Hyperglycaemia and oxidative stress upregulate HSP60 & HSP70 expression in HeLa cells

Heat Shock Proteins 60 & 70 (HSP60 & HSP70) are intracellular protein that has been shown to be present at elevated levels in systemic circulation in Type 2 Diabetes mellitus (T2DM) patients. Conditions that lead to its secretion, and the mechanism of its translocation from cells, have not yet been defined. The aim of this study was to determine if specific cell stressors associated with T2DM, namely hyperglycaemia and oxidative stress, result in the upregulation of HSP60 in human cells in vitro. Human HeLa cells were grown in media supplemented with 100 mM glucose, 200 μM hydrogen peroxide (H₂O₂), and 50 μM sodium azide. Initially, the effect of these treatments on cell growth rate was examined, with each treatment significantly inhibiting growth rate. LDH and MTT assays were also used to successfully demonstrate that these treatments do not significantly increase cell lysis, but do significantly impair mitochondrial dehydrogenase activity. To confirm this mitochondria specific form of inhibition, DCFDA assay were used to investigate any increases in intracellular reactive oxygen species (ROS) generation. All three treatments resulted in significantly increased ROS generation, with greater ROS production occurring with a greater exposure time. Interestingly, when the protein levels of HSP60 and HSP70 were measured after 3 and 7 days of exposure of the HeLa cells to 100 mM glucose, 200 μM H₂O₂, and 50 μM sodium azide significant induction of these two molecular stress proteins were observed ranging from 2.43-5.08 fold compared to untreated control cells

Closed-form sums for some perturbation series involving associated Laguerre polynomials

Infinite series sum_{n=1}^infty {(alpha/2)_n / (n n!)}_1F_1(-n, gamma, x^2), where_1F_1(-n, gamma, x^2)={n!_(gamma)_n}L_n^(gamma-1)(x^2), appear in the first-order perturbation correction for the wavefunction of the generalized spiked harmonic oscillator Hamiltonian H = -d^2/dx^2 + B x^2 + A/x^2 + lambda/x^alpha 0 0, A >= 0. It is proved that the series is convergent for all x > 0 and 2 gamma > alpha, where gamma = 1 + (1/2)sqrt(1+4A). Closed-form sums are presented for these series for the cases alpha = 2, 4, and 6. A general formula for finding the sum for alpha/2 = 2 + m, m = 0,1,2, ..., in terms of associated Laguerre polynomials, is also provided.Comment: 16 page

Observation of Multiple-Gap Structure in Hidden Order State of URu2Si2 from Optical Conductivity

We have measured the far infrared reflectance of the heavy fermion compound URu$_2$Si$_2$ through the phase transition at T$_{HO}$=17.5 K dubbed 'hidden order' with light polarized along both the a- and c-axes of the tetragonal structure. The optical conductivity allows the formation of the hidden order gap to be investigated in detail. We find that both the conductivity and the gap structure are anisotropic, and that the c-axis conductivity shows evidence for a double gap structure, with $\Delta_{1,c}=2.7$ meV and $\Delta_{2,c}=1.8$ meV respectively at 4 K, while the gap seen in the a-axis conductivity has a value of $\Delta_a=3.2$ meV at 4 K. The opening of the gaps does not follow the behaviour expected from mean field theory in the vicinity of the transition.Comment: 6 pages, 5 figure

A note on the probability of generating alternating or symmetric groups

We improve on recent estimates for the probability of generating the alternating and symmetric groups $\mathrm{Alt}(n)$ and $\mathrm{Sym}(n)$. In particular we find the sharp lower bound, if the probability is given by a quadratic in $n^{-1}$. This leads to improved bounds on the largest number $h(\mathrm{Alt}(n))$ such that a direct product of $h(\mathrm{Alt}(n))$ copies of $\mathrm{Alt}(n)$ can be generated by two elements

Scalar Mediated FCNC at the First Muon Collider

In the most general two-Higgs doublet model (generally referred to as Model III), tree level flavor changing neutral couplings exist. It has been noted that the most natural value for such a coupling is of the order of the geometric mean of the Yukawa couplings of the two fermions. Bounds on those couplings that involve the second and third generations, from $\tau,B,D$ and $\mu$ physics, are very weak and are not sensitive to this "natural" value. In this paper, it is pointed out that the process \mu\mu ---> \mu\tau, at a muon collider tuned to the scalar resonance, will easily reach this sensitivity if the scalar mass is below 140 GeV. Hundreds of events are expected for an integrated luminosity of an inverse femtobarn, and there appears to be no background. Failure to observe this process, if the scalar is below 140 GeV, would effectively rule out Model III.Comment: Paragraph added and other wording changed in introduction, some wording changes in text. Calculation unaffected. Version to appear in Phys. Lett.

Access, quality and equity in early childhood education and care: A South Australian study

Australian Journal of Education, 59/2, May/2015 published by SAGE Publishing, All rights reservedWhile much is known about the factors related to student performance beyond Grade 3 less is known about the factors that are related to student performance in early childhood education and the early years in primary school. As part of the 'I go to school' project in South Australia, this study tracked children attending integrated preschool/childcare centres -known as Children's Centres- as they made their transition to school. Results indicated that children who attended early childhood education programs that were of higher quality as characterised by higher staff qualifications and a greater range and more engaging children's activities showed a greater gain in cognitive development than children who attended lower quality programs. Findings also suggested that children who benefited the most from attendance in these programs were children from backgrounds of greater social disadvantage than children from less disadvantaged backgrounds

The Anomalous Magnetic Moment of the Muon and Higgs-Mediated Flavor Changing Neutral Currents

In the two-Higgs doublet extension of the standard model, flavor-changing neutral couplings arise naturally. In the lepton sector, the largest such coupling is expected to be $\mu-\tau-\phi#. We consider the effects of this coupling on the anomalous magnetic moment of the muon. The resulting bound on the coupling, unlike previous bounds, is independent of the value of other unknown couplings. It will be significantly improved by the upcoming E821 experiment at Brookhaven National Lab.Comment: 7 pages Latex, 2 figure

A Model In Vitro System to Study Heat Shock Protein 60 (HSP60) Expression in Response to Mitochondrial Impairment in Human Cells

Heat Shock Proteins (HSPs) are a class of ubiquitously expressed and functionally related proteins found in all living organisms from humans to bacteria. Their expression is increased in response to various cellular stressors in what is referred to as the heat shock response. The induction of one particular HSP, HSP60, has been found to be correlated with mitochondria specific cell stress. Recently HSP60 has been found to be secreted and expressed extracellularly, after first being thought to be strictly intracellular. However, the mechanisms of these mechanisms of translocation and secretion have not been clearly identified. The aim of this study was to develop a model in vitro system for HSP60 expression in human cells so that treatments which resulted in mitochondrial impairment could be investigated. This study looked at several aspects of high glucose, hydrogen peroxide (H₂O₂), and sodium azide treatment on human HeLa cells. At low levels, each treatment had a hormetic effect on HeLa cell growth; however at high concentrations growth was significantly inhibited. Additionally, high treatment concentrations resulted in increased cell lysis as determined by LDH assays. Treatment with concentrations of 100mM glucose, 200μM H₂O₂, and 50μM sodium azide were the only treatment concentrations that did not result in significantly different levels of cell lysis when compared to a control sample. Mitochondrial dehydrogenase activity was also found to be significantly decreased at high treatment concentrations as determined by MTT assays. Thus, 100mM glucose, 200μM H₂O₂, and 50μM sodium azide treatments were identified as optimal conditions for mitochondrial targeted cell stress, as each of these treatments impaired cell growth and inhibited mitochondrial activity while having no significant effect on the degree of cell lysis. The 100mM glucose, 200μM H₂O₂, and 50μM sodium azide treatments were then investigated for the intracellular reactive oxygen species (ROS) activity they induced over treatment periods of 24 hours, 3 and 7 days. After 7 days of treatment, the 200μM H₂O₂ and 50μM sodium azide treatments resulted in an approximate three-fold increase in ROS activity, while the 100mM glucose treatment resulted in almost twice as much ROS compared to a control sample. Finally, the effects of 100mM glucose, 200μM H₂O₂, and 50μM sodium azide treatments on HSP60 and HSP70 expression was also examined over 3 and 7 day time periods. After the 7 day treatment period, the 100mM glucose treatment had induced a 2.43 fold increase in HSP60 expression and a 2.75 fold increase in HSP70 expression, the 200μM H₂O₂ induced a 3.48 fold increase in HSP60 expression and a 3.98 fold increase in HSP70 expression, and finally the 50μM sodium azide induced a 4.74 fold increase in HSP60 expression and a 5.08 fold increase in HSP70 expression. It can therefore be concluded that 100mM glucose, 200μM H₂O₂, and 50μM sodium azide results in the upregulation of HSP60 and HSP70 in human HeLa cells. Therefore this model may be used to investigate further aspects of HSP60 induction, such as its translocation and secretion