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Biomedical subjects

X Yang

Publications and source records attributed to X Yang.

At least 55 records · Page 3Linked to original sources

The head and body lice of humans are genetically distinct (Insecta: Phthiraptera, Pediculidae): evidence from double infestations.

Little is known about the population genetics of the louse infestations of humans. We used microsatellite DNA to study 11 double infestations, that is, hosts infested with head lice and body lice simultaneously. We tested for population structure on a host, and for population structure among seven hosts that shared sleeping quarters. We also sought evidence of migration among louse populations. Our results showed that: (i) the head and body lice on these individual hosts were two genetically distinct populations; (ii) each host had their own populations of head and body lice that were genetically distinct to those on other hosts; and (iii) lice had migrated from head to head, and from body to body, but not between heads and bodies. Our results indicate that head and body lice are separate species.

Animals↗

The regulation of cell migration by PTEN.

In vertebrates, the tumour suppressor PTEN (phosphatase and tensin homologue deleted on chromosome 10) regulates many cellular processes through its PtdIns(3,4,5)P3 lipid phosphatase activity, antagonizing PI3K (phosphoinositide 3-kinase) signalling. Given the important role of PI3Ks in the regulation of directed cell migration and the role of PTEN as an inhibitor of migration, it is somewhat surprising that data now indicate that PTEN is able to regulate cell migration independent of its lipid phosphatase activity. Here, we discuss the role of PTEN in the regulation of cell migration.

Animals↗

In vitro microsomal metabolic studies on a selective mGluR5 antagonist MTEP: characterization of in vitro metabolites and identification of a novel thiazole ring opening aldehyde metabolite.

In vitro liver microsomal studies revealed that [14C] MTEP (3-[2-methyl-1,3-thiazol-4-yl)ethynyl] pyridine) was metabolized into three major oxidative metabolites. Metabolite 1 (M1) was shown to be a hydroxymethyl metabolite; M2 was shown to be a pyridine oxide. Moreover, a novel aldehyde metabolite (M3) was identified from mouse liver microsomes. The structure of the aldehyde M3 was elucidated by LC/MS/MS. In addition, methoxyamine, an aldehyde-trapping agent, and accurate mass measurement using a high-resolution quadrupole-time of flight (Q-TOF) instrument, were used to confirm the proposed thiazole ring-opening structure of M3. A mechanism for aldehyde M3 formation was postulated based on MTEP incubation studies with 18O2 and H2 18O using mouse liver microsomes. MTEP was initially oxidized at sulfur, followed by subsequent C4-C5 of thiazole epoxidation, thiozole ring opening and further oxidative desulfation. This proposed thiazole ring-opening mechanism might represent a novel metabolism pathway for xenobiotics containing a thiazole moiety. Species differences in the metabolism of MTEP were observed in mouse, rat, dog, monkey and human liver microsomes. Mouse appears to generate all three oxidative metabolites to a greater extent than other species examined.

Aldehydes↗

Removal of contaminants released from room surfaces by displacement and mixing ventilation: modeling and validation.

UNLABELLED: This paper presents the experimental and numerical modeling of contaminant dispersion in a full-scale environmental chamber with different room air distribution systems. For the experimental modeling, an area source with uniform emissions of a hypothetical contaminant (SF6) from the entire floor surface is designed and constructed. Two different types of ventilation are studied: displacement and mixing ventilation. A computer model for predicting the contaminant dispersion in indoor spaces was validated with experimental data. The validated model is used to study the effects of airflow and the area-source location on contaminant dispersion. Results show that the global airflow pattern has a strong impact on the distribution of the contaminants. In general, the personal exposure could be estimated by analyzing the relative source positions in the airflow pattern. Accordingly, the location of an exhaust diffuser may not greatly affect the airflow pattern, but can significantly affect the exposure level in the room. PRACTICAL IMPLICATIONS: When designing ventilation in addition to bringing fresh air to occupants, it is important to consider the removal of contaminants released in the off-gassing of building materials. Typical indoor off-gassing examples are emissions of volatile organic compounds from building enclosure surfaces such as flooring and painted walls. In this study, we conducted experimental and numerical modeling of different area sources in a mock-up office setup, with displacement or mixing ventilation. Displacement ventilation was as successful as mixing ventilation in removing the contaminant source from the floor area. Actually, the most important consideration in the removal of these contaminants is the relative position of the area source to the main airflow pattern and the occupied zone.

Air Pollutants↗

Unoperated tetralogy of Fallot: case report of a natural survivor who died in his 73rd year; is it ever too late to operate?

The case history is described of a man in his 73rd year who was one of the oldest surviving patients with uncorrected tetralogy of Fallot (ToF) before succumbing with renal failure. Factors contributing to his longevity included small pulmonary arteries and presumed slow development of subpulmonary obstruction together with moderate concentric left ventricular hypertrophy--features previously seen in long term survivors. Less than 3% of all patients with uncorrected ToF survive beyond their 40s but late operative repair is still a valuable option. Practicalities of renal dialysis in the presence of an intracardiac shunt are considered.

Aged↗

Expression of granulocyte colony stimulating factor receptor in human colorectal cancer.

AIMS: To discover if human colorectal cancer expresses granulocyte colony stimulating factor receptor (G-CSFR) and if granulocyte colony stimulating factor (G-CSF) plays an important part in the development and progression of human colorectal cancer. METHODS: Forty two specimens of colorectal cancer and normal colorectal mucosa were investigated, taken from the colon or rectum in group of colorectal cancer patients. Immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR) technique were used to show G-CSFR expression. The relation between expression of G-CSFR and clinical or pathological factors was analysed. RESULTS: Immucohistochemical analyses showed that G-CSFR was expressed in the human colorectal cancer (25 of 42, 59.52%) and seemed to be up-regulated compared with the normal mucosa (14 of 42, 33.33%, p<0.001). In pronounced contrast with mostly strongly positive tumours, corresponding normal colorectal mucosa was negative or weakly positive. A significant correlation was found between G-CSFR expression and tumour stage (p = 0.001), tumour differentiation (p<0.001), but there was no significant relation between the expression of G-CSFR and the age, sex, and tumour size (p = 0.346, p = 0.686, p = 0.459). In RT-PCR, 21 of all 42 tumours had G-CSFR mRNA expression, while only 11 of 42 normal colorectal mucosa had such expression. CONCLUSIONS: These data show that G-CSFR is commonly expressed in human colorectal cancers, thus supporting a possible role for G-CSF in colorectal cancer physiology.

Adolescent↗

Soft deposition of organic macromolecules with fast atom bombardment mass spectrometry.

In order to investigate the requirements for soft deposition of intact positively charged organic macromolecules, an homogenous series of modal compounds such as polyphenylene dendronized perylenes (PDPs), C(80)H(52), C(200)H(132) and C(320)H(212) and a series of derivatives involving perylene derivative, C(98)H(104)N(8)O(4), terrylene derivative, C(78)H(82)N(6)O(4) and quaterrylene derivative, C(140)H(138)N(10)O(8), were used for soft-landing experiments on a metallic or matrix coated surface using fast atom bombardment mass spectrometry. Soft-landing can be achieved at impact energies below 180 eV with no production of fragments. The deposition rate shows strong energy dependence with similar behavior of the different organic compounds. A single isotope of the molecule was selected and soft-landed at increased resolution.

Journal Article↗

Two cis-acting elements in negative RNA strand of Hepatitis C virus involved in synthesis of positive RNA strand in vitro.

Sequences at the 3'-ends of both positive and negative strands of Hepatitis C virus (HCV) RNA harbor cis-acting elements required for RNA replication. However, little is known about the properties of the negative RNA strand as a template for the synthesis of positive RNA strand. In this study, a purified recombinant HCV RNA-dependent RNA polymerase (RdRp) was used to investigate the synthesis of positive RNA strand using the 3'-terminal region of negative RNA strand ((-)3'T RNA) as template. A mutagenesis analysis was performed to evaluate the role of the 3'-proximal stem-loop and the first 3'-cytidylate (3'C) of the negative RNA strand in the synthesis of the positive RNA strand. A negative RNA strand of wild type (wt) HCV as template was able to direct the synthesis of a full-length positive RNA strand. Deletion of the 3'-proximal stem-loop resulted in an approximately 90% decrease in RNA synthesis. Disruption of the 3'-proximal stem-loop structure by nucleotide substitutions led to a 70-80% decrease in RNA synthesis. However, the restoration of the stem-loop by compensatory mutations in the stem region restored also the RNA synthesis. Likewise, the deletion or substitution of the first 3'C by guanylate (G) led to a 90% decrease in the RNA synthesis; while the substitution by adenylate (A) or uridylate (U) resulted in a 60-80% decrease in the RNA synthesis only. These findings demonstrate that the 3'-proximal stem-loop and the first 3'C of the negative RNA strand of HCV are two cis-acting elements involved in the synthesis of the positive RNA strand.

3' Untranslated Regions↗

Methylation and acetylation characteristics of cloned bovine embryos from donor cells treated with 5-aza-2'-deoxycytidine.

Differentiated somatic cells and embryos cloned from somatic cells by nuclear transfer (NT) have higher levels of DNA methylation than gametes and early embryos produced in vivo. Reducing DNA methylation in donor cells before NT by treating them with chemicals such as the DNA methyl-transferase inhibitor (5-aza-2'-deoxycytidine; 5-aza-dC) may improve cloning efficiency of NT embryos by providing donor cells with similar epigenetic characteristics as in vivo embryos. Previously, high levels of this reagent were used to treat donor cells, and decreased development of cloned embryos was observed. In this study, we tested a lower range (0.005 to 0.08 microM) of this drug and used cell cycle distribution changes as an indicator of changes in the characteristics of donor cells. We found that at 0.01 microM 5-aza-dC induced changes in the cycle stage distribution of donor cells, increased the fusion rate of NT embryos, and had no deleterious effect on the percentage of blastocyst development. Levels of 5-aza-dC greater than 0.01 microM significantly decreased embryo development. Embryos cloned from donor cells treated with a low dose of 5-aza-dC had higher levels of DNA methylation than embryos produced by in vitro fertilization, but they also had higher levels of histone acetylation. Although 5-aza-dC at 0.04 microM or higher reduced DNA methylation and histone acetylation levels to those of in vitro-fertilized embryos, development to blastocyst was reduced, suggesting that this concentration of the drug was detrimental. In summary, 5-aza-dC at 0.01 microM altered donor cell characteristics while showing no deleterious effects on embryos cloned from treated cells.

Acetylation↗

Molecular mapping of Stb1, a potentially durable gene for resistance to septoria tritici blotch in wheat.

Septoria tritici blotch (STB), caused by the ascomycete Mycosphaerella graminicola (anamorph Septoria tritici), was the most destructive disease of wheat in Indiana and adjacent states before deployment of the resistance gene Stb1 during the early 1970s. Since then, Stb1 has provided durable protection against STB in widely grown wheat cultivars. However, its chromosomal location and allelic relationships to most other STB genes are not known, so the molecular mapping of Stb1 is of great interest. Genetic analyses and molecular mapping were performed for two mapping populations. A total of 148 F1 plants (mapping population I) were derived from a three-way cross between the resistant line P881072-75-1 and the susceptible lines P881072-75-2 and Monon, and 106 F6 recombinant-inbred lines (mapping population II) were developed from a cross between the resistant line 72626E2-12-9-1 and the susceptible cultivar Arthur. Bulked-segregant analysis with random amplified polymorphic DNA (RAPD), amplified fragment length polymorphism (AFLP), and microsatellite or simple-sequence repeat (SSR) markers was conducted to identify those that were putatively linked to the Stb1 gene. Segregation analyses confirmed that a single dominant gene controls the resistance to M. graminicola in each mapping population. Two RAPD markers, G7(1200) and H19(520), were tightly linked to Stb1 in wheat line P881072-75-1 at distances of less than 0.68 cM and 1.4 cM, respectively. In mapping population II, the most closely linked marker was SSR Xbarc74, which was 2.8 cM proximal to Stb1 on chromosome 5BL. Microsatellite loci Xgwm335 and Xgwm213 also were proximal to Stb1 at distances of 7.4 cM and 8.3 cM, respectively. The flanking AFLP marker, EcoRI-AGC/ MseI-CTA-1, was 8.4 cM distal to Stb1. The two RAPD markers, G7(1200) and H19(520), and AFLP EcoRI-AGC/ MseI-CTA-1, were cloned and sequenced for conversion into sequence-characterized amplified region (SCAR) markers. Only RAPD allele H19(520) could be converted successfully, and none of the SCAR markers was diagnostic for the Stb1 locus. Analysis of SSR and the original RAPD primers on several 5BL deletion stocks positioned the Stb1 locus in the region delineated by chromosome breakpoints at fraction lengths 0.59 and 0.75. The molecular markers tightly linked to Stb1 could be useful for marker-assisted selection and for pyramiding of Stb1 with other genes for resistance to M. graminicola in wheat.

Ascomycota↗

Analyses of proteolipid protein mutants show levels of proteolipid protein regulate oligodendrocyte number and cell death in vitro and in vivo.

Previous tissue culture studies indicate that the level of native proteolipid protein (PLP) or mutated PLP regulates the number of oligodendrocytes (Olgs). The regulation of Olg number is most likely due to toxicity of over-expression of native PLP or mis-sense mutations of PLP. We tested, in vivo and in vitro, the hypothesis that the absence of native PLP or reduced amounts of mutated PLP leads to an increase in numbers of Olgs and a corresponding decrease in the number of apoptotic Olgs. In cultures derived from PLP deficient mice, the number of Olgs is twofold greater than in wild-type mice. In primary glial cultures or in enriched OLG cultures, in which the synthesis of native PLP is blocked using antisense technology, the number of apoptotic cells is several-fold reduced. Injection of PLP antisense oligodeoxynucleotides into jimpy (jp) mice reduces the number of dying glia in spinal cord 3x compared to controls, and increased the number of myelinated fibers. These studies demonstrate that inhibition of native or mutant PLP synthesis directly reduces apoptosis. The regulation of apoptosis by PLP gene expression occurs independently of myelination, indicating that the PLP gene has multiple primary functions.

Animals↗

Comparison on in vitro fertilized bovine embryos cultured in KSOM or SOF and cryopreserved by slow freezing or vitrification.

The objectives of this study were to identify an improved in vitro cell-free embryo culture system and to compare post-warming development of in vitro produced (IVP) bovine embryos following vitrification versus slow freezing. In Experiment 1, non-selected presumptive zygotes were randomly allocated to four medium treatments without co-culture: (1) SOF + 5% FCS for 9 days; (2) KSOM + 0.1% BSA for 4 days and then KSOM + 1% BSA to Day 9; (3) SOF + 5% FCS for 4 days and then KSOM + 1% BSA to Day 9; and (4) KSOM + 0.1% BSA for 4 days and then SOF + 5% FCS to Day 9. Treatment 4 (sequential KSOM-SOF culture system) improved (P > 0.05) morulae (47%), early blastocysts (26%), Day-7 blastocysts (36%), cell numbers, as well as total hatching rate (79%) compared to KSOM alone (Treatment 2). Embryos cultured in KSOM + BSA alone developed slowly and most of them hatched late on Day 9, compared to other treatments. In Experiment 2, the sequential KSOM-SOF culture system was used and Day-7 blastocysts were subjected to following cryopreservation comparison: (1) vitrification (VS3a, 6.5 M glycerol); or (2) slow freezing (1.36 M glycerol). Warmed embryos were cultured in SOF with 7.5% FCS. Higher embryo development and hatching rates (P < 0.05) were obtained by vitrification at 6h (71%), 24h (64%), and 48h (60%) post-warming compared to slow freezing (48, 40, and 31%, respectively). Following transfer of vitrified embryos to synchronized recipients, a 30% pregnancy rate was obtained. In conclusion, replacing KSOM with SOF after 4 days of culture produced better quality blastocysts. Vitrification using VS3a may be used more effectively to cryopreserve in vitro produced embryos than the conventional slow freezing method.

Animals↗

Identification of multiple genetic loci that regulate adenovirus gene therapy.

A key aspect of the immune response to adenovirus (Ad) gene therapy is the generation of a cytotoxic T-cell (CTL) response. To better understand the genetic network underlying these events, 20 strains of C57BL/6 x DBA/2 (BXD) recombinant inbred (RI) mice were administered with AdLacZ and analyzed at days 7, 21, 30, and 50 for liver beta-galactosidase (LacZ) expression and CTL response. Sera levels of interferon gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) were analyzed at different times after AdLacZ. There was a distinct strain-dependent expression of LacZ, which was strongly correlated with the CTL response. Among the five BXD RI strains that exhibited significantly prolonged LacZ expression, four also exhibited a marked defect in the production of Ad-specific CTL. There was a strong correlation between the sera levels of IFN-gamma, TNF-alpha, and IL-6, but cytokine responses were not significantly correlated with LacZ expression or the CTL response. Quantitative trait loci regulating LacZ on day 30 were found on chromosome (Chr) 19 (33 cM) and Chr 15 (42.8 cM). Cytotoxicity mapped to Chr 7 (41.0 and 57.4-65.2 cM), Chr 15 (61.7 cM), and Chr X (27.8 cM). IFN-gamma production mapped to Chr 18 (22, 27, and 32 cM) and Chr 11 (64.0 cM). TNF-alpha and IL-6 production mapped to Chr 6 (91.5 cM) Chr 9 (42.0 cM) and Chr 8 (52 and 73.0 cM). These results indicate that different strains of mice exhibit different pathways for effective clearance of AdLacZ depending on genetic polymorphisms and interactions at multiple genetic loci.

Adenoviridae↗

Identification of a novel HLA-DRB1 allele (DRB1*1147)* by sequence-based typing in eight siblings.

We report here a novel DRB1 allele (DRB1*1147) identified by sequence-based typing. The DRB1*1147 allele was detected during routine human leukocyte antigen (HLA)-typing of a patient and his family prior to bone marrow transplantation. This allele was found in the patient and his two sisters and five brothers. The new allele is identical to DRB1*110601 at exon 2 except for a single-nucleotide substitution at codon 37 (TAC-->TCC), changing the encoded tyrosine to serine.

Alleles↗

Analysis of the CC chemokine receptor 5 (CCR5) Delta32 polymorphism in Behçet's disease.

Chemokines are important determinants of the early inflammatory response. The CC chemokine receptor 5 (CCR5) Delta32 variant results in a non-functional form of the chemokine receptor, and has been implicated in a variety of immune-mediated diseases. To investigate its role in the pathogenesis of Behçet's disease, we studied 350 patients and 519 healthy controls from three ethnic groups. While significant inter-ethnic variation in allele frequency was observed, no association was identified with disease, even when data were stratified by the known susceptibility gene HLA-B*51.

Alleles↗