Search results for "Wild type"
showing 10 items of 181 documents
Mosaic activating mutations in GNA11 and GNAQ are associated with phakomatosis pigmentovascularis and extensive dermal melanocytosis
2016
Common birthmarks can be an indicator of underlying genetic disease but are often overlooked. Mongolian blue spots (dermal melanocytosis) are usually localized and transient, but they can be extensive, permanent, and associated with extracutaneous abnormalities. Co-occurrence with vascular birthmarks defines a subtype of phakomatosis pigmentovascularis, a group of syndromes associated with neurovascular, ophthalmological, overgrowth, and malignant complications. Here, we discover that extensive dermal melanocytosis and phakomatosis pigmentovascularis are associated with activating mutations in GNA11 and GNAQ, genes that encode Gα subunits of heterotrimeric G proteins. The mutations were det…
A Role for the β1-β2Loop in the Gating of 5-HT3Receptors
2005
Based on theTorpedoacetylcholine receptor structure, Unwin and colleagues (Miyazawa et al., 2003; Unwin, 2005) hypothesized that the transduction of agonist binding to channel gate opening involves a “pin-into-socket” interaction between αV46 at the tip of the extracellular β1-β2loop and the transmembrane M2 segment and M2-M3 loop. We mutated to cysteine the aligned positions in the 5-HT3Aand 5-HT3Bsubunit β1-β2loops K81 and Q70, respectively. The maximal 5-HT-activated currents in receptors containing 5-HT3A/K81C or 5-HT3B/Q70C were markedly reduced compared with wild type. Desensitization of wild-type currents involved fast and slow components. Mutant currents desensitized with only the f…
Thermodynamics and kinetics of ion permeation in wild-type and mutated open active conformation of the human α7 nicotinic receptor
2020
Molecular studies of human pentameric ligand-gated ion channels (LGICs) expressed in neurons and at neuromuscular junctions are of utmost importance in the development of therapeutic strategies for neurological disorders. We focus here on the nicotinic acetylcholine receptor nAChR-α7, a homopentameric channel widely expressed in the human brain, with a proven role in a wide spectrum of disorders including schizophrenia and Alzheimer's disease. By exploiting an all-atom structural model of the full (transmembrane and extracellular) protein in the open, agonist-bound conformation we recently developed, we evaluate the free energy and the mean first passage time of single-ion permeation using …
A proctolin-like peptide is regulated after baculovirus infection and mediates in caterpillar locomotion and digestion
2022
Baculoviruses constitute a large group of invertebrate DNA viruses, predominantly infecting larvae of the insect order Lepidoptera. During a baculovirus infection, the virus spreads throughout the insect body producing a systemic infection in multiple larval tissues, included the central nervous system (CNS). As a main component of the CNS, neuropeptides are small protein-like molecules functioning as neurohormones, neurotransmitters, or neuromodulators. These peptides are involved in regulating animal physiology and behavior and could be altered after baculovirus infection. In this study, we have investigated the effect of Spodoptera exigua multiple nucleopolyhedrovirus (SeMNPV) infection …
Characterization of aSchizosaccharomyces pombemorphological mutant altered in the galactomannan content
1991
In a search for Schizosaccharomyces pombe mutants resistant to the antifungal agent papulacandin B, a morphological mutant was isolated. The mutant is round shaped in contrast to the rod shaped parental strain. This morphological defect segregated as a recessive Mendelian character and was not observed in other papulacandin B resistant mutants belonging to the same complementation group. The mutation mapped in the right arm of S. pombe chromosome III very close to pap1 marker. Mutant cell walls were more susceptible to alkali extraction and Novozyme degradation than those from the wild-type. A specific reduction in the cell wall galactomannan fraction was the only significant difference det…
Inactivation of a small heat shock protein affects cell morphology and membrane fluidity in Lactobacillus plantarum WCFS1.
2011
A small heat shock gene of Lactobacillus plantarum strain WCFS1 was deleted using a Cre-lox based system. Compared to the wild type, the ∆hsp 18.55 mutant strain displayed a similar growth rate when cultivated either under optimal temperature or under different stress conditions such as heat, low pH and salt stress. However, a longer lag phase was observed when the ∆hsp 18.55 mutant strain was cultivated under short intense heat stress (50 °C). This suggests that the hsp 18.55 gene of L. plantarum may be involved in recovery of L. plantarum stressed cells in the early stage of high temperature stress. In addition, morphology of the mutant cells, investigated by scanning electron microscopy,…
Knock out der c-Jun N-terminalen Kinase 2 (JNK2) aggraviert die Entwicklung der chronischen DSS-Colitis unabhängig von der intestinalen Zytokin-Expre…
2008
Background The c-Jun N-terminal kinase 2 (JNK2) is involved in signal transduction of inflammatory bowel diseases (IBD) and regulates the expression of pro-inflammatory cytokines. For this reason, JNK2 is considered as novel target for IBD therapy. The aim of this study was 1.) to examine the function of JNK2 applying a low dose Dextran Sulfate Sodium (DSS) model of chronic experimental colitis in JNK2 knock out mice and 2.) to analyze the expression of JNK2 dependent cytokines. Material and Methods: For induction of a mild chronic colitis, female JNK2 knockout mice (JNK2 ko) and their wildtype controls (WT2) received three cycles of DSS treatment, each consisting of 1.0 % DSS for 5 days, f…
Wild-type JAK2 secondary acute erythroleukemia developing after JAK2-V617F-mutated primary myelofibrosis.
2009
A 54-year-old female patient developed acute erythroleukemia after an 8-year course of primary myelofibrosis. The latter harbors the JAK2-V617F mutation and was treated with hydroxyurea and anagrelide. A bone marrow trephine biopsy disclosed 2 morphologically distinct areas of chronic primary myelofibrosis and acute erythroleukemia. Microdissection and a separate molecular pathological analysis was performed. Although the activating JAK2-V617F mutation was not maintained in blasts of acute erythroleukemia, it was detectable in the chronic phase of primary myelofibrosis, indicating that this mutation did not play a role in the leukemic transformation of erythroid cells.
Independent Generation of Aβ42 and Aβ38 Peptide Species by γ-Secretase
2008
Proteolytic processing of the amyloid precursor protein by beta- and gamma-secretase generates the amyloid-beta (Abeta) peptides, which are principal drug targets in Alzheimer disease therapeutics. gamma-Secretase has imprecise cleavage specificity and generates the most abundant Abeta40 and Abeta42 species together with longer and shorter peptides such as Abeta38. Several mechanisms could explain the production of multiple Abeta peptides by gamma-secretase, including sequential processing of longer into shorter Abeta peptides. A novel class of gamma-secretase modulators (GSMs) that includes some non-steroidal anti-inflammatory drugs has been shown to selectively lower Abeta42 levels withou…
Organophosphonate utilization by the wild‐type strain of cladosporium resinae
1997
We studied the biodegradation of compounds containing phosphorus‐to‐carbon bond by using wild‐type strain of Cladosporium resinae. The substrate specificity of the strain was studied and we found that it is able to utilize a range of structurally diverse organophosphonates as a sole source of phosphorus. This ability is inducible as indicated by the presence of a lag phase of the growth. A popular herbicide glyphosate is also degraded by the fungi. This indicates that Cladosporium resinae may play an important role in biodegradation of this herbicide. The strain which we used, however, did not metabolise any phosphonates when they served as the sole carbon or nitrogen sources.