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Biomedical subjects

H Gu

Publications and source records attributed to H Gu.

At least 19 recordsLinked to original sources

Evidence for a distinct group of nestin-immunoreactive neurons within the basal forebrain of adult rats.

Nestin is an intermediate filament protein serving as a marker for neuroprogenitor and stem cells. Here we report that a cluster of previously unrecognized nestin immunoreactive (nestin-ir) neurons was located in the medial septum-diagonal band of Broca (MS-DBB) of the basal forebrain in adult rats. Nestin-ir neurons were exclusively located in the MS-DBB and intermingled with choline acetyltransferase-ir (ChAT-ir), parvalbumin-ir (PV-ir), or nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase reactive (NADPHd-reactive) neurons. However, there was no colocalization between nestin-ir and PV-ir in single neurons in MS-DBB; only about 35% of nestin-ir neurons were ChAT-ir, and 8%-12% of nestin-ir neurons were NADPHd-reactive. Morphologically, nestin-ir neurons showed a larger size of somata than that of ChAT-ir or PV-ir neurons and the distribution of nestin-ir neurons spread across the rostro-caudal extent of the MS-DBB. Moreover, retrograde tracing revealed that a significant portion of these nestin-ir neurons projected to the thalamus and hippocampus. These results, for the first time, provide strong evidence that there exists a cluster of previously unrecognized nestin-ir neurons in MS-DBB of the basal forebrain in adult rats and that these nestin-ir neurons are distinguishable from ChAT-ir, PV-ir, and NADPHd-reactive neurons.

Acetylcholine↗

Over-expression of a flower-specific transcription factor gene AtMYB24 causes aberrant anther development.

In plants, MYB transcription factors play important roles in many developmental processes and various defense responses. AtMYB24, as a member of R2R3-MYB gene family in Arabidopsis, was found mainly expressed in flowers, especially in microspores and ovules using Northern blots and in situ hybridization. It was further found that the expression of AtMYB24 was tightly regulated during anther development. Over-expression of AtMYB24 in transgenic plants resulted in pleiotropic phenotypes, including dwarfism and flower development defects, in particular, producing abnormal pollen grains and non-dehiscence anthers. Further analysis showed that the anther development of the AtMYB24-ox lines was retarded starting from the anther developmental stages 10-11. At stages 12 and 13, the septum and stomium cells of anthers would not break, and fewer or no fibrous bands were found in the endothecium and connective cells in the AtMYB24-ox plants. Similar aberrant anther phenotype was also observed in the AtMYB24-GR-ox lines treated with dexamethasone (DEX). Quantitative real-time PCR showed expression of genes involved in phenylpropanoid biosynthetic pathway, such as CHS and DFR, and AtGTP2 were altered in AtMYB24-ox lines. These results suggest an important role of AtMYB24 in the normal development of anthers in Arabidopsis.

Amino Acid Sequence↗

Single-locus sex determination in the parasitoid wasp Cotesia glomerata (Hymenoptera: Braconidae).

The parasitoid Cotesia glomerata usually produces female-biased sex ratios in the field, which are presumably caused by inbreeding and local mate competition (LMC); yet, sibling mating increases the production of males, leading to the male-biased sex ratio of broods in the laboratory. Previous studies have suggested that the sex allocation strategy of C. glomerata is based on both partial LMC in males and inbreeding avoidance in females. The current study investigated the presence of single-locus complementary sex determination (sl-CSD) as a sex-determining mechanism in this species through inbreeding experiment, cytological examination and microsatellite analysis. Cytological examination detected diploid males in nine of 17 single pairs of sibling mating, thus in agreement with the proportion of matched matings predicted by the sl-CSD model. Sex ratio shifts in these matched sibling matings were consistent with the sl-CSD model with less viable diploid males. The haploid males have a single set of maternal chromosomes (n = 10), whereas diploid males possess a double set of chromosomes (2n = 20). Microsatellite analyses confirmed that diploid males produced from the matched matings inherited segregating genetic materials from both parents. Thus, this study provides the first solid evidence for the presence of sl-CSD as a sex-determining mechanism in the braconid genus Cotesia.

Animals↗

Polycystic kidneys and del (4)(q21.1q21.3): further delineation of a distinct phenotype.

A three year-old boy was evaluated because of growth and developmental delay, hypotonia and dysmorphic features. G-banding analysis revealed a small interstitial deletion of the long arm of chromosome four described as 46,XY,del (4)(q21.1q21.3). This patient's findings on physical exam included relative macrocephaly, frontal bossing, short fingers with clinodactyly and were consistent with the phenotypes of previously reported deletions involving the 4q21--> 4q22 band region (Am. J. Med. Genet. 68 (1997) 400-405). To date there are 10 reported live-born cases with such deletions and similar features. The case reported here delimits a minimal critical region for this phenotype to chromosomal region 4q21. Our patient was also found to have cysts in both his kidneys. The gene for type II polycystic kidney disease (PKD2) has been mapped to chromosomal region 4q21--> 4q23. FISH analysis, with a probe including the PKD2 gene, demonstrated hemizygosity at this locus. Thus the absence of one of the PKD2 alleles in the case reported here is associated with early bilateral cyst development. Kidney ultrasound/autopsy studies were reported in seven of the patients with the characteristic phenotype, and were positive for cysts in four cases including the one presented here (Clin. Genet. 31 (1987) 199-205; Am. J. Med. Genet. 68 (1997) 400-405; Am. J. Med. Genet. 40 (1991) 77-790. Our report supports the presence of a distinct phenotype associated with a deleted chromosomal region within 4q21. Hemizygosity for the PKD2 gene is likely in such deletions and may lead to renal cyst formation.

Abnormalities, Multiple↗

Identification of a novel HLA-DMB allele (DMB*0107) in the Korean population.

A novel allele for human leukocyte antigen-DMB was identified in the Korean population. DMB*0107 was identical to DMB*0101 at exon 2, apart from three mismatches at nucleotide positions 82 (A-->G), 146 (A-->T) and 212 (G-->A). These mutations resulted in codon changes at positions 10 (Thr-->Ala), 31 (Asp-->Val) and 53 (Ser-->Asn).

Alleles↗

Identification of four novel HLA-DOA alleles, DOA*010106, DOA*0102, DOA*0103, and DOA*0104N, by sequence-based typing*.

DOA sequences are currently known to have identical protein sequences. However, in this study, we report four novel allele types of human leucocyte antigen-DOA, including one synonymous and three non- synonymous amino acid changes from the Korean population. DOA*010106 has identical protein sequence with previously known DOA*010103 except one nucleotide difference at codon 45 (TCG-->TCA). In contrast, DOA*0102 and DOA*0103 have a sequence change at codon 99 (CTG-->GTG) and codon 105 (CGC-->TGC), causing non-synonymous amino acid changes, Leu99Val and Arg105Cys, respectively. In addition, DOA*0104N has a sequence deletion at codon 36 (CCC-->CC-), resulting in a frame shift leading to a stop codon at codon 62.

Alleles↗

Genetic relationship between olfactory response and fitness in Cotesia glomerata (L.).

The flight response of the parasitic wasp Cotesia glomerata (L.) to semiochemicals from a plant-host complex is subject to genetic variation. The significance of additive genetic variance for the odour-guided behaviour has been demonstrated by bidirectional selection. In order to understand the potential and constraints for phenotypic evolution in olfactory response under the pressure of natural selection, this study was to investigate genetic covariation between the odour-guided behaviour and life-history traits and its genetic correlation with the efficiency of parasitism. A paternal half-sib analysis revealed that there was no significant genetic correlation between this behavioural character and any of three life-history traits examined (the development time of immature stages, the body size of female wasps, the number of female wasps per brood). Comparisons between the selected high and low olfactory-response strains showed the lack of correlated responses in these life-history traits to bidirectional selection on the odour-guided behaviour. On the other hand, genotypic differences in the ability of olfactory response significantly affected the efficiency of parasitism. In comparison with the low olfactory-response strain, female wasps from the high olfactory-response strain were able to parasitize more host larvae in a wider area of habitats. This study provides the first evidence of links between olfactory response and population success in parasitoids from a genetic perspective.

Animals↗

Telomerase activation by Epstein-Barr virus latent membrane protein 1 is associated with c-Myc expression in human nasopharyngeal epithelial cells.

Latent membrane protein 1 (LMP1), one of the oncoproteins encoded by Epstein-Barr virus is sufficient for the development of nasopharyngeal carcinoma in vivo and nasopharyngeal epithelial cellular immortalization in vitro. It has also been shown to increase the telomerase activity in primary human nasopharyngeal epithelial cells by an unknown mechanism. We reported here that LMP1 could increase telomerase activity in coordination with LMP1-induced c-Myc expression in LMP1-transfected primary human nasopharyngeal epithelial cells or in a dual-stable LMP1 integrated nasopharyngeal carcinoma cell line with Tet-on regulatory system, named Tet-on-LMP1 HNE2 by PCR-ELISA analysis and reporter gene assay. Blocking of LMP1 expression decreased telomerase activity and c-myc transactivation. Mutagenesis of Myc-responsive E-box elements in the minimal core of hTERT promoter could inhibit the hTERT expression induced by LMP1. Moreover, blocking of c-myc transactivation could further decrease LMP1-mediated hTERT expression. It has been suggested that LMP1 can be used to aid myc control telomerase. In addition, we also found that C-terminus of LMP1, including CTAR1 and CTAR2 domains participated in telomerase activation. Together, these findings suggested that LMP1 activated telomerase via c-myc.

Blotting, Western↗

The Great Wall of China: a physical barrier to gene flow?

One population from each of six plant species along both sides of the Juyong-guan Great Wall, together with one population from each of five species along both sides of a path on a mountain top near Juyong-guan, were selected to study the effect of the Great Wall as a barrier on genetic differentiation between two subpopulations using RAPD markers. Significant genetic differentiation was found between the subpopulations on both sides of the Great Wall. A wind-pollinated woody species, Ulmus pumila, showed less genetic differentiation than four insect-pollinated species: Prunus armeniaca, Ziziphus jujuba, Vitex negundo, and Heteropappus hispidus. Cleistogenes caespitosa, a wind-pollinated perennial herb, displayed more genetic differentiation between subpopulations than the insect-pollinated species because of its propagation strategy. Although AMOVA analysis showed that subpopulations divided by a mountain path had diverged genetically, the variance component between the subpopulations on both sides of the Great Wall was significantly larger than that between the subpopulations at the control site. Therefore, it is reasonable to deduce that the Juyong-guan Great Wall has served as a physical barrier to gene flow between subpopulations separated for more than 600 years.

Biological Evolution↗

Selection on olfactory response to semiochemicals from a plant-host complex in a parasitic wasp.

Parasitic wasps (parasitoids) use volatiles from the plants infested by phytophagous insects to locate host herbivores, but their behavioural response to such semiochemicals is highly variable. Bi-directional selection on Cotesia glomerata (Hymenoptera: Braconidae) was conducted to investigate the importance of genetic variation in the olfactory response of parasitoids. Female wasps were assessed for flight orientation and landing success in response to the hexane extract from a plant-host complex in a wind tunnel. After the first generation of selection, two strains significantly differentiated in both flight orientation and landing success, and their divergence continued with further selection. The two selected strains genetically differentiated in olfactory perception rather than upwind flight ability. The realized heritability was estimated as 0.248 for flight orientation and 0.216 for landing success. The selection experiment further demonstrated that a prior exposure to the semiochemicals significantly enhanced the subsequent response of female wasps, independent of genetic differences. These results suggest that both genetic component and environmental conditioning have played an important role in the evolution of host selection and utilization by the parasitoid in a tritrophic system.

Animals↗

Progression to AIDS, a clinical AIDS condition and mortality: psychosocial and physiological predictors.

BACKGROUND: The primary aim of this study is to examine prospectively the association of stressful life events, social support, depressive symptoms, anger, serum cortisol and lymphocyte subsets with changes in multiple measures of human immunodeficiency virus (HIV) disease progression. METHODS: Ninety-six HIV-infected gay men without symptoms or anti-retroviral medication use at baseline were studied every 6 months for up to 9 years. Disease progression was defined in three ways using the Centers for Disease Control (CDC) classifications (e.g. AIDS, clinical AIDS condition and mortality). Cox regression models with time-dependent covariates were used, adjusting for control variables (e.g. race, age, baseline, CD4 T cells and viral load, number of anti-retroviral medications). RESULTS: Higher cumulative average stressful life events and lower cumulative average social support predicted faster progression to both the CDC AIDS classification and a clinical AIDS condition. Higher anger scores and CD8 T cells were associated with faster progression to AIDS, and depressive symptoms were associated with faster development of an AIDS clinical condition. Higher levels of serum cortisol predicted all three measures of disease progression. CONCLUSIONS: These results suggest that stressful life events, dysphoric mood and limited social support are associated with more rapid clinical progression in HIV infection, with serum cortisol also exerting an independent effect on disease progression.

Acquired Immunodeficiency Syndrome↗

Different classifications of UPOs in the parametrically different chaotic ISI series of a neural pacemaker.

Various interspike intervals (ISIs) in a series of spontaneous discharges of experimental neural pacemakers were identified as chaotic and as lying between stable period 2 and stable period 3. The method of So et al. for detection of unstable periodic orbits (UPOs) was applied to analyze two chaotic ISI series generated under the action of [Ca2+]o in different concentrations. In the chaotic ISI series near the stable period 2, an unstable period 2 orbit was detected. In the chaotic ISI series near the stable period 3, both an unstable period 2 orbit and an unstable period 3 orbit were detected. The location of the unstable period 2 orbit was close to that of the stable period 2 in the return map, while the location of the unstable period 3 orbit was close to that of the stable period 3. The results not only revealed the structures of various chaotic ISI series, but also indicated that the classification of UPOs could reflect the experimental control parameters at which the chaotic ISI series were generated. The previously discovered period adding bifurcation in the ISI series generated by experimental neural pacemakers [12] was further described in terms of the evolution of the period orbits.

Action Potentials↗

Essential role for Gab2 in the allergic response.

Dos/Gab family scaffolding adapters (Dos, Gab1, Gab2) bind several signal relay molecules, including the protein-tyrosine phosphatase Shp-2 and phosphatidylinositol-3-OH kinase (PI(3)K); they are also implicated in growth factor, cytokine and antigen receptor signal transduction. Mice lacking Gab1 die during embryogenesis and show defective responses to several stimuli. Here we report that Gab2-/- mice are viable and generally healthy; however, the response (for example, degranulation and cytokine gene expression) of Gab2-/- mast cells to stimulation of the high affinity immunoglobulin-epsilon (IgE) receptor Fc(epsilon)RI is defective. Accordingly, allergic reactions such as passive cutaneous and systemic anaphylaxis are markedly impaired in Gab2-/- mice. Biochemical analyses reveal that signalling pathways dependent on PI(3)K, a critical component of Fc(epsilon)RI signalling, are defective in Gab2-/- mast cells. Our data identify Gab2 as the principal activator of PI(3)K in response to Fc(epsilon)RI activation, thereby providing genetic evidence that Dos/Gab family scaffolds regulate the PI(3)K pathway in vivo. Gab2 and/or its associated signalling molecules may be new targets for developing drugs to treat allergy.

Adaptor Proteins, Signal Transducing↗

Characterization of iodonium salts differing in the anion.

The properties and reactivity of a series of iodonium salts with different anions were compared. The nucleophilicity of the anions in such compounds can be characterized by their melting points and NMR spectra. When using Quinaldine Red as indicator and CH3CN as solvent, the acid release rate of the iodonium salts correlated very well with their polymerization results in acid-sensitive epoxides.

Journal Article↗