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Biomedical subjects

W X Li

Publications and source records attributed to W X Li.

At least 19 recordsLinked to original sources

One-dimensional PtO2 at Pt steps: formation and reaction with CO.

Using core-level spectroscopy and density functional theory we show that a one-dimensional (1D) oxide structure forms at the steps of the Pt(332) surface after exposure. The 1D oxide is found to be stable in an oxygen pressure range, where bulk oxides are only metastable, and is therefore argued to be a precursor to the Pt oxidation. As an example of the consequences of such a precursor exclusively present at the steps, we investigate the reaction of CO with oxygen covered Pt(332). Albeit more strongly bound, the oxidic oxygen is found to react more easily with CO than oxygen chemisorbed on the Pt terraces.

Journal Article↗

Animal virus replication and RNAi-mediated antiviral silencing in Caenorhabditis elegans.

The worm Caenorhabditis elegans is a model system for studying many aspects of biology, including host responses to bacterial pathogens, but it is not known to support replication of any virus. Plants and insects encode multiple Dicer enzymes that recognize distinct precursors of small RNAs and may act cooperatively. However, it is not known whether the single Dicer of worms and mammals is able to initiate the small RNA-guided RNA interference (RNAi) antiviral immunity as occurs in plants and insects. Here we show complete replication of the Flock house virus (FHV) bipartite, plus-strand RNA genome in C. elegans. We show that FHV replication in C. elegans triggers potent antiviral silencing that requires RDE-1, an Argonaute protein essential for RNAi mediated by small interfering RNAs (siRNAs) but not by microRNAs. This immunity system is capable of rapid virus clearance in the absence of FHV B2 protein, which acts as a broad-spectrum RNAi inhibitor upstream of rde-1 by targeting the siRNA precursor. This work establishes a C. elegans model for genetic studies of animal virus-host interactions and indicates that mammals might use a siRNA pathway as an antiviral response.

Animals↗

Inhibition of the PI3K pathway sensitizes fludarabine-induced apoptosis in human leukemic cells through an inactivation of MAPK-dependent pathway.

In the present study, we have investigated the effects of PI3K/Akt pathway on the response of human leukemia cells to fludarabine. Inhibition of PI3K/Akt pathway with a selective inhibitor (e.g., LY294002, or wortmannin) in leukemic cells markedly potentiated fludarabine-induced apoptosis. Inhibition of the PI3K/Akt downstream target mTOR by rapamycin also significantly enhanced fludarabine-induced apoptosis. The co-treatment of fludarabine/LY294002 resulted in significant attenuation in the levels of both phospho-Erk1/2 and phospho-Akt, as well as a marked increase in the level of phospho-JNK. The broad spectrum caspase inhibitor BOC-D-fmk markedly blocked fludarabine/LY-induced apoptosis, had no effect on cytochrome c release to the cytosol, and did abrogate caspase and PARP cleavage. This indicates that mitochondrial dysfunction is upstream of the caspase cascade. Moreover, constitutive activation of the MEK/Erk pathway completely blocked apoptosis induced by the combination of fludarabine/LY294002. Additionally, either constitutive activation of Akt or blockage of the JNK pathway significantly diminished apoptosis induced by the combination. Collectively, these findings demonstrate that inactivation of MAPK, Akt, and activation of the JNK pathway contributes to the induction of apoptosis induced by fludarabine/LY. Comparatively, MAPK inactivation plays a crucial role in fludarabine/LY-induced apoptosis. These results also strongly suggest that combining fludarabine with an inhibitor of the PI3K/Akt/mTOR pathway may represent a novel therapeutic strategy for hematological malignancies.

Apoptosis↗

Effects of trans-resveratrol from Polygonum cuspidatum on bone loss using the ovariectomized rat model.

trans-Resveratrol (resveratrol) has been shown in several studies to significantly modulate biomarkers of bone metabolism. But, there is no direct evidence supporting its inhibitory effect towards bone loss. In the present study, effects of resveratrol on bone mineral density (BMD) and bone calcium content (BCC) were examined in the ovariectomized (OVX) rat model. Female Wistar rats were divided into four groups: SHAM group (sham-operated), OVX group (OVX control), OVX + ALD group (OVX and treated with 1.0 mg/kg of body weight of alendronate sodium), and OVX + RES group (OVX and treated with 0.7 mg/kg of body weight of resveratrol). Tested materials were given by gavage for 12 weeks after ovariectomy. Results showed that rats in the OVX, OVX + ALD, and OVX + RES groups had significantly higher body weights and feed efficiency than those in the SHAM group (P < .01). The OVX group had significantly lower femoral epiphysis BMD than the SHAM group, and epiphysis BMD in the OVX + ALD and OVX + RES groups was significantly greater than that in the OVX group (P < .05). However, the femoral midpoint BMD was not significantly different among the four groups. Additionally, animals in the OVX group had significantly lower BCC compared with the SHAM group, while the BCC of the OVX + ALD and OVX + RES groups was significantly higher than that of the OVX group (P < .05). These results indicated that resveratrol could increase epiphysis BMD and inhibit the decrease of femur BCC in OVX rats, suggesting that it could play a role in protecting against bone loss induced by estrogen deficiency.

Absorptiometry, Photon↗

Oxidation of Pt(110).

Using scanning tunneling microscopy and temperature programmed desorption we investigate the Pt(110) surface under strongly oxidizing conditions involving either high-pressure O2 or atomic oxygen exposure. At low temperatures, only disordered Pt oxide structures are observed. After annealing ordered surface oxide islands are observed to coexist with a highly stable reconstructed (12x2)-O chemisorption structure. From density functional theory calculations a model for the surface oxide phase is revealed. The phase is found to be metastable, and its presence is explained in terms of stabilizing defects in the chemisorption layer and reduced Pt mobility.

Journal Article↗

Two-step reaction on a strained, nanoscale segmented surface.

By means of scanning tunneling microscopy and density functional theory calculations we demonstrate that on the Rh(110)-(10 x 2)-O surface, a prototypical multiphase surface of an oxidized transition metal model catalyst, water formation upon H2 exposure is a two-step reaction, with each step requiring special active sites. The 1st step initiates at (2 x 1)p2mg-O defect islands in the (10 x 2) structure and propagates across the surface as a reaction front, removing half of the adsorbed oxygen. The oxygen decorated Rh ridges of the (10 x 2) structure lose their tensile strain upon this reduction step, whereby nanoscale patches of clean Rh become exposed and act as special reaction sites in the 2nd reaction step, which therefore initiates homogeneously over the entire surface.

Journal Article↗

Role of subsurface oxygen in oxide formation at transition metal surfaces.

We present a density-functional theory trend study addressing the incorporation of oxygen into the basal plane of the late 4d transition metals (TMs) from Ru to Ag. Occupation of subsurface sites is always connected with a significant distortion of the host lattice, rendering it initially less favorable than on-surface chemisorption. Penetration starts only after a critical coverage theta(c), which is lower for the softer metals towards the right of the TM series. The computed theta(c) are found to be very similar to those above which the bulk oxide phase becomes thermodynamically more stable, thus suggesting that the initial incorporation of O actuates the formation of a surface oxide on TM surfaces.

Journal Article↗

Construction and characterization of a cDNA library from 4-week-old human embryo.

Development and differentiation studies of early human embryos have been severely impeded by general difficulties in obtaining suitable samples. In order to isolate and identify new genes expressed during early human development, we constructed and characterized a PCR-based cDNA library using a 4-week-old chorion-free human embryo. The constructed cDNA library contained 6.3 x 10(6) directional recombinants, and its insert size ranged from 0.4 to 1.8 kb. The cDNA library proportionally represents the mRNA population, containing beta-actin, tPA and LINE1 repetitive sequences at the expected frequencies as in other conventionally constructed and PCR-based cDNA libraries. PCR analyses of the library for specific genes have also revealed the presence of cDNAs for developmentally important genes such as CD59, MCP, Quox-1 and ZNF268. Among the 70 randomly selected cDNA clones, 53% encoded previously known genes, 26% matched with anonymous sequences, and 17% showed no sequence similarity and were designated as human early embryo-specific ESTs. These results demonstrate the sequence complexity and relatively low redundancy of our cDNA library. Furthermore, approximately 40% of those randomly analyzed clones contained full-length encoding regions. To our knowledge, this is the first description of the PCR-based cDNA library from a 4-week-old chorion-free human embryo, and the presence of novel sequences within this library makes it a valuable and unique resource for studying gene expression and regulatory mechanisms that underlie the early process of human embryogenesis.

Cloning, Molecular↗

Chronic morphine potentiates the inflammatory response by disrupting interleukin-1beta modulation of the hypothalamic-pituitary-adrenal axis.

Interleukin-1-beta (IL-1beta) can promote inflammation by up-regulating vascular adhesion molecules and inhibit inflammation by activating the hypothalamic-pituitary-adrenal (HPA) axis to produce anti-inflammatory glucocorticoids. In this study, chronic morphine was shown to suppress IL-1beta-induction of corticotropin releasing factor (CRF) mRNA and plasma corticosterone levels. Leukocyte-endothelial adhesion (LEA) in rat mesenteric venules increased during IL-1beta- and FMLP-induced inflammation. Chronic morphine potentiated the LEA response to either IL-1beta or FMLP alone, and greatly enhanced LEA in response to combined IL-1beta and FMLP. Thus, it appears that chronic morphine exposure may promote a potentially damaging inflammatory reaction by disrupting the balance between IL-1beta-mediated local inflammation and the anti-inflammatory effects of the HPA axis.

Animals↗

Cloning and characterization of a novel Krüppel-like zinc finger gene, ZNF268, expressed in early human embryo.

With the aim of identifying genes involved in early human embryonic development, we have isolated a cDNA clone representing a novel human zinc finger gene ZNF268 from 3 week old human embryo cDNA library using a differential hybridization strategy. The complete cDNA sequence of ZNF268 contained an open reading frame of 2841 nucleotides that encodes a 947 amino acid protein with an N-terminal Krüppel-associated box (KRAB) domain and 24 C-terminal zinc fingers. Northern blot analysis showed that ZNF268 mRNA is mainly expressed in 3-5 week old human embryos suggesting it could play certain roles in the embryogenesis. The gene consists of six exons spanning about 22 kb of genomic DNA. According to the genomic sequence from the HTGS database, the ZNF268 gene is assigned to human chromosome 5.

Amino Acid Sequence↗

Precursor nucleotide sequence and genomic organization of BmTXKS1, a new scorpion toxin-like peptide from Buthus martensii Karsch.

Scorpion venom contains a variety of small peptides, which can modulate Na+, K+, Ca2+ and Cl- channel conductance in excitable and non-excitable tissues. A novel full-length cDNA encoding a new toxin-like peptide (named BmTXKS1) was isolated from the venom gland cDNA library of Buthus martensii Karsch. The precursor consists of 60 amino acid residues, with a putative signal peptide of 28 residues and an extra residue, and a mature peptide of 31 residues with an amidated C-terminal. BmTXKS1 shared close homology with BmP01 in 5'UTR and the region encoding the putative signal peptide; especially, the positions of six cysteines are highly conserved among BmTXKS1, PbTX1 and P01-type subfamily of scorpion K+ channel toxins, suggesting that they all should present a common three-dimensional fold, namely the Cysteine-Stabilized alphabeta(CSalphabeta) motif. By PCR amplification of the genomic region encoding BmTXKS1, we have confirmed the identity of our cloned cDNA, and found that BmTXKS1 gene contains an intron, which is completely identical with that of the characterized scorpion K+-channel-ligands in the size, consensus junctions, putative branch point and A+T abundance.

Amino Acid Sequence↗

Molecular cloning and characterization of four scorpion K(+)-toxin-like peptides: a new subfamily of venom peptides (alpha-KTx14) and genomic analysis of a member.

Four full-length cDNAs encoding the precursors of four K(+)-toxin-like peptides (named BmKK(1), BmKK(2), BmKK(3) and BmmKK(4), respectively) were first isolated from a venom gland cDNA library of the Chinese scorpion Buthus martensii Karsch. The deduced precursors of BmKK(1), BmKK(2) and BmKK(3) are all made of 54 amino acid residues including a signal peptide of 23 residues, and a mature toxin of 31 residues with three disulfide bridges. The precursor of BmKK(4) is composed of 55 amino acid residues including a signal peptide of 23 residues, a mature toxin of 30 residues cross-linked by three disulfide bridges, and an extra Gly-Lys tail which should be removed in the processing step. The four peptides displayed 24-97% sequence identity with each other, and less than 27% homology with any other scorpion toxins described. However, they shared a common disulfide bridge pattern, which was consistent with that of most short-chain K(+)-toxins, suggesting they represent a new class of scorpion toxins and their target receptors may be a subfamily of K(+) channels. We classified the BmKK toxin subfamily as alpha-KTx14 according to the classification rules. The genomic sequence of BmKK(2) was also cloned and sequenced. It consisted of two exons, disrupted by an intron of 79 bp inserted in the region encoding the C-terminal part of the signal peptide. This structure was very similar to that of other K(+)-toxins described previously.

3' Untranslated Regions↗

Viral suppressors of RNA silencing.

The suppression of RNA silencing by plant viruses represents a viral adaptation to a novel host antiviral defense. Three types of viral suppressors have been identified through the use of a variety of silencing suppression assays. The first two types of suppressor are capable of a complete or partial reversal of pre-existing RNA silencing; the third type does not reverse RNA silencing but can instead prevent its systemic signaling.

Cysteine Endopeptidases↗

Precursor of a novel scorpion venom peptide (BmKn1) with no disulfide bridge from Buthus martensii Karsch.

A full-length cDNA sequence encoding the precursor of a novel venom peptide (named BmKn1) with no disulfide bridge was first isolated from the venom gland cDNA library of Chinese scorpion Buthus martensii Karsch. The encoded precursor consisted of 70 amino acid residues including two parts: a signal peptide of 23 residues, and a putative mature venom peptide (BmKn1) of 47 residues. The sequence of BmKn1 showed no similarity to those of other scorpion venom peptides. BmKn1 may be the first member of a new venom peptide family from scorpion. Future research will be interesting to unravel further the pharmacological function of this novel scorpion venom peptide.

Amino Acid Sequence↗

Suppression of post-transcriptional gene silencing by a plant viral protein localized in the nucleus.

Post-transcriptional gene silencing (PTGS) is a homology-dependent RNA degradation process that may target RNA exclusively in the cytoplasm. In plants, PTGS functions as a natural defense mechanism against viruses. We reported previously that the 2b protein encoded by cucumber mosaic cucumovirus (CMV) is a virulence determinant and a suppressor of PTGS initiation in transgenic Nicotiana benthamiana. By fusion with the green fluorescent protein, we now show that the CMV 2b protein localizes to the nuclei of tobacco suspension cells and whole plants via an arginine-rich nuclear localization signal, (22)KRRRRR(27). We further demonstrate that the nuclear targeting of the 2b protein is required for the efficient suppression of PTGS, indicating that PTGS may be blocked in the nucleus. In addition, our data indicate that the PTGS suppressor activity is important, but not sufficient, for virulence determination by the 2b protein.

Amino Acid Sequence↗

Nine novel precursors of Buthus martensii scorpion alpha-toxin homologues.

The cDNAs encoding nine novel alpha-toxin homologues were isolated from the venom gland cDNA library of the Chinese scorpion Buthus martensii Karsch (BmK). They are rich in AAAA and TTTT elements at the 5' UTRs. The flanking region of the translation initiation codon ATG is AAAATGAA, which is highly conserved in scorpion Na(+), K(+) and Cl(-) channel toxin genes. These putative scorpion alpha-toxins shared 45.5-98.4% homology with the characterized BmK alpha-toxins, and were completely conserved in the positions of all eight cysteines. This showed, together with higher homology at nucleotide level than that at amino acid level, that these toxins may originate from a common ancestor. The discovery of a series of homologues of scorpion alpha-toxin with a different degree of natural mutation in the primary structure will provide us with a valuable system for studying the structure-function relationship of scorpion toxins.

Amino Acid Sequence↗

Cloning and characterization of the cDNA sequences of two venom peptides from Chinese scorpion Buthus martensii Karsch (BmK).

From a cDNA library made from venom glands of Chinese scorpions of Buthus martensii Karsch, full-length cDNAs encoding precursors of two venom peptides have been isolated using a cDNA probe synthesized by polymerase chain reaction. Sequence analysis of the cDNAs revealed that one encoded precursor was 85 amino acid residues long including a signal peptide of 19 residues and a mature peptide (named BmK T) of 66 residues, and another encoded precursor was 84 residues long containing the same length signal peptide and a mature peptide (BmK M4 isoform, named BmK M4') of 64 residues. The analysis of amino acid sequence similarity indicated that the BmK T was homologous with both mammalian and insect toxins from BmK scorpion or other scorpions, and the BmK M4' was highly homologous with the members of the mammalian neurotoxin family of BmK, having two point mutations in amino acid residue sequence compared to BmK M4, a natural toxin from BmK.

Animals↗