Biomedical subjects

Zhiyong Yang

Publications and source records attributed to Zhiyong Yang.

At least 19 recordsLinked to original sources

PubMed2006

Requirement for Bhlhb5 in the specification of amacrine and cone bipolar subtypes in mouse retina.

The mammalian retina comprises six major neuronal cell types and one glial type that are further classified into multiple subtypes based on their anatomical and functional differences. Nevertheless, how these subtypes arise remains largely unknown at the molecular level. Here, we demonstrate that the expression of Bhlhb5, a bHLH transcription factor of the Olig family, is tightly associated with the generation of selective GABAergic amacrine and Type 2 OFF-cone bipolar subtypes throughout retinogenesis. Targeted deletion of Bhlhb5 results in a significant reduction in the generation of these selective bipolar and amacrine subtypes. Furthermore, although a Bhlhb5-null mutation has no effect on the expression of bHLH-class retinogenic genes, Bhlhb5 expression overlaps with that of the pan-amacrine factor NeuroD and the expression of Bhlhb5 and NeuroD is negatively regulated by ganglion cell-competence factor Math5. Our results reveal that a bHLH transcription factor cascade is involved in regulating retinal cell differentiation and imply that Bhlhb5 functions downstream of retinogenic factors to specify bipolar and amacrine subtypes.

Amacrine Cells↗

PubMed2006

Transgenically expressed viral RNA silencing suppressors interfere with microRNA methylation in Arabidopsis.

HEN1-dependent methylation of the 3'-terminal nucleotide is a crucial step in plant microRNA (miRNA) biogenesis. Here we report that several viral RNA silencing suppressors (P1/HC-Pro, p21 and p19) inhibit miRNA methylation. These suppressors have distinct effects on different miRNAs. We also show that miRNA* is methylated in vivo in a suppressor-sensitive manner, suggesting that the viral proteins interfere with miRNA/miRNA* duplexes. p19 and p21 bind both methylated and unmethylated miRNA/miRNA* duplexes in vivo. These findings suggest miRNA/miRNA* as the in vivo substrates for the HEN1 miRNA methyltransferase and raise intriguing possibilities regarding the cellular location of miRNA methylation.

Arabidopsis↗

PubMed2006

Reactions of molybdenum(VI) with metal ion reductants.

The reactions of aqueous H2MoO4 at low pH with titanium(II), titanium(III), europium(II), vanadium(II), and germanium(II), as monitored at 430 nm, give biphasic profiles featuring a sharp rise in absorbance followed by a marked decrease (Fig. 1). The final product is the dimeric Mo(V) cation, [Mo2O4]2+, and the strongly absorbing intermediate is taken as a monomeric Mo(V) species. The molar absorbances of the transients from different reductants are not the same, nor are the rate laws governing the fadings. None of the decay curves exhibits evidence of a second order dependence on the transient. The kinetic behaviors of these systems are consistent with the intervention of successor complexes of the type [Chemical structure: see text], (formed by inner sphere reductions of Mo(VI)), which decompose, via first-order processes, to a monomeric Mo(V) species. The latter then experiences rapid dimerization, which is kinetically silent. The possibility that Ge(II) bypasses the unstable tripositive state by reducing Mo(VI) to Mo(IV) (which then undergoes rapid Mo(VI)-Mo(IV) comproportionation) is considered.

Journal Article↗

PubMed2006

Osteoprotegerin (OPG)--a potential new role in the regulation of endothelial cell phenotype and tumour angiogenesis?

The progression of cancer depends on the establishment of a tumour blood supply, and therefore tumour angiogenesis has been identified as a major target for new anticancer agents. Recent reports have suggested that osteoprotegerin (OPG) is involved in the control of endothelial cell survival through the inhibition of the activity of tumour necrosis factor- (TNF) related apoptosis-inducing ligand (TRAIL). The role of OPG in human tumour development and angiogenesis is currently unknown. In the present study we demonstrate the ability of OPG to support endothelial cell survival, as well as the formation of cord-like structures in vitro using a matrigel tubule formation assay. Investigation of various human cancers demonstrated endothelial OPG expression in 59% of malignant tumours (n=512), but in contrast, OPG was absent in endothelial cells associated with benign tumours and normal tissues (n=178). In a series of 400 breast tumours, endothelial OPG expression was associated with high tumour grade and certain histological types. Our data show a clear separation in endothelial OPG expression between malignant tumours and nonmalignant tissues, supporting a potential biological role for this molecule in the development and/or maintenance of the tumour vasculature. This is the first study to report the proangiogenic effects of OPG in vitro, as well as correlating expression of OPG by tumour endothelial cells with clinicopathological data in human tumours.

Breast Neoplasms↗

PubMed2006

Spectral statistics in natural scenes predict hue, saturation, and brightness.

The perceptual color qualities of hue, saturation, and brightness do not correspond in any simple way to the physical characteristics of retinal stimuli, a fact that poses a major obstacle for any explanation of color vision. Here we test the hypothesis that these basic color attributes are determined by the statistical covariations in the spectral stimuli that humans have always experienced in typical visual environments. Using a database of 1,600 natural images, we analyzed the joint probability distributions of the physical variables most relevant to each of these perceptual qualities. The cumulative density functions derived from these distributions predict the major colorimetric functions that have been reported in psychophysical experiments over the last century.

Color Perception↗

PubMed2006

HEN1 recognizes 21-24 nt small RNA duplexes and deposits a methyl group onto the 2' OH of the 3' terminal nucleotide.

microRNAs (miRNAs) and small interfering RNAs (siRNAs) in plants bear a methyl group on the ribose of the 3' terminal nucleotide. We showed previously that the methylation of miRNAs and siRNAs requires the protein HEN1 in vivo and that purified HEN1 protein methylates miRNA/miRNA* duplexes in vitro. In this study, we show that HEN1 methylates both miRNA/miRNA* and siRNA/siRNA* duplexes in vitro with a preference for 21-24 nt RNA duplexes with 2 nt overhangs. We also demonstrate that HEN1 deposits the methyl group on to the 2' OH of the 3' terminal nucleotide. Among various modifications that can occur on the ribose of the terminal nucleotide, such as 2'-deoxy, 3'-deoxy, 2'-O-methyl and 3'-O-methyl, only 2'-O-methyl on a small RNA inhibits the activity of yeast poly(A) polymerase (PAP). These findings indicate that HEN1 specifically methylates miRNAs and siRNAs and implicate the importance of the 2'-O-methyl group in the biology of RNA silencing.

Escherichia coli Proteins↗

PubMed2006

Floral patterning defects induced by Arabidopsis APETALA2 and microRNA172 expression in Nicotiana benthamiana.

Floral patterning and morphogenesis are controlled by many transcription factors including floral homeotic proteins, by which floral organ identity is determined. Recent studies have uncovered widespread regulation of transcription factors by microRNAs (miRNAs), approximately 21-nucleotide non-coding RNAs that regulate protein-coding RNAs through transcript cleavage and/or translational inhibition. The regulation of the floral homeotic gene APETALA2 (AP2) by miR172 is crucial for normal Arabidopsis flower development and is likely to be conserved across plant species. Here we probe the activity of the AP2/miR172 regulatory circuit in a heterologous Solanaceae species, Nicotiana benthamiana. We generated transgenic N. benthamiana lines expressing Arabidopsis wild type AP2 (35S::AP2), miR172-resistant AP2 mutant (35S::AP2m3) and MIR172a-1 (35S::MIR172) under the control of the cauliflower mosaic virus 35S promoter. 35S::AP2m3 plants accumulated high levels of AP2 mRNA and protein and exhibited floral patterning defects that included proliferation of numerous petals, stamens and carpels indicating loss of floral determinacy. On the other hand, nearly all 35S::AP2 plants accumulated barely detectable levels of AP2 mRNA or protein and were essentially non-phenotypic. Overall, the data indicated that expression of the wild type Arabidopsis AP2 transgene was repressed at the mRNA level by an endogenous N. benthamiana miR172 homologue that could be detected using Arabidopsis miR172 probe. Interestingly, 35S::MIR172 plants had sepal-to-petal transformations and/or more sepals and petals, suggesting interference with N. benthamiana normal floral homeotic gene function in perianth organs. Our studies uncover the potential utility of the Arabidopsis AP2/miR172 system as a tool for manipulation of floral architecture and flowering time in non-model plants.

Arabidopsis↗

PubMed2006

Correlation between protein expression of PTEN in human pancreatic cancer and the proliferation, infiltration, metastasis and prognosis.

In order to investigate the correlation between protein expression of PTEN and the proliferation, infiltration, metastasis and prognosis in pancreatic cancer, immunohistochemical SP method was used to examine the protein expression of PTEN, PCNA, MVD, MMP-2, MMP-9 and TUNEL method to detect the levels of apoptosis of pancreatic cells in 41 pancreatic head cancers from regional pancreatectomy (RP) and 10 normal pancreatic tissues. The results showed that among 41 cases of pancreatic cancers, the positive staining of PTNE (39.02%) was significantly weaker than that in normal pancreatic tissues (P < 0.05). The levels of PCNA labeling index (LI), apoptotic index (AI), microvessel density (MVD), MMP-2 LI and MMP-9 LI were decreased gradually with the increase of the expression intensity of PTEN, and there was a significant difference in the above parameters among the patients having different expression levels of PTEN (P < 0.01 or P < 0.05). There was a negative correlation between the expression of PTEN and PCNA LI, MVD, MMP-2 LI, MMP-9 LI, and a positive correlation between AI and the expression of PTEN. The expression intensity of PTEN was correlated with the postoperative survival of the patients with pancreatic cancer (chi2 = 22.3400, P < 0.0001, RR = 2.030). It was suggested that the expression levels of PTEN protein were closely related with proliferation, infiltration and metastasis in human pancreatic cancer, and the expression of PTEN protein was one of the prognostic factors for pancreatic cancer following RP.

Adult↗

PubMed2006

Effect of HIF-1alpha on VEGF-C induced lymphangiogenesis and lymph nodes metastases of pancreatic cancer.

The effect of hypoxia inducible factor-1alpha (HIF-1alpha) on vascular endothelial growth factor C (VEGF-C) and the correlation between HIF-1alpha and lymphangiogenesis and lymph nodes metastases (LNM) in pancreatic cancer were investigated. Immunohistochemical SP method was used to detect the protein expression of HIF-1alpha and VEGF-C, and Lymphatic vessel density (LVD) was determined by stain of VEGFR-3, collagen type IV in 75 pancreatic head cancers from regional pancreatectomy (RP) during Dec. 2001 to Dec. 2003. The relationship between HIF-1alpha and VEGF-C, lymphangiogenesis, LNM was analyzed statistically. The results showed that the positive expressionrate of HIF-1alpha and VEGF-C in pancreatic cancer tissues was 48.00 % (36/75) and 65.33 % (49/75) respectively. In positive group of HIF-1alpha, the positive rate of VEGF-C and LVD, and LVD rate was 80.56 % (29/36), 13.22+/-3.76 and 88.89 % (32/36) respectively, and in negative group of HIF-1alpha, positive rate of VEGF-C and LVD was 51.28 % (20/39), 5.98+/-2.17 and 66.67 % (26/39) respectively (P<0.01 or P<0.05). It was suggested that HIF-1alpha could promote the expression of VEGF-C, lymphangiogenesis and LNM in pancreatic cancer.

Adult↗

PubMed2006

Endothelial dysfunction and impaired L-arginine transport in hypertension and genetically predisposed normotensive subjects.

The term endothelial dysfunction (ED) generally refers to a pathological circumstance in which normal endothelial regulation of vasomotor tone is disturbed. ED has been described in a broad range of cardiovascular and related disease states. In association, deranged endothelial function also has the potential to result in abnormal platelet aggregation and monocyte adhesion. Over the past decade, it has become apparent that reduced availability of nitric oxide is a key mechanism for ED. A range of biochemical disturbances, including depressed L-arginine, have been shown to be associated with ED, and recent evidence indicates this may be genetically determined.

Arginine↗

PubMed2005

Molybdenum and copper catalysis of reductions by titanium(II) and titanium(III).

Reductions of vanadium(IV), benzoquinone, and tri-iodide, both by titanium(III) and by titanium(II), are catalyzed by molybdenum(VI). The VO(2+)-Ti(II) reaction is catalyzed by copper(II) as well. Reactions of Ti(II) with the oxidant in excess yield Ti(IV), as do reductions by Ti(III). Reactions proceed via competing uncatalyzed and catalyzed paths, with the latter components first order in catalyst. Kinetic patterns indicate that monomeric Mo(v) is the active species, but the dimeric Mo(v) species, [Mo(2)O(4)](2+), is without catalytic action. Catalytic constants pertaining to Ti(III) are remarkably similar to those for Ti(II), despite the 0.47 V difference in the standard potentials of the two reductants.

Benzoquinones↗

PubMed2005

Reductions by titanium(II) as catalyzed by titanium(IV).

The cobalt(III) complexes, [(NH3)5CoBr]2+ and [(NH3)5CoI]2+ are reduced by Ti(II) solutions containing Ti(IV), generating nearly linear (zero-order) profiles that become curved only during the last few percent of reaction. Other Co(III)-Ti(II) systems exhibit the usual exponential traces with rates proportional to [Co(III)]. Observed kinetics of the biphasic catalyzed Ti(II)-Co(III)Br and Ti(II)-Co(III)I reactions support the reaction sequence: [Ti(II)(H20)n]2+ + [Ti(IV)F5]- (k1)<==>(k -1) [Ti(II)(H2O)(n-1)]2+ + [(H2O)Ti(IV)F5]-, [Ti(II)(H2O)(n-1)]2+ + Co(III) (k2)--> Ti(III) + Co(II) with rates determined mainly by the slow Ti(IV)-Ti(II) ligand exchange (k1 = 9 x 10(-3) M(-1) s(-1) at 22 degrees C). Computer simulations of the catalyzed Ti(II)-Co(III) reaction in perchlorate-triflate media yield relative rates for reduction by the proposed active [Ti(II)(H2O)(n-1)]2+ intermediate; k(Br)/k(I) = 8.

Bromine↗

PubMed2005

Conserved ETS domain arginines mediate DNA binding, nuclear localization, and a novel mode of bZIP interaction.

The DNA-binding ETS transcription factor Spi-1/PU.1 is of central importance in determining the myeloid-erythroid developmental switch and is required for monocyte and osteoclast differentiation. Many monocyte genes are dependent upon this factor, including the gene that codes for interleukin-1beta. It has long been known that the conserved ETS DNA-binding domain of Spi-1/PU.1 functionally cooperates via direct association with a diverse collection of DNA-binding proteins, including members of the basic leucine zipper domain (bZIP) family. However, the molecular basis for this interaction has long been elusive. Using a combination of approaches, we have mapped a single residue on the surface of the ETS domain critical for protein tethering by the C/EBPbeta carboxyl-terminal bZIP domain. This residue is also important for nuclear localization and DNA binding. In addition, dependence upon the leucine zipper suggests a novel mode for both protein-DNA interaction and functional cooperativity.

Arginine↗

PubMed2005

Isolation of mRNA from specific tissues of Drosophila by mRNA tagging.

To study the function of specific cells or tissues using genomic tools like microarray analyses, it is highly desirable to obtain mRNA from a homogeneous source. However, this is particularly challenging for small organisms, like Caenorhabditis elegans and Drosophila melanogaster. We have optimized and applied a new technique, mRNA tagging, to isolate mRNA from specific tissues of D.melanogaster. A FLAG-tagged poly(A)-binding protein (PABP) is expressed in a specific tissue and mRNA from that tissue is thus tagged by the recombinant PABP and separated from mRNA in other tissues by co-immunoprecipitation with a FLAG-tag specific antibody. The fractionated mRNA is then amplified and used as probe in microarray experiments. As a test system, we employed the procedures to identify genes expressed in Drosophila photoreceptor cells. We found that most known photoreceptor cell-specific mRNAs were identified by mRNA tagging. Furthermore, at least 11 novel genes have been identified as enriched in photoreceptor cells. mRNA tagging is a powerful general method for profiling gene expression in specific tissues and for identifying tissue-specific genes.

Animals↗

PubMed2005

Methylation protects miRNAs and siRNAs from a 3'-end uridylation activity in Arabidopsis.

Small RNAs of 21-25 nucleotides (nt), including small interfering RNAs (siRNAs) and microRNAs (miRNAs), act as guide RNAs to silence target-gene expression in a sequence-specific manner. In addition to a Dicer homolog, DCL1, the biogenesis of miRNAs in Arabidopsis requires another protein, HEN1. miRNAs are reduced in abundance and increased in size in hen1 mutants. We found that HEN1 is a miRNA methyltransferase that adds a methyl group to the 3'-most nucleotide of miRNAs, but the role of miRNA methylation was unknown. Here, we show that siRNAs from sense transgenes, hairpin transgenes, and transposons or repeat sequences, as well as a new class of siRNAs known as trans-acting siRNAs, are also methylated in vivo by HEN1. In addition, we show that the size increase of small RNAs in the hen1-1 mutant is due to the addition of one to five U residues to the 3' ends of the small RNAs. Therefore, a novel uridylation activity targets the 3' ends of unmethylated miRNAs and siRNAs in hen1 mutants. We conclude that 3'-end methylation is a common step in miRNA and siRNA metabolism and likely protects the 3' ends of the small RNAs from the uridylation activity.

Amino Acid Sequence↗

PubMed2005

The Poggendorff illusion explained by natural scene geometry.

One of the most intriguing of the many discrepancies between perceived spatial relationships and the physical structure of visual stimuli is the Poggendorff illusion, when an obliquely oriented line that is interrupted no longer appears collinear. Although many different theories have been proposed to explain this effect, there has been no consensus about its cause. Here, we use a database of range images (i.e., images that include the distance from the image plane of every pixel in the scene) to show that the probability distribution of the possible locations of line segments across an interval in natural environments can fully account for all of the behavior of this otherwise puzzling phenomenon.

Databases, Factual↗

PubMed2005

Reductions by aquatitanium(II).

Solutions of titanium(II), prepared by dissolving titanium wire in mixtures of hydrofluoric and triflic acids, reduce quinones, nitrosodisulfonate anion, and complexes of cobalt(III). When the oxidant is taken in excess, these reactions yield Ti(IV), whereas with excess reductant, the principal product is Ti(III). These reactions are compared with those by Ti(III). Despite differences in rate laws, it is clear that rate ratios for the two reductants (kTiII/kTiIII) fall well below 10(4), the minimum selectivity corresponding to estimated differences in formal potentials, and in some instances, Ti(II), the stronger reductant, reacts more slowly. For both Ti(III) and Ti(II), reductions within the series [Co(NH3)5X]2+(where X=F, Cl, Br, and I), the fluoro complex reacts much more rapidly than its congeners, and the bromo and iodo complexes are slowest, an order similar to that for Eu2+ reductions, but opposite to that for Cr(II) and Cu(I). The [Co(NH3)5Br]2+ reaction with excess Ti(II) proceeds at rates very nearly independent of [oxidant] during the first 80-90% reaction, implying that initiation occurs via unimolecular conversion of Ti(II) to an activated cationic reducing species, in the same manner as the earlier described reduction of I3- by Ge(II) in aqueous HCl.

Benzoquinones↗

PubMed2005

Deletion of active ADAMTS5 prevents cartilage degradation in a murine model of osteoarthritis.

Human osteoarthritis is a progressive disease of the joints characterized by degradation of articular cartilage. Although disease initiation may be multifactorial, the cartilage destruction appears to be a result of uncontrolled proteolytic extracellular matrix destruction. A major component of the cartilage extracellular matrix is aggrecan, a proteoglycan that imparts compressive resistance to the tissue. Aggrecan is cleaved at a specific 'aggrecanase' site in human osteoarthritic cartilage; this cleavage can be performed by several members of ADAMTS family of metalloproteases. The relative contribution of individual ADAMTS proteases to cartilage destruction during osteoarthritis has not been resolved. Here we describe experiments with a genetically modified mouse in which the catalytic domain of ADAMTS5 (aggrecanase-2) was deleted. After surgically induced joint instability, there was significant reduction in the severity of cartilage destruction in the ADAMTS5 knockout mice compared with wild-type mice. This is the first report of a single gene deletion capable of abrogating the course of cartilage destruction in an animal model of osteoarthritis. These results demonstrate that ADAMTS5 is the primary 'aggrecanase' responsible for aggrecan degradation in a murine model of osteoarthritis, and suggest rational strategies for therapeutic intervention in osteoarthritis.

ADAM Proteins↗