Biomedical subjects

N Qian

Publications and source records attributed to N Qian.

At least 37 records · Page 2Linked to original sources

PubMed1997

The IPL gene on chromosome 11p15.5 is imprinted in humans and mice and is similar to TDAG51, implicated in Fas expression and apoptosis.

We searched for novel imprinted genes in a region of human chromosome 11p15.5, which contains several known imprinted genes. Here we describe the cloning and characterization of the IPL ( I mprinted in P lacenta and L iver) gene, which shows tissue-specific expression and functional imprinting, with the maternal allele active and the paternal allele relatively inactive, in many human and mouse tissues. Human IPL is highly expressed in placenta and shows low but detectable expression in fetal and adult liver and lung. Mouse Ipl maps to the region of chromosome 7 which is syntenic with human 11p15.5 and this gene is expressed in placenta and at higher levels in extraembryonic membranes (yolk sac), fetal liver and adult kidney. Mouse and human IPL show sequence similarity to TDAG51 , a gene which was shown to be essential for Fas expression and susceptibility to apoptosis in a T lymphocyte cell line. Like several other imprinted genes, mouse and human IPL genes are small and contain small introns. These data expand the repertoire of known imprinted genes and will be helpful in testing the mechanism of genomic imprinting and the role of imprinted genes in growth regulation.

Amino Acid Sequence↗

PubMed1996

Binocular receptive field models, disparity tuning, and characteristic disparity.

Disparity tuning of visual cells in the brain depends on the structure of their binocular receptive fields (RFs). Freeman and coworkers have found that binocular RFs of a typical simple cell can be quantitatively described by two Gabor functions with the same gaussian envelope but different phase parameters in the sinusoidal modulations (Freeman and Ohzawa 1990). This phase-parameter-based RF description has recently been questioned by Wagner and Frost (1993) based on their identification of a so-called characteristic disparity (CD) in some cells' disparity tuning curves. They concluded that their data favor the traditional binocular RF model, which assumes on overall positional shift between a cell's left and right RFs. Here we set to resolve this issue by studying the dependence of cells' disparity tuning on their underlying RF structures through mathematical analyses and computer simulations. We model the disparity tuning curves in Wagner and Frost's experiments and demonstrate that the mere existence of approximate CDs in real cells cannot be used to distinguish the phase-parameter-based RF description from the traditional position-shift-based RF description. Specifically, we found that model simple cells with either type RF description do not have a CD. Model complex cells with the position-shift-based RF description have a precise CD, and those with the phase-parameter-based RF description have an approximate CD. We also suggest methods for correctly distinguishing the two types of RF descriptions. A hybrid of the two RF models may be required to fit the behavior of some real cells, and we show how to determine the relative contributions of the two RF models.

Animals↗

PubMed1996

A novel speed illusion involving expansion and rotation patterns.

Using random dot stimuli well controlled for dot speed, we found that the moving features in expanding patterns appear to move faster than those in rotating patterns. The illusion is well correlated with the strength of the global motion signal. For example, in displays where the number of motion directions defining the patterns is reduced, the magnitude of the illusion decreases. Similarly, the strength of the effect diminishes as dot density is reduced. In patterns where only wedge-shaped segments of the stimuli are left exposed, the difference in perceived speed increases with the angular size of the wedge. Stimulus placement relative to the fixation point has little effect on the persistence of this phenomenon-expansion patterns appear to contain elements of greater speed, independent of stimulus eccentricity. These results argue against a local explanation for this perceptual illusion, suggesting that the global motion pattern of the stimulus, per se, is responsible.

Humans↗

PubMed1996

Yellow jacket venom allergens, hyaluronidase and phospholipase: sequence similarity and antigenic cross-reactivity with their hornet and wasp homologs and possible implications for clinical allergy.

Three known allergens of yellow jacket (Vespula vulgaris) venom are antigen 5, hyaluronidase, and phospholipase. Yellow jacket antigen 5 has been previously cloned and expressed in bacteria; it contains 204 amino acid residues, and it has 69% and 60% sequence identities with the homologous proteins of white-faced hornet (Dolichovespula maculata) and wasp (Polistes annularis), respectively. These studies are now extended to yellow jacket hyaluronidase and phospholipase; they contain 331 and 300 amino acid residues, respectively, and they show 92% and 67% sequence identity with their homologs of white-faced hornet. Tests with the natural and the recombinant vespid allergens in mice indicate partial antigenic cross-reactivity of their homologous proteins at both B- and T-cell levels. There is greater cross-reactivity among hornet and yellow jacket allergens than that among hornet or yellow jacket and wasp allergens. The order of cross-reaction of the three vespid allergens is hyaluronidase > antigen 5 > phospholipase. The continuous (linear) B-cell epitopes of vespid allergens show greater cross-reactivity than their discontinuous epitopes do. The discontinuous B-cell epitopes are immunodominant for all vespid allergens. The low degree of cross-reactivity of the immunodominant discontinuous B-cell epitopes of vespid allergens should be taken into consideration in selection of venoms for immunotherapy of patients with sensitivity to multiple vespids.

Allergens↗

PubMed1996

An extended region of biallelic gene expression and rodent-human synteny downstream of the imprinted H19 gene on chromosome 11p15.5.

There is increasing evidence for chromosomal domains containing multiple imprinted genes and for domain-wide disruption of imprinting in certain diseases. In a majority of Wilms' tumors (WTs) there is an abnormal bipaternal pattern of expression at three imprinted loci, H19, IGF2 and KIP2, clustered on chromosome 11p15.5. We previously described biallelic expression of L23MRP, 40 kb downstream of H19. Here we map two additional genes, the first encoding a ubiquitously expressed RNA, 2G7, and the second encoding the fast isoform of skeletal muscle troponin-T (TNNT3), in the 55 kb of DNA downstream of L23MRP. 2G7 RNA is spliced and polyadenylated but lacks long open reading frames. 2G7 and TNNT3 are biallelically expressed in mid-fetal and adult human tissues and 2G7 shows persistent expression in WTs. The rat homologue of L23MRP is highly conserved and lies within 85 kb of H19 in a region of rat chromosome 1 which also contains IGF2 and TNNT3. Parallel expression of H19 and TNNT3 in different adult skeletal muscle types suggests that these genes may share an enhancer. These data outline multiple contiguous loci downstream of H19 which escape functional imprinting in humans. The rodent-human synteny of this region may facilitate a search for an imprinting domain boundary.

Adult↗

PubMed1996

SSN genes that affect transcriptional repression in Saccharomyces cerevisiae encode SIN4, ROX3, and SRB proteins associated with RNA polymerase II.

The RNA polymerase II of Saccharomyces cerevisiae exists in holoenzyme forms containing a complex, known as the mediator, associated with the carboxyl-terminal domain. The mediator includes several SRB proteins and is required for transcriptional activation. Previous work showed that a cyclin-dependent kinase-cyclin pair encoded by SSN3 and SSN8, two members of the SSN suppressor family, are identical to two SRB proteins in the mediator. Here we have identified the remaining SSN genes by cloning and genetic analysis. SSN2 and SSN5 are identical to SRB9 and SRB8, respectively, which encode additional components of the mediator. Genetic evidence implicates the SSN genes in transcriptional repression. Thus, these identities provide genetic insight into mediator and carboxyl-terminal domain function, strongly suggesting a role in mediating transcriptional repression as well as activation. We also show that SSN4 and SSN7 are the same as SIN4 and ROX3, respectively, raising the possibility that these genes also encode mediator proteins.

Base Sequence↗

PubMed1995

Integration of motion and stereopsis in middle temporal cortical area of macaques.

The primate visual system incorporates a highly specialized subsystem for the analysis of motion in the visual field. A key element of this subsystem is the middle temporal (MT) cortical area, which contains a majority of direction-selective neurons. MT neurons are also selective for binocular disparity (depth), which is perplexing given that they are not sensitive to motion through depth. What is the role of disparity in MT? Our data suggest an important link between disparity and transparent motion detection. Motion signals in different directions tend to inhibit each other within a given MT receptive field. This inhibition has an averaging effect which minimizes MT responses to random motion signals created by light intensity changes and other non-motion stimuli (motion noise). But, in the absence of disparity cues, inhibition may also occur between surfaces moving in different directions through the same part of the visual field (transparent motion), thus impairing the detection of either surface. Here we show that inhibition in MT occurs mainly between motion signals with similar disparities. Transparent surface movements at different depths are thus represented independently in MT (that is, without inhibiting each other) whereas spurious motion signals from a given surface tend to cancel out. To our knowledge, these results provide the first evidence for a functional integration of motion and disparity in MT.

Animals↗

PubMed1995

V1 responses to transparent and nontransparent motions.

It is well known that a stimulus composed of two independent sets of random dots moving in opposite directions produces a percept of two overlapping transparent surfaces moving across each other, while a counterphase grating composed of two identical sine wave gratings drifting in opposite directions does not. We recorded from the directionally selective V1 cells of behaving macaque monkeys using these two types of stimuli in order to investigate the physiological basis of transparent motion perception. Previous single-unit recording experiments from our laboratory indicated that many V1 cells respond well to transparent random dot patterns, while MT cells' responses to the same patterns are strongly suppressed in comparison with their preferred direction responses. This observation alone would seem to suggest that V1 activity could better explain transparent motion perception than MT activity. However, one could argue to the contrary based on the psychophysical observation that there is a motion threshold elevation under the transparency condition. We decided to determine the correlation between V1 activity and the transparent motion perception directly by recording from V1 cells using both transparent random dot patterns and nontransparent counterphase gratings. It is found that V1 cells on the average could not reliably tell the two types of patterns apart. Our results further the idea that additional processing beyond V1 is involved in transparent motion analysis.

Animals↗

PubMed1995

Generalization and analysis of the Lisberger-Sejnowski VOR model.

Lisberger and Sejnowski (1992) recently proposed a computational model for motor learning in the vestibular-ocular reflex (VOR) system. They showed that the steady-state gain of the system can be modified by changing the ratio of the two time constants along the feedforward and the feedback projections to the Purkinje cell unit in their model VOR network. Here we generalize their model by including two additional time constant variables and two synaptic weight variables, which were set to fixed values in their original model. We derive the stability conditions of the generalized system and thoroughly analyze its steady-state and transient behavior. It is found that the generalized system can display a continuum of behavior with the Lisberger-Sejnowski model and a static model proposed by Miles et al. (1980b) as special cases. Moreover, although mathematically the Lisberger-Sejnowski model requires two precise relationships among its parameters, the model is robust against small perturbations from the physiological point of view. Additional considerations on the gain of smooth pursuit eye movement, which is believed to share the positive feedback loop with the VOR network, suggest that the VOR network should operate in the parameter range favoring the behavior studied by Lisberger and Sejnowski. Under this condition, the steady-state gain of the VOR is found to depend on all four time constants in the network. The time constant of the Purkinje cell unit should be relatively small in order to achieve effective VOR learning through the modifications of the other time constants. Our analysis provides a thorough characterization of the system and could thus be useful for guiding further physiological tests of the model.

Animals↗

PubMed1994

Efficient product clearance through exit channels in substrate hydrolysis by acetylcholinesterase.

The channels connecting the active site of acetylcholinesterase (AChE) to the protein exterior were mapped by computational techniques in order to find potential exit routes for charged reaction products. 3.9% of the total volume of the AChE monomer is hollow space and over 50% of the void is located in the center; it is partitioned into three chambers, a deep entry channel, below it a wide channel located in a slightly positive region of AChE and ideally suitable for the exit of negatively charged fragments and a small chamber above Trp84 and Met83. The latter serve as gates for the departure of the positively charged choline product of the hydrolysis of acetylcholine into the small cavity. An efficient product clearance is a prerequisite to a very low energy pathway for the irreversible hydrolysis of acetylcholine.

Acetates↗

PubMed1994

Identification of amino acid residues involved in the binding of Huperzine A to cholinesterases.

Huperzine A, a potential agent for therapy in Alzheimer's disease and for prophylaxis of organophosphate toxicity, has recently been characterized as a reversible inhibitor of cholinesterases. To examine the specificity of this novel compound in more detail, we have examined the interaction of the 2 stereoisomers of Huperzine A with cholinesterases and site-specific mutants that detail the involvement of specific amino acid residues. Inhibition of fetal bovine serum acetylcholinesterase by (-)-Huperzine A was 35-fold more potent than (+)-Huperzine A, with KI values of 6.2 nM and 210 nM, respectively. In addition, (-)-Huperzine A was 88-fold more potent in inhibiting Torpedo acetylcholinesterase than (+)-Huperzine A, with KI values of 0.25 microM and 22 microM, respectively. Far larger KI values that did not differ between the 2 stereoisomers were observed with horse and human serum butyrylcholinesterases. Mammalian acetylcholinesterase, Torpedo acetylcholinesterase, and mammalian butyrylcholinesterase can be distinguished by the amino acid Tyr, Phe, or Ala in the 330 position, respectively. Studies with mouse acetylcholinesterase mutants, Tyr 337 (330) Phe and Tyr 337 (330) Ala yielded a difference in reactivity that closely mimicked the native enzymes. In contrast, mutation of the conserved Glu 199 residue to Gln in Torpedo acetylcholinesterase produced only a 3-fold increase in KI value for the binding of Huperzine A.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholinesterase↗

PubMed1994

Purification and characterization of two phosphoglucomutases from Lactococcus lactis subsp. lactis and their regulation in maltose- and glucose-utilizing cells.

Two distinct forms of phosphoglucomutase were found in Lactococcus lactis subsp. lactis, strains 19435 and 65.1, growing on maltose: beta-phosphoglucomutase (beta-PGM), which catalyzes the reversible conversion of beta-glucose 1-phosphate to glucose 6-phosphate in the maltose catabolism, and alpha-phosphoglucomutase (alpha-PGM). beta-PGM was purified to more than 90% homogeneity in crude cell extract from maltose-grown lactococci, and polyclonal antisera to the enzyme were prepared. The molecular mass of beta-PGM was estimated by gel filtration to be 28 kDa; its isoelectric point was 4.8. The corresponding values for alpha-PGM were 65 kDa and 4.4, respectively. The expression of both PGM enzymes was investigated under different growth conditions. The specific activity and amount of beta-PGM per milliliter of cell extract increased with time in lactococci grown on maltose, but the enzyme was absent in lactococci grown on glucose, indicating enzyme synthesis to be induced by maltose in the growth medium. When glucose was added to maltose-grown lactococci, both the specific activity and amount of beta-PGM per milliliter of cell extract decreased rapidly. This suggests that synthesis of beta-PGM is repressed by glucose in the medium. Although the specific activity of alpha-PGM did not change during growth on maltose or glucose, lactococcal strain 19435 showed a much higher specific activity of both alpha- and beta-PGM than strain 65.1 when grown on maltose.

Chromatography, Affinity↗

PubMed1994

Detection of bacterial DNA in cerebrospinal fluid by an assay for simultaneous detection of Neisseria meningitidis, Haemophilus influenzae, and streptococci using a seminested PCR strategy.

Primers specific to conserved and variable regions in the 16S rRNA sequence were selected from the partially sequenced 16S rRNA genes of Neisseria meningitidis, Haemophilus influenzae, Streptococcus pneumoniae, S. agalactiae, and Staphylococcus epidermidis. The PCR assay was divided into two DNA amplifications. The first resulted in a general bacterial amplicon, and the second resulted in a species-specific amplicon. The high specificity of the PCR assay was documented after testing bacteria of 28 different species (133 strains). A total of 304 clinical cerebrospinal fluid samples, including 125 samples from patients with bacterial meningitis, were assayed to investigate the diagnostic sensitivity and specificity for bacterial meningitis. The assay showed high sensitivity (0.94) and specificity (0.96) with the clinical samples, although some false results were obtained, the reasons for which are discussed. With agarose gel electrophoresis for detection of the PCR products, the detection limit for meningococci in cerebrospinal fluid was 3 x 10(2) CFU/ml.

Base Sequence↗

PubMed1994

Transparent motion perception as detection of unbalanced motion signals. I. Psychophysics.

Our visual system can solve the difficult problem of representing multiple motions in the same part of the visual space, the motion transparency problem. We investigated the conditions under which transparent motion perception occurs through psychophysical observations, using a series of visual displays composed of two simple patterns moving in opposite directions. We found that whenever a display has finely balanced opposing motion signals in all local regions, it is perceptually nontransparent. The displays that appeared transparent always contain locally unbalanced motion signals, with some local regions having net motion signals in one direction and some other regions in the opposite direction. These interdigitating net motion signals in both directions appear to be integrated separately to form two overlapping transparent surfaces. Displays that were spatially balanced could be made perceptually transparent if the two components moving in opposite directions were at different stereo depth planes or had different spatial frequency contents. Our results can be explained by proposing a disparity- and spatial frequency-specific suppression stage in the motion pathway, at which motion signals of different directions, but of the same disparity and spatial frequency contents, locally inhibit each other. Such a mechanism would suppress noise input to the motion system, which generally activates several direction channels simultaneously, and would still not eliminate activity evoked by transparent surfaces that are at different depths or have different textures.

Cues↗

PubMed1994

Transparent motion perception as detection of unbalanced motion signals. II. Physiology.

We investigated how the primate visual system solves the difficult problem of representing multiple motion vectors in the same part of the visual space--the problem of motion transparency. In the preceding companion article we reported that displays with locally well-balanced motion signals in opposite directions are perceptually nontransparent (i.e., one does not see two coherent moving surfaces) and that transparent displays always contain locally unbalanced motion signals. This is exemplified by our paired and unpaired dot patterns. Although both types of stimuli contain two sets of dots moving in opposite directions, the former is locally well balanced and appears like flicker while the latter gives a perception of two transparent surfaces. In this article we report our physiological recordings from areas V1 and MT of behaving monkeys, comparing single-cell responses to the paired and the unpaired dot patterns. Although a small proportion of directionally selective V1 cells responded differently to the two types of patterns, the average V1 responses could not reliably distinguish between the paired and the unpaired stimuli. A large fraction of MT cells, on the other hand, responded significantly better to the unpaired dot patterns than to the paired ones. Furthermore, the average response of all MT cells to the unpaired dot patterns was significantly higher than that to the paired dot patterns. These results demonstrate a neural correlate of the perceptual transparency at the level of MT. On the other hand, V1 cells do not generally discriminate between the transparent and nontransparent stimuli, indicating that V1 activity is not well correlated with the perception of motion transparency. Our results are consistent with a two-stage model for motion processing: the first stage measures local motion and the second stage introduces suppression if different directions of motion are present at a local region of the visual field. The first stage is located primarily in V1 and the second stage primarily in MT. Finally, we found a strong and negative correlation between the degree of the opponent-direction suppression of MT cells and their responses to flicker noise stimuli. This result suggests that one of the fundamental roles of the opponent-direction suppression in MT is noise reduction.

Animals↗

PubMed1994

Transparent motion perception as detection of unbalanced motion signals. III. Modeling.

In the preceding two companion articles we studied the conditions under which transparent motion perception occurs through psychophysical experiments, and investigated the underlining neural mechanisms through physiological recordings. The main finding of our perceptual experiments was that whenever a display has finely balanced motion signals in all local areas, it is perceptually nontransparent, and that transparent displays always contain motion signals in different directions that are either spatially unbalanced, or unbalanced in their disparity or spatial frequency contents. In the physiological experiments, we found two stages in the processing of transparent stimuli. The first stage is located primarily in area V1. At this stage motion measurements are made and V1 cells respond well to both the balanced, nontransparent stimuli and the unbalanced, perceptually transparent stimuli. The second stage is located primarily in area MT. MT cells show strong suppression between opposite directions of motion. The suppression for the unbalanced, transparent stimuli is significantly less than that for the balanced, nontransparent stimuli. Therefore, the activity in the second, MT stage correlates better with the perception of motion transparency than the first, V1 stage, which does not distinguish reliably between transparent and nontransparent motion. The above experiments suggest a two-stage model of motion perception with a motion measurement stage in V1 and an opponent-direction suppression stage in area MT. In this article we explicitly test this model through analysis and computer simulations, and compare the response of the model to the perceptual and physiological results using the same balanced and unbalanced stimuli we used in the experiments. In the first stage of the computational model, motion energies in different spatial frequency and disparity ranges are extracted from each local region. Similar to V1, this stage does not distinguish between the balanced and unbalanced stimuli. In the subsequent stage motion energies of opposite directions but with same spatial frequency and disparity contents suppress each other using subtractive or divisive inhibition. This stage responds significantly better to the transparent stimuli than to the nontransparent ones, in agreement with MT activity.

Animals↗

PubMed1993

Key active site residues in the inhibition of acetylcholinesterases by soman.

Molecular modeling (GEMM 7.3) and molecular mechanics calculations (YETI V 5.3) using the X-ray coordinates for acetylcholinesterase (AChE) from Torpedo californica indicate electrostatic stabilization by the active site, Glu-199, of the developing positive charge on the incipient carbonium ion in the dealkylation in the adducts of AChE with PSCR and PSCS diastereomers of 2-(3,3-dimethylbutyl) methylphosphonofluoridate (soman). His-440 is indispensable as a general acid catalyst of C-O bond breaking in the dealkylation reaction and that of bond breaking to the Ser gamma-O in reactivation. This demand for catalysis seems to be satisfied for the reactivation of enzyme from the PSCS diastereomer of soman, but not from the P(S)C(R) diastereomer.

Acetylcholinesterase↗

PubMed1990

When is an inhibitory synapse effective?

Interactions between excitatory and inhibitory synaptic inputs on dendrites determine the level of activity in neurons. Models based on the cable equation predict that silent shunting inhibition can strongly veto the effect of an excitatory input. The cable model assumes that ionic concentrations do not change during the electrical activity, which may not be a valid assumption, especially for small structures such as dendritic spines. We present here an analysis and computer simulations to show that for large Cl- conductance changes, the more general Nernst-Planck electrodiffusion model predicts that shunting inhibition on spines should be much less effective than that predicted by the cable model. This is a consequence of the large changes in the intracellular ionic concentration of Cl- that can occur in small structures, which would alter the reversal potential and reduce the driving force for Cl-. Shunting inhibition should therefore not be effective on spines, but it could be significantly more effective on the dendritic shaft at the base of the spine. In contrast to shunting inhibition, hyperpolarizing synaptic inhibition mediated by K+ currents can be very effective in reducing the excitatory synaptic potentials on the same spine if the excitatory conductance change is less than 10 nS. We predict that if the inhibitory synapses found on cortical spines are to be effective, then they should be mediated by K+ through GABAB receptors.

Animals↗