Biomedical subjects

L Liang

Publications and source records attributed to L Liang.

At least 55 records · Page 3Linked to original sources

PubMed2001

[The effects of E1A gene on the proliferation and the cell cycle of human lung adenoma cell line].

OBJECTIVE: To investigate the effects of E1A gene on the proliferation rate and the cell cycle of human lung adenoma cell line. METHODS: The characteristics of human adenoma cells transfected and untransfected with E1A gene were studied including the cell growth rate in vitro, the tumorigenicity in nude mouse, and cell cycle analyzed by flow cytometry. The level of P16, P21, P53 and cyclinB1 was assayed using Western blot. RESULTS: The proliferation rate in vitro and the tumorigenicity in vivo of the human lung adenoma cells transfected with E1A gene (Anip973-E1A) were suppressed and cell cycle was retarded at G2/M phase. There was no significant change in the level of P16, P21 and P53, however, the level of cyclinB1 diminished remarkedly. CONCLUSIONS: E1A gene could suppress the proliferation of human adenoma cells in vitro and in vivo. The expression level of cyclinB1, one of the key G2/M checkpoint modulators, was inhibited by E1A, resulting in retardation at G2/M phase. It may be one of the mechanisms of E1A as a tumor-suppressing gene.

Adenovirus E1A Proteins↗

PubMed2000

Atmospheric mercury deposition in Guizhou, China

The atmospheric deposition of mercury including total gas phase mercury (TGM), gas phase divalent mercury (Hg2+), and gas phase monomethyl mercury (MMHg) was investigated. Samples were collected from central cities and nature reserve areas across the province. Techniques and equipment including moss bags, KCl-coated denuder and GARDIS-1A portable mercury vapor analyzer were employed for sample collection and analysis. The reliability of techniques and analytical methods used for the project was evaluated. The deposition of atmospheric mercury was reported in species in this important mercury polluted province for the first time. The spatial and temporal variability of mercury emissions were investigated and reported. Contribution of coal mercury emissions to the atmosphere mercury deposition of the province was also investigated.

Journal Article↗

PubMed2000

Calmodulin binds to and inhibits the activity of the membrane distal catalytic domain of receptor protein-tyrosine phosphatase alpha.

cDNA expression library screening revealed binding between the membrane distal catalytic domain (D2) of protein-tyrosine phosphatase alpha (PTPalpha) and calmodulin. Characterization using surface plasmon resonance showed that calmodulin bound to PTPalpha-D2 in a Ca(2+)-dependent manner but did not bind to the membrane proximal catalytic domain (D1) of PTPalpha, to the two tandem catalytic domains (D1D2) of PTPalpha, nor to the closely related D2 domain of PTPepsilon. Calmodulin bound to PTPalpha-D2 with high affinity, exhibiting a K(D) approximately 3 nm. The calmodulin-binding site was localized to amino acids 520-538 in the N-terminal region of D2. Site-directed mutagenesis showed that Lys-521 and Asn-534 were required for optimum calmodulin binding and that restoration of these amino acids to the counterpart PTPepsilon sequence could confer calmodulin binding. The overlap of the binding site with the predicted lip of the catalytic cleft of PTPalpha-D2, in conjunction with the observation that calmodulin acts as a competitive inhibitor of D2-catalyzed dephosphorylation (K(i) approximately 340 nm), suggests that binding of calmodulin physically blocks or distorts the catalytic cleft of PTPalpha-D2 to prevent interaction with substrate. When expressed in cells, full-length PTPalpha and PTPalpha lacking only D1, but not full-length PTPepsilon, bound to calmodulin beads in the presence of Ca(2+). Also, PTPalpha was found in association with calmodulin immunoprecipitated from cell lysates. Thus calmodulin does associate with PTPalpha in vivo but not with PTPalpha-D1D2 in vitro, highlighting a potential conformational difference between these forms of the tandem catalytic domains. The above findings suggest that calmodulin is a possible specific modulator of PTPalpha-D2 and, via D2, of PTPalpha.

Amino Acid Sequence↗

PubMed2000

Chromosome instability contributes to loss of heterozygosity in mice lacking p53.

The p53 tumor suppressor protein participates in multiple cellular processes including cell cycle checkpoints and programmed cell death. In cell lines, loss of p53 function is associated with increased genetic instability including aneuploidy, gene amplification, and point mutation. Although similar genetic instability often accompanies the progression of malignancy in tumors, its role in tumor initiation in normal cells is not clear. To study whether or not loss of p53 leads to genetic instability in normal cells in vivo, we have examined mechanisms of loss of heterozygosity (LOH) at the Aprt (adenine phosphoribsyltransferase) and flanking loci in normal fibroblasts and T lymphocytes of p53-deficient mice. Somatic cell variants that arose in vivo as a consequence of genetic or epigenetic alterations abolishing Aprt function were selected and expanded in vitro by virtue of their resistance to 2,6-diaminopurine (DAP). We observed that p53 null mice produced about three times as many DAP-resistant fibroblast colonies than wild-type mice, but the frequency of DAP-resistant T lymphocyte colonies was not significantly changed. Mitotic recombination, but not point mutation, partly accounted for the increase in the frequency of DAP-resistant fibroblasts. Most significantly, chromosome loss/duplication and interstitial deletion, which were extremely rare events in the wild-type mice, represented a significant proportion of LOH events in both fibroblasts and T lymphocytes of p53 null mice. Also, increased interstitial deletion was observed in fibroblasts of p53 heterozygous mice. These data suggest that increased genetic variation, including chromosome instability, starts at the initiation stage of tumorigenesis when functional p53 is absent or reduced.

Aneuploidy↗

PubMed2000

Regulation of the calcium/NF-AT T cell activation pathway by the D2 domain of CD45.

CD45 contains tandem repeated protein tyrosine phosphatase (PTP) domains and is essential for the initiation of the earliest activation events resulting from Ag ligation of the TCR. The second PTP domain (D2) contains four CK2 phosphorylation sites in a unique 19-aa insert, which are targets of CK2 phosphorylation. This study was designed to evaluate the roles of these Ser residues in T cell activation. Transient transfection of the CD45- T cell line, J45.01, with CD45 cDNA incorporating four Ser to Ala (S/A) mutations in the 19-aa insert did not affect the magnitude of NF-AT activation resulting from TCR ligation. However, the basal level of NF-AT activity in unstimulated cells expressing the CD45 S/A mutation was elevated 9- to 10-fold. Increased basal NF-AT was dependent on extracellular Ca2+ stores as judged by EGTA treatment. In additional experiments, isolation of stable clones derived from transfection of the CD45 S/A mutant into CD45- H45.01 cells showed sustained calcium flux after TCR engagement. The sustained calcium flux returned to baseline levels after addition of EGTA, suggesting that the expression of the CD45 S/A mutant may have prevented deactivation of plasma membrane calcium channels. Consideration of both transient and stable transfection systems suggests that in addition to being essential for initial events in T cell triggering, the intact CD45 D2, 19-aa insert is necessary for regulation of TCR-mediated calcium signaling pathways.

Amino Acid Substitution↗

PubMed2000

Crystalline versus amorphous content of lumaxistrade mark analog XP280 using X-ray and electron diffraction methods.

In the course of the development of Lumaxistrade mark (roxifiban), the physical state of XP280 (the besylate salt of the active metabolites of roxifiban) and SC887 (the mesylate salt of the free base of roxifiban) were characterized. Powder X-ray diffraction patterns of XP280 were ambiguous in that a high degree of background signal was present and potentially indicative of the existence of an amorphous phase. Herein the results of combined synchrotron X-ray diffraction and electron microscopy (diffraction and imaging) studies on XP280 and SC887 are reported. The combination of these two techniques allowed an unambiguous assessment of the crystallinity, as well as determination of four of the unit cell parameters of XP280 and complete determination of the unit cell parameters for SC887.

Amidines↗

PubMed2000

Three cases of spinal dural AVF: evaluation with first-pass, gadolinium-enhanced, three-dimensional MR angiography.

A first-pass, contrast-enhanced three-dimensional (3D) magnetic resonance (MR) angiography with short acquisition time was performed for three consecutive cases with suspected spinal arteriovenous fistula (AVF). This MR technique demonstrated the feeding arteries and draining veins of the spinal dural AVF, and was very useful for the definite diagnosis of the lesions as a disease with arteriovenous shunt. With this MR technique, we could localize the feeding artery and shunt before conventional angiography. J. Magn. Reson. Imaging 2000;12:949-952.

Aged↗

PubMed2000

Determination of mercury in crude oil by in-situ thermal decomposition using a simple lab built system.

A simple system based on thermal decomposition for the one step determination of mercury has been built. This system was applied to the analysis of crude oil and related products. Samples were directly introduced into the system without the use of chemicals and digestion procedures. After 4 min, matrices and mercury compounds were decomposed, and elemental mercury was collected on a gold sand trap, and then detected by atomic fluorescence spectroscopy (AFS). In principle, any sample can be analyzed by this method provided the sample can be introduced into the system quantitatively. The method detection limit was approximately 0.2 ng/g for 0.04 g of crude oil introduced to the system. Various other samples including, biological, environmental, and general merchandise have been analyzed. Results obtained have been compared with established traditional methods including radiochemical neutron activation analysis (RNAA). Good agreement of results between methods was found. Recoveries were close to 100% for certified reference materials. Results were independent of mercury species and sample types.

Journal Article↗

PubMed2000

Civil liability, criminal law, and other policies and alcohol-related motor vehicle fatalities in the United States: 1984-1995.

This study examines the associations between alcohol policies and motor vehicle fatality rates from 1984 to 1995 in the United States. State policies and state characteristics variables were merged with motor vehicle fatality rates over an 11 year period and analyzed using minimum logit chi-square method and fixed effects to create a quasi time-series analysis. Laws allowing individuals to sue bars for the drunken behavior of their patrons were the policies most strongly associated with lower minor and adult fatality rates. The mandatory first offense fine was associated with lower minor fatality rates but not adult fatality rates, while minor and adult rates fell after administrative per se license suspension and anti-consumption laws for all vehicle occupants. Many other public policies evaluated were not associated with lower fatality rates.

Accidents, Traffic↗

PubMed2000

Identification of candidate genes for psychiatric disorders on 18p11.

Linkage studies have suggested a locus for bipolar disorder as well as schizophrenia in the pericentric region of chromosome 18. Several candidate genes have been identified in the region including ACTH, IMP, and G(olf), however no reports of mutations in families showing linkage to the 18p11 locus have been reported. Recently, mild linkage disequilibrium has been observed with a polymorphic marker that maps within the G(olf) gene and schizophrenia in families from Germany and Israel, suggesting that a gene mapping near G(olf) may be involved in psychiatric disorders. A BAC and cosmid contig around the G(olf) locus has been generated and BAC clones were used for cDNA selection experiments. Several novel genes have been identified which are expressed in the brain. These genes may be possible candidate genes for psychiatric illness.

Bipolar Disorder↗

PubMed2000

Altered gene expression in kidneys of mice with 2,8-dihydroxyadenine nephrolithiasis.

BACKGROUND: We have developed a knockout mouse model for adenine phosphoribosyltransferase (APRT) deficiency, a condition that often leads to 2,8-dihydroxyadenine (DHA) nephrolithiasis in humans. Aprt knockout male mice develop severe renal damage by three months of age, but this is strain specific. Renal damage in female mice is less pronounced than in males. The gene level changes that promote renal injury in APRT-deficient mice are not known. METHODS: We used mRNA differential display polymerase chain reaction (DD-PCR) to analyze renal gene expression changes in APRT-deficient male and female mice (strain C3H) compared with age- and sex-matched Aprt heterozygote controls. The differentially amplified bands were reamplified, cloned, sequenced, and queried against the National Center for Biotechnology Information nonredundant databases using the Basic Alignment Search Tool. Relative quantitative reverse transcription-polymerase chain reaction was used to confirm the results of DD-PCR for a selected number of genes in one-, three-, and six-month-old male and female mice. RESULTS: Sixty-three differentially amplified bands were identified, including 21 for known genes, and 8 of these were examined further. In three-month-old APRT-deficient male mice, the expression of C10 was increased tenfold, and there was a fourfold to sevenfold increase in the expression of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS-1), MGP (matrix Gla protein), and lysyl oxidase (LOX). The expression of cholecystokinin-A receptor (CCKAR), imprinted multimembrane-spanning polyspecific transporter-like gene 1 (IMPT-1), and kidney androgen-regulated protein (KAP) was diminished twofold to fourfold, but there was little or no change in the expression of organic anion transporter (OATP). Except for a more than tenfold increase in C10 expression and up to tenfold decrease in KAP expression, APRT-deficient female mice did not show significant changes in gene expression compared with controls. CONCLUSIONS: These findings suggest that (1) there are sex-related differences in gene expression in DHA lithiasis, possibly caused by increased deposition of DHA crystals in male compared with female kidneys; and (2) the expression of certain genes (for example, C10) may simply be an indication of nonspecific cellular stimulation and may not be related to renal injury.

Adenine↗

PubMed2000

Dynamic MR imaging of neurohypophyseal germ cell tumors for differential diagnosis of infundibular diseases.

PURPOSE: To investigate the MR dynamic patterns of neurohypophyseal germ cell tumors (GCTs) for differential diagnosis of infundibular diseases affecting young people. MATERIAL AND METHODS: Eleven patients with neurohypophyseal GCTs underwent dynamic MR studies with Tl-weighted spin-echo (SE) or turbo SE techniques. Other infundibular lesions, including adenohypophysitis (n=3), Langerhans' cell histiocytosis (LCH, n=2), and 1 hemangioblastoma from von Hippel-Lindau disease, were also evaluated. Serial images were obtained every 15 s (turbo SE) or 30 s (SE technique) for 240 s after rapid injection of contrast medium. The dynamic patterns were analyzed quantitatively with the contrast medium enhancement ratio. RESULTS: On dynamic MR images, GCTs typically showed a gradual enhancement increase with a peak between 105 s and 180 s, while two showed a relatively rapid increase. LCH and hemangioblastoma showed a dynamic pattern similar to GCTs, while adenohypophysitis demonstrated a sharp rise and a steeper wash-out with an obvious peak before 90 s. CONCLUSION: Typical dynamic pattern of GCTs was the gradual enhancement increase without wash-out. Dynamic MR imaging can distinguish GCTs from adenohypophysitis, but is not useful for differentiation from LCH.

Adolescent↗

PubMed2000

A homolog of voltage-gated Ca(2+) channels stimulated by depletion of secretory Ca(2+) in yeast.

In animal cells, capacitative calcium entry (CCE) mechanisms become activated specifically in response to depletion of calcium ions (Ca(2+)) from secretory organelles. CCE serves to replenish those organelles and to enhance signaling pathways that respond to elevated free Ca(2+) concentrations in the cytoplasm. The mechanism of CCE regulation is not understood because few of its essential components have been identified. We show here for the first time that the budding yeast Saccharomyces cerevisiae employs a CCE-like mechanism to refill Ca(2+) stores within the secretory pathway. Mutants lacking Pmr1p, a conserved Ca(2+) pump in the secretory pathway, exhibit higher rates of Ca(2+) influx relative to wild-type cells due to the stimulation of a high-affinity Ca(2+) uptake system. Stimulation of this Ca(2+) uptake system was blocked in pmr1 mutants by expression of mammalian SERCA pumps. The high-affinity Ca(2+) uptake system was also stimulated in wild-type cells overexpressing vacuolar Ca(2+) transporters that competed with Pmr1p for substrate. A screen for yeast mutants specifically defective in the high-affinity Ca(2+) uptake system revealed two genes, CCH1 and MID1, previously implicated in Ca(2+) influx in response to mating pheromones. Cch1p and Mid1p were localized to the plasma membrane, coimmunoprecipitated from solubilized membranes, and shown to function together within a single pathway that ensures that adequate levels of Ca(2+) are supplied to Pmr1p to sustain secretion and growth. Expression of Cch1p and Mid1p was not affected in pmr1 mutants. The evidence supports the hypothesis that yeast maintains a homeostatic mechanism related to CCE in mammalian cells. The homology between Cch1p and the catalytic subunit of voltage-gated Ca(2+) channels raises the possibility that in some circumstances CCE in animal cells may involve homologs of Cch1p and a conserved regulatory mechanism.

ATP-Binding Cassette Transporters↗

PubMed2000

Insulin receptor substrate-1-mediated enhancement of growth hormone-induced mitogen-activated protein kinase activation.

Interaction of GH with the cell-surface GH receptor (GHR) causes activation of the GHR-associated tyrosine kinase, JAK2, and consequent triggering of signaling cascades including the STAT, Ras/Raf/MEK1/MAP kinase, and insulin receptor substrate-1(IRS-1)/PI3kinase pathways. We previously showed that IRS- and GHR-deficient 32D cells that stably express the rabbit GHR and rat IRS-1 (32D-rbGHR-IRS-1) exhibited markedly enhanced GH-induced proliferation and MAP kinase (ERK1 and ERK2) activation compared with cells expressing only the GHR (32D-rbGHR). We now examine biochemical mechanism(s) by which IRS-1 augments GH-induced MAP kinase activation. Time-course experiments revealed a similarly transient (maximal at 15 min) GH-induced ERK1 and ERK2 activation in both 32D-rbGHR and 32D-rbGHR-IRS-1 cells, but, consistent with our prior findings, substantially greater activation was seen in the IRS-1-containing cells. In both cells, GH-induced MAP kinase activation was markedly blunted by the MEK1 inhibitor, PD98059, but not by the PKC inhibitor, GF109203X. Interestingly, pretreatment with the PI3K inhibitor, wortmannin (EC50 approximately 10 nM), significantly reduced GH-induced MAP kinase activation in both 32D-rbGHR and 32D-rbGHR-IRS-1 cells. This same pattern in both cells of IRS-1-dependent augmentation and IRS-1-independent wortmannin sensitivity was also observed for GH-induced activation of Akt and MEK1 (using state-specific antibody blotting for both), despite the lack of difference in GHR, JAK2, SHP-2, p85, Akt, Ras, Raf-1, MEK1, ERK1, or ERK2 abundance between the two cells. A different PI3K inhibitor, LY294002 (50 microM), substantially inhibited (roughly 72%) GH-induced MAP kinase activation in 32D-rbGHR-IRS-1 cells, but only marginally (and statistically insignificantly) inhibited GH-induced MAP kinase activation in 32D-rbGHR cells. Because GH-induced Akt activation was completely inhibited in both cells by the same concentration of LY294002, these findings indicate that the wortmannin sensitivity of both the IRS-1-independent and -dependent GH-induced MAP kinase activation may reflect the activity of another wortmannin-sensitive target(s) in addition to PI3K in mediation of GH-induced MAP kinase activation in these cells. Notably, GH-induced STAT5 tyrosine phosphorylation, unlike Akt or MAPK activation, did not differ between the cells. Finally, while GH promoted accumulation of activated Ras in both cells, both basal and GH-induced activated Ras levels were greater in cells expressing IRS-1 than in 32D-rbGHR cells. These data indicate that while GH induces tyrosine phosphorylation of STAT5 and activation of the Ras/Raf/MEK1/MAPK and PI3K pathways, IRS-1 expression augments the latter two more than the former.

Androstadienes↗

PubMed2000

Reducing harmful alcohol-related behaviors: effective regulatory methods.

OBJECTIVE: This article examines the effects of tort liability, criminal law, administrative regulation, price and availability of alcohol, and personal and state characteristics on the decisions to engage in heavy episodic drinking and to drink and drive. METHOD: Individual behavior data from the Behavioral Risk Factor Surveys (1984-95) were used in a logit analysis of the probability that a respondent engaged in heavy episodic drinking (n = 86,273), drinking and driving (n = 87,087) and drinking and driving if also a heavy episodic drinker (n = 22,261). RESULTS: Imposing tort liability on bars reduced self-reported incidents of drunk driving among all drinkers (p = .043) but did not reduce the probability of heavy episodic drinking or drinking and driving among heavy drinkers. In this first national study of the impact of social host liability, we found that such liability lowered the self-reported probability of heavy episodic drinking (p = .0004) and drinking and driving among all drinkers (p = .0005). CONCLUSIONS: Although several criminal and administrative regulations were also effective in reducing heavy episodic drinking and drunk driving, the imposition of tort liability represents a useful addition to the arsenal of alcohol-control policies.

Adult↗

PubMed2000

In vivo loss of heterozygosity in T-cells of B6C3F1 Aprt(+/-) mice.

We have used B6C3F1 mice heterozygous at Aprt (adenine phosphoribosyltransferase) as a model to study in vivo loss of heterozygosity (LOH) in normal splenic T-lymphocytes. APRT-deficient T-cells were selected in medium containing 50 microg/ml 2, 6-diaminopurine (DAP), an adenine analog that is toxic only to cells with APRT enzyme activity. DAP-resistant (DAP(r)) T-cell variants were recovered at an average frequency of 3 x 10(-5) from 21 B6C3F1 Aprt(+/-) mice. Allele-specific PCR of Aprt showed that about 70% of 122 DAP(r) colonies were caused by loss of the nontargeted Aprt allele (Aprt(+)). Analysis of microsatellite markers along the length of chromosome 8 suggested that mitotic recombination, or chromosome loss, with or without duplication of the remaining chromosome are the predominant mechanisms resulting in loss of Aprt(+). DNA sequencing of Aprt RT-PCR products from the DAP(r) variants that retained Aprt(+) indicated that point mutation as well as other mechanisms could cause this second class of variants. The high spontaneous frequency of in vivo Aprt LOH in mouse T-cells, mediated by LOH mechanisms that are also known to produce human cancers, suggests that the Aprt heterozygous mouse is a valid model for studying the diversity of mechanisms for in vivo somatic mutagenesis.

Adenine Phosphoribosyltransferase↗

PubMed2000

Posttherapeutic intraaxial brain tumor: the value of perfusion-sensitive contrast-enhanced MR imaging for differentiating tumor recurrence from nonneoplastic contrast-enhancing tissue.

BACKGROUND AND PURPOSE: Differentiation of tumor recurrence from treatment-related changes may be difficult with conventional MR imaging when newly enhancing lesions appear. Our aim was to determine the value of perfusion-sensitive contrast-enhanced MR imaging for differentiating recurrent neoplasm from nonneoplastic contrast-enhancing tissue. METHODS: Twenty patients in whom new enhancing lesions developed within irradiated regions were examined prospectively with perfusion-sensitive contrast-enhanced MR imaging. Twelve of them also underwent thallous chloride Tl 201 single-photon emission tomography (201Tl-SPECT). Normalized relative cerebral blood volume (rCBV) ratios and thallium indexes were evaluated to determine whether the new enhancing lesions were recurrent or not. Five instances of tumor recurrence and one of radiation necrosis were verified histologically; in the others, tumor recurrence was distinguished by lesions that progressively increased in size on serial MR examinations over at least 5 months, and nonneoplastic contrast-enhancing tissue was distinguished by lesions that disappeared or decreased in size on serial MR studies over at least 9 months. RESULTS: When normalized rCBV ratios were higher than 2.6 or lower than 0.6, enhancing lesions were either recurrent (n = 5) or nonneoplastic contrast-enhancing tissue (n = 3), respectively. All nonneoplastic contrast-enhancing tissue had a low thallium index, whereas three of four recurrent lesions had a high index. CONCLUSION: An enhancing lesion with a normalized rCBV ratio higher than 2.6 or lower than 0.6 may suggest tumor recurrence or nonneoplastic contrast-enhancing tissue, respectively. In these cases, further examination with 201Tl-SPECT may not be necessary. However, when the normalized rCBV ratio is between 0.6 and 2.6, 201Tl-SPECT may be useful in making the differentiation.

Adolescent↗

PubMed2000

Dynamic readjustment of parental methylation patterns of the 5'-flank of the mouse H19 gene during in vitro organogenesis.

Gametic marks are stably propagated in order to manifest parent of origin-specific expression patterns of imprinted genes in the developing conceptus. Although the character of the imprint has not yet been fully elucidated, there is compelling evidence that it involves a methylation mark. This is exemplified by a region upstream of the H19 gene, which is not only methylated in a parent of origin-specific manner, but also regulates the silencing of the maternal Igf2 and paternal H19 alleles, respectively. We show here that the parental-specific methylation patterns within the differentially methylated domain (DMD) are perturbed in the soma during in vitro organogenesis. Under these conditions, the paternal DMD allele becomes partially demethylated, whereas the maternal DMD allele gains methylation. Despite these effects, there were no changes in allelic Igf2 or H19 expression patterns in the embryo. Finally, we show that although TSA derepresses the paternal H19 allele in ectoplacental cone when in vitro developed, there is no discernible effect on the methylation status of the paternally inherited 5'-flank in comparison to control samples. Collectively, this data demonstrates that the parental mark is sensitive to a subset of environmental cues and that a certain degree of plasticity of the gametic mark is tolerated without affecting the manifestation of the imprinted state.

Alleles↗