Biomedical subjects

Yongli Zhang

Publications and source records attributed to Yongli Zhang.

11 recordsLinked to original sources

PubMed2006

Analysis of in-vivo LacR-mediated gene repression based on the mechanics of DNA looping.

Interactions of E. coli lac repressor (LacR) with a pair of operator sites on the same DNA molecule can lead to the formation of looped nucleoprotein complexes both in vitro and in vivo. As a major paradigm for loop-mediated gene regulation, parameters such as operator affinity and spacing, repressor concentration, and DNA bending induced by specific or non-specific DNA-binding proteins (e.g., HU), have been examined extensively. However, a complete and rigorous model that integrates all of these aspects in a systematic and quantitative treatment of experimental data has not been available. Applying our recent statistical-mechanical theory for DNA looping, we calculated repression as a function of operator spacing (58-156 bp) from first principles and obtained excellent agreement with independent sets of in-vivo data. The results suggest that a linear extended, as opposed to a closed v-shaped, LacR conformation is the dominant form of the tetramer in vivo. Moreover, loop-mediated repression in wild-type E. coli strains is facilitated by decreased DNA rigidity and high levels of flexibility in the LacR tetramer. In contrast, repression data for strains lacking HU gave a near-normal value of the DNA persistence length. These findings underscore the importance of both protein conformation and elasticity in the formation of small DNA loops widely observed in vivo, and demonstrate the utility of quantitatively analyzing gene regulation based on the mechanics of nucleoprotein complexes.

Base Sequence↗

PubMed2006

DNA translocation and loop formation mechanism of chromatin remodeling by SWI/SNF and RSC.

ATP-dependent chromatin-remodeling complexes (remodelers) modulate gene transcription by regulating the accessibility of highly packaged genomic DNA. However, the molecular mechanisms involved at the nucleosomal level in this process remain controversial. Here, we monitor the real-time activity of single ySWI/SNF or RSC complexes on single, stretched nucleosomal templates under tensions above 1 pN forces. We find that these remodelers can translocate along DNA at rates of approximately 13 bp/s and generate forces up to approximately 12 pN, producing DNA loops of a broad range of sizes (20-1200 bp, average approximately 100 bp) in a nucleosome-dependent manner. This nucleosome-specific activity differs significantly from that on bare DNA observed under low tensions and suggests a nucleosome-remodeling mechanism through intranucleosomal DNA loop formation. Such loop formation may provide a molecular basis for the biological functions of remodelers.

Adenosine Triphosphate↗

PubMed2006

Effect of force on mononucleosomal dynamics.

Using single-molecule optical-trapping techniques, we examined the force-induced dynamic behavior of a single nucleosome core particle. Our experiments using the DNA construct containing the 601 nucleosome-positioning sequence revealed that the nucleosome unravels in at least two major stages. The first stage, which we attributed to the unraveling of the first DNA wrap around the histone octamer, could be mechanically induced in a reversible manner, and when kept at constant force within a critical force range, exhibited two-state hopping behavior. From the hopping data, we determined the force-dependent equilibrium constant and rates for opening/closing of the outer wrap. Our investigation of the second unraveling event at various loading rates, which we attributed to the inner DNA wrap, revealed that this unraveling event cannot be described as a simple two-state process. We also looked at the behavior of the mononucleosome in a high-salt buffer, which revealed that the outer DNA wrap is more sensitive to changes in the ionic environment than the inner DNA wrap. These findings are needed to understand the energetics of nucleosome remodeling.

Chemical Phenomena↗

PubMed2006

[Effects of nitrogen and phosphorus application rate on population growth and grain yield of hybrid wheat C6-38/ Py85-1].

This paper studied the effects of different nitrogen and phosphorous application rates (112.5-337.5 kg N x hm(-2) and 90-270 kg P2O5 x hm(-2)) on the population growth and grain yield of hybrid wheat C6-38/Py85-1 under field condition. The results showed that the total number of population stems (PS), population dry weight (PDW), leaf area index (LAI) , photosynthetic potential (PP) and crop growth rate (CGR) were the lowest under low fertilization rate (112.5 kg N x hm(-2) and 90 kg P2O5 x hm(-2)), PS and PDW were higher under high fertilization rate (337.5 kg N x hm(-2) and 270 kg P2O5, hm(-2)) than under medium fertilization rate (225 kg N hm(-2) and 180 kg P2O5 x hm(-2)), and LAI, PP and CGR were higher under high than under medium fertilization rate before flagging, jointing, and anthesis stage, respectively, but in adverse after these stages. Under low and medium fertilization rates, PS had no mid-parent heterosis (Hm), while under high fertilization rate, it had the positive values of 6.3%, 49.7%, 4.2% and 10.8% at before winter, jointing, anthesis, and maturing stages, respectively. The Hm of LAI and PDW increased significantly with increasing fertilization rate, except that the Hm of LAI was 3.8% higher under medium than under high fertilization rate at filling stage while that of PDW had no significant difference between these two fertilization rates at maturing stage. The Hm values of PP and CGR were the lowest in the whole growth period under low fertilization rate, and lower before jointing-flagging and flagginganthesis stage but higher after these stages respectively under medium than under high fertilization rate. The grain yield and its Hm of the hybrid wheat were the highest under medium fertilization rate, lower under high fertilization rate, and the lowest under low fertilization rate. The grain yield under medium fertilization rate was 216.2 kg x hm(-2) higher than that under high fertilization rate, but its Hm had no significant difference between these two fertilization rates.

Biomass↗

PubMed2005

Statistical-mechanical theory of DNA looping.

The lack of a rigorous analytical theory for DNA looping has caused many DNA-loop-mediated phenomena to be interpreted using theories describing the related process of DNA cyclization. However, distinctions in the mechanics of DNA looping versus cyclization can have profound quantitative effects on the thermodynamics of loop closure. We have extended a statistical mechanical theory recently developed for DNA cyclization to model DNA looping, taking into account protein flexibility. Notwithstanding the underlying theoretical similarity, we find that the topological constraint of loop closure leads to the coexistence of multiple classes of loops mediated by the same protein structure. These loop topologies are characterized by dramatic differences in twist and writhe; because of the strong coupling of twist and writhe within a loop, DNA looping can exhibit a complex overall helical dependence in terms of amplitude, phase, and deviations from uniform helical periodicity. Moreover, the DNA-length dependence of optimal looping efficiency depends on protein elasticity, protein geometry, and the presence of intrinsic DNA bends. We derive a rigorous theory of loop formation that connects global mechanical and geometric properties of both DNA and protein and demonstrates the importance of protein flexibility in loop-mediated protein-DNA interactions.

Binding Sites↗

PubMed2004

Predicting indirect readout effects in protein-DNA interactions.

Recognition of DNA by proteins relies on direct interactions with specific DNA-functional groups, along with indirect effects that reflect variable energetics in the response of DNA sequences to twisting and bending distortions induced by proteins. Predicting indirect readout requires knowledge of the variations in DNA curvature and flexibility in the affected region, which we have determined for a series of DNA-binding sites for the E2 regulatory protein by using the cyclization kinetics method. We examined 16 sites containing different noncontacted spacer sequences, which vary by more than three orders of magnitude in binding affinity. For 15 of these sites, the variation in affinity was predicted within a factor of 3, by using experimental curvature and flexibility values and a statistical mechanical theory. The sole exception was traced to differential magnesium ion binding.

Base Sequence↗

PubMed2003

High-throughput approach for detection of DNA bending and flexibility based on cyclization.

We have developed a high-throughput approach to the labor-intensive problems of DNA cyclization, which we use to characterize DNA curvature and mechanical properties. The method includes a combinatorial approach to make the DNA constructs needed and automated real-time measurement of the kinetics using fluorescence. We validated the approach and investigated the flexibility of two kinds of nicked DNA and AT dinucleotide repeats. We found that, although the nicks hardly alter the bending flexibility, they significantly increase the torsional flexibility, and that the AT repeat has 28% (+/-12%) lower bending rigidity than a generic DNA sequence.

Base Sequence↗

PubMed2003

Statistical mechanics of sequence-dependent circular DNA and its application for DNA cyclization.

DNA cyclization is potentially the most powerful approach for systematic quantitation of sequence-dependent DNA bending and flexibility. We extend the statistical mechanics of the homogeneous DNA circle to a model that considers discrete basepairs, thus allowing for inhomogeneity, and apply the model to analysis of DNA cyclization. The theory starts from an iterative search for the minimum energy configuration of circular DNA. Thermodynamic quantities such as the J factor, which is essentially the ratio of the partition functions of circular and linear forms, are evaluated by integrating the thermal fluctuations around the configuration under harmonic approximation. Accurate analytic expressions are obtained for equilibrium configurations of homogeneous circular DNA with and without bending anisotropy. J factors for both homogeneous and inhomogeneous DNA are evaluated. Effects of curvature, helical repeat, and bending and torsional flexibility in DNA cyclization are analyzed in detail, revealing that DNA cyclization can detect as little as one degree of curvature and a few percent change in flexibility. J factors calculated by our new approach are well consistent with Monte Carlo simulations, whereas the new theory has much greater efficiency in computations. Simulation of experimental results has been demonstrated.

Algorithms↗

PubMed2003

Surgical experience of 179 cases with craniopharyngiomas.

OBJECTIVE: To retrospectively review 179 cases surgical treatments of craniopharyngiomas over a 7-year period, surgical experience as following. METHODS: Dependent on the locations of the tumors to the floor of the third ventricle, they were classified into the superior type of the third ventricle floor in which tumors grew on the superior part of the third ventricle floor, and the inferior type of the third ventricle floor in which tumors grew from the pituitary stalk, infundibulum, tuber cinereum upwards the floor of the third ventricle developing the obstruction of the third ventricle or downward to the intral sella through the foramen of sellar septum. As the tumor of the inferior type, the pterional approaches were performed in 150 patients and the subfrontal approach in 16 patients. As the superior type, transcallosum into the anterior third ventricle part were undergone in 13 cases. Great care was made to preservie the perforating arteries to the neural structures of the third ventricular floor for the tumor of the inferior type. Avoidance of injury was required to the neural structures of the third ventricular floor when used by the transcallosum approach to the anterior part of the third ventricular floor for the tumor of the superior floor. RESULTS: Total, subtotal and partial removal of the tumor was achieved in 161, 12 and 6 patients, respectively. Four (2.2%) deaths occurred at early postoperative stage. All patients were followed-up from 3 months to 5 years (mean, 1.5 years), with 154 (88%) patients regained normal life, 14 (8%) had their self-life and the 7 (4%) need assist life. Seven (3.9%) patients experienced their tumor recurrence on MR imaging by following-up. Of them, 4 patients were followed up their tumor recurrence within half-year and 3 patients within one year. Five patients with recurrent tumor were reoperated on and the other 2 patients were undergone the external radiation of the tumor and gamma-knife of the tumor respectively. CONCLUSION: Craniopharyngiomas can be treated surgically with a good result. It is the key to avoid injury of the hypothalamic structures and preserve the perforating arteries to hypothalamus to achieve good surgical results, while attempt was made to completely remove the tumor.

Craniopharyngioma↗

PubMed2002

[Induction of human cervical carcinoma by human papilloma virus and tumor promoters].

OBJECTIVE: To study the effect of human papillomavirus (HPV) and tumour promoters spermidine (SPD and N-butyrate) on malignant transformation of human embryo cervical cells. METHODS: Plasmid HPV16E6/E7 was constructed and transfected into human embryo cervical cells obtained by induced labor from pregnant women with severe heart diseases. Twenty-one scid mice were divided into 4 groups: experimental group (n = 7, incubated subcutaneously with the transfected cervical cells at the right shoulder, and then injected subcutaneously with spermidine and N-butyrate at the left shoulder three days after the incubation once a week for 12 times), virus-infected group B (n = 5, incubated subcutaneously with transfected cervical cell only), tumor promoter group (n = 5, incubated with untransfected cervical cells and SPD and N-butyrate), and control group (n = 4, incubated subcutaneously with only untransfected cervical cells). Twelve weeks after incubation, the mice were killed. Pathological reexamination was conducted to detect the existence of tumor. PCR was used to detect HPV16E6/E7 gene in tumor tissues. RESULT: Tumor, diagnosed as fibrosarcoma by pathology, was found in 5 out of the 7 mice in the experimental group. The tumor-forming rate was 0 in other groups. Expression of HPV16E6/E7 gene was detected in tumour tissues by PCR. CONCLUSION: HPV16E6/E7 gene containing retrovirus infection, synergized by spermidine and N-butyrate acid, causes malignant transformation in human cervical cells.

Animals↗

PubMed2002

A new haplogroup pattern displayed in Fujian Han in China.

Human Y-chromosomal binary polymorphisms have been considered to preserve the paternal genetic legacy and provide evidence on human evolution and the genetic relationships among and demographic history of different populations. To reveal the genetic origin and immigration of the Fujian Han, 13 binary markers on the Y chromosome were used to screen Fujian Han by allele-specific polymerase chain reaction. The results indicated that the M9G marker was highly prevalent (96.20%), suggesting a significant genetic drift. In addition, M122C frequency was only 22.78%, and M45A and M103T were default. The distinctive haplogroup frequencies (H1, H5, and H6/7/8) imply that the haplogroup pattern is a relatively ancestral and interim type.

Asian People↗