skin cells, keratinocytes and fibroblasts. Furthermore, reactive oxygen species (ROS) production tests demonstrated the high capacity of our films to reduce the oxidative stress induced in cells, which is responsible for various skin diseases. 相似文献
80.