[Triple staining of immunohistochemistry].
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Adenocarcinoma↗
Biomedical subjects
Min Lin
Publications and source records attributed to Min Lin.
Mechanistic mapping of ontogenetic growth based on biological principles.
Ontogenetic growth can be described by mathematical equations constructed on the goodness of fit. Recently, the biological mechanism underlying mathematical growth equations has been explored using basic cellular properties. Here, we derive a general statistical model for understanding the genetic regulation of ontogenetic growth by integrating those biologically-proven meaningful growth equations into a quantitative trait locus (QTL) mapping framework. We can characterize the dynamic patterns of effects of QTL governing growth curves and estimate the global effect of the underlying QTL throughout the entire course of growth. The model provides the basis for deciphering genetic relationships for growth rates and the timing of life history events for any kind of organisms.
Animals↗
[A monitoring technique in detecting the depth of anesthesia by bispectral index].
At the present time, a kind of monitoring technology assuring highly effectual anesthesia is urgently required in the clinical practice. Electroencephalogram (EEG) assumes a dominant position in the current research of the depth detection of anesthesia. In this paper, the monitoring technique of the depth detection of anesthesia by bispectral index (BIS) is systematically showed. The bispectral index is a compound parameter which is composed of time domain, frequency domain, and high order spectral subparameters of the electroencephalograph. This nonlinear compound calculation method is worth research and is of great significance to the development of a new monitor of closed-loop control of anesthesia.
Anesthesia↗
[Analysis for the near infrared spectrum characteristic of tea based on orthogonal wavelet packet].
According to the high co-linearity and dimension in the near infrared (NIR) spectrum of tea, the present paper describes quantitatively the characteristic of tea NIR spectra with wavelet packet by introducing the retained energy and number of zeros, based on the decorrelation capacity of orthogonal wavelet packet. Results show that the energy retained is as high as 99.98% after compressing, while the percentage for number of zeros is 95.87%. It was concluded that orthogonal wavelet packet has a good compressibility for NIR spectra, which has significance in storing, searching and processing the NIR spectrogram.
English Abstract↗
Structure of the murine constitutive androstane receptor complexed to androstenol: a molecular basis for inverse agonism.
The nuclear receptor CAR is a xenobiotic responsive transcription factor that plays a central role in the clearance of drugs and bilirubin while promoting cocaine and acetaminophen toxicity. In addition, CAR has established a "reverse" paradigm of nuclear receptor action where the receptor is active in the absence of ligand and inactive when bound to inverse agonists. We now report the crystal structure of murine CAR bound to the inverse agonist androstenol. Androstenol binds within the ligand binding pocket, but unlike many nuclear receptor ligands, it makes no contacts with helix H12/AF2. The transition from constitutive to basal activity (androstenol bound) appears to be associated with a ligand-induced kink between helices H10 and H11. This disrupts the previously predicted salt bridge that locks H12 in the transcriptionally active conformation. This mechanism of inverse agonism is distinct from traditional nuclear receptor antagonists thereby offering a new approach to receptor modulation.
Androstenols↗
[Dynamic change of apoptosis of alveolar cells in ischemia-reperfusion induced pulmonary injury: an experimental study with rats].
OBJECTIVE: To observe the dynamic changes of alveolar apoptosis in ischemia-reperfusion (IR) induced pulmonary injury, and to evaluate the roles of these two cell death styles, apoptosis and necrosis, in the progress of lung function deterioration in pulmonary IR injury. METHODS: Fifty-four Sprague-Dawley rats were made ischemia/reperfusion models by ischemia and reperfusion in situ in single lung. Thirty-six of the 54 rats in the experimental group were re-divided into 6 equal subgroups to undergo detection of partial pressure of oxygen (PaO2) of blood in left atrium, detection of lung tissue wet weight/dry weight ratio, histology of lung by light microscope, examination of ultrastructural changes of cells by transmission electron microscopy, and quantitative detection of apoptotic cells in the right middle lobe by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) 0 h, 0.5 h, 1 h, 2 h, 6 h, and 12 h respectively after the reperfusion (subgroups R0, R(0.5), R1, R2, R6, and R12). Another 18 rats in the experimental group were re-divided into 3 subgroups of 6 rats to undergo insertion of venous catheter into the main pulmonary artery via right ventricle to perfuse trypan blue so as to evaluate the cell death degree. The death index was observed under light microscope and the necrosis index was indirectly calculated by the equation: death index = apoptotic index + necrosis index. Thirty-six rats underwent sham operation. Twelve rats were used as preoperative blank controls. RESULTS: Proliferation of alveolar type II, but not alveolar type I cell, accompanied by ultrastructural morphological changes were seen 1 h, 2 h, and 6 h after reperfusion, the most prominently 2 h after reperfusion. Apoptotic index was elevated since 1 h after reperfusion, and peaked 2 h after reperfusion. Statistical analysis indicated that, compared with apoptotic index, the necrotic index was of more prominent correlation with blood oxygen partial pressure and wet/dry weight ratio. CONCLUSION: Alveolar apoptosis occurs in the early stage of reperfusion, and becomes the most prominent 2 h after reperfusion. Most apoptotic cells are alveolar type II cells. In the two styles of cell death in pulmonary IR injury, alveolar necrosis is more prominently correlated with progress of lung function deterioration.
Animals↗
Differential expression of glucose-regulated protein 78 during spermatogenesis.
The aim of the present study was to isolate and identify proteins involved in the process of spermatogenesis. To achieve this goal we used the technique of proteomic analysis. Comparison of testis protein patterns obtained by high-resolution two-dimensional gel electrophoresis from 1-week- and 7-week-old mice showed significant differences in protein spot intensities. Subsequently several of these variant protein spots were identified by mass spectrometry. Glucose-regulated protein (GRP) 78 (Bip) was one of them. GRP78, expressed at a lower level in 1-week-old mouse testes compared to 7-week-old mouse testes, is a member of the heat shock 70 protein family. It has recently been shown to be important for protecting cells from apoptosis in somatic cells, especially in progressively growing tumor cells. Further, immunohistochemical (IHC) analyses of mouse and human testes sections were performed to determine the cellular distribution of this protein. A strong GRP78 staining was seen beginning with pachytene spermatocytes. These findings suggested that GRP78 might perform an important function in the process of spermatogenesis.
Age Factors↗
Nanoprobe implantation into mammalian cells by cationic transfection.
Submicron-sized Au particles and Au/SiO(2) nanocomposites (superparticles) as large as 670 nm have been introduced into tsA201 cells with minimal cell trauma by cationic transfection systems. Successful implantations can be characterized by the expression of co-transfected DNA.
Animals↗
Identification of a second flagellin gene and functional characterization of a sigma70-like promoter upstream of a Leptospira borgpetersenii flaB gene.
Leptospira borgpetersenii, one of the causative agents of leptospirosis in both animals and humans, is a bacterial pathogen with characteristic motility that is mediated by the rotation of two periplasmic flagella (PF). The flaB gene coding for a core polypeptide subunit of PF was previously characterized by sequence analysis of its open reading frame (ORF) (M. Lin, J Biochem Mol Biol Biophys 2:181-187, 1999). The present study was undertaken to isolate and clone the uncharacterized sequence upstream of the flaB gene by using a PCR-based genome walking procedure. This has resulted in a 1470-bp genomic DNA sequence in which an 846-bp ORF coding for a 281-amino acid polypeptide (31.3 kDa) is identified 455 bp upstream from the flaB start codon. The encoded protein exhibits 72% amino acid identity to the deduced FlaB protein sequence of L. borgpetersenii and a high degree of sequence homology to the FlaB proteins of other spirochaetes. This has demonstrated for the first time that a second flaB gene homolog is present in a Leptospira species. The newly identified gene is designated flaB1, and the previously cloned flaB renamed flaB2. Within the intergenic sequence between flaB1 and flaB2, a potential stem-loop structure (12-bp inverted repeats) was identified 25 bp downstream of the flaB1 stop codon; this could serve as a transcription terminator for the flaB1 mRNA. Three E. coli-like promoter regions (I, II, and III) for binding Esigma(70), a regulatory sequence uncommonly found in flagellar genes, were predicted upstream of the flaB2 ORF. Only promoter region II contains a promoter that is functional in E. coli, as revealed at phenotypic and transcriptional levels by its capability of directing the expression of the chloramphenicol acetyltransferase (CAT) gene in the promoter probe vector pKK232-8. These observations may suggest that flaB1 and flaB2 are transcribed separately and do not form a transcriptional operon controlled by a single promoter.
Bacterial Proteins↗
Cerebellar activation of cortical motor regions: comparisons across mammals.
This chapter discusses the nature of mammalian cerebello-thalamo-cortical projections. These play an important role in motor control, but with species differences evident in the innervation patterns of thalamo-cortical (T-C) fibers relaying cerebellar inputs. A phylogenetic comparison of the mode of cerebellar activation of cortical motor regions reveals that cerebellar inputs are relayed by the deep and superficial T-C projections in the cat, but predominately by the latter in rat and monkey. Another difference across mammals is the nature of cerebellar activation of cortical neurons. Fast-conducting pyramidal tract neurons in the cat routinely receive fast-rising EPSPs from the deep cerebellar nuclei (CN). This tendency is not observed in rat and monkey, however. These findings suggest that the responsiveness of cortical output neurons also shows species differences, these having bearing on the development of species-specific motor skills. Common to all three species, however, are fast-rising and large CN-EPSP responses of layer III pyramidal neurons to CN input. It is argued that layer III pyramidal neurons modulate cerebellar input to layer V pyramidal neurons, which latter cells provide command signals from the motor cortex to the lower centers.
Animals↗
Rho-regulatory proteins in breast cancer cell motility and invasion.
The importance of the Rho-GTPases in cancer progression, particularly in the area of metastasis, is becoming increasingly evident. This review will provide an overview of the role of the Rho-regulatory proteins in breast cancer metastatis.
Breast Neoplasms↗
Identification and characteristics of a novel E1 like gene nUBE1L in human testis.
A gene, presumably involved in spermatogenesis, was identified and characterized by using cDNA microarray. Hybridization intensity was 2.13 fold higher in adult testis than that in fetal testis. The full length of this gene was 4288 bp and it encoded a 578 amino acid protein. Conserved structure and amino acid sequence analysis revealed that the protein contained 1 Thif-domain, 2 UBACT-domains, and a functional active site cysteine lay upstream of UBACT domain, all of them also existed in ubiquitin-activating enzyme E1 and E1 like proteins. So we named this gene as a novel ubiquitin-activating enzyme E1 like gene (nUBE1L). Expression profile showed that nUBE1L was predominantly expressed in testis. Comparison of the expression of nUBE1L in different developmental stages of testis indicated that it was highly expressed in adult testis. In conclusion, nUBE1L is a novel human E1 like gene highly expressed in adult testis, which plays key role in ubiquitin system, and accordingly influences spermatogenesis and male fertility.
Adult↗
Identification of antigenic regions of the Erns protein for pig antibodies elicited during classical swine fever virus infection.
The structural glycoprotein E(rns) of classical swine fever virus (CSFV) is one of the major antibody targets upon infection of pigs with the virus. Molecular dissection of the structure of E(rns) would define the minimal immunodominant regions that induce antibody responses after infection and may thus help design an effective diagnostic reagent or vaccine. In this study, deletion analysis was made within amino acids (aa) 297 to 776 of the CSFV Alfort/187 polyprotein containing the large C-terminal portion of the E(rns) protein (aa 27 to 227), the entire E1 protein (aa 1 to 195), and the N-terminal portion of the E2 protein (aa 1 to 87). Various protein fragments with target deletions from N- or/and C-terminal ends were constructed with pET30, expressed in Escherichia coli and probed on Western blots with antisera from pigs infected with CSFV. This has resulted in the identification within E(rns) of three overlapping antigenic regions: AR1(E(rns)aa 65-145), AR2 (E(rns)aa 84-160) and AR3 (E(rns)aa 109-220). N- or C-terminal deletions as small as 3 residues introduced into these regions disrupt their reactivity with antibodies, indicating that they are the minimum requirements for recognition by pig antibodies. The three minimal antigenic regions correlated well with the hydropathy profiles and the 3D structural model of E(rns). Each individual region and a protein fragment containing AR1, AR2 and AR3 reacted equally well with pig anti-CSFV sera. Since variable and conserved sequences are present within the three overlapping antigenic regions of E(rns) of different pestiviruses, specific serological detection of CSFV infection or broad detection of pestivirus infections may be achieved with the use of a single E(rns) region or a combination of two or three E(rns) regions.
Amino Acid Sequence↗
Functional mapping of quantitative trait loci underlying growth trajectories using a transform-both-sides logistic model.
The incorporation of developmental control mechanisms of growth has proven to be a powerful tool in mapping quantitative trait loci (QTL) underlying growth trajectories. A theoretical framework for implementing a QTL mapping strategy with growth laws has been established. This framework can be generalized to an arbitrary number of time points, where growth is measured, and becomes computationally more tractable, when the assumption of variance stationarity is made. In practice, however, this assumption is likely to be violated for age-specific growth traits due to a scale effect. In this article, we present a new statistical model for mapping growth QTL, which also addresses the problem of variance stationarity, by using a transform-both-sides (TBS) model advocated by Carroll and Ruppert (1984, Journal of the American Statistical Association 79, 321-328). The TBS-based model for mapping growth QTL cannot only maintain the original biological properties of a growth model, but also can increase the accuracy and precision of parameter estimation and the power to detect a QTL responsible for growth differentiation. Using the TBS-based model, we successfully map a QTL governing growth trajectories to a linkage group in an example of forest trees. The statistical and biological properties of the estimates of this growth QTL position and effect are investigated using Monte Carlo simulation studies. The implications of our model for understanding the genetic architecture of growth are discussed.
Biometry↗
A general framework for analyzing the genetic architecture of developmental characteristics.
The genetic architecture of growth traits plays a central role in shaping the growth, development, and evolution of organisms. While a limited number of models have been devised to estimate genetic effects on complex phenotypes, no model has been available to examine how gene actions and interactions alter the ontogenetic development of an organism and transform the altered ontogeny into descendants. In this article, we present a novel statistical model for mapping quantitative trait loci (QTL) determining the developmental process of complex traits. Our model is constructed within the traditional maximum-likelihood framework implemented with the EM algorithm. We employ biologically meaningful growth curve equations to model time-specific expected genetic values and the AR(1) model to structure the residual variance-covariance matrix among different time points. Because of a reduced number of parameters being estimated and the incorporation of biological principles, the new model displays increased statistical power to detect QTL exerting an effect on the shape of ontogenetic growth and development. The model allows for the tests of a number of biological hypotheses regarding the role of epistasis in determining biological growth, form, and shape and for the resolution of developmental problems at the interface with evolution. Using our newly developed model, we have successfully detected significant additive x additive epistatic effects on stem height growth trajectories in a forest tree.
Algorithms↗
The molecular characteristics of polycystic ovary syndrome (PCOS) ovary defined by human ovary cDNA microarray.
Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders; it is characterized by polycystic ovaries, hyperandrogenism and chronic anovulation. To obtain a global view of those genes that might be involved in the development of this complex clinical disorder, we used recently developed cDNA microarray technology to compare differential gene expressions between normal human ovary and ovaries from PCOS patients. A total of 9216 clones randomly selected from a commercial human ovary cDNA library were screened. Among them, 290 clones showed differential expressions, including 119 known genes and 100 known or unknown expressed sequence tags (ESTs). Among 119 known genes, 88 were upregulated and 31 downregulated in the PCOS ovary, as compared with normal human ovary. These differentially expressed genes are involved in various biologic functions, such as cell division/apoptosis, regulation of gene expression and metabolism, reflecting the complexity of clinical manifestations of PCOS. The molecular characteristics established from our study will further our understanding of the pathogenesis of PCOS and help us to identify new targets for further studies and for the development of new therapeutic interventions.
Base Sequence↗
Vitamin K2 regulation of bone homeostasis is mediated by the steroid and xenobiotic receptor SXR.
Vitamin K2 is a critical nutrient required for blood clotting that also plays an important role in bone formation. Vitamin K2 supplementation up-regulates the expression of bone markers, increases bone density in vivo, and is used clinically in the management of osteoporosis. The mechanism of vitamin K2 action in bone formation was thought to involve its normal role as an essential cofactor for gamma-carboxylation of bone matrix proteins. However, there is evidence that suggests vitamin K2 also has a transcriptional regulatory function. Vitamin K2 bound to and activated the orphan nuclear receptor SXR and induced expression of the SXR target gene, CYP3A4, identifying it as a bona fide SXR ligand. Vitamin K2 treatment of osteosarcoma cells increased mRNA levels for the osteoblast markers bone alkaline phosphatase, osteoprotegerin, osteopontin, and matrix Gla protein. The known SXR activators rifampicin and hyperforin induced this panel of bone markers to an extent similar to vitamin K2. Vitamin K2 was able to induce bone markers in primary osteocytes isolated from wild-type murine calvaria but not in cells isolated from mice deficient in the SXR ortholog PXR. We infer that vitamin K2 is a transcriptional regulator of bone-specific genes that acts through SXR to favor the expression of osteoblastic markers. Thus, SXR has a novel role as a mediator of bone homeostasis in addition to its role as a xenobiotic sensor. An important implication of this work is that a subset of SXR activators may function as effective therapeutic agents for the management of osteoporosis.
Alkaline Phosphatase↗
Clinical significance of detecting elevated serum DcR3/TR6/M68 in malignant tumor patients.
TR6/DcR3/M68 is a soluble receptor that belongs to the TNF receptor family. It is expressed in malignant cells of several tumor types and has been postulated to help tumor cells to gain survival advantage by inhibiting apoptosis and by interfering with immune surveillance. In our study, we assessed for the first time serum TR6 in tumor patients to explore its diagnostic and prognostic value. We examined serum TR6 levels with ELISA in 146 tumor patients, 19 patients with acute infection, 5 patients with liver cirrhosis and 29 healthy individuals. TR6 expression in tumor mass was studied with immunohistochemistry. TR6 gene copy number in tumor tissues was evaluated by real time PCR. Ninety-seven point nine percent (47 of 48 cases) of healthy individuals and patients with acute infection were serum TR6-negative. In contrast, 56.2% (82 of 146 cases) of the tumor patients were serum TR6-positive. Almost all serum TR6-positive individuals (98.8%, 82 out of 83 cases) had malignancy, excluding the cases of liver cirrhosis. In gastric carcinomas, serum TR6 levels were closely correlated with tumor differentiation status and TNM classification. Tumor mass was the source of serum TR6 because its levels decreased drastically after curative tumor resection. TR6 gene amplification occurred in about half of liver carcinomas, but not in gastric or pancreatic carcinomas, indicating plural mechanisms of TR6 upregulation. Our study demonstrated that serum TR6 should be considered as a novel parameter for the diagnosis, treatment and prognosis of malignancies.
Adenocarcinoma, Follicular↗