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Lei Du

Publications and source records attributed to Lei Du.

At least 19 recordsLinked to original sources
PubMed2006

The effects of a high-fat, high-fructose, and combination diet on learning, weight, and glucose regulation in C57BL/6 mice.

The objective of the study was to determine the effects of a high-fructose diet, a high-fat diet and a combination high-fructose/high-fat diet on weight gain, blood glucose regulation, and cognitive function in C57BL/6 mice. Thirty-eight male mice aged 7 weeks were placed on one of four different diets for 3 months: standard chow and water (n=8), standard diet and access to a fructose solution as the only intake of water (n=8), high-fat diet and water (n=11), and high-fat diet and fructose solution (n=11). Weights were measured 10 times over a 3-month period. Blood glucose regulation was measured using a glucose tolerance test. Cognitive testing consisted of learning an operant bar-pressing task and was performed in the absence of fructose intake. At the end of the experiment, the density of the fructose-specific glucose transporter GLUT5 was measured in the hippocampus, frontal cortex, sensori-motor cortex and cerebellum. The high-fat and the combined high-fat/high-fructose groups gained significantly more weight than the control group. The high-fat group and combined group had significantly higher levels of blood glucose than the control group. The high-fructose group learned the operant task faster than the control group, but the high-fat/high-fructose group was not different from control indicating that the facilitative effect of prior fructose intake was abolished when a high-fat diet was added. Addition of fructose to the diet did not result in an increase of brain GLUT5 density suggesting that the learning improvement were not dependent on plastic upregulation of GLUT5 fructose transporter. The results show that, contrary to high-fat diets, access to fructose in mice did not lead to increased weight and impaired glucose tolerance. The present experiment confirm the deleterious impact of high-fat diets on glucose regulation and weight but suggest that high-fructose diets, contrary to what has been observed in hamsters, do not have the same effect.

Animals↗
PubMed2006

Analysis of one million base pairs of Neanderthal DNA.

Neanderthals are the extinct hominid group most closely related to contemporary humans, so their genome offers a unique opportunity to identify genetic changes specific to anatomically fully modern humans. We have identified a 38,000-year-old Neanderthal fossil that is exceptionally free of contamination from modern human DNA. Direct high-throughput sequencing of a DNA extract from this fossil has thus far yielded over one million base pairs of hominoid nuclear DNA sequences. Comparison with the human and chimpanzee genomes reveals that modern human and Neanderthal DNA sequences diverged on average about 500,000 years ago. Existing technology and fossil resources are now sufficient to initiate a Neanderthal genome-sequencing effort.

Animals↗
PubMed2006

Nitric oxide signaling in stretch-induced apoptosis of neonatal rat cardiomyocytes.

Pressure overload associated with hypertension is an important pathological factor leading to heart remodeling and ultimately heart failure partially due to cardiomyocyte apoptosis. Here we show that endogenous NO signaling plays a critical role in mechanical stretch-induced cardiomyocyte apoptosis. Mechanical stretch induced elevated expression of both eNOS and inducible NO synthase (iNOS) and increased synthesis of NO. A sustained increase in iNOS expression was also found in hearts of hypertensive rats in vivo. Blockade of NO signaling by inhibitors of NOS (L-NAME and AMT) or downstream guanylyl cyclase (ODQ) strongly inhibited stretch-induced apoptosis, mitochondria depolarization, and cytochrome c release, suggesting that NO is required in stretch-induced cardiomyocyte apoptosis. The expression of iNOS, but not eNOS, was blocked by L-NAME and ODQ, indicating that the iNOS induction is NO dependent. The initial elevation of NO is likely due to Ca(2+)-dependent activation of eNOS because elimination of intracellular calcium by EGTA-AM inhibited both iNOS induction and NO elevation. Other calcium signaling inhibitors (nifedipine, ryanodine, thapsigargin, and ionic gadolinium) also attenuated the initial NO elevation. These data indicate that mechanical signals initiate Ca(2+)-dependent NO synthesis, which is further amplified by activation of NO-induced iNOS expression, to regulate cardiomyocyte apoptosis.

Animals↗
PubMed2006

Multiplex sequencing of paired-end ditags (MS-PET): a strategy for the ultra-high-throughput analysis of transcriptomes and genomes.

The paired-end ditagging (PET) technique has been shown to be efficient and accurate for large-scale transcriptome and genome analysis. However, as with other DNA tag-based sequencing strategies, it is constrained by the current efficiency of Sanger technology. A recently developed multiplex sequencing method (454-sequencing) using picolitre-scale reactions has achieved a remarkable advance in efficiency, but suffers from short-read lengths, and a lack of paired-end information. To further enhance the efficiency of PET analysis and at the same time overcome the drawbacks of the new sequencing method, we coupled multiplex sequencing with paired-end ditagging (MS-PET) using modified PET procedures to simultaneously sequence 200,000 to 300,000 dimerized PET (diPET) templates, with an output of nearly half-a-million PET sequences in a single 4 h machine run. We demonstrate the utility and robustness of MS-PET by analyzing the transcriptome of human breast carcinoma cells, and by mapping p53 binding sites in the genome of human colorectal carcinoma cells. This combined sequencing strategy achieved an approximate 100-fold efficiency increase over the current standard for PET analysis, and furthermore enables the short-read-length multiplex sequencing procedure to acquire paired-end information from large DNA fragments.

Binding Sites↗
PubMed2006

Decision forest analysis of large-scale sib-pair identical-by-decent profiles for locating the underlying disease genes for alcoholism in human.

OBJECTIVE: To extract the relevant SNPs for alcoholism using sib-pair IBD profiles of pedigrees. METHODS: We used the ensemble decision approach, a supervised learning approach based on decision forests, to locate alcoholism relevant SNPs using genome-wide SNP data. RESULTS: Application to a publicly available large dataset of 100 simulated replicates for three American populations (http://www.gaworkshop.org/) demonstrates that the proposed approach has successfully located all of the simulated true loci. CONCLUSION: The numerical results establish the proposed decision forest analysis to be a powerful and practical alternative for large-scale family-based association study.

Alcoholism↗
PubMed2006

Novel strategies to identify relevant molecular signatures for complex human diseases based on data of identical-by-decent profiles and genomic context.

OBJECTIVE: To develop novel strategies to identify relevant molecular signatures for complex human diseases based on data of identical-by-decent profiles and genomic context. METHODS: In the proposed strategies, we define four relevancy criteria for mapping SNP-phenotype relationships-point-wise IBD mean difference, averaged IBD difference for window, Z curve and averaged slope for window. RESULTS: Application of these criteria and permutation test to 100 simulated replicates for two hypothetical American populations to extract the relevant SNPs for alcoholism based on sib-pair IBD profiles of pedigrees demonstrates that the proposed strategies have successfully identified most of the simulated true loci. CONCLUSION: The data mining practice implies that IBD statistic and genomic context could be used as the informatics for locating the underlying genes for complex human diseases. Compared with the classical Haseman-Elston sib-pair regression method, the proposed strategies are more efficient for large-scale genomic mining.

Alcoholism↗
PubMed2006

Discovery of Time-Delayed Gene Regulatory Networks based on temporal gene expression profiling.

BACKGROUND: It is one of the ultimate goals for modern biological research to fully elucidate the intricate interplays and the regulations of the molecular determinants that propel and characterize the progression of versatile life phenomena, to name a few, cell cycling, developmental biology, aging, and the progressive and recurrent pathogenesis of complex diseases. The vast amount of large-scale and genome-wide time-resolved data is becoming increasing available, which provides the golden opportunity to unravel the challenging reverse-engineering problem of time-delayed gene regulatory networks. RESULTS: In particular, this methodological paper aims to reconstruct regulatory networks from temporal gene expression data by using delayed correlations between genes, i.e., pairwise overlaps of expression levels shifted in time relative each other. We have thus developed a novel model-free computational toolbox termed TdGRN (Time-delayed Gene Regulatory Network) to address the underlying regulations of genes that can span any unit(s) of time intervals. This bioinformatics toolbox has provided a unified approach to uncovering time trends of gene regulations through decision analysis of the newly designed time-delayed gene expression matrix. We have applied the proposed method to yeast cell cycling and human HeLa cell cycling and have discovered most of the underlying time-delayed regulations that are supported by multiple lines of experimental evidence and that are remarkably consistent with the current knowledge on phase characteristics for the cell cyclings. CONCLUSION: We established a usable and powerful model-free approach to dissecting high-order dynamic trends of gene-gene interactions. We have carefully validated the proposed algorithm by applying it to two publicly available cell cycling datasets. In addition to uncovering the time trends of gene regulations for cell cycling, this unified approach can also be used to study the complex gene regulations related to the development, aging and progressive pathogenesis of a complex disease where potential dependences between different experiment units might occurs.

Algorithms↗
PubMed2006

Unique features of a highly pathogenic Campylobacter jejuni strain.

Campylobacter jejuni, a major human enteric pathogen, exhibits significant strain-to-strain differences which result in differences in pathogenic potential. C. jejuni 81-176 is a highly virulent strain that exhibits unique pathogenic features and is used by many research laboratories. We have determined the nucleotide sequence of its genome and compared it to the genomes of other sequenced C. jejuni strains. We identified a number of unique genetic features which may confer specific metabolic and pathogenic properties on this strain. We have also identified regions of the C. jejuni genome that are hot spots for the integration of horizontally acquired genetic material. This information should help the understanding of the pathogenesis of C. jejuni and, in particular, the unique features of this highly pathogenic strain.

Animals↗
PubMed2006

Filter connected with three-way cock in remove of the vehicle in triamcinolone acetonide.

PURPOSE: To evaluate the clinical effect of 5-microm pore filter connected with three-way cock by removing the vehicle in triamcinolone acetonide(TA) suspension. METHODS: Through 5-microm pore filter connected with three-way cock, TA suspension was replaced by intraocular irrigating solution. The new suspension has been applied to 60 cases of diabetic branch retinal vein occlusion, diabetic macular edema and age-related macular degeneration patients through intravitreal injection. It was also been applied to 41 cases of diabetic retinopathy, epimacular membrane, proliferative vitreoretinopathy and idiopathic macular hole patients to assist pas plana vitrectomy (PPV). Whether TA particles can adhere to posterior hyaloid cortex, epiretinal membrane and internal limiting membrane during the surgery have been observed. During follow up, corrected visual acuity and intraocular pressure were recorded. RESULTS: Five microm pore filter connected with three-way cock can remove the vehicle in TA suspension successfully and retain TA particles. When the new suspension was applied to assist PPV, it can adhere to posterior hyaloid cortex, epiretinal membrane, internal limiting membrane and visualized them clearly. In all the 41 cases that underwent PPV surgery, visual acuity of 30 cases increased or remained stable. Intraocular hypertension happened in 4 cases. Two cases of the 41 patients had cataract formation during follow up. In the 60 cases that underwent TA intravitreal injection, 45 cases increased their visual acuity at least 2 lines. Intraocular hypertension happened in 17 cases and 4 patients had cataract formation. None of the 101 patients caught endophthalmitis or other serious complications. CONCLUSION: Filter connected with three-way cock can remove the vehicle in TA suspension effectively and this procedure can be applied to intravitreal injection or PPV. This manipulation is so simple that it deserves to be popularized for clinical use.

Administration, Topical↗
PubMed2006

[Angiography characters changes of melanoma of choroid: a case report].

PURPOSE: To report the ophthalmologic graphic characters of a case of melanoma of Choroid. METHODS: Retrospectively analysis the characters of fundus fluorescein angiography (FA), indocyanine green angiography (ICGA), B-ultrasonic scan and optical coherence tomography (OCT) of a melanoma of choroid patient whose diagnosis has been made by pathology. RESULTS: FFA of the left eye indicated there were large sheets of obscure fluorescence and scattered hyperfluorescence spots in the early stage. In the late stage we found confluent hyperfluorescence spots strengthened in the focus area and no obvious abnormal vessels or typical "double circulation sign" appeared. ICGA's early stage showed hypofluorescence in the focus area and hyperfluorescence spots of choroid blood capillarys. In the late stages of ICGA, we found sheets of hyperfluorescence upon the focus area and no obvious "barrette-like" or "comb-like" abnormal vessel signs. OCT found all layers of the retina and the choroidcapillary layer hunched to the vitreous cavity. B-ultrasonic scan indicated high-echo mass situated in the posterior pole. CONCLUSION: The melanoma of choroid's FA and ICGA can display different forms, so we should apply to other examinations besides these two angiography examinations and have frequently followed up when we are confronted with atypical melanoma of choroid patients.

Aged↗
PubMed2006

[Recording rod ON and OFF responses in ERG and multifocal ERG].

PURPOSE: To investigate feasibility and recording conditions of recording rod on and off responses in electroretinograms (ERG) and multifocal electroretinograms (mf-ERG), and observe character and influence factors of these responses. METHODS: ERG responses were recorded using the rectangle stimulus, sawtooth rapid-on and rapid-off stimulus in normal subjects after dark adaptation. Flash frequency and flash intensities varied to obtain appropriate recording conditions for clinical use. Mf-ERG responses were recorded in using simulated rectangle stimulus, saw tooth rapid-on and rapid-off stimulus. RESULTS: A large positive wave was found in ERG of rectangle stimulus and rapid-on stimulus. Increasing flash frequency decreased response amplitudes, however, the latency time changed little. A small negative wave with 80 ms latency time was found in ERG of rapid-off stimulus, and a very small positive wave with 75 ms latency time was found in the downhill of the negative wave. Increasing flash frequency increased latency time of the negative wave, but decreased the amplitude of the small positive wave. Oscillatory wave-like waves were found in the responses when flash frequency increased to 3 Hz. A large negative wave following a positive wave was found in mf-ERG of simulated rapid-off stimulus, which was difference from the wave of simulated rectangle stimulus and rapid-on stimulus. CONCLUSIONS: Rod on and off responses of ERG can be recorded with sawtooth rapid-on and rapid-off stimulus. There is a small positive wave in downhill of negative wave in rod off response. Rod on response of mf-ERG can be recorded with simulated rapid-on stimulus. The flash frequency of 0.5-1 Hz and small flash intensity were suggested to appropriate conditions for recording rod on and off responses in ERG. The simulated rapid-on, sawtooth rapid-on and rapid-off stimulus can be used to investigate retinal disease.

Adult↗
PubMed2005

Genome sequencing in microfabricated high-density picolitre reactors.

The proliferation of large-scale DNA-sequencing projects in recent years has driven a search for alternative methods to reduce time and cost. Here we describe a scalable, highly parallel sequencing system with raw throughput significantly greater than that of state-of-the-art capillary electrophoresis instruments. The apparatus uses a novel fibre-optic slide of individual wells and is able to sequence 25 million bases, at 99% or better accuracy, in one four-hour run. To achieve an approximately 100-fold increase in throughput over current Sanger sequencing technology, we have developed an emulsion method for DNA amplification and an instrument for sequencing by synthesis using a pyrosequencing protocol optimized for solid support and picolitre-scale volumes. Here we show the utility, throughput, accuracy and robustness of this system by shotgun sequencing and de novo assembly of the Mycoplasma genitalium genome with 96% coverage at 99.96% accuracy in one run of the machine.

Electrophoresis, Capillary↗
PubMed2005

Phylogenetic relationships of sheep populations from coastal areas in East Asia.

Using the method of random sampling in typical colonies of the central area of the habitat and several electrophoresis techniques, the variations of 12 structural loci encoding blood protein of 60 Small-tailed Han sheep were examined and compared with those of four other sheep populations from coastal areas in East Asia to explore their phylogenetic relationships. Average heterozygosity of the five populations was: Kharkhorin sheep 0.3447, Ulaanbaatar sheep 0.3285, Small-tailed Han sheep 0.3157, Hu sheep 0.3884, and Cham Tribe sheep 0.2300. The earlier researchers' conclusion through documentary research, indicating that Small-tailed Han sheep and Hu sheep both evolved from Mongolian sheep, was further verified by the results of this study. Hu sheep, Small-tailed Han sheep, and Cham Tribe sheep were decreasingly affected by the bloodline of Mongolian sheep. A 1partial founder population, i.e., Mongolian sheep forming current Small-tailed Han sheep, possibly made a contribution to the bloodline of Cham Tribe sheep.

Animals↗
PubMed2005

A robust hybrid between genetic algorithm and support vector machine for extracting an optimal feature gene subset.

Development of a robust and efficient approach for extracting useful information from microarray data continues to be a significant and challenging task. Microarray data are characterized by a high dimension, high signal-to-noise ratio, and high correlations between genes, but with a relatively small sample size. Current methods for dimensional reduction can further be improved for the scenario of the presence of a single (or a few) high influential gene(s) in which its effect in the feature subset would prohibit inclusion of other important genes. We have formalized a robust gene selection approach based on a hybrid between genetic algorithm and support vector machine. The major goal of this hybridization was to exploit fully their respective merits (e.g., robustness to the size of solution space and capability of handling a very large dimension of feature genes) for identification of key feature genes (or molecular signatures) for a complex biological phenotype. We have applied the approach to the microarray data of diffuse large B cell lymphoma to demonstrate its behaviors and properties for mining the high-dimension data of genome-wide gene expression profiles. The resulting classifier(s) (the optimal gene subset(s)) has achieved the highest accuracy (99%) for prediction of independent microarray samples in comparisons with marginal filters and a hybrid between genetic algorithm and K nearest neighbors.

Algorithms↗
PubMed2005

[The influence of leukocyte depletion filter-LD-1 on leukocytes, IL-6, MPO and the pathologic changes of myocardic tissues during cardiopulmonary bypass].

OBJECTIVE: To elucidate the influence of the leukocyte depletion filter (LD-1) on leukocytes, IL-6, myeloperoxidase enzyme (MPO) and the pathological changes of myocardic tissues during cardiopulmonary bypass(CPB). METHODS: Twelve dogs were used in this study. The LD-1, designed and made by ourselves, was fixed on the venous line in the trial group (n=6). It was used during the first 5 min after 2 min of CPB. LD-1 was not installed in the control group (n=6). Circulating leukocytes were counted before CPB, at 10 min, 40 min, 75 min during CPB, at the end of CPB, and 2 h after CPB. Plasma levels of IL-6 and MPO were also determined at the same time. The pathologic changes of left ventricular biopsies were observed before CPB, 5 min after protamine was given, and 2 h after CPB. RESULTS: The CPB 10 min WBC Count fell to 36% of that Before CPB in LD-1 group, which was lower than the WBC count in the control group synchronously (P < 0.01). But after CPB 2 h, both of them were close to the levels Before CPB in the two groups. In LD-1 group, IL-6 increased at CPB 40 min and reached to the top. But after wards it dropped continuously. The changes were of no significance in MPO and in the pathological examination of myocardic tissues (P > 0.05). CONCLUSION: The LD-1 on venous line was capable of decreasing WBC count effectively. As a result, the inflammation factors that leukocytes released were lower, so the program chain of inflammation by CPB was shorter. But LD-1 was not superior in myocardial preservation.

Animals↗
PubMed2005

[Effects of leukocyte depletion filter on canine kidney during cardiopulmonary bypass].

OBJECTIVE: To explore the effect of a reforming leukocyte depletion filter (LDF-1) on the functional and pathologic changes of canine kidney during cardiopulmonary bypass (CPB). METHODS: Twelve Mongolian dogs were randomly allocated into a control group (no LDF-1, n = 6) or a leukocyte-depleted filter group (LDF-1 placed in venous line, n = 6). CPB of the dogs anestheitized with sodium pentobarbitone at 25 mg/kg was set up. After 10 min of CPB, aorta was clamped and St. Thomas cardioplegic solution at 20 mg/kg was immediately injected into the root of aorta. The aortic cross-clamp was released and CPB was closed at 70 min. Dogs were observed for 2 h after weaning from CPB. LDF-1 was opened at 2 min and stoped at 7 min during initially running CPB in the LDF-1 group. Circulating leukocytes, plasma L-selectin, and plasma IL-8 were respectively counted before CPB, at 10 minutes, 40 min, and 75 min during CPB, the end of CPB, and 2 h after CPB. The urine analysis and renal pathology, which were obtained before CPB and 2 h after CPB, were observed. RESULTS: The number of leukocytes significantly decreased by 55% - 68% in the LDF-1 group compared with the baseline during CPB. The value at 10 min of CPB in the LDF-1 group was lower than that in the control group (P < 0.05). Plasma levels of L-selectin and IL-8 obviously increased in the 2 groups compared with the baseline during CPB, but both levels at 2 h after CPB in the LDF-1 group were lower than those in the control group (P <0. 05). No statistic difference was found in plasma levels of urea and creatinine, but hematuria was observed in the 2 groups at 2 hours after CPB. The pathologic changes of kidney, which was mainly renal tubule swelling accompanied partly with vacuolar degeneration, were similar under the light microscope in the 2 groups at 2 h after CPB. Obvious glomerular damage was not found. CONCLUSION: LDF-1 can effectively decrease leukocyte counts and the inflammatory reaction, but it can not bring about excellent protective effect on kidney during CPB when used alone. Attention to should be paid the renal protection in the postoperative CPB.

Acute Kidney Injury↗
PubMed2005

[The pulmonary protective effects of leukocyte depletion with a modified filter located at the cardiopulmonary bypass (CPB) venous line in canine].

OBJECTIVE: To investigate the pulmonary protective effects of short-term leukocyte depletion with a modified filter located at the CPB venous line in canine. METHODS: Sixteen healthy hybrid canines were randomly allocated to the LD-1 group, with an LD-1 filter installed in the CPB venous-line for a 5-minute leukocyte depletion at the beginning of the CPB, and to the control group. Blood samples were taken for routine test respectively at 9 time-points, namely pre-CPB, at 5, 10, 40, 70 min of the CPB, 5 min after aortic cross-clamp being off, at the discontinuation of the CPB, 5 min after protamine being administered, and 2 h after the CPB. Oxygen index (OI), pulmonary pathology and levels of interleukin-6 (IL-6) and interleukin-8 (IL-8) in plasma were measured at pre-CPB, 5 min after protamine being administered and 2 h after the CPB respectively. The levels of IL-6 and IL-8 in the bronchial alveolar lavage fluid (BALF) were measured at 2 h after the CPB. RESULTS; In LD-1 group, white blood cell (WBC) counts were significantly less than those in control group at 5 min of the CPB (P < 0.05), the filtration rate of WBC was (65.72 +/- 9.36)%. The WBC counts showed no significant difference in either group from 40 min of the CPB to 2 h after the CPB. OI was higher in LD-1 group than that in control group (P < 0.05) at 5 min after protamine being administered and 2 h after the CPB. There was significantly less WBC infiltration and alveolar edema of the lung in LD-1 group than that in control group at 5 min after protamine being administered and 2 h after the CPB. There were no significant differences of IL-6 and IL-8 in plasma between the two groups at 5 min after protamine being administered (P > 0.05), but the levels of IL-6 and IL-8 were much lower in the LD-1 group than those in the control group at 2 h after CPB. At 2 h after the CPB, IL-6 level in the BALF showed no significant difference in each group (P > 0.05); however, the level of IL-8 was lower in LD-1 group than that in control group (P < 0.05). CONCLUSION: The LD-1 filter in the CPB venous-line in canine model used for short-term leukocyte depletion filtration could reduce WBC counts significantly, decrease the levels of IL-6 and IL-8 in plasma, attenuate inflammatory response in the lung after CPB, so it has protective effect on canine lung.

Animals↗