Disease relevance of mnb

• Isolation of human and murine homologues of the Drosophila minibrain gene: human homologue maps to 21q22.2 in the Down syndrome "critical region" [1].
• Severe mustard poisoning in humans is associated with systemic injury, which is manifested as headache, epigastric distresses, anorexia, diarrhea, and cachexia and is usually observed at mustard doses of 1000 mg/min/m3 with damage to hematopoietic tissues and progressive leucopenia [2].
• When astrocyte cultures were subjected to a period of hypoxia followed by reoxygenation, induction of RA410 mRNA was observed within 15 min of reoxygenation, reaching a maximum by 60 min [3].
• When flies are shifted to 25 degrees C after 30 min of heat stress, the time-dependent decrease in hsp70 mRNA levels occurs more rapidly in young flies than in old ones [4].
• Moreover, an inducible protein from E. coli was detected after 15 min of induction and identified using DIGE preparatively [5].

Psychiatry related information on mnb

• A corresponding human gene with similar function to mnb could provide important insights into both normal brain development and the abnormal brain development and mental retardation observed in many congenital disorders [6].
• Volado mutants display impaired olfactory memories within 3 min of training, indicating that the integrin is required for short-term memory processes [7].
• There is clearly a burst of ribosome synthesis starting as early as 30 min after copulation and declining after 6 h [8].
• When quinpirole-induced locomotor activity was analyzed for 90 min, we found hypomotility after the first day or nighttime drug injection [9].
• In Drosophila, disruption of the homolog minibrain gene results in flies with reduced neuroblast proliferation, decreased numbers of central brain neurons, and learning/memory deficits [10].

High impact information on mnb

• The cellular memory traces first appear at 30 min after conditioning and persist for at least 1 hr, a time window during which DPM neuron synaptic transmission is required for normal memory [11].
• This region contains the human homologue of a Drosophila gene, minibrain, and strongly implicates it in learning defects associated with Down syndrome [12].
• We have identified and characterized c-hairy1, an avian homolog of the Drosophila segmentation gene, hairy. c-hairy1 is strongly expressed in the presomitic mesoderm, where its mRNA exhibits cyclic waves of expression whose temporal periodicity corresponds to the formation time of one somite (90 min) [13].
• Embryonic synthesis of histone mRNA begins at 90 min after oviposition, making the histone genes among the first to be transcribed by embryonic nuclei [14].
• Flies exhibit a mutant phenotype when hemizygous for a min allele, but flies having two doses are wild-type [15].

Chemical compound and disease context of mnb

• Ethanol toxicity was assessed by exposing females of different ages to a 50% or a 75% (v/v) solution for 60 min and counting the surviving flies 24 h later [16].
• Females of line 101 were found to respond to 60 min of heat stress (38 degrees C) by an increase in the abundance of both E and 20E, while in males of this line the amount of 20E increased and that of E declined [17].

Biological context of mnb

• The mnb kinases share extensive sequence similarities with kinases involved in the regulation of cell division [18].
• The three mammalian genes are highly conserved, >99% identical at the protein level over their 763-amino-acid (aa) open reading frame; in addition, the mammalian genes are 83% identical over 414 aa to the smaller 542-aa mnb protein [1].
• PCR screening of cDNA libraries derived from various human and murine tissues indicated that DYRK and Dyrk are expressed both during development and in the adult [1].
• Since epithelial cells are highly mitotic cells and since mnb shares sequence similarities with the cdk kinases involved in the regulation of cell division, this result may indicate a important role of mnb in the cell cycle control [19].
• An unusual enzymatic property of Dyrk-related kinases is their ability to catalyze tyrosine-directed autophosphorylation as well as phosphorylation of serine/threonine residues in exogenous substrates [20].

Anatomical context of mnb

• As a consequence, the adult mnb brain exhibits a specific and marked size reduction of the optic lobes and central brain hemispheres [18].
• In situ hybridization of Dyrk to mouse embryos (13, 15, and 17 days postcoitus) indicates a differential spatial and temporal pattern of expression, with the most abundant signal localized in brain gray matter, spinal cord, and retina [1].
• Wdr68 interacts with two minibrain-related kinases, Dyrk1a and Dyrk1b, required for embryonic growth and myotube differentiation, respectively [21].
• Following individual free centrosomes through multiple focal planes for 45 min after the injection of aphidicolin reveals that they do not undergo normal modulation of their astral dynamics nor do they undergo multiple rounds of duplication and separation [22].
• Once nuclear envelopes are saturated with pores, however, the number of annulate lamellae pores increases more than 10-fold in 9 min [23].

Associations of mnb with chemical compounds

• Mnb is a human homologue of the Drosophila minibrain gene which encodes a serine/threonine protein kinase that is required in distinct neuroblast proliferation centers during postembryonic neurogenesis [19].
• Actinomycin D added 5 min after the start of temperature treatment has little effect on subsequent protein synthesis [24].
• The reflex also shows brief sensitization application of concentrated sucrose solution to the proboscis increases subsequent responsiveness to tarsal stimulation for 2-5 min [25].
• PArg and PCr returned to basal levels within 5 min of the restoration of blood flow [26].
• Pharmacologicially disrupting integrin function at normal NMJs phenocopies features of mutant transmission and plasticity within 30-60 min, demonstrating that integrins acutely regulate functional transmission [27].

Other interactions of mnb

• Expression of the mnb (dyrk) protein in adult and embryonic mouse tissues [19].

Analytical, diagnostic and therapeutic context of mnb

• Western blot analysis and immunohistochemical methods were used to define the detailed distribution of mnb in adult brain and 17 days mouse embryos [19].
• DNA of cloned genes injected into 15-30 min Drosophila embryos reaches nearly all the cells of the later embryo and its expression can be detected by Northern blot hybridisation [28].
• Both immunoprecipitation and peptide mapping confirmed that the species labeled at 0.5 min are immature forms of the vitellogenin polypeptides [29].
• Nucleotide-free DKH340 can be produced by gel filtration in the absence of Mg2+, but it reforms tightly bound ADP slowly in the presence of MgATP (t1/2 > or = 10 min), and thus it is likely to be in a conformational state which is not produced during steady state ATP hydrolysis [30].
• Reversed phase high performance liquid chromatography coupled with a photodiode array UV-visible absorbance detector and mass spectrometer revealed a major product eluting at a retention time, t(r), of 3.5 min with a lambda(max) of approximately 324 nm and with a base peak in the mass spectrum at m/z 285 [31].

References