Biomedical subjects

Lei Ma

Publications and source records attributed to Lei Ma.

22 records · Page 2Linked to original sources

PubMed2002

Cloning and characterization of Disc1, the mouse ortholog of DISC1 (Disrupted-in-Schizophrenia 1).

We cloned the mouse ortholog of DISC1 (Disrupted-in-Schizophrenia 1), a candidate gene for schizophrenia. Disc1 is 3163 nucleotides long and has 60% identity with the human DISC1. Disc1 encodes 851 amino acids and has 56% identity with the human protein. Disc1 maps to the DISC1 syntenic region in the mouse, and genomic structure is conserved. A Disc1 splice variant deletes a portion of Disc1 beginning at amino acids orthologous to the human truncation. Bioinformatic analysis and cross-species comparisons revealed sequence conservation distributed across the genes and conservation of leucine zipper and coiled-coil domains in both orthologs. In situ hybridization in adult mouse brain revealed a restricted expression pattern, with highest levels in the dentate gyrus of the hippocampus and lower expression in CA1-CA3 of the hippocampus, cerebellum, cerebral cortex, and olfactory bulbs. Identification of Disc1 will facilitate the study of DISC1's function and creation of mouse models of DISC1 disruption.

Alternative Splicing↗

PubMed2002

Presenilin-dependent gamma-secretase activity modulates neurite outgrowth.

Demonstration that cleavage of both APP and Notch are dependent on the product of the early onset Alzheimer's disease gene, presenilin-1 (PS1), has raised the possibility that Notch function may be altered in AD. This finding also suggests that Notch may be affected by APPgamma-secretase inhibitors under development for the treatment of Alzheimer's disease, as these target PS1. Data that address these questions have been lacking, due to inability to specifically modulate PS1 activity in a system directly relevant to the adult human brain. Using novel highly specific inhibitors of PS1/gamma-secretase, we demonstrate that modulation of PS1 activity in human CNS neurons not only affects Abeta generation, but also has unanticipated effects on Notch and its activity. We demonstrate that intracellular trafficking of Notch in human CNS neurons is altered by inhibition of PS1 and is accompanied by dramatic changes in neurite morphology, consistent with inhibition of Notch activity. These data, together with immunohistochemical evidence of elevation of Notch pathway expression in AD brain, suggest that Notch dysregulation may contribute to the neuritic dystrophy characteristically seen in Alzheimer's disease brain. In addition, they raise the possibility that inhibition of gamma-secretase/PS1 may have clinically beneficial effects on the neuritic pathology of AD, in addition to its expected effect to reduce amyloid burden.

Adaptor Proteins, Signal Transducing↗

PubMed2002

[Cloning and sequence analysis of full-length trypsin cDNA of Culex pipiens pallens].

The expression difference of trypsin gene between deltamethrin-resistant strain and -susceptible strain of Culex pipiens pallens was further investigated, and the results showed that the expression of trypsin gene were respectively 4.3 and 3.9 fold more in the resistant strain than in the susceptible strain, by reverse Northern blot and Northern blot assays. A full-length trypsin cDNA of 909 base pairs (GenBank/NCBI AY034060) with an open reading frame of 786 base pairs was cloned from the constructed cDNA library by the rapid amplification of cDNA ends, and the deduced protein of 261 amino acids was 55% homologous with Anopheles gambiae trypsin.

Amino Acid Sequence↗

PubMedDate not supplied

Long-term renormalization of chromatic mechanisms following cataract surgery.

The optical density of the human crystalline lens progressively increases with age, the greatest increase in the visible spectrum being at short wavelengths. This produces a gradual shift in the spectral distribution of the light reaching the retina, yet color appearance remains relatively stable across the life span, implying that the visual system adapts to compensate for changes in spectral sensitivity. We explored properties of this adaptive renormalization by measuring changes in color appearance following cataract surgery. When the lens is removed, cataract patients often report a large perceptual shift in color appearance that can last for months. This change in color appearance was quantified for four cataract patients (63-84 years) by determining the chromaticity of stimuli that appeared achromatic before surgery, and at various intervals after surgery for up to 1 year. Stimuli were presented on a calibrated CRT as 9.5-deg spots, with 3-s duration and 3-s interstimulus intervals (ISIs). Chromaticity was adjusted by the subjects in CIE L*a*b* color space with luminance fixed at 32 cd/m2, on a dark background. We also estimated the optical density of the cataractous lens by comparing absolute scotopic thresholds from 410 nm to 600 nm before and after surgery. The results demonstrated that immediately following surgery there is a large increase in the short-wave light reaching the retina, mainly below 500 nm. The achromatic settings generally showed an initial large shift in the "yellow" direction after surgery that gradually (but never fully) returned to the original achromatic point before surgery. The shifts in the achromatic point occur over a number of months and appear to occur independently of the fellow eye.

Adaptation, Ocular↗