Disease relevance of MMEL1

• It will be important to test whether MMEL2 defects are associated with diseases such as hereditary motor sensory neuropathy 2A, Schwartz-Jampel-Aberfeld syndrome, or neuroblastoma, which all map to this locus [1].
• Visual (VEP), brainstem auditory (BAEP), and somatosensory (SEP) evoked potential tests were performed in 45 patients representing ten types of inherited disorders in which ataxia was the most prominent symptom [2].
• SEP results were often more severely abnormal in patients with Friedreich's ataxia [2].
• Overall, 9 of 13 patients with neurological manifestations had SEP abnormalities [3].
• Somatosensory, brainstem auditory and pattern-reversal visual evoked potentials (SEP, BAEP and VEP) were studied in 16 patients with Wilson's disease and 16 family members [3].

Psychiatry related information on MMEL1

• It was concluded that later SEP amplitude correlates of psychopathology are little influenced by AP and TR drugs, but that VEP and AEP results are modified [4].
• The following cerebral SEP components, within 100 ms after the stimulus, were also depressed during motor activity [5].
• The following variables were recorded at baseline and for 50 min after drug administration: electroencephalographic (EEG) data, somatosensory-evoked late cortical responses (SEP) elicited by intracutaneous stimulation of the fingertip (2-3 fold pain threshold), heart rate, mean arterial blood pressure, and end-tidal PETCO2 via a tight-fitting mask [6].
• We hypothesized that initial SEP amplitudes from cutaneous (sural nerve, SN) and muscle afferent (tibial nerve, TN) sources are dependent on the relevance of the specific afferent information to task performance [7].
• Reaction time, subjective pain intensities and evoked vertex potentials to laser (LEP) and electrical (SEP) stimuli were recorded and compared with auditory evoked potentials (AEP) [8].

High impact information on MMEL1

• Aortic valve area (AVA) was calculated with the equation AVA = CO/(SEP X mean velocity), where CO is cardiac output measured by thermodilution and SEP is the systolic ejection period derived from the Doppler tracings [9].
• Recently, a mouse NL1 protein, a novel member of the family, was identified and shown to be expressed mainly in the testis as a secreted protein [10].
• Thus, our findings suggest that one of the roles of NL1 in mice is related to sperm function and that NL1 modulates the processes of fertilization and early embryonic development in vivo [10].
• NL1 acted in concert with NL0 and NL2 to stimulate nuclear uptake of the agonist-treated receptor, but also directed the complete nuclear localization of MR in response to treatment with steroid antagonist [11].
• Changes in synaptic strength and unmasking inputs secondary to disconnection of the normally dominant inputs to the 'median nerve' cortex may be the mechanisms underlying ulnar nerve SEP changes [12].

Chemical compound and disease context of MMEL1

• Bacillus subtilis ribonuclease P protein (P protein) is predominantly unfolded (D) at physiological pH and low ionic strength; however, small molecule anionic ligands (e.g., sulfate) directly bind to and stabilize the folded state (NL2) [13].
• Administration of lisuride (0.1 mg iv) reduced the severity of the reflex and spontaneous myoclonus, but had no effect on, or increased the size of the SEP. Two of the patients also received 1 mg clonazepam iv [14].
• PURPOSE: In dogs, vigabatrin (VGB) has been associated with intramyelinic edema producing delayed central conduction in somatosensory and visual evoked potentials (SEP, VEP) [15].
• When conjugates were prepared using these adriamycin-bound linkers, conjugates had no loss of binding affinity and specificity for common acute lymphoblastic leukemia antigen (CALLA) expressed on the Daudi cell surfaces as the target of NL-1 antibody [16].
• Covariates included sepsis (SEP), chronological age, gestational age (GA), birth weight, current weight, gender, Apgar score at 1 (AP1) and 5 (AP2) minutes, plasma C-reactive protein and serum creatinine [17].

Biological context of MMEL1

• The MMEL2 protein contains the zinc-binding consensus sequence HEXXH and all the residues known to be essential for the enzymatic activity of other members of the family [1].
• Molecular cloning, tissue distribution, and chromosomal localization of MMEL2, a gene coding for a novel human member of the neutral endopeptidase-24.11 family [1].
• Among these potential motifs, site-directed mutational analysis showed that NL1, residing from - 35 to - 28 bp, was most critical for mediating the transactivation by Nurr1 [18].
• Nerve conduction, evoked potential studies (SEP, BAEP, VEP), and abnormalities on cerebral MRI did not improve [19].
• Here, we show the conservation of E-function in rice (Oryza sativaL.) by characterizing tissue culture-induced mutants of two MADS-box genes, OsMADS1and OsMADS5, which form a subclade within the well-supported clade of SEP-genes (E-function) phylogeny [20].

Anatomical context of MMEL1

• Unlike clinical examination using a pin or needle, pain SEP is considered to be an objective and quantitative test to investigate functions of peripheral and central sensory pathways responsible for pain-temperature sensation (A delta fibres and the spinothalamic tract) [21].
• Somatosensory (SEP) to left and right median nerve stimuli, visual (VEP), and auditory (AEP) EPs were recorded from one eye and 14 scalp leads [4].
• In 21 normal subjects, far-field somatosensory potentials were recorded from the scalp after stimulation of the tibial nerve at the ankle (tibial SEP) [22].
• Nuclear localization of the rat glucocorticosteroid receptor (rGR) transiently expressed in COS-7 cells appears to be mediated by two nuclear localization signals, NL1 and NL2, in a hormone-dependent mechanism [23].
• In patients with cervical myelopathy, SEP was the most useful procedure, especially when upper and lower limbs were studied [24].

Associations of MMEL1 with chemical compounds

• Differential effects of isoflurane on SEP recorded over parietal and frontal scalp [25].
• Nasal fluid vanadium increased in boilermakers between NL1 and NL2 (median < 1.0 versus 4.7 ppb, respectively, p < 0.05), then decreased at NL3 (median, 4.7 versus < 1.0 ppb, respectively, p < 0. 05) [26].
• These include the pair of aspartate residues in the transmembrane domains II and VII compared with the aspartate/asparagine arrangement in mammalian receptors, the amino acid PEY motif in extracellular loop III (SEP in mammals), and the presence of a carboxyl-terminal tail [27].
• NL1 is a glycoprotein that, among the members of the family, shows the strongest sequence identity with neprilysin [28].
• A novel linker consisting of poly(ethylene glycol) (PEG) and dipeptide was used for conjugation of adriamycin with tumor-specific monoclonal antibody, NL-1, to confirm that the linker can be cleaved selectively with the tumor specific enzyme to express cytotoxicity of the anti-tumor agent [16].

Other interactions of MMEL1

• The MMEL2 protein has the structural characteristics of type II transmembrane proteins, although the presence of a furin-like cleavage site in the ectodomain suggests that it may be released into the medium following proteolytic cleavage [1].

Analytical, diagnostic and therapeutic context of MMEL1

• The human MMEL2 gene was mapped to 1p36 by fluorescence in situ hybridization [1].
• Northern blot analysis and in situ hybridization showed that NL1 mRNA was found predominantly in testis, specifically in round and elongated spermatids [28].
• Strikingly, however, both DNase I footprinting and electrophoretic mobility shift assays showed that NL3, but not NL1 or NL2, has high binding affinity to Nurr1 [18].
• CONCLUSIONS: SEP monitoring has acceptable sensitivity for detecting neurological damage during different neurosurgical procedures [29].
• Meta-analysis of series comprising 3,028 patients undergoing carotid endarterectomies shows that SEP deteriorated in 5.6% of cases, with 20% of these having postoperative deficits, but more might have had deficits if they had not been shunted [30].

References