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Biomedical subjects

J Xiao

Publications and source records attributed to J Xiao.

At least 55 records · Page 3Linked to original sources

A convenient method for the synthesis of DNA-recognizing polyamides in solution.

A convenient method for the synthesis of polyamides containing N-methylpyrrole (Py) and N-methylimidazole (Im) in solution has been developed. Most of the building blocks have been prepared by a haloform reaction in a simple way that column chromatography can be avoided. By use of the DCC/HOBT coupling reaction, the building blocks prepared have been effectively connected to construct a variety of subchains and polyamides without employing amino protection and deprotection. By use of the present method, an eight-ring polyamide, PyPyPyPygammaPyImImPybetaDp (gamma is gamma-aminobutyric acid, beta is beta-alanine, Dp is N, N-dimethylpropyldiamine), has been synthesized by the coupling of two four-ring subchains in one step.

DNA↗

Participation of syntaxin 1A in membrane trafficking involving neurite elongation and membrane expansion.

Syntaxin 1A has been implicated to play an important role in neurotransmitter release by regulating synaptic vesicle fusion. The protein is also suggested to be required for other types of membrane fusion such as cellularization during embryonic development. In the current study, we overexpressed syntaxin 1A, SNAP-25b, and VAMP-2 in PC12 cells using recombinant adenoviruses, and determined their effects on membrane trafficking involving neurite outgrowth. It was found that overexpression of syntaxin 1A inhibited NGF-induced neurite extension, and the expressed syntaxin was localized to the plasma membrane, intracellular membranes, and the neurite tips. SNAP-25 overexpression slightly enhanced neurite elongation, whereas no significant changes in neurite growth was observed in VAMP-overexpressing cells. The effect of syntaxin 1A in general membrane trafficking was further studied by transient transfection of non-neuronal cells. Syntaxin 1A expression in HEK 239 and NIH3T3-L1 caused the cells to lose their normal morphology, leading to round and smaller cells. Deletion of the C-terminal sequence containing the H3 helix and the membrane anchoring domains of syntaxin abolished its ability to induce cell morphology changes, whereas removal of the N-terminal 1-170 amino acid sequence did not affect this activity. These findings suggest that in addition to its well documented role in synaptic vesicle fusion, syntaxin may function in other non-synaptic membrane trafficking such as neurite outgrowth and membrane expansion.

3T3 Cells↗

Drosophila Dscam is an axon guidance receptor exhibiting extraordinary molecular diversity.

A Drosophila homolog of human Down syndrome cell adhesion molecule (DSCAM), an immunoglobulin superfamily member, was isolated by its affinity to Dock, an SH3/SH2 adaptor protein required for axon guidance. Dscam binds directly to both Dock's SH2 and SH3 domains. Genetic studies revealed that Dscam, Dock and Pak, a serine/threonine kinase, act together to direct pathfinding of Bolwig's nerve, containing a subclass of sensory axons, to an intermediate target in the embryo. Dscam also is required for the formation of axon pathways in the embryonic central nervous system. cDNA and genomic analyses reveal the existence of multiple forms of Dscam with a conserved architecture containing variable Ig and transmembrane domains. Alternative splicing can potentially generate more than 38,000 Dscam isoforms. This molecular diversity may contribute to the specificity of neuronal connectivity.

Amino Acid Sequence↗

Gene microarray identification of redox and mitochondrial elements that control resistance or sensitivity to apoptosis.

Multigenic programs controlling susceptibility to apoptosis in response to ionizing radiation have not yet been defined. Here, using DNA microarrays, we show gene expression patterns in an apoptosis-sensitive and apoptosis-resistant murine B cell lymphoma model system both before and after irradiation. From the 11,000 genes interrogated by the arrays, two major patterns emerged. First, before radiation exposure the radioresistant LYar cells expressed significantly greater levels of message for several genes involved in regulating intracellular redox potential. Compared with LYas cells, LYar cells express 20- to 50-fold more mRNA for the tetraspanin CD53 and for fructose-1,6-bisphosphatase. Expression of both of these genes can lead to the increase of total cellular glutathione, which is the principle intracellular antioxidant and has been shown to inhibit many forms of apoptosis. A second pattern emerged after radiation, when the apoptosis-sensitive LYas cells induced rapid expression of a unique cluster of genes characterized by their involvement in mitochondrial electron transport. Some of these genes have been previously recognized as proapoptotic; however others, such as uncoupling protein 2, were not previously known to be apoptotic regulatory proteins. From these observations we propose that a multigenic program for sensitivity to apoptosis involves induction of transcripts for genes participating in mitochondrial uncoupling and loss of membrane potential. This program triggers mitochondrial release of apoptogenic factors and induces the "caspase cascade." Conversely, cells resistant to apoptosis down-regulate these biochemical pathways, while activating pathways for establishment and maintenance of high intracellular redox potential by means of elevated glutathione.

Animals↗

Excitatory and inhibitory receptive fields of tectal cells are differentially modified by magnocellular and parvocellular divisions of the pigeon nucleus isthmi.

It has been known that magnocellular and parvocellular divisions of the pigeon nucleus isthmi exert excitatory and inhibitory actions on tectal cells, respectively. The present study shows that injection of N-methyl-D-aspartate into the parvocellular division results in an increase in responsive strength and extent of the inhibitory receptive fields, which expand into the excitatory receptive fields of tectal cells. This injection concurrently leads to a decrease in responsiveness and extent of the excitatory fields. On the other hand, injection of acetylcholine into the magnocellular division enhances visual responsiveness, although the excitatory field is not obviously changed in extent. Meanwhile, strength and extent of the inhibitory fields are decreased by acetylcholine. The excitatory and inhibitory fields are reduced in both strength and extent by magnocellular and parvocellular injection of lidocaine, respectively. It suggests that isthmic inputs from both parvocellular and magnocellular divisions converge onto the same tectal cells, and the magnocellular and parvocellular subnuclei can modulate excitatory and inhibitory receptive fields of tectal cells, respectively, with some interactions between both fields.

Acetylcholine↗

Y chromosome haplotypes reveal prehistorical migrations to the Himalayas.

By using 19 Y chromosome biallelic markers and 3 Y chromosome microsatellite markers, we analyzed the genetic structure of 31 indigenous Sino-Tibetan speaking populations (607 individuals) currently residing in East, Southeast, and South Asia. Our results showed that a T to C mutation at locus M122 is highly prevalent in almost all of the Sino-Tibetan populations, implying a strong genetic affinity among populations in the same language family. Furthermore, the extremely high frequency of H8, a haplotype derived from M122C, in the Sino-Tibetan speaking populations in the Himalayas including Tibet and northeast India indicated a strong bottleneck effect that occurred during a westward and then southward migration of the founding population of Tibeto-Burmans. We, therefore, postulate that the ancient people, who lived in the upper-middle Yellow River basin about 10,000 years ago and developed one of the earliest Neolithic cultures in East Asia, were the ancestors of modern Sino-Tibetan populations.

China↗

Conformational stability of CH3CH2PH2BH3 from temperature dependent FT-IR spectra of xenon solutions and r0 structural parameters.

Variable temperature (-55--100 degrees C) studies of the infrared spectra (3500-400 cm(-1)) of ethylphosphine-borane, CH3CH2PH2BH3, and ethylphosphine-borane-d5 dissolved in liquid xenon have been recorded. From these data, the enthalpy difference has been determined to be 86 +/- 8 cm(-1) (1.03 +/- 0.10 kJ/mol), with the trans conformer the more stable rotamer. Complete vibrational assignments are presented for both conformers, which are consistent with the predicted frequencies obtained from the ab initio MP2/6-31G(d) calculations. The optimized geometries, conformational stabilities, harmonic force fields, infrared intensities, Raman activities, and depolarization ratios have been obtained from RHF/6-31G(d) and/or MP2/6-31G(d) ab initio calculations. These quantities are compared to the corresponding experimental quantities when appropriate as well as with some corresponding results for some similar molecules. The r0 structural parameters have been obtained from a combination of the previously reported microwave rotational constants and ab initio predicted parameters.

Boranes↗

Distribution of three HIV-1 resistance-conferring polymorphisms (SDF1-3'A, CCR2-641, and CCR5-delta32) in global populations.

Chemokine receptors (CCR5, CXCR4 and CCR2) have been shown to be important co-receptors for HIV infection. Mutations at CCR5 (CCR5-delta2), CCR2 (CCR2-641), and stromal-derived factor SDF1 (SDF1-3'A), a primary ligand for CXCR4, are known to have protective effects against HIV-1 infection and the onset of AIDS symptoms. We studied the three-locus genotype frequency distributions in 70worldwide populations from a sample of 2341 individuals without any known history of HIV-1 infection and AIDS symptoms. From these data, we estimated the risk of AIDS onset (relative hazard, RH) of each population. This survey shows that the substantial allele frequency differences of each of these mutations translate into an extensive variation in relative hazards for AIDS in worldwide populations. However, no evidence of natural selection against the mutant gene carriers is detected. Finally, the combined three-locus genotype data predict the highest relative hazard (RH) in South-East Asia and Africa where AIDS is known to be more prevalent.

Chemokine CXCL12↗

An assessment of the effects of casemix funding on hospital utilisation: a Northern Territory perspective.

This article is concerned with the methodological issues of assessing the effects of casemix funding on hospital utilisation. Time-series analysis and intervention analysis are proposed to ascertain the effects. It was found there had been a decline in average length of stay and number of bed-days, an increase in weighted separations for teaching and non-teaching hospitals, and no apparent increase of costliness in terms of a comprehensive casemix index. No evidence of decline in quality of care can be established in terms of readmission rates. The long-term effects of casemix funding, and specific issues in terms of the funding model used, patients and cost shifting between hospital services and community health services, remain to be studied.

Diagnosis-Related Groups↗

Construction and characterization of murine cytomegaloviruses that contain transposon insertions at open reading frames m09 and M83.

A transposon derived from Escherichia coli Tn3 was introduced into the genome of murine cytomegalovirus (MCMV) to generate a pool of viral mutants, including two recombinant viruses that contained the transposon sequence within open reading frames m09 and M83. Our studies provide the first direct evidence to suggest that m09 is not essential for viral replication in mouse NIH 3T3 cells. Studies in cultured cells and in both BALB/c-Byj and CB17 severe combined immunodeficient (SCID) mice indicated that the transposon insertion is stable during viral propagation both in vitro and in vivo. Moreover, the virus that contained the insertion mutation in m09 exhibited a titer similar to that of the wild-type virus in the salivary glands, lungs, livers, spleens, and kidneys of both the BALB/c and SCID mice and was as virulent as the wild-type virus in killing the SCID mice when these animals were intraperitoneally infected with these viruses. These results suggest that m09 is dispensable for viral growth in these organs and that the presence of the transposon sequence in the viral genome does not significantly affect viral replication in vivo. In contrast, the virus that contained the insertion mutation in M83 exhibited a titer of at least 60-fold lower than that of the wild-type virus in the organs of the SCID mice and was attenuated in killing the SCID mice. These results demonstrate the utility of using the Tn3-based system as a mutagenesis approach for studying the function of MCMV genes in both immunocompetent and immunodeficient animals.

Animals↗

In vitro and in vivo characterization of a murine cytomegalovirus with a transposon insertional mutation at open reading frame M43.

We have recently generated a pool of murine cytomegalovirus (MCMV) mutants by using a Tn3-based transposon mutagenesis approach. In this study, one of the MCMV mutants, RvM43, which contained the transposon inserted in open reading frame M43, was characterized. Our results provide the first direct evidence to suggest that M43 is not essential for viral replication in vitro in NIH 3T3 cells. Moreover, RvM43 exhibited a titer similar to that of the wild-type virus in the lungs, livers, spleens, and kidneys of both BALB/c and SCID mice and was as virulent as the wild-type virus in killing SCID mice that had been intraperitoneally infected with the viruses. In contrast, titers of the mutant virus in the salivary glands of the infected animals at 21 days postinfection were significantly (100 to 1,000-fold) lower than those of the wild-type virus and a rescued virus that restored the M43 region and its expression. Thus, M43 appears to be not essential for viral growth in vivo in the lungs, livers, spleens, and kidneys of infected animals and is also dispensable for virulence in killing SCID mice. Moreover, our results suggest that M43 is an MCMV determinant for growth in the salivary glands. Studies of viral genes required for replication in the salivary glands are important in understanding the mechanism of viral tropism for the salivary glands and shedding in saliva, which is believed to be one of the major routes of CMV transmission among healthy human populations.

3T3 Cells↗

Murine cytomegalovirus containing a mutation at open reading frame M37 is severely attenuated in growth and virulence in vivo.

A pool of murine cytomegalovirus (MCMV) mutants was generated by using a Tn3-based transposon mutagenesis procedure. One of the mutants, RvM37, which contained the transposon sequence at open reading frame M37, was characterized both in tissue culture and in immunocompetent BALB/c and immunodeficient SCID mice. Our results provide the first direct evidence to suggest that M37 is not essential for viral replication in vitro in NIH 3T3 cells. Compared to the wild-type strain and a rescued virus that restored the M37 region, the viral mutant was severely attenuated in growth in both BALB/c and SCID mice after intraperitoneal infection. Specifically, titers of the Smith strain and rescued virus in the salivary glands, lungs, spleens, livers, and kidneys of the SCID mice at 21 days postinfection were about 5 x 10(5), 2 x 10(5), 5 x 10(4), 5 x 10(3), and 1 x 10(4) PFU/ml of organ homogenate, respectively; in contrast, titers of RvM37 in these organs were less than 10(2) PFU/ml of organ homogenate. Moreover, the virulence of the mutant virus appeared to be significantly attenuated because none of the SCID mice infected with RvM37 had died by 120 days postinfection, while all animals infected with the wild-type and rescued viruses had died by 26 days postinfection. Our results suggest that M37 probably encodes a virulence factor and is required for MCMV virulence in SCID mice and for optimal viral growth in vivo.

3T3 Cells↗

[Differentiation genes are involved in homologous recombination in Streptomyces coelicolor].

In S. coelicolor, the rapid increase of SCP2* plasmid conjugation efficiency and that of plasmid homologous recombination efficiency associates with development of aerial mycelium. Results of test of SCP2* plasmid conjugation and plasmid homologous recombination in one bld mutant and in three whi mutants show that while whiA mutant causes unstable plasmid conjugation efficiency, the other three mutants show no influence on plasmid conjugation, plasmid homologous recombination efficiency drops however more than 10 times in the four mutants.

Genes, Bacterial↗

[Viability and dynamic observation of stretchback of the continuously expanded skin flap in the pig model].

OBJECTIVE: To investigate the viability of the continuously expanded skin flap and the dynamic change of flap stretchback in the pig model. METHODS: White piglets and a constant pressure-infusing pump were employed to establish a continuous tissue expansion model. The animals were divided into two groups. The short rectangular expander of 180 ml was used in group A and the long rectangular expander of 210 ml was used in group B. Three days after completion of the continuous expansion, normal random and expanded skin flaps were created to assess flap viability and stretchback. RESULTS: Flap survival length in group A and B increased by 92.60% and 91.96% respectively versus normal random flap. But there was no significant difference in survival length between group A and B. Obvious flap stretchback was observed in the early stage. Eight weeks after flap operation the flap width of group A and B restored to that of the random skin flaps (P > 0.05). CONCLUSION: Continuously fast-expanded skin flaps are reliable in viability for soft tissue reconstruction. Larger expanders cannot further enhance the viability of the expanded flap.

Animals↗

Calcitonin gene-related peptide: an endogenous mediator of preconditioning.

Preconditioning of the heart induced by a brief ischemia or hyperthermia is exerted in two phases, early and delayed protection. The cardioprotection of ischemic preconditioning is related to the release of endogenous mediators. Calcitonin gene-related peptide (CGRP), a principal transmitter of capsaicin-sensitive sensory nerves, is involved in the mediation of ischemic preconditioning, and CGRP-mediated ischemic preconditioning has been shown to protect the endothelial cells. The cardioprotection mediated by endogenous CGRP is also found in heat stress reaction. Drug-induced preconditioning, such as by nitroglycerin, may be related to stimulated release of CGRP. These findings suggest that CGRP may be an endogenous myocardial protective substance and plays an important role in the mediation of preconditioning.

Animals↗

[Expression of telomerase and its RNA in nasopharyngeal carcinoma].

OBJECTIVE: To study the activity of telomerase and the expression of its RNA in nasopharyneal carcinoma (NPC) and HNE1 cell lines of NPC. METHODS: Telomerase activity was detected with telomeric repeat amplification protocol (TRAP) PCR ELISA kit in 41 cases of NPC, 14 cases of tissues adjacent to the carcinoma, and 19 cases of chronic nasopharyngitis, HNE1 cell lines of NPC, HL60 cell lines of leukemia, TUL1 cell lines of lung cancer, as well as three other kinds of normal control cells. The sensitivity and specificity of telomerase assay were also analyzed. Moreover, the expression of human telomerase RNA (hTR) was studied in 27 cases of NPC, 19 cases of adjacent nasopharyngeal tissues, and 17 cases of control groups by RT-nested PCR. RESULTS: The telomerase activity was found increased in NPC and in tissues adjacent to NPC with absorbance value (A value) of 1.15 U +/- 0.78 U and 1.04 U +/- 0.67 U respectively, compared with chronic nasopharyngitis (A = 0.18 U +/- 0.09 U). In NPC with cervical lymphnodes involvement the telomerase activity (A = 1.25 U +/- 0.79 U) was higher than in those without involvement (A = 1.02 U +/- 0.71 U), P < 0.05. The telomerase activity was also observed in HNE1 cell lines (A = 1.26 U +/- 0.97 U) and in other two kinds of cancer cell lines, but not in the three kinds of normal control cells. By contrast, no significant difference was seen in the expression of hTR among the three nasopharyngeal biopsy groups (P > 0.05). Finally, the sensitivity of telomerase assay was high (at an amount of 10(2) HNE1 cells), and the specificity was also high (after inactivation by heat or RNase, the telomerase activity was very low). CONCLUSIONS: A high frequency of telomerase activity is commonly seen in NPC, adjacent nasopharyngeal tissues, and HNE1 cell lines and is closely associated with NPC with cervical lymphnodes involvement. Both sensitivity and specificity of the telomerase assay are high. However, owing to the fact that the expression of hTR has no obvious difference between NPC and normal tissues and does not always correspond with the telomerase activity, it would be better to do TRAP as well as hTR assays for the activity and expression in assessing the carcinogenesis of NPC. So, more intensive study on the role of hTR in the carcinogenesis of NPC and on the exact relationship between hTR and telomerase is needed.

Adult↗