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S Liu

Publications and source records attributed to S Liu.

At least 19 recordsLinked to original sources

Population Genomics of Almond (Prunus dulcis) Reveals Region-Specific Selection and a Complex History of Domestication.

The domestication of perennial crops in the Mediterranean Basin remains unclear, particularly regarding the genomic consequences of human-mediated demographic shifts and selection. We analysed 8.1 million single nucleotide polymorphisms from 96 cultivated almond (Prunus dulcis) accessions from Europe, North America, Central Asia, and New Zealand, alongside four wild relatives. Population structure analyses revealed four geographically differentiated cultivated groups (Central Asian, North American, and two European) and three wild populations (P. spinosissima, P. orientalis, and P. fenzliana). Cultivated almonds retained high genetic diversity, consistent with weak domestication bottlenecks typical of outcrossing perennials. Elevated diversity and private allele counts in Central Asian cultivars, together with limited evidence of crop-wild gene flow, support Central Asia as an important reservoir of ancestral cultivated diversity that may have played a major role during the early stages of almond domestication. In contrast, allele sharing consistent with historical wild-to-crop introgression-especially involving P. orientalis-has contributed to the genomic composition of European and North American almonds. Genome-wide scans for selective sweeps showed most genes overlapping candidate sweep regions were population-specific, though often associated with similar biological functions, including stress responses and agronomic traits. This suggests repeated targeting of comparable pathways during and post-domestication, despite distinct selection histories. Notably, a subset of candidate genes detected in cultivated populations also occurs in wild relatives, particularly P. orientalis. This overlap is consistent with shared ancestral variation, introgression/gene flow between wild and cultivated lineages, and/or parallel adaptation. Altogether, our results support a complex domestication and diversification history for almonds, shaped by geographic expansion, gene flow with wild relatives, and recurrent selection acting in different regions. This study highlights wild relatives as important reservoirs of genetic diversity and emphasises the need for broader geographic sampling to clarify their contributions to almond domestication and adaptation.

Prunus dulcis↗

Immunoreactivity of Hu proteins facilitates identification of myenteric neurones in guinea-pig small intestine.

Hu proteins, together with neurone-specific enolase (NSE), protein gene product 9.5 (PGP-9.5), microtubule-associated protein-2 (MAP-2) and tubulin beta III isoform, were evaluated immunohistochemically as neuronal markers in whole-mount preparations and cultures obtained from the myenteric plexus of guinea-pig small intestine. Anti-Hu immunostaining marked the ganglion cell somas and nuclei without staining of the neuronal processes in the whole-mounts and cultures. The ganglion cell bodies were not obscured by staining of multiple neuronal fibres and this facilitated accurate counting of the neurones. MAP2 immunostaining also provided clear images of individual neurones in both whole mounts and cultures. Immunoreactivity for NSE, PGP-9.5 and tubulin beta III isoform provided sharp images of the ganglion cells in culture, but not in whole-mount preparations. Strong staining of the neuronal processes in the whole-mount preparations obscured the profiles of the ganglion cell bodies to such an extent that accurate counting of the total neuronal population was compromised. Anti-Hu immunostaining was judged to be an acceptable method for obtaining reliable estimates of total numbers of myenteric neurones in relation to other specific histochemical properties such as histamine binding.

Animals↗

Partial return of motor function in paralyzed legs after surgical bypass of the lesion site by nerve autografts three years after spinal cord injury.

Spinal cord injuries often result in irreversible loss of motor and somatosensory functions below the lesion level. Treatment is limited to physiotherapy aimed at compensating disability. We previously showed that re-establishment of tissue continuity can be achieved in animal models through nerve autografts implanted between the rostral spinal ventral horn and the caudal ventral roots. Rostral motor neuron axons could thus reach peripheral targets, leading to some return of motor function. We used a similar approach in a paraplegic patient with stabilized clinical states three years after spinal cord traumatic damage at the T9 level. Three segments from autologous sural nerves were implanted into the right and left antero-lateral quadrant of the cord at T7-8 levels, then connected to homolateral L2-4 lumbar ventral roots, respectively. Eight months after surgery, voluntary contractions of bilateral adductors and of the left quadriceps were observed. Muscular activity was confirmed by motor unit potentials in response to attempted muscle contraction. Motor-evoked potentials from these muscles were recorded by transcranial magnetic stimulation. These data support the hypothesis that muscles have been re-connected to supra-spinal centers through motor neurons located in the rostral stump of the damaged cord. They suggest that delayed surgical reconstruction of motor pathways may contribute to partial functional recovery.

Electromyography↗

Robust active control of broadband noise in finite ducts.

This study focuses on robust active control of broadband noise in finite ducts. Our analytical and experimental studies suggest the existence of several technical flaws in the path models of conventional active noise control (ANC) systems. These are sensitivity of the path model with respect to boundary conditions, and nonminimum phase (NMP) secondary and reference paths. For finite ducts with small cross sections, the traveling wave model (TWM) may be adopted to find an effective solution to these problems and lead to a robust ANC system. Since many practical "noisy" ducts are finite with small cross sections, the proposed ANC has many practical applications. Its robustness and ability to suppress broadband noise will be explained theoretically and verified experimentally.

Journal Article↗

Lymphoid apoptosis and myeloid hyperplasia in CCAAT displacement protein mutant mice.

CCAAT displacement protein (cux/CDP) is an atypical homeodomain protein that represses expression of several developmentally regulated lymphoid and myeloid genes in vitro, including gp91-phox, immunoglobulin heavy chain, the T-cell receptor beta and gamma chains, and CD8. To determine how this activity affects cell development in vivo, a hypomorphic allele of cux/CDP was created by gene targeting. Homozygous mutant mice (cux/CDP(Delta HD/Delta HD)) demonstrated a partial neonatal lethality phenotype. Surviving animals suffered from a wasting disease, which usually resulted in death between 2 and 3 weeks of age. Analysis of T lymphopoiesis demonstrated that cux/CDP(Delta HD/Delta HD) mice had dramatically reduced thymic cellularity due to enhanced apoptosis, with a preferential loss of CD4(+)CD8(+) thymocytes. Ectopic CD25 expression was also observed in maturing thymocytes. B lymphopoiesis was also perturbed, with a 2- to 3-fold reduction in total bone marrow B-lineage cells and a preferential loss of cells in transition from pro-B/pre-BI to pre-BII stages due to enhanced apoptosis. These lymphoid abnormalities were independent of effects related to antigen receptor rearrangement. In contrast to the lymphoid demise, cux/CDP(Delta HD/Delta HD) mice demonstrated myeloid hyperplasia. Bone marrow reconstitution experiments identified that many of the hematopoietic defects were linked to microenvironmental effects, suggesting that underexpression of survival factors or overexpression of death-inducing factors accounted for the phenotypes observed. Tumor necrosis factor (TNF) levels were elevated in several tissues, especially thymus, suggesting that TNF may be a target gene for cux/CDP-mediated repression. These data suggest that cux/CDP regulates normal hematopoiesis, in part, by modulating the levels of survival and/or apoptosis factors expressed by the microenvironment.

Animals↗

Sequence and structure of the mouse gene for RPE65.

PURPOSE: To determine the genomic organization of the mouse gene for the retinal pigment epithelium (RPE) specific protein RPE65. METHODS: A genomic clone containing the entire Rpe65 gene was isolated from a mouse genomic P1 library. Fragments of this clone were subcloned and sequenced by automated fluorescent dideoxy DNA sequencing and analyzed. Direct sequencing of PCR amplification products was used to complete the structure. Primer extension analysis was used to determine the transcription start site. RESULTS: Southern hybridization of restriction digests of mouse genomic DNA reveals a likely single autosomal gene for Rpe65 with no evidence of pseudogenes. Sequence analysis of the mouse P1 clone for Rpe65 and fragments thereof reveals 14 exons distributed over 27 kbp. The transcription start site is located 57 bp upstream of the initiation codon. The protein encoded by the mouse Rpe65 gene is highly conserved when compared with RPE65s from other species. CONCLUSIONS: RPE65 is a highly conserved protein and it appears that the genes for the mouse and human RPE65s, at least, are also conserved in overall structure.

Amino Acid Sequence↗

Human sex reversal due to impaired nuclear localization of SRY. A clinical correlation.

SRY, an architectural transcription factor encoded by the sex-determining region of the Y chromosome, initiates testicular differentiation in mammalian embryogenesis. The protein contains a high-mobility group (HMG) box, a DNA-bending motif conserved among a broad class of nuclear proteins. Mutations causing human sex reversal (46, XY pure gonadal dysgenesis) are clustered in this domain. Basic N- and C-terminal regions of the HMG box are each proposed to provide nuclear localization signals. The significance of the C-terminal basic cluster (SRY residues 130-134) is uncertain, however, as its activity in cell culture varies with assay conditions. To test its importance, we have investigated a C-terminal sex-reversal mutation (R133W, position 78 of the HMG box). This de novo mutation impairs nuclear localization but not specific DNA binding or sharp DNA bending. Correlation between these properties and the phenotype of the patient suggests that nuclear localization of SRY is required for testicular differentiation and directed in part by the C-terminal basic cluster. To our knowledge, these results provide the first example of impaired organogenesis due to a nuclear localization signal mutation.

Amino Acid Sequence↗

Non-amines, drugs without an amine nitrogen, potently block serotonin transport: novel antidepressant candidates?

The serotonin transporter (SERT) is a principal site of action of therapeutic antidepressants in the brain. Without exception, these inhibitors of serotonin transport contain an amine nitrogen in their structure. We previously demonstrated that novel compounds without an amine nitrogen in their structure (non-amines), blocked dopamine transport in cells transfected with the human dopamine transporter. The present study investigated whether, in the absence of an amine nitrogen, certain non-amines bind selectively to the SERT and block the transport of serotonin. At 10 microM concentration, select non-amines displayed no, or little, affinity for 9 serotonin, 5 dopamine, 7 adrenergic, 5 muscarinic cholinergic, 3 opiate and histamine receptors. The affinities of non-amines for [(3)H]citalopram binding sites on the SERT and their potencies for blocking [(3)H]serotonin transport were measured in cloned human SERT stably or transiently expressed in HEK-293. Whether oxa- or carba-based, non-amines bound to [(3)H]citalopram-labeled sites and blocked [(3)H]serotonin transport in the low nanomolar range, at values equal to or higher than those of some conventional antidepressants. A non-amine, O-1809, was 99-fold more selective for the serotonin over the dopamine transporter. As substituents on the aromatic ring of non-amines confer high affinity for the SERT, we investigated the hypothesis that aromatic-aromatic interactions may contribute significantly to non-amine/transporter association. A SERT mutant was produced in which a highly conserved aromatic amino acid, phenylalanine 548, was replaced by an alanine (F548A). Although the affinities of several non-amines were unchanged in the mutant SERT, the affinity of imipramine was decreased, revealing possible differences in amine and non-amine binding domains on the SERT. The similar affinities of non-amines and conventional antidepressant drugs for the SERT support the view that an amine nitrogen is not essential for drugs to block serotonin transport with high affinity. Non-amines open avenues for developing a new generation of antidepressants.

Amines↗

P2X(7) receptors in the enteric nervous system of guinea-pig small intestine.

The P2X(7) purinergic receptor subtype has been cloned and emphasized as a prototypic P2Z receptor involved in neurotransmission in the central nervous system and ATP-mediated lysis of macrophages in the immune system. Less is known about the neurobiology of P2X(7) receptors in the enteric nervous system (ENS). We studied the distribution of the receptor with indirect immunofluorescence and used selective agonists and antagonists to analyze pharmacologic aspects of its electrophysiologic behavior as determined with intracellular "sharp" microelectrodes and patch-clamp recording methods in neurons identified morphologically by biocytin injection in the ENS. Application of ATP or 2'- (or-3'-) O-(4-benzoylbenzoyl) adenosine 5'-triphosphate (BzBzATP) activated an inward current in myenteric neurons. Brilliant blue G, a selective P2X(7) antagonist, suppressed the responses to both agonists. Potency of the antagonist was greatest (smaller IC(50)) for the current evoked by BzBzATP. The P2X(7) antagonists 1-[N,O-bis (1,5-isoquinolinesulfonyl)-N-methyl-l-tyrosyl]-4-piperazine (KN-62) and oxidized ATP also suppressed the BzBzATP-activated current. Micropressure application of BzBzATP evoked rapidly activating depolarizing responses in intracellular studies with "sharp" microelectrodes. Oxidized-ATP suppressed these responses in both myenteric and submucosal neurons. Rapidly activating depolarizing responses evoked by application of nicotinic, serotonergic 5-HT(3), or gamma-aminobutyric acid A (GABA(A)) receptor agonists were unaffected by brilliant blue G. Immunoreactivity for the P2X(7) receptor was widely distributed surrounding ganglion cell bodies and associated with nerve fibers in both myenteric and submucous plexuses. P2X(7) immunoreactivity was colocalized with synapsin and synaptophysin and surrounded ganglion cells that contained either calbindin, calretinin, neuropeptide Y, substance P, or nitric oxide synthase. The mucosa, submucosal blood vessels, and the circular muscle coat also showed P2X(7) receptor immunoreactivity.

Animals↗

Oxidative dehydrogenation on the alpha-carbon of 4-pyridylacetonitrile complexes of pentaammineruthenium(II).

The oxidation of Ru(NH(3))(5)NCCH(2)py(2+) in 0.10 M HCl turns the solution from yellow to greenish blue with an absorption at lambda = 791 nm. The absorbance reaches its maximum value when the complex undergoes a two-electron oxidation. The IR and (1)H NMR spectra of the product indicate that the metal center remains as Ru(II) and that the ligand is oxidized. The (13)C NMR spectral results suggest that the oxidation product is [(NH(3))(5)RuNCC(pyH)C(pyH)CNRu(NH(3))(5)](ClO(4))(6). Cyclic voltammetry of the product solution also indicates that the oxidation proceeds in two one-electron steps corresponding to [Ru(III),Ru(II)] + e(-) <= => [Ru(II),Ru(II)] and [Ru(III),Ru(III)] + e(-) <= => [Ru(III),Ru(II)]. The structure of the product in deprotonated form [(NH(3))(5)RuNCC(py)C(py)CNRu(NH(3))(5)](ClO(4))(4)(H(2)O)(2) was determined crystallographically. [(NH(3))(5)RuNCC(py)C(py)CNRu(NH(3))(5)](ClO(4))(4)(H(2)O)(2) crystallizes in the orthorhombic Pbca space group with cell constants a = 13.7138 (16) A, b = 15.7553 (18) A, c = 17.831(2) A, and Z = 4. A mechanism for the oxidation has been proposed on the basis of the kinetic studies in the region of 0.01-0.20 M acid concentrations.

Journal Article↗

Prostate cancer risk: associations with ultraviolet radiation, tyrosinase and melanocortin-1 receptor genotypes.

Exposure to ultraviolet radiation may reduce prostate cancer risk, suggesting that polymorphism in genes that mediate host pigmentation will be associated with susceptibility to this cancer. We studied 210 prostate cancer cases and 155 controls to determine whether vitamin D receptor (VDR, Taql and Fokl variants), tyrosinase (TYR, codon 192 variant) and melanocortin-1 receptor (MC1R, Arg151Cys, Arg160Trp, Val92Met, Asp294His and Asp84Glu variants) genotypes are associated with risk. UV exposure was determined using a questionnaire. MC1R Arg(160)/Arg(160) homozygotes were at increased risk (P = 0.027, odds ratio = 1.94) while TYR A2/A2 homozygotes were at reduced risk of prostate cancer (P = 0.033, odds ratio = 0.48). These associations remained significant after correction for UV-exposure. Stratification of cases and controls by quartiles of exposure, showed that the protective effect of TYR A1A2 (P = 0.006, odds ratio 0.075) and A2A2 (P = 0.003, odds ratio 0.055) was particularly strong in subjects who had received the greatest exposure. Our data show for the first time, that allelism in genes linked with skin pigment synthesis is associated with prostate cancer risk possibly because it mediates the protective effects of UV. Importantly, susceptibility is associated with an interaction between host predisposition and exposure.

Adult↗

Secular trends in congenital anomaly-related fetal and infant mortality in Canada, 1985-1996.

Prenatal diagnosis of major congenital anomalies and subsequent termination of affected pregnancies has been widely available as part of routine obstetric care in recent years. In this study, vital statistical data on stillbirths, live births, and infant deaths were used to examine secular trends in gestational age-specific and category-specific fetal and infant mortality due to congenital anomalies in Canada (excluding Ontario and Newfoundland) from 1985-1996. Comparisons of the rates between 1985-1987 and 1994-1996 were made using relative risks and 95% confidence intervals (CI). The overall fetal mortality rate due to congenital anomalies increased significantly, from 68.0 per 100,000 total births in 1985-1987 to 78.6 per 100,000 total births in 1994-1996, while the overall infant mortality rate due to congenital anomalies decreased significantly over the same period, from 2.47 to 1.79 per 1,000 live births. The fetal death rate due to congenital anomalies at 20-21 weeks of gestation increased approximately five-fold (relative risk [RR] = 4.83, 95% CI = 3.28-7.11) from 4.5 to 21.5 per 100,000 fetuses at risk, while the rate at 37-41 weeks decreased by 30% (RR = 0.70, 95% CI = 0.50-0.97). Fetal death rates among pregnancies at 20-25 weeks of gestation increased in all categories of congenital anomaly except anencephaly and respiratory system anomalies. Congenital anomaly-related fetal and infant deaths have increased at early gestation but declined at later gestation in Canada. These changes suggest an increase in prenatal diagnosis and selective termination of pregnancies with congenital anomalies in recent years.

Canada↗

Increasing thyroid cancer incidence in Canada, 1970-1996: time trends and age-period-cohort effects.

We examined time trends in thyroid cancer incidence in Canada by age, time period and birth cohort between 1970 and 1996. Age-specific incidence rates by time period and birth cohort were calculated and age-period-cohort modelling used to estimate effects underlying the observed trends. Overall age-adjusted incidence rates of thyroid cancer doubled, from 3.3 and 1.1 per 100 000 in 1970-72 to 6.8 and 2.2 per 100 000 in 1994-96, among females and males respectively. Almost all the increase between 1970-72 and 1994-96 was due to papillary carcinoma of the thyroid. Age, birth cohort and period effects significantly improved the fit of the model for females, while age and birth cohort effects were significant determinants of the incidence among males. There were significant differences in the patterns/curvature for age, period and birth cohort effects between women and men. Our results suggest that the increases in thyroid cancer incidence in Canada may be associated with more intensive diagnostic activities and change in radiation exposure in childhood and adolescence. Temporal changes in reproductive factors among young women may explain some of the gender differences observed.

Adolescent↗

A new complex variant t(4;15;17) in acute promyelocytic leukemia: fluorescence in situ hybridization confirmation and literature review.

We report a 37-year-old male with acute promyelocytic leukemia (APL) harboring a complex translocation (4;15;17). Karyotypic analysis with R-banding of bone marrow cells revealed 46,XY,t(4;15;17)(q21;q22;q21). Fluorescence in situ hybridization analysis using painting probes for chromosomes 4, 15 and 17 and reverse transcriptase polymerase chain reaction analysis revealed three derivative chromosomes: der(4)t(4;15)(q21;q22), der(15)t(4;15;17)(q21;q22;q21), and del(17)(q21q22). This is the third report of such a translocation and the first confirmed by molecular methods. Considering reported similar cases, it is possible that 4q21 is a nonrandom breakpoint in APL with complex translocations and the gene involved in 4q21 should be investigated.

Chromosomes, Human, Pair 15↗

Topoisomerase II poisoning by ICRF-193.

Antineoplastic bis(dioxopiperazine)s, such as meso-2,3-bis(2,6-dioxopiperazin-4-yl)butane (ICRF-193), are widely believed to be only catalytic inhibitors of topoisomerase II. However, topoisomerase inhibitors have little or no antineoplastic activity unless they are topoisomerase poisons, a special subclass of topoisomerase-targeting drugs that stabilize topoisomerase-DNA strand passing intermediates and thus cause the topoisomerase to become a cytotoxic DNA-damaging agent. Here we report that ICRF-193 is a very significant topoisomerase II poison. Detection of topoisomerase II poisoning by ICRF-193 required the use of a chaotropic protein denaturant in the topoisomerase poisoning assays. ICRF-193 caused dose-dependent cross-linking of human topoisomerase IIbeta to DNA and stimulated topoisomerase IIbeta-mediated DNA cleavage at specific sites on (32)P-end-labeled DNA. Human topoisomerase IIalpha-mediated DNA cleavage was stimulated to a lesser extent by ICRF-193. In vivo experiments with MCF-7 cells also showed the requirement of a chaotropic protein denaturant in the assays and selectivity for the beta-isozyme of human topoisomerase II. Studies with two topoisomerase IIbeta-negative cell model systems confirmed significant topoisomerase II poisoning by ICRF-193 in the wild type cells and were consistent with beta-isozyme selectivity. Common use of only the detergent, SDS, in assays may have led to failure to detect topoisomerase II poisoning by ICRF-193 in earlier studies.

Base Sequence↗

Analyses of p53 target genes in the human genome by bioinformatic and microarray approaches.

The completion of the human genome sequence (International Human Genome Sequence Consortium (2001) Nature 409, 860-921; Venter, J. C., et al. (2001) Science 291, 1304-1351) allows for new ways to analyze global cellular regulatory mechanisms. Here we present a strategy to identify genes regulated by specific transcription factors in the human genome, and apply it to p53. We first collected promoters or introns of all genes available using two methods: GenBank(TM) annotation and a computationally derived transcript map. 4,852 genes analyzed in this way contained at least one p53 consensus binding sequence. Of 13 genes randomly selected for mRNA analysis, 11 were shown to respond to p53 expression. Five promoters were analyzed by chromatin immunoprecipitation, which revealed that all were bound by p53 in vivo. We then analyzed 33,615 unique human genes on cDNA microarrays, identifying 1,501 genes that respond to p53 expression. A parameter was derived that demonstrates that in silico prediction greatly enriches for genes that are activated and repressed by p53 and assists us to suggest other signaling pathways that may be connected to p53. The methods shown here illustrate a novel approach to analysis of global gene regulatory network through the integration of human genomic sequence information and genome-wide gene expression analysis.

Computational Biology↗