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Biomedical subjects

Z Jiang

Publications and source records attributed to Z Jiang.

At least 19 recordsLinked to original sources

Landau-level splitting in graphene in high magnetic fields.

The quantum Hall (QH) effect in two-dimensional electrons and holes in high quality graphene samples is studied in strong magnetic fields up to 45 T. QH plateaus at filling factors nu = 0, +/-1, +/-4 are discovered at magnetic fields B > 20 T, indicating the lifting of the fourfold degeneracy of the previously observed QH states at nu = +/-4(absolute value(n) + 1/2), where n is the Landau-level index. In particular, the presence of the nu = 0, +/-1 QH plateaus indicates that the Landau level at the charge neutral Dirac point splits into four sublevels, lifting sublattice and spin degeneracy. The QH effect at nu = +/-4 is investigated in a tilted magnetic field and can be attributed to lifting of the spin degeneracy of the n = 1 Landau level.

Journal Article↗

The bovine fatty acid binding protein 4 gene is significantly associated with marbling and subcutaneous fat depth in Wagyu x Limousin F2 crosses.

Fatty acid binding protein 4 (FABP4), which is expressed in adipose tissue, interacts with peroxisome proliferator-activated receptors and binds to hormone-sensitive lipase and therefore, plays an important role in lipid metabolism and homeostasis in adipocytes. The objective of this study was to investigate associations of the bovine FABP4 gene with fat deposition. Both cDNA and genomic DNA sequences of the bovine gene were retrieved from the public databases and aligned to determine its genomic organization. Primers targeting two regions of the FABP4 gene were designed: from nucleotides 5433-6106 and from nucleotides 7417-7868 (AAFC01136716). Direct sequencing of polymerase chain reaction (PCR) products on two DNA pools from high- and low-marbling animals revealed two single nucleotide polymorphisms (SNPs): AAFC01136716.1:g.7516G>C and g.7713G>C. The former SNP, detected by PCR-restriction fragment length polymorphism using restriction enzyme MspA1I, was genotyped on 246 F2 animals in a Waygu x Limousin F2 reference population. Statistical analysis showed that the FABP4 genotype significantly affected marbling score (P = 0.0398) and subcutaneous fat depth (P = 0.0246). The FABP4 gene falls into a suggestive/significant quantitative trait loci interval for beef marbling that was previously reported on bovine chromosome 14 in three other populations.

Animals↗

Detection of prostate cancer by alpha-methylacyl CoA racemase (P504S) in needle biopsy specimens previously reported as negative for malignancy.

AIMS: To investigate the possibility of detecting small focal prostatic cancer by alpha-methylacyl CoA racemase (AMACR)/P504S immunohistochemistry on needle biopsy specimens that were previously interpreted as negative for carcinoma on routine haematoxylin and eosin (H&E)-stained sections. METHODS: Prostate needle biopsy specimens (n = 793) previously interpreted as benign prostatic tissue by conventional morphology from 239 patients with prostatic cancer diagnosed in other biopsy cores taken at the same biopsy session were stained with the P504S monoclonal antibody. If a biopsy specimen stained positively, two pathologists independently reviewed the original corresponding H&E-stained sections to establish the malignant diagnosis. RESULTS: Eighty-four of the 793 biopsy specimens showed AMACR immunoreactivity; nine of these (9/793, 1.1%) contained previously unrecognized small focal prostatic carcinoma (Gleason 6, N = 8; Gleason 8, N = 1). Six of nine (67%) carcinomas showed foamy/pseudohyperplastic (N = 3) or atrophic (N = 3) features. Additionally, five biopsy specimens (5/793, 0.6%) with positive AMACR staining that did not meet the criteria for prostatic cancer on the original H&E slides were considered to be atypia. CONCLUSIONS: In this study, we found a 1.1% false-negative rate for carcinoma on routine H&E-stained sections. AMACR immunohistochemical staining has shown the ability to improve detection of small focal prostatic carcinoma that could be missed by conventional histological examination.

Biopsy, Needle↗

TLR signaling pathways: opportunities for activation and blockade in pursuit of therapy.

The identification of the TLRs as key sensors of microbial infection has presented a series of new targets for drug development. The TLRs are linked to the most powerful inflammatory pathways in mammals. The question arises from the start: do we wish to stimulate TLR signaling in order to eradicate specific infections and/or neoplastic diseases? Or do we wish to block TLR signaling to treat inflammatory diseases? If we accept that it would be useful to modulate TLR signaling, the next step is to identify the correct molecular target(s) for the task. Perhaps it might even be possible to exercise selectivity, modulating some aspects of TLR signaling and not others. Classical and reverse genetic analyses offer insight into the possibilities that exist, and point to specific checkpoints within signaling pathways at which modulation might normally be imposed.

Anti-Inflammatory Agents↗

Association of a single nucleotide polymorphism in the calpastatin gene with carcass and meat quality traits of beef cattle.

Calpastatin (CAST) is a naturally occurring protein that inhibits the normal tenderization of meat as it ages postmortem. A SNP was identified in the CAST gene (a G to C substitution) and genotyped on crossbred commercially fed heifers (n = 163), steers (n = 226), and bulls (n = 61) from beef feedlots, and steers (n = 178) from a University of Guelph feeding trial. The association of the CAST SNP with carcass and meat quality traits was studied. Carcass traits included fat, lean, and bone yield; grade fat; LM area; and HCW. Meat quality traits included marbling grade; i.m. fat content of LM; tenderness evaluation of LM (Warner-Bratzler shear force) at 2, 7, 14, and 21 d of postmortem aging; and tenderness evaluation of semitendinosus muscle at 7 d of postmortem aging. The mixed model used in the analyses included fixed effects of CAST genotype, sex, slaughter group, and breed composition (linear covariate); sire was a random effect. For the analysis of shear force, i.m. fat content of LM was also included in the model as a linear covariate. Shear force measures were analyzed within days of postmortem aging and by repeated measures analysis. The CAST SNP allele C was more frequent (63%) in the crossbred population than allele G. The CAST SNP was associated with shear force across days of postmortem aging (P = 0.005); genotype CC yielded beef that was more tender than GG (-0.32 kg +/- 0.13), and CG had intermediate tenderness. The corresponding average allele substitution effect (G to C substitution) was also highly significant (-0.15 +/- 0.05 kg, P = 0.002). A lower percentage of unacceptably tough steaks (shear force > 5.7 kg) at 2 and 7 d postmortem was associated with an increasing number of C alleles (P < or = 0.05). At 7 d postmortem, the percentage of unacceptably tough steaks decreased by 24 and 35%, respectively, for animals carrying 1 and 2 copies of the C allele relative to animals with no C alleles. However, genotype CC had a greater fat yield (+1.44 +/- 0.56%; P = 0.037) than genotype GG, with a corresponding allele substitution effect of 0.67 +/- 0.27% (P = 0.015). Therefore, the CAST SNP allele C was associated with increased LM tenderness across days of postmortem aging and, importantly for the beef industry, had a significant reduction in the percentage of steaks rated unacceptably tough by consumers based on an assumed threshold level.

Animals↗

Detection and characterization of amplified fragment length polymorphism markers for clinical mastitis in Canadian Holsteins.

Mastitis is the most frequent, complex, and costly disease in dairy cattle. Genetic improvement of milk production traits has accompanied an increased susceptibility to mastitis. To determine genome-wide quantitative trait locus-linked markers for mastitis resistance, a total of 200 cows, comprising 100 top clinical mastitis- (CM) resistant and 100 top CM-susceptible cows, were screened by selective DNA pooling and amplified fragment length polymorphism (AFLP) technique. The AFLP analysis on resistant and susceptible pools using 89 selective primer combinations revealed 27 significant AFLP markers at a false discovery rate (FDR) of < 5%. The most promising AFLP marker was then selected for further characterization. Individual AFLP genotyping of the marker on all selected animals confirmed a significant difference. Sequence analysis detected a single nucleotide polymorphism (A<-->G) responsible for the AFLP polymorphism, which was named CGIL4. The PCR-RFLP analysis indicated that the frequency of allele A was significantly higher in the resistant group. The logistic regression analysis demonstrated that the marker was significantly associated with somatic cell score, CM residual values, and production traits. Radiation hybrid mapping assigned the marker to Bos taurus autosome 22. The present study provides promising markers for marker-assisted selection for CM resistance. Our results also demonstrated the capability of AFLP on selective DNA pools as a method for detection of genome regions containing quantitative trait loci.

Amplified Fragment Length Polymorphism Analysis↗

An examination of the number of required apertures for step-and-shoot IMRT.

We have examined the degree to which step-and-shoot IMRT treatment plans can be simplified (using a small number of apertures) without sacrificing the dosimetric quality of the plans. A key element of this study was the use of direct aperture optimization (DAO), an inverse planning technique where all of the multi-leaf collimator constraints are incorporated into the optimization. For seven cases (1 phantom, 1 prostate, 3 head-and-neck and 2 lung), DAO was used to perform a series of optimizations where the number of apertures per beam direction varied from 1 to 15. In this work, we attempt to provide general guidelines for how many apertures per beam direction are sufficient for various clinical cases using DAO. Analysis of the optimized treatment plans reveals that for most cases, only modest improvements in the objective function and the corresponding DVHs are seen beyond 5 apertures per beam direction. However, for more complex cases, some dosimetric gain can be achieved by increasing the number of apertures per beam direction beyond 5. Even in these cases, however, only modest improvements are observed beyond 9 apertures per beam direction. In our clinical experience, 38 out of the first 40 patients treated using IMRT plans produced using DAO were treated with 9 or fewer apertures per beam direction. The results indicate that many step-and-shoot IMRT treatment plans delivered today are more complex than necessary and can be simplified without sacrificing plan quality.

Algorithms↗

Toxicogenomic profile of 2,3,7,8-tetrachlorodibenzo-p-dioxin in the murine fetal heart: modulation of cell cycle and extracellular matrix genes.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and similar environmental contaminants have been demonstrated to be potent cardiovascular teratogens in developing piscine and avian species. In the present study, we investigated the effects of TCDD on gene expression during murine cardiovascular development. C57Bl6N pregnant mice were dosed with 1.5, 3.0, or 6.0 microg TCDD/kg on gestational day (GD) 14.5, and microarray analysis was used to characterize the global changes in fetal cardiac gene expression on GD 17.5. TCDD significantly altered expression of a number of genes involved in xenobiotic metabolism, cardiac homeostasis, extracellular matrix production/remodeling, and cell cycle regulation. Interestingly, while the AhR-responsive genes Cyp1A1, Cyp1B1, Ugt1a6, and Ahrr, were all induced by TCDD in the fetal murine heart, other AhR-responsive genes, Cyp1a2, Nqo1, and Gsta1, were not. Quantitative real-time polymerase chain reactions confirmed the changes in expression of several G1/S-type cyclins and extracellular matrix-related genes. These results demonstrate the global changes in cardiac gene expression that result from TCDD exposure of the fetal murine heart and implicate genes involved in cell cycle and extracellular matrix regulation in TCDD-induced cardiac teratogenicity and functional deficits.

Animals↗

Spectral line-by-line pulse shaping.

We experimentally demonstrate pulse-shaping experiments in which the individual spectral lines that are present in the output of a mode-locked laser (8.5 GHz mode spacing, centered at 1542 nm) are resolved. The shaped pulses overlap in time, and this leads to a new way to observe fluctuations of the comb-offset frequency in the time domain.

Journal Article↗

Thermal conductance of Andreev interferometers.

We calculate the thermal conductance G(T) of diffusive Andreev interferometers, which are hybrid loops with one superconducting arm and one normal-metal arm. The presence of the superconductor suppresses G(T); however, unlike a conventional superconductor, G(T)/G(T)(N) does not vanish as the temperature T-->0, but saturates at a finite value that depends on the resistance of the normal-superconducting interfaces, and their distance from the path of the temperature gradient. The reduction of G(T) is determined primarily by the suppression of the density of states in the proximity-coupled normal metal along the path of the temperature gradient. G(T) is also a strongly nonlinear function of the thermal current, as found in recent experiments.

Journal Article↗

Involvement of extracellular signal-regulated kinases 1/2 and (phosphoinositide 3-kinase)/Akt signal pathways in acquired resistance against neurotoxin of 6-hydroxydopamine in SH-SY5Y cells following cell-cell interaction with astrocytes.

Glial cells interact with neurons and play important roles in the development, differentiation, maintenance and repair of the nervous system. Human neuroblastoma cells (SH-SY5Y) became dramatically resistant to neurotoxin 6-hydroxydopamine (6-OHDA), when co-cultured with mouse astrocytes. In order to further delineate the molecular mechanism involved in the neuroprotection in this selective cell-cell interaction, we assessed the activation of two signal pathways, namely, the MAP kinases (extracellular signal-regulated kinases, ERK1/2) and phosphoinositide 3-kinase (PI3-K)/Akt signal pathways in response to 6-OHDA insult and subsequent neuronal survival. Western blot revealed that 6-OHDA significantly increased the phosphorylation of ERK1/2 and Akt in mono-cultured SH-SY5Y cells. However, the increase in ERK1/2 in SH-SY5Y cells after co-cultured with astrocytes occurred as early as 3 h after 6-OHDA treatment in oppose to the increase after 12 h in monocultures. The phosphorylation of Akt in the co-cultured SH-SY5Y cells was much pronounced 3 h after 6-OHDA treatment compared with that in the mono-cultured cells. The anti-apoptotic protein bcl-2 was also increased in the co-cultured SH-SY5Y cells 3 h after treatment with 6-OHDA. Selective inhibitor of PI3-K/Akt signal pathway blocked the acquired resistance to 6-OHDA in SH-SY5Y cells following interaction with astrocytes. Inhibition of ERK1/2 signal pathway did not affect the cell survival. Our data suggest that PI3-K/Akt signal pathway, but not ERK1/2, is involved the acquired resistance in SH-SY5Y cells following cell-cell interaction with astrocytes against the neurotoxic 6-OHDA insult.

Adrenergic Agents↗

[Perfusion MR imaging for initial diagnosis and follow-up of brain tumors].

OBJECT: To discuss the pertinency of perfusion MR imaging for initial diagnosis and follow up of brain tumors. METHODOLOGY: Dynamic susceptibility contrast MR imaging was applied. Images were thus obtained with intensities proportional to the cerebral blood volume (CBV). Relative cerebral blood volume (rCBV) maps were then generated by normalizing the signal intensities with respect to measurements made in healthy tissue. RESULTS: The method provided interesting data for establishing the differential diagnosis between different kinds of lesions, in particular between lymphoma and pilocytic astrocytoma, and for grading gliomas. DISCUSSION AND CONCLUSION: Limits of the approach are discussed, in particular with respect to quantification aspects and interpretation of the results. The approach could be particularly useful for grading oligodendrogliomas, for which histological diagnosis on biopsy is sometimes difficult.

Astrocytoma↗

Frequency distribution of a Cys430Ser polymorphism in peroxisome proliferator-activated receptor-gamma coactivator-1 (PPARGC1) gene sequence in Chinese and Western pig breeds.

Identification of major genes, that genetically impact fat tissue formation is important for successful selection of lean animals with good meat quality. Because of its central role in fat cell differentiation and muscle fibre type determination, PPARGC1 is a potential candidate gene affecting fattening traits and pig meat quality. In this study, a T/A substitution at position 1378 (GenBank accession no. AY346131) in the porcine PPARGC1 gene causing a Cys430Ser amino acid substitution at position 430 was genotyped on a total of 239 animals, including 101 from seven Chinese and 138 from six Western pig breeds. Bayesian analysis revealed that the mean frequency of allele T (Cys) was 92.64 +/- 4.82% in Chinese pigs, and 45.99 +/- 4.13% in Western pigs. The 95% interval of the posterior mean frequency of allele T was 0.82-1.00 in Chinese pigs and 0.38-0.54 in Western pigs, indicating these two groups of pigs diverged at this locus during genetic evolution of the breed. Because marked differences in fat and lean tissue deposition exist between Western and Chinese pig breeds, this Cys430Ser exchange in the PPARGC1 gene deserves further evaluation to determine its phenotypic effect on fattening and carcass traits in commercial pig populations.

Amino Acid Substitution↗

An independent confirmation of a quantitative trait locus for milk yield and composition traits on bovine chromosome 26.

Several reports have demonstrated that bovine chromosome 26 (BTA26) harbours significant or suggestive quantitative trait loci (QTL) for milk production and composition traits in dairy cattle. Our previous study showed that a C/T substitution in the bovine TCF7L2 gene on BTA26 was significantly linked to QTL for protein yield (PY) in a Canadian dairy cattle population. Actually, this polymorphism was one of the markers derived from a genome-wide screening of QTL for milk PY using an amplified fragment length polymorphism technique combined with a DNA pooling strategy. In the present study, 990 Holstein bulls with complete genotype and phenotype data from 14 sire families were analysed to confirm, if the QTL effects exist in other populations. Statistical analysis revealed that this marker was significantly associated with PY, protein percentage, milk yield and fat yield (FY) (p < 0.001) in the US Holstein population. These results indicate that this QTL region has a pleiotrophic effecton different milk traits and is portable in different populations.

Analysis of Variance↗

Molecular evolution of the human chromosome 15 pericentromeric region.

We present a detailed molecular evolutionary analysis of 1.2 Mb from the pericentromeric region of human 15q11. Sequence analysis indicates the region has been subject to extensive interchromosomal and intrachromosomal duplications during primate evolution. Comparative FISH analyses among non-human primates show remarkable quantitative and qualitative differences in the organization and duplication history of this region - including lineage-specific deletions and duplication expansions. Phylogenetic and comparative analyses reveal that the region is composed of at least 24 distinct segmental duplications or duplicons that have populated the pericentromeric regions of the human genome over the last 40 million years of human evolution. The value of combining both cytogenetic and experimental data in understanding the complex forces which have shaped these regions is discussed.

Animals↗