Search results for "DOM"
showing 10 items of 12668 documents
Gene expression profiles uncover individual identities of gnathal neuroblasts and serial homologies in the embryonic CNS of Drosophila.
2015
The numbers and types of progeny cells generated by neural stem cells in the developing CNS are adapted to its region-specific functional requirements. In Drosophila, segmental units of the CNS develop from well-defined patterns of neuroblasts. Here we constructed comprehensive neuroblast maps for the three gnathal head segments. Based on the spatiotemporal pattern of neuroblast formation and the expression profiles of 46 marker genes (41 transcription factors), each neuroblast can be uniquely identified. Compared with the thoracic ground state, neuroblast numbers are progressively reduced in labial, maxillary and mandibular segments due to smaller sizes of neuroectodermal anlagen and, part…
Fungal Infections of the Central Nervous System in Children.
2017
Although uncommon in children, fungal infections of the central nervous system can be devastating and difficult to treat. A better understanding of basic mycologic, immunologic, and pharmacologic processes has led to important advances in the diagnosis and management of these diseases, but their mortality rates remain unacceptably high. In this focused review, we examine the epidemiology and clinical features of the most common fungal pathogens of the central nervous system in children and explore recent advances in diagnosis and antifungal therapy.
Abstract CT046: A phase I basket study of the PI3K inhibitor taselisib (GDC-0032) in PIK3CA-mutated locally advanced or metastatic solid tumors
2018
Abstract Background: PIK3CA, a gene that encodes the α-isoform of the catalytic subunit of Class I PI3K (PI3Kα), is frequently mutated or amplified in solid tumors. Taselisib is an oral, potent, selective inhibitor of Class I PI3Kα, γ, and δ isoforms with enhanced activity against PIK3CA-mutated cancer models. Preclinical and clinical data demonstrated that single-agent taselisib has activity in multiple PIK3CA-mutated tumor types. Methods: This open-label phase I study (Cohort X of PMT4979g; NCT01296555) enrolled patients (pts) with PIK3CA-mutated tumors who had progressed after, or failed to respond to, at least one prior treatment regimen and were not candidates for regimens known to pro…
Structural Basis of TRPV4 N Terminus Interaction with Syndapin/PACSIN1-3 and PIP2
2018
Summary Transient receptor potential (TRP) channels are polymodally regulated ion channels. TRPV4 (vanilloid 4) is sensitized by PIP2 and desensitized by Syndapin3/PACSIN3, which bind to the structurally uncharacterized TRPV4 N terminus. We determined the nuclear magnetic resonance structure of the Syndapin3/PACSIN3 SH3 domain in complex with the TRPV4 N-terminal proline-rich region (PRR), which binds as a class I polyproline II (PPII) helix. This PPII conformation is broken by a conserved proline in a cis conformation. Beyond the PPII, we find that the proximal TRPV4 N terminus is unstructured, a feature conserved across species thus explaining the difficulties in resolving it in previous …
Myelin: Methods for Purification and Proteome Analysis
2019
Molecular characterization of myelin is a prerequisite for understanding the normal structure of the axon/myelin-unit in the healthy nervous system and abnormalities in myelin-related disorders. However, reliable molecular profiles necessitate very pure myelin membranes, in particular when considering the power of highly sensitive "omics"-data acquisition methods. Here, we recapitulate the history and recent applications of myelin purification. We then provide our laboratory protocols for the biochemical isolation of a highly pure myelin-enriched fraction from mouse brains and for its proteomic analysis. We also supply methodological modifications when investigating posttranslational modifi…
LipidMS: An R Package for Lipid Annotation in Untargeted Liquid Chromatography-Data Independent Acquisition-Mass Spectrometry Lipidomics.
2018
High resolution LC-MS untargeted lipidomics using data independent acquisition (DIA) has the potential to increase lipidome coverage, as it enables the continuous and unbiased acquisition of all eluting ions. However, the loss of the link between the precursor and the product ions combined with the high dimensionality of DIA data sets hinder accurate feature annotation. Here, we present LipidMS, an R package aimed to confidently identify lipid species in untargeted LC-DIA-MS. To this end, LipidMS combines a coelution score, which links precursor and fragment ions with fragmentation and intensity rules. Depending on the MS evidence reached by the identification function survey, LipidMS provi…
Mass Spectrometry Imaging Differentiates Chromophobe Renal Cell Carcinoma and Renal Oncocytoma with High Accuracy
2020
Background: While subtyping of the majority of malignant chromophobe renal cell carcinoma (cRCC) and benign renal oncocytoma (rO) is possible on morphology alone, additional histochemical, immunohistochemical or molecular investigations are required in a subset of cases. As currently used histochemical and immunohistological stains as well as genetic aberrations show considerable overlap in both tumors, additional techniques are required for differential diagnostics. Mass spectrometry imaging (MSI) combining the detection of multiple peptides with information about their localization in tissue may be a suitable technology to overcome this diagnostic challenge. Patients and Methods: Formalin…
Evolution of Ciona intestinalis Tumor necrosis factor alpha ( Ci TNFα): Polymorphism, tissues expression, and 3D modeling
2017
Although the Tumor necrosis factor gene superfamily seems to be very conserved in vertebrates, phylogeny, tissue expression, genomic and gene organization, protein domains and polymorphism analyses showed that a strong change has happened mostly in invertebrates in which protochordates were a constraint during the immune-molecules history and evolution. RT PCR was used to investigate differential gene expression in different tissues. The expression shown was greater in the pharynx. Single-nucleotide polymorphism has been investigated in Ciona intestinalis Tumor necrosis factor alpha (CiTNFα) mRNA isolated from the pharynx of 30 ascidians collected from Licata, Sicily (Italy), by denaturing …
Enhanced autophagic-lysosomal activity and increased BAG3-mediated selective macroautophagy as adaptive response of neuronal cells to chronic oxidati…
2019
Oxidative stress and a disturbed cellular protein homeostasis (proteostasis) belong to the most important hallmarks of aging and of neurodegenerative disorders. The proteasomal and autophagic-lysosomal degradation pathways are key measures to maintain proteostasis. Here, we report that hippocampal cells selected for full adaptation and resistance to oxidative stress induced by hydrogen peroxide (oxidative stress-resistant cells, OxSR cells) showed a massive increase in the expression of components of the cellular autophagic-lysosomal network and a significantly higher overall autophagic activity. A comparative expression analysis revealed that distinct key regulators of autophagy are upregu…
Antibacterial properties and reduction of MRSA biofilm with a dressing combining polyabsorbent fibres and a silver matrix
2016
Objective: This study was designed to evaluate the antibacterial activity of a wound dressing which combines polyacrylate fibres and a silver lipido-colloid matrix (UrgoClean Ag, silver polyabsorbent dressing), against biofilm of methicillin-resistant Staphylococcus aureus (MRSA). Method: Samples of silver polyabsorbent dressing and the neutral form of this dressing (UrgoClean) were applied to biofilms of MRSA formed on a collagen I-coated surface, cultured for 24 hours. Different exposure times were tested (1, 2, 4 and 7 days) without dressing change. The biofilm reduction was quantified by using culture methods and by confocal laser scanning microscopy experiments. Results: The applicatio…