Biomedical subjects
Publications and source records attributed to Fei Zou.
This white paper by eighty members of the Complex Trait Consortium presents a community's view on the approaches and statistical analyses that are needed for the identification of genetic loci that determine quantitative traits. Quantitative trait loci (QTLs) can be identified in several ways, but is there a definitive test of whether a candidate locus actually corresponds to a specific QTL?
Brassica oleracea is closely related to the model plant, Arabidopsis thaliana. Despite this relationship, it has been difficult to both identify the most closely related segments between the genomes and determine the degree of genome replication within B. oleracea relative to A. thaliana. These difficulties have arisen in part because both species have replicated genomes, and the criteria used to identify orthologous regions between the genomes are often ambiguous. In this report, we compare the positions of sequenced Brassica loci with a known position on a B. oleracea genetic map to the positions of their putative orthologs within the A. thaliana genome. We use explicit criteria to distinguish orthologous from paralogous loci. In addition, we develop a conservative algorithm to identify collinear loci between the genomes and a permutation test to evaluate the significance of these regions. The algorithm identified 34 significant A. thaliana regions that are collinear with >28% of the B. oleracea genetic map. These regions have a mean of 3.3 markers spanning 2.1 Mbp of the A. thaliana genome and 2.5 cM of the B. oleracea genetic map. Our findings are consistent with the hypothesis that the B. oleracea genome has been highly rearranged since divergence from A. thaliana, likely as a result of polyploidization.
This article addresses the identification of genetic loci (QTL and elsewhere) that influence nonnormal quantitative traits with focus on experimental crosses. QTL mapping is typically based on the assumption that the traits follow normal distributions, which may not be true in practice. Model-free tests have been proposed. However, nonparametric estimation of genetic effects has not been studied. We propose an estimation procedure based on the linear rank test statistics. The properties of the new procedure are compared with those of traditional likelihood-based interval mapping and regression interval mapping via simulations and a real data example. The results indicate that the nonparametric method is a competitive alternative to the existing parametric methodologies.
Obesity is a strong risk factor for the development of type 2 diabetes. We have previously reported that in adipose tissue of obese (ob/ob) mice, the expression of adipogenic genes is decreased. When made genetically obese, the BTBR mouse strain is diabetes susceptible and the C57BL/6J (B6) strain is diabetes resistant. We used DNA microarrays and RT-PCR to compare the gene expression in BTBR-ob/ob versus B6-ob/ob mice in adipose tissue, liver, skeletal muscle, and pancreatic islets. Our results show: 1) there is an increased expression of genes involved in inflammation in adipose tissue of diabetic mice; 2) lipogenic gene expression was lower in adipose tissue of diabetes-susceptible mice, and it continued to decrease with the development of diabetes, compared with diabetes-resistant obese mice; 3) hepatic expression of lipogenic enzymes was increased and the hepatic triglyceride content was greatly elevated in diabetes-resistant obese mice; 4) hepatic expression of gluconeogenic genes was suppressed at the prediabetic stage but not at the onset of diabetes; and 5) genes normally not expressed in skeletal muscle and pancreatic islets were expressed in these tissues in the diabetic mice. We propose that increased hepatic lipogenic capacity protects the B6-ob/ob mice from the development of type 2 diabetes.
OBJECTIVE: To investigate the changes in the morphology and biochemistry of neonatal rat hippocampal pyramidal cells (HPCs)apoptosis in high-temperature environment. METHODS: In vitro culture of HPCs was established and then subjected to environmental stimulation with high temperatures (37, 40, and 42 degrees Celsius respectively) for 1 h. All the cells were collected at different time points after the treatment and examined by flow cytometery, fluorescence staining, agarose gel electrophoresis and in situ cell apoptosis detection kit. RESULTS: The apoptotic rate and the number of apoptotic bodies increased as the temperature was elevated. DNA ladder was presented on agarose gel electrophoresis, and the germination of the apoptotic body was observed by fluorescence microscope. CONCLUSIONS: Hyperthermia may induce the apoptosis in HPCs in vitro, and the extend of apoptosis and apoptotic behavior may vary with the temperature and treatment duration.
OBJECTIVE: To study the effects of heat exposure and trauma stress on the level of motilin (MTL) in plasma and the distribution of MTL gastroduodenal mucosa and its mechanism in rabbits. METHODS: The rabbits were randomly divided into four groups, control group, trauma group (23 centigrade degree), heat exposure group (38 centigrade degree) and heat exposure combined trauma group. The MTL was measured by radioimmunoassay (RIA). The rabbit model of heat exposure with trauma was established. The levels of the MTL were measured at 0, 0.5, 1, 1.5 and 2 hours during experiment. RESULTS: In control group, the concentration of MTL was highest in gastric corpus, and then were gastric fundus, pylorus and Duodenal mucous membrane. The concentration of MTL was higher in plasma than that in tissues. After heat exposure and trauma, the concentration of MTL decreased in tissues and increased in plasma. CONCLUSION: The concentration of MTL was different in different parts of gastroduodenal mucosa. The heat exposure and trauma stress may result in the converse changes of the level of MTL in plasma and tissues. The mechanism might be that the destroyed Mo cells released MTL and increasing level of bombesin stimulated by stress induced the release of MTL.
OBJECTIVE: To study the gene expression profiles of human bone marrow derived mesenchymal stem cells and tendon cells. METHODS: Total RNA extracted from human bone marrow derived mesenchymal stem cells and tendon cells underwent reverse transcription, and the products were labeled with alpha-(32)P dCTP. The cDNA probes of total RNA were hybridized to cDNA microarray with 1176 genes, and then the signals were analyzed by Atlas Image analysis software Version 1.01a. RESULTS: Fifteen genes associated with cell proliferation and signal transduction were up-regulated, and one gene that takes part in cell-to-cell adhesion was down-regulated in tendon cells. CONCLUSION: The 15 up-regulated and one down-regulated genes may be beneficial to the orientational differentiation of mesenchymal stem cells into tendon cells.
OBJECTIVE: To study the expression and distribution of nerve growth factor (NGF) and low-affinity neurophin receptor p75 during human hair keratin conduit-induced repair of rabbit tibial nerves. METHODS: Rabbit tibial nerves were transected and connected by either routine suture or by conduits made of human hair keratin (HHK), and after different time periods, paraffin-embedded sections of the nerve tissue at the damaged sites and the adjacent tissues, with normal rabbit tibial nerve sections as control, were prepared for immunohistochemistry. RESULTS: No positive NGF staining was observed in normal tibial nerve tissues, but 76 days after the surgery, strong NGF positivity was detected in the newly generated nerve tissue around the HHK implants until 100 days after the surgery, which was absent in the tissues around the suture. As for p75, there was no positive staining observed in normal tibial nerve tissue. Light positive p75 staining was found in the mature nerve tissues around the HHK implants, where the newly generated tissues were strongly p75-positive during the period between 76-and loo-days after surgery. CONCLUSIONS: HHK and its degenerative product, but not routine suture, can induce the production of NGF and p75 to create a favorable micro-environment for nerve regeneration. More NGF and p75 are produced in newly generated neurons than in mature ones.
OBJECTIVE: To understand whether there are genes differentially expressed in association with heat adaptation in resting heat-adapted rats at normal temperature, and to evaluate the feasibility of investigating heat adaptation mechanism in light of gene differential expression. METHODS: The mRNAs were extracted from rat liver tissues and reverse transcripted into double-strand cDNAs. Suppression subtractive hybridization (SSH) was applied to compare the gene expression profiles between heat adaptation group and normal temperature control group, and cDNA subtraction libraries of the differentially expressed genes were constructed. PCR-selective differential screening technique was used to identify the differentially expressed genes. RESULTS: Six cDNA fragments were identified in the preliminary experiment to be differentially expressed. CONCLUSIONS: There are genes differentially expressed in the liver of resting heat-adapted rats in association with heat adaptation at normal temperature, and these genes may be involved in maintaining heat adaptation. This study also indicates the feasibility of investigating heat adaptation mechanism by isolating differentially expressed genes associated with heat adaptation.
OBJECTIVE: To study the early change of serum nitric oxide (NO) after acute heat exposure with trauma and the effect of NO on mean arterial pressure (MAP), thus to provide theoretical basis for studying the mechanism of NO effect in acute stress. METHODS: The rabbit model of acute heat exposure combined with trauma was established. The animals were divided into four groups, including control, trauma, hyperthermia and hyperthermia combined with trauma. The levels of NO were measured at different time points: 0 h, 1 h, 2 h and MAP was monitored throughout the whole experiment. RESULTS: The concentration of NO declined at first and then increased at 1 h or so after acute heat exposure and trauma. The levels of NO in hyperthermia with trauma group at 1 h, 2 h were (42.75 +/- 8.24), (59.54 +/- 9.05) micro mol/L respectively (P < 0.05), while those in control group were (56.63 +/- 3.79) and (55.22 +/- 7.15) micro mol/L, the difference at 1h between two groups was significant (P < 0.05). Under the circumstance of hyperthermia and trauma, the level of MAP declined to the lowest point at 60 - 70 min and then showed a transient rise, after that, the level declined rapidly. CONCLUSIONS: At the early stage of acute heat exposure and trauma, the concentration of serum NO declined at first and then increased, and had certain relationship with the change of MAP.
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OBJECTIVE: To evaluate the effect of conduits made of human hair keratin (HHK) in repairing injured peripheral nerve. METHODS: Twenty-five normal New Zealand rabbits were used in this study, which were divided into 3 groups including a control group (n=5) and 2 experiment groups. The tibial nerves of rabbits in the 2 experiments groups were transected to create a 10-mm gap, then were either routinely sutured (group II, n=10) or repaired by inserting both nerve stumps into the lumen of the conduit, followed by suturing the epineurium of the nerve stumps with HHK conduits using 9-0 nylon (group III, n=10). Electrophysiological, anatomic and histological examinations were performed at different time points after surgery. RESULTS: Noteworthy improvement in healing could be seen from electrophysiological results of group III, in which HHK conduits were partially degraded and embedded in white tissue, crisp and fragile. Large amount of infantile myelinated nerve fibers and schwann cells were observed under optical microscope to regenerate around HHK, which was partially degraded and absorbed, 92 d postoperatively. One year after the operation, the severed tibial nerves were perfectly repaired and HHK completely degraded. Transmission electron microscopy identified Schwann cell proliferation and myelinization around HHK 92 d after operation, but the delamination of the myelin was not manifest until observed with greater magnifications. There were nerve fibrils in the myelin, where organelles such as mitochondrion could be seen. CONCLUSION: As an ideal material for nerve injury repair, HHK conduits can guide tibial nerve elongation across a 10-mm gap.
OBJECTIVE: To establish an accurate and efficient system for acquiring the complete blood pressure wave parameters in rats. METHODS: With the help of Powlab, the equipment for physiological data recording, and Chart (soft ware), the basal parameters of the the blood pressure waves were acquired in rats, including the parameters of a single wave and the average parameters recorded in 1 min, which were then processed according to mathematical formulas or calculated approximately to acquire other parameters. RESULTS: Through the system the complete parameters of the blood pressure waves were acquired accurately in rats. Compared with the actual values, the results from some approximate calculation showed little difference. CONCLUSION: A precise and automated system for acquiring complete parameters of the blood pressure waves is successfully established in rats, which makes possible more comprehensive and convincing analysis of the blood pressure waves in rats.