Search results for "DOM"
showing 10 items of 12668 documents
Structural and mechanistic insights into the interaction of the circadian transcription factor BMAL1 with the KIX domain of the CREB-binding protein
2019
JBC papers in press xx, 16604-16619 (2019). doi:10.1074/jbc.RA119.009845
Uncoupling of dynamin polymerization and GTPase activity revealed by the conformation-specific nanobody dynab
2017
Dynamin is a large GTPase that forms a helical collar at the neck of endocytic pits, and catalyzes membrane fission (Schmid and Frolov, 2011; Ferguson and De Camilli, 2012). Dynamin fission reaction is strictly dependent on GTP hydrolysis, but how fission is mediated is still debated (Antonny et al., 2016): GTP energy could be spent in membrane constriction required for fission, or in disassembly of the dynamin polymer to trigger fission. To follow dynamin GTP hydrolysis at endocytic pits, we generated a conformation-specific nanobody called dynab, that binds preferentially to the GTP hydrolytic state of dynamin-1. Dynab allowed us to follow the GTPase activity of dynamin-1 in real-time. We…
Micro-RNA profile and proteins in peritoneal fluid from women with endometriosis: their relationship with sterility.
2018
Objective: To define the microRNA (miRNA) profile and its relationship with cytokines content in peritoneal fluid (PF) from endometriosis patients. Design: Case-control study. Setting: University hospital, research institute. Patient(s): One hundred twenty-six women with endometriosis (EPF) and 45 control women (CPF). Main Outcomes Measure(s): MiRNA arrays were prepared from six EPF and six CPF. Quantitative reverse transcription-polymerase chain reaction validation of nine selected miRNAs (miR-29c-3p, -106b-3p, -130a-3p, -150-5p, -185-5p, -195-5p, -451a, -486-5p, and -1343-5p) was performed. Vascular endothelial growth factor-A (VEGF-A), thrombospondin-1 (TSP-1), urokinase plasminogen acti…
Biomarkers for the Noninvasive Diagnosis of Endometriosis: State of the Art and Future Perspectives
2020
Background: Early and accurate diagnosis of endometriosis is crucial for the management of this benign, yet debilitating pathology. Despite the advances of modern medicine, there is no common ground regarding the pathophysiology of this disease as it continues to affect the quality of life of millions of women of reproductive age. The lack of specific symptoms often determines a belated diagnosis. The gold standard remains invasive, surgery followed by a histopathological exam. A biomarker or a panel of biomarkers is easy to measure, usually noninvasive, and could benefit the clinician in both diagnosing and monitoring the treatment response. Several studies have advanced the idea of biomar…
miRNAs Regulation and Its Role as Biomarkers in Endometriosis.
2016
MicroRNAs (miRNAs) are small non-coding RNAs (18-22 nt) that function as modulators of gene expression. Since their discovery in 1993 in C. elegans, our knowledge about their biogenesis, function, and mechanism of action has increased enormously, especially in recent years, with the development of deep-sequencing technologies. New biogenesis pathways and sources of miRNAs are changing our concept about these molecules. The study of the miRNA contribution to pathological states is a field of great interest in research. Different groups have reported the implication of miRNAs in pathologies such as cancer, diabetes, cardiovascular, and gynecological diseases. It is also well-known that miRNAs…
Identification and structural characterization of LytU, a unique peptidoglycan endopeptidase from the lysostaphin family
2017
AbstractWe introduce LytU, a short member of the lysostaphin family of zinc-dependent pentaglycine endopeptidases. It is a potential antimicrobial agent for S. aureus infections and its gene transcription is highly upregulated upon antibiotic treatments along with other genes involved in cell wall synthesis. We found this enzyme to be responsible for the opening of the cell wall peptidoglycan layer during cell divisions in S. aureus. LytU is anchored in the plasma membrane with the active part residing in the periplasmic space. It has a unique Ile/Lys insertion at position 151 that resides in the catalytic site-neighbouring loop and is vital for the enzymatic activity but not affecting the …
Evolutionary Analysis of DELLA-Associated Transcriptional Networks
2017
DELLA proteins are transcriptional regulators present in all land plants which have been shown to modulate the activity of over 100 transcription factors in Arabidopsis, involved in multiple physiological and developmental processes. It has been proposed that DELLAs transduce environmental information to pre-wired transcriptional circuits because their stability is regulated by gibberellins (GAs), whose homeostasis largely depends on environmental signals. The ability of GAs to promote DELLA degradation coincides with the origin of vascular plants, but the presence of DELLAs in other land plants poses at least two questions: what regulatory properties have DELLAs provided to the behavior of…
Effects of PSA Removal from NCAM on the Critical Period Plasticity Triggered by the Antidepressant Fluoxetine in the Visual Cortex.
2016
Neuronal plasticity peaks during critical periods of postnatal development and is reduced towards adulthood. Recent data suggests that windows of juvenile-like plasticity can be triggered in the adult brain by antidepressant drugs such as Fluoxetine. Although the exact mechanisms of how Fluoxetine promotes such plasticity remains unknown, several studies indicate that inhibitory circuits play an important role. The polysialylated form of the neural cell adhesion molecules (PSA-NCAM) has been suggested to mediate the effects of Fluoxetine and it is expressed in the adult brain by mature interneurons. Moreover, the enzymatic removal of PSA by neuroaminidase-N not only affects the structure of…
Phosphorylated immunoreceptor tyrosine-based activation motifs and integrin cytoplasmic domains activate spleen tyrosine kinase via distinct mechanis…
2018
Spleen tyrosine kinase (Syk) is involved in cellular adhesion and also in the activation and development of hematopoietic cells. Syk activation induced by genomic rearrangement has been linked to certain T-cell lymphomas, and Syk inhibitors have been shown to prolong survival of patients with B-cell lineage malignancies. Syk is activated either by its interaction with a double-phosphorylated immunoreceptor tyrosine-based activation motif (pITAM), which induces rearrangements in the Syk structure, or by the phosphorylation of specific tyrosine residues. In addition to its immunoreceptor function, Syk is activated downstream of integrin pathways, and integrins bind to the same region in Syk a…
CD38-Specific Biparatopic Heavy Chain Antibodies Display Potent Complement-Dependent Cytotoxicity Against Multiple Myeloma Cells
2018
CD38 is overexpressed by multiple myeloma cells and has emerged as a target for therapeutic antibodies. Nanobodies are soluble single domain antibody fragments derived from the VHH variable domain of heavy chain antibodies naturally occurring in camelids. We previously identified distinct llama nanobodies that recognize three non-overlapping epitopes of the extracellular domain of CD38. Here, we fused these VHH domains to the hinge, CH2, and CH3 domains of human IgG1, yielding highly soluble chimeric llama/human heavy chain antibodies (hcAbs). We analyzed the capacity of these hcAbs to mediate complement-dependent cytotoxicity (CDC) to CD38-expressing human multiple myeloma and Burkitt lymp…