Search PubMed⌕ Search

Biomedical subjects

W M Liu

Publications and source records attributed to W M Liu.

At least 19 recordsLinked to original sources
PubMed1998

Prediction and classification of domain structural classes.

Can the coupling effect among different amino acid components be used to improve the prediction of protein structural classes? The answer is yes according to the study by Chou and Zhang (Crit. Rev. Biochem. Mol. Biol. 30:275-349, 1995), but a completely opposite conclusion was drawn by Eisenhaber et al. when using a different dataset constructed by themselves (Proteins 25:169-179, 1996). To resolve such a perplexing problem, predictions were performed by various approaches for the datasets from an objective database, the SCOP database (Murzin, Brenner, Hubbard, and Chothia. J. Mol. Biol. 247:536-540, 1995). According to SCOP, the classification of structural classes for protein domains is based on the evolutionary relationship and on the principles that govern the 3D structure of proteins, and hence is more natural and reliable. The results from both resubstitution tests and jackknife tests indicate that the overall rates of correct prediction by the algorithm incorporated with the coupling effect among different amino acid components are significantly higher than those by the algorithms without using such an effect. It is elucidated through an analysis that the main reasons for Eisenhaber et al. to have reached an opposite conclusion are the result of (1) misusing the component-coupled algorithm, and (2) using a conceptually incorrect rule to classify protein structural classes. The formulation and analysis presented in this article are conducive to clarify these problems, helping correctly to apply the prediction algorithm and interpret the results.

Algorithms↗
PubMed1998

Shear numbers of protein beta-barrels: definition refinements and statistics.

The original definition of shear number for a beta-barrel is not unique if it contains one or more uneven beta-bulges. We define the shear number of a beta-barrel as the minimal change of residue numbers in the backbone direction for all closed paths on the beta-barrel. We also discuss how to overcome some computational difficulties. It is pointed out that some closed beta-sheets should not be considered as beta-barrels. The pertinent statistics obtained from a representative list of the Protein Data Bank entries are summarized. All beta-barrels have positive shear numbers, i.e. they are right-twisted. The shear numbers of most beta-barrels are even, but exceptions do exist. The sizes of beta-ladders in a beta-barrel vary significantly. Most beta-barrels contain uneven beta-bulges, which may have important biological functions.

Animals↗
PubMed1998

Singular points of protein beta-sheets.

Protein beta-sheets can be regarded as surfaces. Two surfaces can be connected along a common edge to form a larger surface, or two edges of a surface can coalesce to form a closed sheet such as a beta-barrel. Singular points are locations where these connections are not perfect. In protein beta-sheets, a singular point is characterized by a residue separating two beta-ladders. In this paper, we study the singular points of protein beta-sheets from the surface topologic viewpoint, summarize our search results from the protein structural data in the Protein Data Bank, and present examples where singular points are near the active sites and may contribute to forming the proper relative positions of catalytic residues.

Binding Sites↗
PubMed1998

Effects of haemopoietic growth factors in combination with etoposide on sister chromatid exchange frequencies in peripheral blood mononuclear cells.

Prior to work on the influence of dosing and scheduling of the drug etoposide in bone marrow cells, the DNA-damaging effects of three haemopoietic growth factors, either alone or in combination with etoposide, were investigated. Sister chromatid exchange (SCE) frequencies in phytohaemagglutinin-stimulated mononuclear cells of six normal volunteers were used as an indicator of DNA damage. The effects of three growth factors on SCEs were investigated at concentrations ranging between 0 and 100 ng/ml and those of etoposide alone, at concentrations varying between 0 and 2 microM. The effect of combinations of growth factor (GF) and etoposide were assessed at a 40-ng/ml concentration of each cytokine and at 0.4 microM etoposide. Results showed not only a dose-dependent rise in SCE frequency in cells treated with etoposide but also a cytokine effect. Stem-cell factor did not cause a significant change in SCE numbers. However, cytokines with activity at the progenitor cell level induced small but significant increases in SCE numbers at concentrations of 50 and 100 ng/ml (P < 0.001). Results of combination studies indicated a significant 60% increase in SCE numbers in cells treated with GF and etoposide as compared with etoposide alone (P < 0.00001). This finding suggests a sensitivity of peripheral blood mononuclear cells to SCE induction by GFs given either as single agents or in combination with etoposide.

Antineoplastic Agents, Phytogenic↗
PubMed1998

Phylogenetic evidence for the improved RNA higher-order structure in internal ribosome entry sequences of HCV and pestiviruses.

The strong requirement for a small segment of the 5'-proximal coding sequence of hepatitis C virus (HCV) is one of the most remarkable features in the internal initiation of HCV mRNA translation. Phylogenetic analysis and RNA folding indicate a common RNA structure of the 5' untranslated region (UTR) of HCV and the animal pestiviruses, including HCV types 1-11, bovine viral diarrhea (BVDV), border disease virus (BDV) and hog cholera (HoCV). Although the common RNA structure shares similar features to that proposed for the internal ribosome entry sequence (IRES) of picornavirus, phylogenetic evidence suggests four new tertiary interactions between conserved terminal hairpin loops and between the terminal hairpin loop of F2b and the short coding sequence for HCV and pestiviruses. We suggest that the higher-order structures of IRES cis-acting elements for HCV and animal pestivirus are composed of stem-loop structures B-C, domains E-H, stem-loop structure J and four additional tertiary interactions. The common structure of IRES elements for these viruses forms a compact structure by these tertiary interactions and stem stacking. The active structural core is centered in the junction domain of E-H that is also conserved in all members of picornaviruses. Our model suggests that the requirement for a small segment of the 5' coding sequence is to form the distinct tertiary structure that facilitates the cis-acting function of the HCV IRES in the internal initiation of the translational control.

5' Untranslated Regions↗
PubMed1998

Prediction of protein structural classes by modified mahalanobis discriminant algorithm.

We first discuss quantitative rules for determining the protein structural classes based on their secondary structures. Then we propose a modification of the least Mahalanobis distance method for prediction of protein classes. It is a generalization of a quadratic discriminant function to the case of degenerate covariance matrices. The resubstitution tests and leave-one-out tests are carried out to compare several methods. When the class sample sizes or the covariance matrices of different classes are significantly different, the modified method should be used to replace the least Mahalanobis distance method. Two lemmas for the derivation of our new algorithm are proved in an appendix.

Algorithms↗
PubMed1997

Nonlinear oscillations in models of immune responses to persistent viruses.

This paper compares several population models for HIV dynamics. The effect of perfect or nonperfect drugs proposed by Ho, Perelson, and others are considered in the more complicated models of Nowak and Bangham for immune responses to persistent viruses. It is pointed out that two models proposed by Nowak and Bangham have different dynamical behaviors. One of them can have sustained oscillations via the Hopf bifurcation and the other does not. To overcome the difficulty in symbolic computations for complicated systems, we use parameter transforms and introduce a semisymbolic method. This method is very efficient in finding Hopf bifurcation parameters and can be used for other models.

Antibody Formation↗
PubMed1997

Ureteral injury after laparoscopic surgery.

Ureteral injuries are uncommon but serious complications of laparoscopic pelvic surgery. When unrecognized, patients experience fever, abdominal pain, signs of peritonitis, and leukocytosis usually 48 to 72 hours after the surgical procedure. A 48-year-old woman underwent laparoscopic-assisted vaginal hysterectomy, bilateral salpingo-oophorectomy, and anterior and posterior colporrhapy due to a large, symptomatic uterine myoma. Postoperatively, she suffered from progressive left lower quadrant pain, with drainage of yellowish fluid from the subumbilical puncture wound 5 days after the operation. Significant urinary ascites was present. Intravenous pyelogram revealed injury to the lower third of the left ureter about 3 cm away from the ureterovesical junction. Left-sided percutaneous nephrostomy was performed after transurethral placement of a ureteral stent failed. Reanastomosis of the ureter was performed successfully 3 months later, and the patient fully recovered without compromise of the genitourinary tract.

Female↗
PubMed1997

Is there a Möbius band in closed protein beta-sheets?

Protein beta-strands can form beta-barrels and other complicated structures. This paper defines bifurcations and pseudobifurcations of beta-sheets. They are important structural elements for protein folding. This paper also presents a characteristic number that can be used to test whether the surface of a closed beta-sheet is one- or two-sided. Searching the whole Protein Data Bank released in April 1997 with the definition of beta-structures given by the DSSP program, we do not find any one-sided beta-Möbius band. However, there are interesting structures such as beta-bands with odd number of antiparallel ladders and odd number of bifurcations. There are also beta-structures that are closed only at a singular point. Adding a small patch near the singular point in different ways can make it a one- or two-sided surface. The catalytic triad of a GMP synthetase (1GPM) is near the singular point of such a beta-sheet.

Bacteriophage P22↗
PubMed1996

Diamond Blackfan anaemia: differential pattern of in vitro progenitor response to macrophage inflammatory protein 1-alpha.

The congenital disorder of erythropoiesis Diamond Blackfan anaemia (DBA) exhibits a defect in the stem/progenitor cell compartment, located at the erythroid progenitor level (CFU-GEMM, BFU-E, CFU-E). Treatment of DBA with interleukin-3 (IL-3) has had limited effect, despite in vitro studies suggesting that progenitor cells were capable of responding to IL-3. Whether IL-3 is not reaching the appropriate defective target cell, the cells cannot respond, or the marrow humoral inhibitory system is overriding it, is not clear. To investigate humoral inhibitory activities we examined the response of 15 DBA bone marrows in vitro to the inhibitory chemokine macrophage inflammatory protein 1-alpha (MIP1-alpha) in the presence of the stimulatory cytokines erythropoietin, granulocyte-macrophage colony-stimulating factor, IL-3, and stem cell factor. In vitro data agreed with our previous work showing that our patients formed three statistically different groups in response to stimulatory cytokines (type I DBA erythroid colony numbers approximately normal > type II DBA > type III DBA). Addition of MIP1-alpha to cultures caused average erythroid and myeloid suppression, which sequentially increased with DBA type (type I inhibition < type II < type III). The differential level of inhibition shown by MIP1-alpha in these DBA patients lends further evidence for the presence of distinct subgroups in this disorder.

Adolescent↗
PubMed1996

A novel approach to investigating the erythroid lineage, using both receptor analysis and haemoglobin detection.

Progenitor cell failure in the erythroid lineage is a particular problem in bone marrow failure. To provide insight into early erythopoietic development we used sensitive techniques to examine the effects of SCF, IL-3 and MIP-1 alpha on two developmentally arrested progenitor cell lines, HEL and K562. Quantitative flowcytometric analysis showed that both expressed receptors (SCF > MIP-1 alpha > IL-3). Qualitative analysis revealed HEL cells expressed more receptors than K562 cells. Clonogenic assays with sensitive haemoglobin detection showed that SCF and IL-3 did not support HEL development and reduced haemoglobin production. MIP-1 alpha reduced partially developed HEL colonies and haemoglobin in developed colonies. SCF increased development, but not haemoglobin in K562 cells, with IL-3 being more effective in both. MIP-1 alpha increased the proportion of well-developed K562 colonies but not haemoglobin. This suggests SCF, IL-3 and MIP-1 alpha all have a role to play in early erythroid cellular development, with differing actions depending on the stage of development.

Cell Differentiation↗
PubMed1996

The use of recombinant SCF protein for rapid determination of c-kit expression in normal and abnormal erythropoiesis.

Stem cell factor (SCF) is the ligand for the dimeric c-kit tyrosine kinase receptor. Binding of SCF to c-kit is a crucial element in the developmental stimulus of late stem cells and early progenitor cells. In the erythroid lineage the SCF stimulus is important not only for proliferation and differentiation, but is also known to enhance later haemoglobin production. In an earlier report we described a rapid non-radioactive technique using the extended ester-attached labelled SCF protein itself for detecting c-kit expression in marrow and peripheral blood mononuclear populations. In the present study we have taken this a step further to analyse c-kit expression in developing erythroid cells in vitro, principally using normal donor samples. This was designed for use as a foundation for the comparison of haematological disorders. In this case we tested 4 patients with the congenital disorder of erythropoiesis, Diamond-Blackfan anaemia (DBA), finding that in all cases DBA c-kit expression was elevated over normal, in 1 case as high as 348% of the normal average. This may be indicative of the reduced state of progenitor development in these patients. These results show that the described technique is beneficial for analysis in the stem and progenitor compartment.

Adult↗
PubMed1995

RNA polymerase III promoter and terminator elements affect Alu RNA expression.

Promoter elements derived from the 7SL RNA gene stimulate RNA polymerase III (Pol III) directed Alu transcription in vitro. These elements also stimulate expression of Alus transfected into 293 cells, but transcripts from these same constructs are undetectable in HeLa cells. A terminator resembling the terminator for the 7SL RNA gene has no effect on in vitro Alu template activity, but increases expression in vivo in a position independent manner. Alu transcripts generated from templates with and without this terminator have identical half-lives, indicating that this terminator stimulates expression by increasing template activity. Together, these results show that Alu expression may be regulated at multiple levels and can respond to cis-acting elements. This new found ability to express Alu transcripts by transient transfection provides an opportunity to monitor their post-transcriptional fate. Primary Alu transcripts are not extensively adenylated or deadenylated following transcription, but are short-lived compared to 118 nt scAlu RNA. In addition to Alu RNA, transfected templates encode scAlu RNA, but very high levels of Alu RNA expression does not increase the abundance of scAluRNA. ScAluRNA is not merely a transient RNA degradation product, but is instead tightly regulated by factors other than the abundance of primary transcripts.

Base Sequence↗
PubMed1995

Cell stress and translational inhibitors transiently increase the abundance of mammalian SINE transcripts.

The abundance of Alu RNA is transiently increased by heat shock in human cell lines. This effect is specific to Alu repeats among Pol III transcribed genes, since the abundance of 7SL, 7SK, 5S and U6 RNAs is essentially unaffected by heat shock. The rapid induction of Alu expression precedes the heat shock induction of mRNAs for the ubiquitin and HSP 70 heat shock genes. Heat shock mimetics also transiently induce Alu expression indicating that increased Alu expression is a general cell-stress response. Cycloheximide treatment rapidly and transiently increases the abundance of Alu RNA. Again, compared with other genes transcribed by Pol III, this increase is specific to Alu. However, as distinguished from the cell stress response, cycloheximide does not induce expression of HSP 70 and ubiquitin mRNAs. Puromycin also increases Alu expression, suggesting that this response is generally caused by translational inhibition. The response of mammalian SINEs to cell stress and translational inhibition is not limited to SINEs which are Alu homologues. Heat shock and cycloheximide each transiently induce Pol III directed expression of B1 and B2 RNAs in mouse cells and C-element RNA in rabbit cells. Together, these three species exemplify the known SINE composition of placental mammals, suggesting that mammalian SINEs are similarly regulated and may serve a common function.

3T3 Cells↗
PubMed1994

High-density cultivation of sporeformers.

Sporeformers are sources of a large number of industrially important biological products including enzymes, antibiotics, and bioinsecticides. Cultivation of these microorganisms to high cell densities offers potential for enhancing the rates of formation as well as the concentration of the desired products in the fermentation broths in bioreactors. With this objective, investigations have been carried out involving fed-batch cultivation of Bacillus thuringiensis, which is known to produce an insecticidal crystal protein during sporulation. With appropriate management of aeration and nutrient supply, it was possible to grow the cells to > 50 g DW/l density. Nevertheless, the achievement of high cell density did not enhance the formation of crystal protein in the same proportion as the cell concentration. Further examination of this system suggested a complex interplay of energetic requirements for protein turnover during sporulation. Energy reserve material, poly-beta-hydroxybutyric acid, appeared to be linked to formation of spores and crystal protein during the sporulation phase.

Bacillus thuringiensis↗