Search results for "Atom"
showing 10 items of 31559 documents
Genetics and Gene Therapy of Anderson-Fabry Disease.
2018
Fabry's disease is a genetic disorder of X-linked inheritance caused by mutations in the alpha galactosidase A gene resulting in deficiency of this lysosomal enzyme. The progressive accumulation of glycosphingolipids, caused by the inadequate enzymatic activity, is responsible of organ dysfunction and thus of clinical manifestations. In the presence of a high clinical suspicion, a careful physical examination and specific laboratory tests are required, finally diagnosis of Fabry's disease is confirmed by the demonstration of absence or reduced alpha-galactosidase A enzyme activity in hemizygous men and gene typing in heterozygous females; in fact the performance of enzymatic activity assay …
IL-17A mediated endothelial breach promotes metastasis formation
2015
Abstract The role of the IL23/IL17A axis in tumor–immune interactions is a matter of controversy. Although some suggest that IL17A-producing T cells (TH17) can suppress tumor growth, others report that IL17A and IL23 accelerate tumor growth. Here, we systematically assessed the impact of IL17A-secreting lymphocytes in several murine models of tumor lung metastasis. Genetic fate mapping revealed that IL17A was secreted within lung metastases predominantly by γδ T cells, whereas TH17 cells were virtually absent. Using different tumor models, we found Il17a−/− mice to consistently develop fewer pulmonary tumor colonies. IL17A specifically increased blood vessel permeability and the expression …
Wnt-Dependent Oligodendroglial-Endothelial Interactions Regulate White Matter Vascularization and Attenuate Injury
2020
Recent studies have indicated oligodendroglial-vascular crosstalk during brain development, but the underlying mechanisms are incompletely understood. We report that oligodendrocyte precursor cells (OPCs) contact sprouting endothelial tip cells in mouse, ferret and human neonatal white matter. Using transgenic mice, we show that increased or decreased OPC density results in cognate changes in white matter vascular investment. Hypoxia promoted both increased OPC numbers and higher white matter vessel density, and endothelial cell expression of the Wnt pathway targets Apcdd1 and Axin2, suggesting paracrine OPC-endothelial signaling. Conditional knockout of OPC Wntless resulted in diminished w…
Response to: 'Artery tertiary lymphoid organs in giant cell arteritis are not exclusively located in the media of temporal arteries' by Graver et al
2017
We thank Graver et al 1 for their interest in our recently published article on artery tertiary lymphoid organs (ATLOs) in giant cell arteritis (GCA).2 The authors stained temporal artery biopsies of 21 biopsy-proven GCA patients (71% female, mean duration of disease of 2.3±0.9 months) that fulfilled the 1990 American College of Rheumatology classification criteria with anti-CD20 and anti-CD3 antibodies. On the basis of this experimental approach, they confirmed the presence of ATLOs only in the adventitia of inflamed arteries of GCA patients and not in the media as demonstrated in our study. This statement, however, is not supported in our opinion by the experimental approach chosen …
Caretakers and Gatekeepers
2017
It has now been generally accepted that the genes responsible for familial cancer syndromes can be divided into two categories, known as caretakers and gatekeepers. Caretakers are genes that control the maintenance of the genetic information integrity in each cell while gatekeepers are those genes which directly regulate tumor growth, codifying for proteins which either stimulate or inhibit proliferation, differentiation or apoptosis. Keywords: gatekeeper genes; caretaker genes; tumor suppressor genes; cell cycle; hereditary syndromes
Ethical Aspects of Nuclear and Mitochondrial DNA Transfer
2016
Somatic cell nuclear transfer (SCNT) (cloning), as a reproductive or therapeutic method, and mitochondrial DNA transfer, as a method to prevent the transmission of mitochondrial diseases, are analyzed in this paper from a bioethics perspective. The licit purpose of being able to treat certain diseases, as in the case of SCNT, cannot justify, in any case, resorting to illicit means such as the manipulation, selection, and elimination of human embryos in the blastocyst phase, by using cell lines obtained from them. Crossing this line paves the way (as utilitarian ethics advocates) to assuming any cost in scientific experimentation so long as satisfactory results are obtained. With mitochondr…
Mutations in PRDM15 Are a Novel Cause of Galloway-Mowat Syndrome
2021
Background Galloway-Mowat syndrome (GAMOS) is characterized by neurodevelopmental defects and a progressive nephropathy, which typically manifests as steroid-resistant nephrotic syndrome. The prognosis of GAMOS is poor, and the majority of children progress to renal failure. The discovery of monogenic causes of GAMOS has uncovered molecular pathways involved in the pathogenesis of disease. Methods Homozygosity mapping, whole-exome sequencing, and linkage analysis were used to identify mutations in four families with a GAMOS-like phenotype, and high-throughput PCR technology was applied to 91 individuals with GAMOS and 816 individuals with isolated nephrotic syndrome. In vitro and in vivo st…
Transcriptional and Epigenetic Control of Astrogliogenesis
2017
Abstract Astrocytes exert pivotal functions in the brain ranging from homeostasis to plasticity and their malfunctioning may contribute to neurodegenerative diseases. With increased recognition of their importance, more efforts are being dedicated to decoding the molecular mechanisms that control the generation of astrocytes from neural stem cells, a process referred to as astrogliogenesis. In this chapter, we highlight the discoveries that have shed light on the role of transcription factors, DNA methylation, histone modifications, and microRNAs in driving the transcriptional programs that underlie astrocyte generation. We further discuss the current understanding of gene regulatory pathwa…
Genetic Analysis of Human Preimplantation Embryos
2016
Preimplantation development comprises the initial stages of mammalian development, before the embryo implants into the mother's uterus. In normal conditions, after fertilization the embryo grows until reaching blastocyst stage. The blastocyst grows as the cells divide and the cavity expands, until it arrives at the uterus, where it "hatches" from the zona pellucida to implant into the uterine wall. Nevertheless, embryo quality and viability can be affected by chromosomal abnormalities, most of which occur during gametogenesis and early embryo development; human embryos produced in vitro are especially vulnerable. Therefore, the selection of chromosomally normal embryos for transfer in assis…
Molecular cause and functional impact of altered synaptic lipid signaling due to a prg‐1 gene SNP
2015
Loss of plasticity-related gene 1 (PRG-1), which regulates synaptic phospholipid signaling, leads to hyperexcitability via increased glutamate release altering excitation/inhibition (E/I) balance in cortical networks. A recently reported SNP in prg-1 (R345T/ mutPRG-1) affects ~5 million European and US citizens in a monoallelic variant. Our studies show that this mutation leads to a loss-of-PRG-1 function at the synapse due to its inability to control lysophosphatidic acid (LPA) levels via a cellular uptake mechanism which appears to depend on proper glycosylation altered by this SNP. PRG-1 +/ mice, which are animal correlates of human PRG-1 +/mut carriers, showed an altered cortical networ…