Inhibition of DNA polymerase reactions by pyrimidine nucleotide analogues lacking the 2-keto group

To investigate the influence of the pyrimidine 2-keto group on selection of nucleotides for incorporation into DNA by polymerases, we have prepared two C nucleoside triphosphates that are analogues of dCTP and dTTP, namely 2-amino-5-(2′-deoxy-β-d-ribofuranosyl) pyridine-5′-triphosphate (d*CTP) and 5-(2′-deoxy-β-d-ribofuranosyl)-3-methyl-2-pyridone-5′-triphosphate (d*TTP) respectively. Both proved strongly inhibitory to PCR catalysed by Taq polymerase; d*TTP rather more so than d*CTP. In primer extension experiments conducted with either Taq polymerase or the Klenow fragment of Escherichia coli DNA polymerase I, both nucleotides failed to substitute for their natural pyrimidine counterparts. Neither derivative was incorporated as a chain terminator. Their capacity to inhibit DNA polymerase activity may well result from incompatibility with the correctly folded form of the polymerase enzyme needed to stabilize the transition state and catalyse phosphodiester bond formatio

Circular polarised antenna fabricated with low-cost 3D and inkjet printing equipment

The fabrication of a patch antenna using low-cost 3D printing equipment is presented. A circular polarised (CP) patch antenna is manufactured by combining inkjet printing and stereolithography (SLA) technology. The substrate has been fabricated by curing photosensitive resin while the patch element of the antenna has been inkjet printed using silver ink. The printed antenna satisfies the required reflection coefficient, axial ratio and radiation pattern at 1575 MHz. The aim is to demonstrate an inexpensive technology that could be used for the fabrication of antennas on customised 3D printed substrates. The performance of the antenna is summarised through simulations and experimental results

Development and Validation of an Instrument for Measuring Attitudes and Beliefs about Complementary and Alternative Medicine (CAM) Use among Cancer Patients

Despite cancer patients' extensive use of complementary and alternative medicine (CAM), validated instruments to measure attitudes, and beliefs predictive of CAM use are lacking. We aimed at developing and validating an instrument, attitudes and beliefs about CAM (ABCAM). The 15-item instrument was developed using the theory of planned behavior (TPB) as a framework. The literature review, qualitative interviews, expert content review, and cognitive interviews were used to develop the instrument, which was then administered to 317 outpatient oncology patients. The ABCAM was best represented as a 3-factor structure: expected benefits, perceived barriers, and subjective norms related to CAM use by cancer patients. These domains had Eigenvalues of 4.79, 2.37, and 1.43, and together explained over 57.2% of the variance. The 4-item expected benefits, 7-item perceived barriers, and 4-item subjective norms domain scores, each had an acceptable internal consistency (Cronbach's alpha) of 0.91, 0.76, and 0.75, respectively. As expected, CAM users had higher expected benefits, lower perceived barriers, and more positive subjective norms (all P < 0.001) than those who did not use CAM. Our study provides the initial evidence that the ABCAM instrument produced reliable and valid scores that measured attitudes and beliefs related to CAM use among cancer patients

Changes in the Expression of miR-381 and miR-495 Are Inversely Associated with the Expression of the MDR1 Gene and Development of Multi-Drug Resistance

Multidrug resistance (MDR) frequently develops in cancer patients exposed to chemotherapeutic agents and is usually brought about by over-expression of P-glycoprotein (P-gp) which acts as a drug efflux pump to reduce the intracellular concentration of the drug(s). Thus, inhibiting P-gp expression might assist in overcoming MDR in cancer chemotherapy. MiRNAome profiling using next-generation sequencing identified differentially expressed microRNAs (miRs) between parental K562 cells and MDR K562 cells (K562/ADM) induced by adriamycin treatment. Two miRs, miR-381 and miR-495, that were strongly down-regulated in K562/ADM cells, are validated to target the 3'-UTR of the MDR1 gene. These miRs are located within a miR cluster located at chromosome region 14q32.31, and all miRs in this cluster appear to be down-regulated in K562/ADM cells. Functional analysis indicated that restoring expression of miR-381 or miR-495 in K562/ADM cells was correlated with reduced expression of the MDR1 gene and its protein product, P-gp, and increased drug uptake by the cells. Thus, we have demonstrated that changing the levels of certain miR species modulates the MDR phenotype in leukemia cells, and propose further exploration of the use of miR-based therapies to overcome MDR.The authors would like to declare that we received funding from a commercial source, i.e. Bioplatforms Australia. This does not alter the authors' adherence to all PLOS ONE policies on sharing data and materials

Association of functional polymorphisms in CYP19A1 with aromatase inhibitor associated arthralgia in breast cancer survivors

INTRODUCTION: Aromatase inhibitor-associated arthralgia (AIAA) is a common and often debilitating symptom in breast cancer survivors. Since joint symptoms have been related to estrogen deprivation through the menopausal transition, we hypothesized that genetic polymorphisms in CYP19A1, the final enzyme in estrogen synthesis, may be associated with the occurrence of AIAA. METHODS: We performed a cross-sectional study of postmenopausal women with stage 0 to III breast cancer receiving adjuvant aromatase inhibitor (AI) therapy. Patient-reported AIAA was the primary outcome. DNA was genotyped for candidate CYP19A1 polymorphisms. Serum estrogen levels were evaluated by radioimmunoassay. Multivariate analyses were performed to examine associations between AIAA and genetic variants controlling for possible confounders. RESULTS: Among 390 Caucasian participants, 50.8% reported AIAA. Women carrying at least one 8-repeat allele had lower odds of AIAA (adjusted odds ratio (AOR) 0.41, 95% confidence interval (CI) 0.21 to 0.79, P = 0.008) after adjusting for demographic and clinical covariates. Estradiol and estrone were detectable in 47% and 86% of subjects on AIs, respectively. Although these post-AI levels were associated with multiple genotypes, they were not associated with AIAA. In multivariate analyses, women with more recent transition into menopause (less than five years) were significantly more likely to report AIAA than those greater than ten years post-menopause (AOR 3.31, 95% CI 1.72 to 6.39, P < 0.001). CONCLUSIONS: Functional polymorphism in CYP19A1 and time since menopause are associated with patient-reported AIAA, supporting the hypothesis that the host hormonal environment contributes to the pathophysiology of AAIA. Prospective investigation is needed to further delineate relationships between host genetics, changing estrogen levels and AIAA

Highly localized interactions between sensory neurons and sprouting sympathetic fibers observed in a transgenic tyrosine hydroxylase reporter mouse

<p>Abstract</p> <p>Background</p> <p>Sprouting of sympathetic fibers into sensory ganglia occurs in many preclinical pain models, providing a possible anatomical substrate for sympathetically enhanced pain. However, the functional consequences of this sprouting have been controversial. We used a transgenic mouse in which sympathetic fibers expressed green fluorescent protein, observable in live tissue. Medium and large diameter lumbar sensory neurons with and without nearby sympathetic fibers were recorded in whole ganglion preparations using microelectrodes.</p> <p>Results</p> <p>After spinal nerve ligation, sympathetic sprouting was extensive by 3 days. Abnormal spontaneous activity increased to 15% and rheobase was reduced. Spontaneously active cells had Aαβ conduction velocities but were clustered near the medium/large cell boundary. Neurons with sympathetic basket formations had a dramatically higher incidence of spontaneous activity (71%) and had lower rheobase than cells with no sympathetic fibers nearby. Cells with lower density nearby fibers had intermediate phenotypes. Immunohistochemistry of sectioned ganglia showed that cells surrounded by sympathetic fibers were enriched in nociceptive markers TrkA, substance P, or CGRP. Spontaneous activity began before sympathetic sprouting was observed, but blocking sympathetic sprouting on day 3 by cutting the dorsal ramus in addition to the ventral ramus of the spinal nerve greatly reduced abnormal spontaneous activity.</p> <p>Conclusions</p> <p>The data suggest that early sympathetic sprouting into the sensory ganglia may have highly localized, excitatory effects. Quantitatively, neurons with sympathetic basket formations may account for more than half of the observed spontaneous activity, despite being relatively rare. Spontaneous activity in sensory neurons and sympathetic sprouting may be mutually re-enforcing.</p

Study of the neutron star structure in strong magnetic fields including the anomalous magnetic moments

We study the effects of strong magnetic fields on the neutron star structure. If the interior field of a star is on the same order of the surface field currently observed, the influences of the magnetic field on the star mass and radius are negligible. If one assumes that the internal magnetic field can be as large as that estimated from the scalar virial theorem, considerable effects can be induced. The maximum mass of stars is arisen substantially while the central density is largely suppressed. For two equal-mass stars the radius of the magnetic star can be larger by about 10% $\sim$ 20% than the nonmagnetic star.Comment: 26 pages, 5 postscript figures; replaced by the revised version, Chin. J. Astron. Astrophys., accepte

Unusual Fermi Surface Sheet-Dependent Band Splitting in Sr2RuO4 Revealed by High Resolution Angle-Resolved Photoemission

High resolution angle-resolved photoemission measurements have been carried out on Sr2RuO4. We observe clearly two sets of Fermi surface sheets near the (\pi,0)-(0,\pi) line which are most likely attributed to the surface and bulk Fermi surface splitting of the \beta band. This is in strong contrast to the nearly null surface and bulk Fermi surface splitting of the \alpha band although both have identical orbital components. Extensive band structure calculations are performed by considering various scenarios, including structural distortion, spin-orbit coupling and surface ferromagnetism. However, none of them can explain such a qualitative difference of the surface and bulk Fermi surface splitting between the \alpha and \beta sheets. This unusual behavior points to an unknown order on the surface of Sr2RuO4 that remains to be uncovered. Its revelation will be important for studying and utilizing novel quantum phenomena associated with the surface of Sr2RuO4 as a result of its being a possible p-wave chiral superconductor and a topological superconductor.Comment: 13 pages, 4 figure