Biomedical subjects

X Yi

Publications and source records attributed to X Yi.

At least 19 recordsLinked to original sources

PubMed2001

Recombinant paramyosin (rec-Sj-97) tested for immunogenicity and vaccine efficacy against Schistosoma japonicum in mice and water buffaloes.

A primary vaccine candidate antigen against schistosomiasis is paramyosin (pmy), a myofibrillar protein found exclusively in invertebrates. Here we report the results of vaccine trials against the Asian schistosome undertaken on inbred and outbred mice and water buffaloes using a bacterially expressed and purified form of Schistosoma japonicum pmy (rec-Sj-97). Vaccination of the mice resulted in high levels of specific anti-pmy IgG antibodies when compared with adjuvant controls and significant reduction in worm burdens and in liver eggs. Furthermore, a significant reduction in liver eggs was recorded in two of the three water buffalo vaccine trials undertaken and, in all three trials, high levels of specific anti-pmy IgG antibodies were generated. There was no evidence of any toxic effects and the vaccine preparations and Quil A adjuvant were clearly well tolerated. The development of a vaccine intended for livestock animals such as bovines would be beneficial in two ways; directly by blocking transmission of schistosomiasis to humans and economically by contributing to healthier livestock. We are encouraged by the consistent efficacy in the mouse and the buffalo vaccine trials that resulted in a significant decrease in liver eggs. Indeed, predictions from mathematical models indicate that an egg reduction effect of 42-45% in buffaloes would be sufficient when combined with human treatment to control schistosomiasis japonica in the marshes and lakes along the middle and upper reaches of the Yangtze River, the most highly endemic areas for the disease in China.

Animals↗

PubMed2001

Quantitation of telomerase components and hTERT mRNA splicing patterns in immortal human cells.

Telomerase is a reverse transcriptase that adds telomeric repeats to chromosomal ends. In most normal human somatic cells, telomerase is repressed and telomeres progressively shorten, leading to limited proliferative life-span. Telomerase reactivation is associated with cellular immortalization and is a frequent event during tumorigenesis. The telomerase ribonucleoprotein complex consists of two essential components, a catalytic protein subunit [human telomerase reverse transcriptase (hTERT)] and a template RNA (hTR). hTR is constitutively expressed, while hTERT is almost universally absent in telomerase-negative cells. Although repression of telomerase is transcriptional in telomerase-negative cells, post-transcriptional and assembly processes are likely to play important roles in regulating telomerase activity in those that are telomerase-positive. The telomerase transcript can also be alternatively spliced into a variety of non-functional forms. To establish the quantitative relationships between telomerase activity and its various components, we determined the numbers of molecules of hTR and hTERT mRNA, and the levels of alternatively spliced hTERT mRNA variants in normal, in vitro immortalized and cancer cell lines. We report here that there is surprisingly little variation in the proportion of alternatively spliced forms of hTERT in different cell lines. The only variation observed occurred when a change in splicing to non-functional forms appeared in response to conditions that repress telomerase activity in IDH4 cells. We also found that most telomerase-positive cell lines only contain a few molecules of potentially functional hTERT mRNA, and there is a correlation between telomerase activity and the levels of both hTR and hTERT +alpha+beta mRNA.

Alternative Splicing↗

PubMed2001

cDNA cloning and promoter analysis of rat caspase-9.

Caspase-9 is the apex caspase of the mitochondrial pathway of apoptosis, which plays a critical role in apoptotic initiation and progression. However, gene regulation of caspase-9 is largely unknown. This is in part due to the lack of information on the gene promoter. Here we have cloned the full-length cDNA of rat caspase-9 and have isolated promoter regions of this gene. The rat caspase-9 cDNA of 2058 bp predicts a protein of 454 amino acids, which contains a caspase-recruitment domain ('CARD') at the N-terminus and enzymic domains at the C-terminus. The enzyme's active site, with a characteristic motif of QACGG, was also identified. Overall, rat and human caspase-9 have 71% identity. With the cDNA sequence, we subsequently isolated the proximal 5'-flanking regions of rat caspase-9 by the procedure of genomic walking. The 2270 bp genomic segment is 'TATA-less', but contains several GC boxes. Elements binding known transcription factors such as Sp-1, Pit-1, CCAAT-enhancer-binding protein (C/EBP), glucocorticoid receptor and hypoxia-inducible factor 1 (HIF-1) were also identified. When cloned into reporter gene vectors, the genomic segment showed significant promoter activity, indicating that the 5'-flanking regions isolated by genomic walking contain the gene promoter of rat caspase-9. Of significance is that the cloned promoter segments were activated by severe hypoxia, conditions inducing caspase-9 transcription. Thus, the genomic sequences reported here contain not only the basal promoter of rat caspase-9 but also regulatory elements responsive to pathophysiological stimuli including hypoxia.

3T3 Cells↗

PubMed2001

Hydrogen exchange reveals a stable and expandable core within the aspartate receptor cytoplasmic domain.

Intensive study of bacterial chemoreceptors has not yet revealed how receptor methylation and ligand binding alter the interactions between the receptor cytoplasmic domain and the CheA kinase to control kinase activity. Both monomeric and dimeric forms of an Asp receptor cytoplasmic fragment have been shown to be highly dynamic, with a small core of slowly exchanging amide hydrogens (Seeley, S. K., Weis, R. M., and Thompson, L. K. (1996) Biochemistry 35, 5199-5206). Hydrogen exchange studies of the wild-type cytoplasmic fragment and an S461L mutant thought to mimic the kinase-inactivating state are used to investigate the relationship between the stable core and dimer dissociation. Our results establish that (i) decreasing pH stabilizes the dimeric state, (ii) the stable core is present also in the transition state for dissociation, and (iii) this core is expanded significantly by small changes in electrostatic and hydrophobic interactions. These kinase-inactivating changes stabilize both the monomeric and the dimeric states of the protein, which has interesting implications for the mechanism of kinase activation. We conclude that the cytoplasmic domain is a flexible region poised for stabilization by small changes in electrostatic and hydrophobic interactions such as those caused by methylation of glutamate residues and by ligand-induced conformational changes during signaling.

Calorimetry↗

PubMed2001

Anterior approach to the second thoracic vertebral body for surgical treatment (vertebrectomy, bone grafting, and titanium alloy plate fixation).

The surgical approach to the second thoracic vertebral body is difficult from the anterior side. A 38-year-old woman suffering from plasmacytoma in the second thoracic vertebra showed paraplegia for 2 weeks prior to surgery. X-ray, computed tomography (CT), and magnetic resonance imaging (MRI) examinations indicated breakdown of the second thoracic vertebral body and arch, associated with spinal cord compression. A 99mTc bone scintigram showed accumulation only in the second thoracic vertebra. After one course of chemotherapy with cyclophosphamide and prednisone (CP protocol), surgery was carried out. The incision was made on the right side of the anterior of the neck, from the middle half of the sternocleidomastoideus along the anterior edge to the jugular notch of the sternum. After cutting the platysma, severing the sternohyoideus, splitting the sternothyroid muscle, and forming a compartment between the esophagus and vagina carotica, we extended the incision to the sternum. Without wedging the sternum, we separated tissue from the posterior of the sternum to the second and third thoracic vertebrae, excised the second thoracic vertebra to expose the hard spinal meninges, and removed the tumor in the vertebral canal to release the compression on the spinal cord. An autogeneous bone graft, taken from the right ilium (1.5 x 1.5 x 3 cm in size), was implanted between the first and third thoracic vertebrae, and a spinal titanium alloy plate was used to increase fixation between the first and third thoracic vertebrae from the front. During the surgery, 800 ml of blood was transfused. On the fifth postsurgical day, the patient could walk normally with a neck collar, and the paraplegia was completely alleviated, with no complications.

Adult↗

PubMed2001

[Clinical significance of the expression of lung resistance protein in non-small cell lung carcinomas].

OBJECTIVE: To investigate the expression of the lung resistance-related protein (LRP) in non-small cell lung carcinomas (NSCLC) and evaluate its clinical significance. METHODS: Using immunohistochemistry, LRP was examined in 69 NSCLC specimens obtained by either transbronchial biopsy via fibrobronchoscopy or transcutaneous needle biopsy or surgical resection. Of the 69 patients from whom tumor specimens were obtained, 52 were male and 17 were female. RESULTS: LRP expression was detected in 39/69 (57%) tumor specimens. There was no correlation between LRP expression and NSCLC histological classification (P > 0.05). No significant differences were found in gender and among age groups. The positive rates of LRP were 67% (18/27), 55% (17/31), 52% (23/44), 64% (16/25), 83% (5/6), 57% (36/63) and 50% (3/6) in adenocarcinoma, squamous, staging T1-2, T3-4, N3, M0 and M1 respectively. It was shown that LRP expression was not associated with primary tumor size and metastasis status (N,M). NSCLC patients with positive LRP expression responded more poorly to chemotherapy than those with negative LRP expression (P < 0.05). CONCLUSIONS: The frequencies of multidrug resistance caused by LRP are similar between adenocarcinoma and squamous. Expression of LRP is related to multidrug resistance of NSCLC, which in turn related to the efficacy and prognosis of chemotherapy. The examination of LRP expression may be valuable for choice of chemotherapy regimen.

ATP-Binding Cassette Transporters↗

PubMed2000

Direct electrochemistry of horseradish peroxidase immobilized on a colloid/cysteamine-modified gold electrode.

Direct electron transfer of immobilized horseradish peroxidase on gold colloid and its application as a biosensor were investigated by using electrochemical methods. The Au colloids were associated with a cysteamine monolayer on the gold electrode surface. A pair of redox peaks attributed to the direct redox reaction of horseradish peroxidase (HRP) were observed at the HRP/Au colloid/cysteamine-modified electrode in 0.1 M phosphate buffer (pH 7.0). The surface coverage of HRP immobilized on Au colloid was about 7.6 x 10(-10) mol/cm(2). The sensor displayed an excellent electrocatalytic response to the reduction of H(2)O(2) without the aid of an electron mediator. The calibration range of H(2)O(2) was 1. 4 microM to 9.2 mM with good linear relation from 1.4 microM to 2.8 mM. A detection limit of 0.58 microM was estimated at a signal-to-noise ratio of 3. The sensor showed good reproducibility for the determination of H(2)O(2). The variation coefficients were 3. 1 and 3.9% (n = 10) at 46 microM and 2.8 mM H(2)O(2), respectively. The response showed a Michaelis-Menten behavior at higher H(2)O(2) concentrations. The K(app)(M) value for the H(2)O(2) sensor was found to be 2.3 mM.

Biosensing Techniques↗

PubMed2000

Immunogenicity and immunolocalization of the 22.6 kDa antigen of Schistosoma japonicum.

The 22.6 kDa tegumental-associated antigens of Schistosoma mansoni (Sm22.6) and Schistosoma japonicum (Sj22.6) are of recognized interest in schistosomiasis vaccine development, although no direct vaccination/challenge experiments using either Sm22.6 or Sj22.6 had been previously described. We report that Escherichia coli-expressed reSj22.6 failed to protect mice or water buffaloes against subsequent challenge with S. japonicum cercariae. This was despite the fact that specific IgG (buffaloes) and IgG and IgE (CBA mice) antibodies were generated against the 22.6 kDa molecule, observations consistent with some of our earlier findings. We could find no evidence from immunolocalization studies that Sj22.6 is expressed or exposed on the surface of the adult parasite since it appears to be restricted to the apical cytoplasm of the tegument and is not associated with the apical or basal membrane or any membrane-bound structures in the apical cytoplasm. Nevertheless, Sj22.6 must be released to the immune system during the course of infection because specific anti-Sj22.6 IgG antibodies were present in the sera of nonvaccinated but challenged mice. We conclude that it may be necessary to produce reSj22.6 in a more relevant expression system, such as baculovirus, to further establish its vaccine potential and that detailed immunochemical and immunolocalization studies of early developmental stages may be necessary to determine how Sj22.6 is released or shed in S. japonicum infections.

Animals↗

PubMed2000

Clevidipine blockade of L-type Ca2+ currents: steady-state and kinetic electrophysiological studies in guinea pig ventricular myocytes.

Steady-state and transient effects of clevidipine, a rapidly degraded dihydropyridine (DHP) L-type Ca2+ channel antagonist, were examined on I(Ca) in guinea pig ventricular myocytes. When myocytes were voltage-clamped with holding potential (V(H)) at -80 mV, 10 nM clevidipine decreased I(Ca) at 0 mV by approximately 30%, but >50% when V(H) was -40 mV. Rapid (<50 ms) perfusion switching and repeated depolarizations delivered at 0.5-2 Hz were used to determine the time constants of onset (tau(on)) and recovery from (tau(off)) clevidipine inhibition of I(Ca). The tau(on) and tau(off) were monoexponential functions of time. The tau(on) of I(Ca) inhibition decreased from 21.5 +/- 1.2 to 9.9 +/- 0.9 s when the rapidly applied [clevidipine] was increased from 10 to 100 nM at V(H) = -80 mV; tau(off) was independent of the applied [clevidipine] and was 23.9 +/- 1.1 s. The dissociation constant (K(D)) calculated for clevidipine at V(H) = -80 mV was 65 +/- 3 nM, similar to the IC50 of 78 nM determined in steady-state measurements. Decreasing V(H) to -40 mV increased tau(off) more than threefold to 81 +/- 6 s, and K(D) was markedly decreased to 9.0 +/- 0.8 nM (IC50, 7.1 nM at V(H) = -40 mV). The increased affinity at depolarized V(H) may contribute to the varying concentration-effect relation observed in vivo.

Animals↗

PubMed2000

Corneal epithelial tight junctions and their response to lipopolysaccharide challenge.

PURPOSE: To investigate the expression and cellular distribution of putative tight junction (TJ) proteins occludin, ZO-1, ZO-2, and claudin-1 in rat corneal epithelium and alterations of TJs in cultured human corneal epithelial cells in response to lipopolysaccharide (LPS) challenge. METHODS: Immunohistochemistry was used to determine tissue distribution of occludin, ZO-1, ZO-2, and claudin-1 in the rat cornea. Reverse transcription-polymerase chain reaction was used to reveal the expression of mRNAs for claudins in simian virus (SV)40-immortalized human corneal epithelial (THCE) cells. To assess epithelial response to LPS challenge, THCE cells were cultured on the upper chamber of Transwell filters (Costar, Cambridge, MA), transepithelial electrical resistance (TER) was measured using a voltohmmeter. Immunocytochemistry and immunoblotting were used to assess alteration in the levels and localization of TJ-associated proteins occludin, ZO-1, and ZO-2 in LPS-treated THCE cells. RESULTS: Occludin, ZO-1, and ZO-2 were found at the cell borders of the superficial layer, whereas claudin-1 was localized mainly in the basal and wing cell layers of rat corneal epithelium. In addition to claudin-1, the transcripts for several other isotypes of claudins-2, -3, -7, -9, -14, and -15 were identified in THCE cells. Treatment of cultured THCE cells with LPS caused a dose- and time-dependent increase in monolayer permeability as assessed by TER measurements. The maximal decrease of TER was observed at approximately 6 to 9 hours after LPS challenge. The TER was then recovered gradually and returned to baseline after 24 hours. Examination of specific proteins associated with TJs by immunoblot analysis and immunomicroscopy revealed changes in the expression levels and localization of some of these proteins after their exposure to LPS. Specifically, LPS challenge resulted in a decrease in the levels of ZO-1 and ZO-2 compared with untreated cells. Reduction of the ZO-2 level was associated with the disappearance of ZO-2 staining from cell borders in 6-hour LPS-treated cells. CONCLUSIONS: Occludin, ZO-1, and ZO-2, but not claudin-1, are components of corneal epithelial TJs. LPS induces breakdown of the epithelial barrier through disruption of TJs, and ZO-1 and ZO-2 are targets for the induction.

Animals↗

PubMed2000

[Effects of stress level on the biomechanical behavior of the temporomandibular joint disc in domestic pigs].

This study aimed to examine the responses of the temporomandibular joint (TMJ) disc against compression, to clarify the property of viscoelasticity and permeability of the disc, and to provide experimental data for further analyzing the mechanism of stress dissipation within the TMJ disc. With the use of confined compression mechanics and biphasic theory, creep experiments on eight TMJ discs of four domestic pigs were performed under three stress levels(0.07 MPa, 0.13 MPa and 0.30 MPa). The results showed that at 0.07 stress level, the compressive stiffness at 2 seconds of the anterior band(AB), intermediate zone(IZ) and posterior band(PB) of the disc was 4.48 MPa, 3.93 MPa and 6.31 MPa, respectively; the coefficient K of permeability was 0.272 x 10(-12) m4/NS, 0.30 x 10(-12) m4/NS, and 0.042 x 10(-12) m4/NS. At 0.30 Mpa level, the compressive stiffness increased to 14.07 MPa, 13.68 Mpa and 14.00 MPa; the coefficient K lowered to 0.017 x 10(-12) m4/NS, 0.012 x 10(-12) m4/NS and 0.005 x 10(-12) m4/NS. In conclusion, the TMJ disc has viscoelastic and biobiphasic properties against compression. The stiffness of the disc increases with the increment of stress level but the coefficient of permeability decreases. These findings demonstrate that the modulation of stress and of permeability may be two important factors influencing stress dissipation and shock absorption behavior of the disc during compressive and impact loads.

Animals↗

PubMed2000

[Biomechanics of temporomandibular joint].

Temporomandibular joint (TMJ) is one of the most intricate and complicate loading joints in the human body. Articular cartilage is characteristic of low infiltrative, porous viscoelastic material. In physiological condition, there is a stress-absorbing architecture system in the TMJ cartilage, which consists of collagen-proteoglycan-water gel network. TMJ disc is a specific connective tissue as stress concentration absorber between condyle and articular fossa, but it does not belong to fibrocartilage. Retrodiscal tissue has high compliance of which the role is to play volume-compensating mechanism in joint movement. Lateral wall is a complexed structure out of ligament and capsule with weak tensile strength and tensile rigidity. Therefore, prolonged oral parafunction will result in joint fatigue and failure.

Biomechanical Phenomena↗

PubMed1999

A kinetic epoxidation assay for chloroperoxidase.

Chloroperoxidase exhibits a wide variety of enantioselective epoxidation reactions. Until now, the epoxidation activities have been mainly evaluated using elaborate gas chromatographic methods. This paper reports a rapid and convenient spectrophotometric assay for CPO. The disappearance of indene by catalytic epoxidation is monitored at 250 nm and this is used as an index of enzyme activity. This method will prove to be highly useful in large-scale screening of mutants.

Chloride Peroxidase↗

PubMed1999

Lattice-fluid model for gas-liquid chromatography.

Lattice-fluid models describe molecular ensembles in terms of the number of lattice sites occupied by molecular species (r-mers) and the interactions between neighboring molecules. The lattice-fluid model proposed by Sanchez and Lacombe (Macromolecules, 1978;11:1145-1156) was used to model specific retention volume data for a series of n-alkane solutes with n-alkane, polystyrene, and poly(dimethylsiloxane) stationary liquid phases. Theoretical equations were derived for the specific retention volume and also for the temperature dependence and limiting (high temperature) values for the specific retention volume. The model was used to predict retention volumes within 10% for the n-alkanes phases; 22% for polystyrene; and from 20 to 70% for PDMS using no adjustable parameters. The temperature derivative (enthalpy) could be calculated within 5% for all of the solutes in nine stationary liquid phases. The limiting value for the specific retention volume at high temperature (entropy controlled state) could be calculated within 10% for all of the systems. The limiting data also provided a new chromatographic method to measure the size parameter, r, for any chromatographic solute using characteristic and size parameters for the stationary phase only. The calculated size parameters of the solutes were consistent, i.e. independent of the stationary phase and agreed within experimental error with the size parameters previously reported from saturated vapor pressure, latent heat of vaporization or density data.

Alkanes↗

PubMed1999

Replacement of the proximal heme thiolate ligand in chloroperoxidase with a histidine residue.

Chloroperoxidase is a versatile heme enzyme which can cross over the catalytic boundaries of other oxidative hemoproteins and perform multiple functions. Chloroperoxidase, in addition to catalyzing classical peroxidative reactions, also acts as a P450 cytochrome and a potent catalase. The multiple functions of chloroperoxidase must be derived from its unique active site structure. Chloroperoxidase possesses a proximal cysteine thiolate heme iron ligand analogous to the P450 cytochromes; however, unlike the P450 enzymes, chloroperoxidase possesses a very polar environment distal to its heme prosthetic group and contains a glutamic acid residue in close proximity to the heme iron. The presence of a thiolate ligand in chloroperoxidase has long been thought to play an essential role in its chlorination and epoxidation activities; however, the research reported in this paper proves that hypothesis to be invalid. To explore the role of Cys-29, the amino acid residue supplying the thiolate ligand in chloroperoxidase, Cys-29 has been replaced with a histidine residue. Mutant clones of the chloroperoxidase genome have been expressed in a Caldariomyces fumago expression system by using gene replacement rather than gene insertion technology. C. fumago produces wild-type chloroperoxidase, thus requiring gene replacement of the wild type by the mutant gene. To the best of our knowledge, this is the first time that gene replacement has been reported for this type of fungus. The recombinant histidine mutants retain most of their chlorination, peroxidation, epoxidation, and catalase activities. These results downplay the importance of a thiolate ligand in chloroperoxidase and suggest that the distal environment of the heme active site plays the major role in maintaining the diverse activities of this enzyme.

Amino Acid Substitution↗

PubMed1999

A rabbit model of proliferative vitreoretinopathy induced by injection of astrocytic cultures.

1. The objective of this study was to decipher whether proliferation of astrocytes and invasion of astrocytic processes into the retina could contribute to retinal detachment in a rabbit model. 2. Cultures of astrocytes were injected intravitreally into the eyes of albino rabbits. 3. Two weeks after injection, proliferation of astrocytes on the retinal surfaces was observed. Vascular endothelial growth factor (VEGF) and proliferative cell nuclear antigen (PCNA) were found by immunohistochemistry to be expressed in the center of the astrocytic growth. 4. Using the same immunohistochemical technique to visualize glial fibrillary acidic protein (GFAP), a marker for astrocytes, processes of astrocytes in the growth were observed to penetrate into the host retina. 5. Retinal detachment was then confirmed by ultrasound, histologically, and grossly 2 weeks after injection of astrocytes. 6. Histochemistry on esterase indicated chloroesterase positive cells inside the growth. The secretion of this form of esterase might soften the vitreous and enhanced retinal detachment. 7. Six weeks after injection, VEGF and PCNA decreased in the astrocytic growth but astrocytic processes still attached onto and penetrated the host retina. 8. This study suggests that astrocytes could be a major factor in inducing retinal detachment.

Animals↗

PubMed1999

Both transcriptional and posttranscriptional mechanisms regulate human telomerase template RNA levels.

The human telomerase RNA component (hTR) is present in normal somatic cells at lower levels than in cancer-derived cell lines. To understand the mechanisms regulating hTR levels in different cell types, we have compared the steady-state hTR levels in three groups of cells: (i) normal telomerase-negative human diploid cells; (ii) normal cells transfected with the human telomerase catalytic subunit, hTERT; and (iii) cells immortalized in vitro and cancer cells expressing their own endogenous hTERT. To account for the differences in steady-state hTR levels observed in these cell types, we compared the transcription rate and half-life of hTR in a subset of these cells. The half-life of hTR in telomerase-negative cells is about 5 days and is increased 1.6-fold in the presence of hTERT. The transcription rate of hTR is essentially unchanged in cells expressing exogenous hTERT, and the increased steady-state hTR level appears to be due to the increased half-life. However, the transcription rate of hTR is greatly increased in cells expressing endogenous hTERT, suggesting some overlap in transcriptional regulatory control. We conclude that the higher hTR level in cells expressing an endogenous telomerase can be a result of both increased transcription and a longer half-life and that the longer half-life might be partially a result of protection or stabilization by the telomerase catalytic subunit. The 4-week half-life of hTR in H1299 tumor cells is the longest half-life yet reported for any RNA.

Animals↗

PubMed1999

Two inactive fragments of the integral RNA cooperate to assemble active telomerase with the human protein catalytic subunit (hTERT) in vitro.

We have mapped the 5' and 3' boundaries of the region of the human telomerase RNA (hTR) that is required to produce activity with the human protein catalytic subunit (hTERT) by using in vitro assembly systems derived from rabbit reticulocyte lysates and human cell extracts. The region spanning nucleotides +33 to +325 of the 451-base hTR is the minimal sequence required to produce levels of telomerase activity that are comparable with that made with full-length hTR. Our results suggest that the sequence approximately 270 bases downstream of the template is required for efficient assembly of active telomerase in vitro; this sequence encompasses a substantially larger portion of the 3' end of hTR than previously thought necessary. In addition, we identified two fragments of hTR (nucleotides +33 to +147 and +164 to +325) that cannot produce telomerase activity when combined separately with hTERT but can function together to assemble active telomerase. These results suggest that the minimal sequence of hTR can be divided into two sections, both of which are required for de novo assembly of active telomerase in vitro.

Animals↗