Search results for "PORT"
showing 10 items of 20457 documents
Haploinsufficiency of the Primary Familial Brain Calcification Gene SLC20A2 Mediated by Disruption of a Regulatory Element
2020
OBJECTIVE Primary familial brain calcification (PFBC) is a rare cerebral microvascular calcifying disorder with diverse neuropsychiatric expression. Five genes were reported as PFBC causative when carrying pathogenic variants. Haploinsufficiency of SLC20A2, which encodes an inorganic phosphate importer, is a major cause of autosomal-dominant PFBC. However, PFBC remains genetically unexplained in a proportion of patients, suggesting the existence of additional genes or cryptic mutations. We analyzed exome sequencing data of 71 unrelated, genetically unexplained PFBC patients with the aim to detect copy number variations that may disrupt the expression of core PFBC-causing genes. METHODS Afte…
Deregulated Lipid Sensing by Intestinal CD36 in Diet-Induced Hyperinsulinemic Obese Mouse Model
2016
International audience; The metabolic syndrome (MetS) greatly increases risk of cardiovascular disease and diabetes and is generally associated with abnormally elevated postprandial triglyceride levels. We evaluated intestinal synthesis of triglyceride-rich lipoproteins (TRL) in a mouse model of the MetS obtained by feeding a palm oil-rich high fat diet (HFD). By contrast to control mice, MetS mice secreted two populations of TRL. If the smaller size population represented 44% of total particles in the beginning of intestinal lipid absorption in MetS mice, it accounted for only 17% after 4 h due to the secretion of larger size TRL. The MetS mice displayed accentuated postprandial hypertrigl…
Case report : partial uniparental disomy unmasks a novel recessive mutation in the LYST gene in a patient with a severe phenotype of Chediak-Higashi …
2021
Síndrome de Chédiak-Higashi; LYST; Disomia uniparental Síndrome de Chédiak-Higashi; LYST; Disomía uniparental Chédiak-Higashi syndrome; LYST; Uniparental disomy Chédiak-Higashi syndrome (CHS) is a rare autosomal recessive (AR) immune disorder that has usually been associated to missense, nonsense or indels mutations in the LYST gene. In this study, we describe for the first time the case of a CHS patient carrying a homozygous mutation in the LYST gene inherited as a result of a partial uniparental isodisomy (UPiD) of maternal origin. Sanger sequencing of the LYST cDNA and single nucleotide polymorphism (SNP)-arrays were performed to identify the causative mutation and to explain the molecul…
The role of Plasma Membrane Calcium ATPases (PMCAs) in neurodegenerative disorders
2017
Selective degeneration of differentiated neurons in the brain is the unifying feature of neurodegenerative disorders such as Parkinson's disease (PD) or Alzheimer's disease (AD). A broad spectrum of evidence indicates that initially subtle, but temporally early calcium dysregulation may be central to the selective neuronal vulnerability observed in these slowly progressing, chronic disorders. Moreover, it has long been evident that excitotoxicity and its major toxic effector mechanism, neuronal calcium overload, play a decisive role in the propagation of secondary neuronal death after acute brain injury from trauma or ischemia. Under physiological conditions, neuronal calcium homeostasis is…
Patients With Cancer and COVID-19: A WhatsApp Messenger-Based Survey of Patients' Queries, Needs, Fears, and Actions Taken
2020
PURPOSE This descriptive investigation was undertaken at three oncology units to report queries, needs, and fears related to severe acute respiratory syndrome coronavirus 2 (COVID-19) of patients with cancer and to avoid uncontrolled treatment delays or withdrawal, behavioral mistakes, and panic. PATIENTS AND METHODS All queries spontaneously delivered through the WhatsApp instant messaging system commonly used by patients to communicate with oncology units were collected and grouped by homology in five categories. Responses to the queries were given according to recommendations by the Italian Association of Medical Oncology through WhatsApp and by subsequent phone calls. Patients were also…
Cationic Amino Acid Transporter-1-Mediated Arginine Uptake Is Essential for Chronic Lymphocytic Leukemia Cell Proliferation and Viability
2019
Interfering with tumor metabolism by specifically restricting the availability of extracellular nutrients is a rapidly emerging field of cancer research. A variety of tumor entities depend on the uptake of the amino acid arginine since they have lost the ability to synthesize it endogenously, that is they do not express the rate limiting enzyme for arginine synthesis, argininosuccinate synthase (ASS). Arginine transport through the plasma membrane of mammalian cells is mediated by eight different transporters that belong to two solute carrier (SLC) families. In the present study we found that the proliferation of primary as well as immortalized chronic lymphocytic leukemia (CLL) cells depen…
Clinical Impact of Cystatin C/Cathepsin L and Follistatin/Activin A Systems in Breast Cancer Progression: A Preliminary Report.
2016
This study was directed to assess the clinical impact of the circulating cathepsin L, cystatin C, activin A, and follistatin in breast cancer patients. The serum concentrations of these molecules were determined by immunoenzymatic assays, and their association with some clinico-pathological parameters of breast cancer progression was evaluated. Our results identified cystatin C and activin A as predictive markers for the presence of breast cancer and bone metastasis, respectively. Therefore, these proteins may have a clinical role as circulating biomarkers in the diagnosis and therapeutic monitoring of breast cancer patients.
A Pan-Cancer Approach to Predict Responsiveness to Immune Checkpoint Inhibitors by Machine Learning
2019
Immunotherapy by using immune checkpoint inhibitors (ICI) has dramatically improved the treatment options in various cancers, increasing survival rates for treated patients. Nevertheless, there are heterogeneous response rates to ICI among different cancer types, and even in the context of patients affected by a specific cancer. Thus, it becomes crucial to identify factors that predict the response to immunotherapeutic approaches. A comprehensive investigation of the mutational and immunological aspects of the tumor can be useful to obtain a robust prediction. By performing a pan-cancer analysis on gene expression data from the Cancer Genome Atlas (TCGA, 8055 cases and 29 cancer types), we …
2-Methoxyestradiol Affects Mitochondrial Biogenesis Pathway and Succinate Dehydrogenase Complex Flavoprotein Subunit A in Osteosarcoma Cancer Cells.
2017
Background/aim Dysregulation of mitochondrial pathways is implicated in several diseases, including cancer. Notably, mitochondrial respiration and mitochondrial biogenesis are favored in some invasive cancer cells, such as osteosarcoma. Hence, the aim of the current work was to investigate the effects of 2-methoxyestradiol (2-ME), a potent anticancer agent, on the mitochondrial biogenesis of osteosarcoma cells. Materials and methods Highly metastatic osteosarcoma 143B cells were treated with 2-ME separately or in combination with L-lactate, or with the solvent (non-treated control cells). Protein levels of α-syntrophin and peroxisome proliferator-activated receptor gamma, coactivator 1 alph…
Lack of a peroxiredoxin suppresses the lethality of cells devoid of electron donors by channelling electrons to oxidized ribonucleotide reductase
2017
The thioredoxin and glutaredoxin pathways are responsible of recycling several enzymes which undergo intramolecular disulfide bond formation as part of their catalytic cycles such as the peroxide scavengers peroxiredoxins or the enzyme ribonucleotide reductase (RNR). RNR, the rate-limiting enzyme of deoxyribonucleotide synthesis, is an essential enzyme relying on these electron flow cascades for recycling. RNR is tightly regulated in a cell cycle-dependent manner at different levels, but little is known about the participation of electron donors in such regulation. Here, we show that cytosolic thioredoxins Trx1 and Trx3 are the primary electron donors for RNR in fission yeast. Unexpectedly,…