Diet-induced hypercholesterolemia promotes androgen-independent prostate cancer metastasis via IQGAP1 and caveolin-1

Obesity and metabolic syndrome are associated with several cancers, however, the molecular mechanisms remain to be fully elucidated. Recent studies suggest that hypercholesterolemia increases intratumoral androgen signaling in prostate cancer, but it is unclear whether androgenindependent mechanisms also exist. Since hypercholesterolemia is associated with advanced, castrate-resistant prostate cancer, in this study, we aimed to determine whether and how hypercholesterolemia affects prostate cancer progression in the absence of androgen signaling. We demonstrate that diet-induced hypercholesterolemia promotes orthotopic xenograft PC-3 cell metastasis, concomitant with elevated expression of caveolin-1 and IQGAP1 in xenograft tumor tissues. In vitro cholesterol treatment of PC-3 cells stimulated migration and increased IQGAP1 and caveolin-1 protein level and localization to a detergent-resistant fraction. Down-regulation of caveolin-1 or IQGAP1 in PC-3 cells reduced migration and invasion in vitro, and hypercholesterolemia-induced metastasis in vivo. Double knock-down of caveolin-1 and IQGAP1 showed no additive effect, suggesting that caveolin-1 and IQGAP1 act via the same pathway. Taken together, our data show that hypercholesterolemia promotes prostate cancer metastasis independent of the androgen pathway, in part by increasing IQGAP1 and caveolin-1. These results have broader implications for managing metastasis of cancers in general as IQGAP1 and hypercholesterolemia are implicated in the progression of several cancers.

The impact of inter-fraction set-up errors on the probability of pulmonary and cardiac complication in left-sided breast cancer patients

Purpose This study evaluated the impact of patient set-up errors on the probability of pulmonary and cardiac complications in the irradiation of left-sided breast cancer. Methods and Materials Using the CMS XiO Version 4.6 (CMS Inc., St Louis, MO) radiotherapy planning system's NTCP algorithm and the Lyman -Kutcher-Burman (LKB) model, we calculated the DVH indices for the ipsilateral lung and heart and the resultant normal tissue complication probabilities (NTCP) for radiation-induced pneumonitis and excess cardiac mortality in 12 left-sided breast cancer patients. Results Isocenter shifts in the posterior direction had the greatest effect on the lung V20, heart V25, mean and maximum doses to the lung and the heart. Dose volume histograms (DVH) results show that the ipsilateral lung V20 tolerance was exceeded in 58% of the patients after 1cm posterior shifts. Similarly, the heart V25 tolerance was exceeded after 1cm antero-posterior and left-right isocentric shifts in 70% of the patients. The baseline NTCPs for radiation-induced pneumonitis ranged from 0.73% - 3.4% with a mean value of 1.7%. The maximum reported NTCP for radiation-induced pneumonitis was 5.8% (mean 2.6%) after 1cm posterior isocentric shift. The NTCP for excess cardiac mortality were 0 % in 100% of the patients (n=12) before and after setup error simulations. Conclusions Set-up errors in left sided breast cancer patients have a statistically significant impact on the Lung NTCPs and DVH indices. However, with a central lung distance of 3cm or less (CLD <3cm), and a maximum heart distance of 1.5cm or less (MHD<1.5cm), the treatment plans could tolerate set-up errors of up to 1cm without any change in the NTCP to the heart.

Microbial ecology of the equine hindgut during oligofructose-induced laminitis

Alimentary carbohydrate overload is a significant cause of laminitis in horses and is correlated with drastic shifts in the composition of hindgut microbiota. Equine hindgut streptococcal species (EHSS), predominantly Streptococcus lutetiensis, have been shown to be the most common microorganisms culturable from the equine caecum prior to the onset of laminitis. However, the inherent biases of culture-based methods are estimated to preclude up to 70% of the normal caecal microbiota. The objective of this study was to evaluate bacterial population shifts occurring in the equine caecum throughout the course of oligofructose-induced laminitis using several culture-independent techniques and to correlate these with caecal lactate, volatile fatty acid and degrees of polymerization 3-7 fructo-oligosaccharide concentrations. Our data conclusively show that of the total microbiota present in the equine hindgut, the EHSS S. lutetiensis is the predominant microorganism that proliferates prior to the onset of laminitis, utilizing oligofructose to produce large quantities of lactate. Population shifts in lactobacilli and Escherichia coli subpopulations occur secondarily to the EHSS population shifts, thus confirming that lactobacilli and coliforms have no role in laminitis. A large, curved, Gram-negative rod previously observed during the early phases of laminitis induction was most closely related to the Anaerovibrio genus and most likely represents a new, yet to be cultured, genus and species. Correlation of fluorescence in situ hybridization and quantitative real-time PCR results provide evidence supporting the hypothesis that laminitis is associated with the death en masse and rapid cell lysis of EHSS. If EHSS are lysed, liberated cellular components may initiate laminitis.

Photo-induced double-strand DNA and site-specific protein cleavage activity of L-histidine (mu-oxo)diiron(III) complexes of heterocyclic bases

Three oxo-bridged diiron(III) complexes of L-histidine and heterocyclic bases [Fe-2(mu-O)(L-his)(2)(B)(2)](ClO4)(2) (1-3), where B is 2,2'-bipyridine (bpy),1,10-phenanthroline (phen), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq), were prepared and characterized. The bpy complex 1 was structurally characterized by X-ray crystallography. The molecular structure showed a {Fe-2(mu-O)} core in which iron(III) in a FeN4O2 coordination is bound to tridentate monoanionic L-histidine and bidentate bpy ligands. The Fe center dot center dot center dot Fe distance is similar to 3.5 angstrom. The Fe-O-Fe unit is essentially linear, giving a bond angle of similar to 172 degrees. The complexes showed irreversible cyclic voltammetric cathodic response near -0.1 V vs. SCE in H2O-0.1 M KCl. The binuclear units displayed antiferromagnetic interaction between two high-spin (S = 5/2) iron(III) centers giving a -J value of -110 cm(-1). The complexes showed good DNA binding propensity giving a binding constant value of similar to 10(5) M-1. Isothermal titration calorimetric data indicated single binding mode to the DNA. The binding was found to be driven by negative free energy change and enthalpy. The dpq complex 3 showed oxidative double-strand DNA cleavage on exposure to UV-A and visible light. The phen complex 2 displayed single-strand photocleavage of DNA. The DNA double-strand breaks were rationalized from theoretical molecular docking calculations. Mechanistic investigations showed formation of hydroxyl radicals as the reactive species through photodecarboxylation of the L-histidine ligand. The complexes exhibited good binding propensity to bovine serum albumin (BSA) protein in Tris-HCl/NaCl buffer medium. The dpq complex 3 showed UV-A light-induced site-specific oxidative BSA cleavage forming fragments of similar to 45 kDa and similar to 20 kDa molecular weights via SOH pathway.

Sorghum stay-green QTL individually reduce post-flowering drought-induced leaf senescence

Sorghum is an important source of food, feed, and biofuel, especially in the semi-arid tropics because this cereal is well adapted to harsh, drought-prone environments. Post-flowering drought adaptation in sorghum is associated with the stay-green phenotype. Alleles that contribute to this complex trait have been mapped to four major QTL, Stg1-Stg4, using a population derived from BTx642 and RTx7000. Near-isogenic RTx7000 lines containing BTx642 DNA spanning one or more of the four stay-green QTL were constructed. The size and location of BTx642 DNA regions in each RTx7000 NIL were analysed using 62 DNA markers spanning the four stay-green QTL. RTx7000 NILs were identified that contained BTx642 DNA completely or partially spanning Stg1, Stg2, Stg3, or Stg4. NILs were also identified that contained sub-portions of each QTL and various combinations of the four major stay-green QTL. Physiological analysis of four RTx7000 NILs containing only Stg1, Stg2, Stg3, or Stg4 showed that BTx642 alleles in each of these loci could contribute to the stay-green phenotype. RTx7000 NILs containing BTx642 DNA corresponding to Stg2 retained more green leaf area at maturity under terminal drought conditions than RTx7000 or the other RTx7000 NILs. Under post-anthesis water deficit, a trend for delayed onset of leaf senescence compared with RTx7000 was also exhibited by the Stg2, Stg3, and Stg4 NILs, while significantly lower rates of leaf senescence in relation to RTx7000 were displayed by all of the Stg NILs to varying degrees, but particularly by the Stg2 NIL. Greener leaves at anthesis relative to RTx7000, indicated by higher SPAD values, were exhibited by the Stg1 and Stg4 NILs. The RTx7000 NILs created in this study provide the starting point for in-depth analysis of stay-green physiology, interaction among stay-green QTL and map-based cloning of the genes that underlie this trait.

Pressure induced polymorphous crystallization in bulk Ge20Te80 glass

The pressure and temperature dependence of the electrical resistivity of bulk glassy Ge20Te80 is reported. The effect of annealing is also studied. The glass undergoes a polymorphous or congruent crystallization under high pressures. The high pressure phase is found to have fcc structure with Image . Under thermal treatment the glass undergoes the double stage crystallization. The sample annealed at the first crystallization temperature shows a pressure induced semiconductor-to-metal transition at 4.0 GPa pressure and the crystalline Ge20Te80 samples show the transition at 7 GPa pressure.

Instabilities induced by variation of Brunt-Vaisala frequency in compressible stratified shear flows

The stability characteristics of a Helmholtz velocity profile in a stably stratified, compressible fluid in the presence of a lower rigid boundary are studied. A jump in the Brunt-Vaisala frequency at a level different from the shear zone is introduced and the variation of the Brunt-Vaisala frequency with respect to the vertical coordinate in the middle layer of the three-layered model is considered. An analytic solution in each of the layers is obtained, and the dispersion relation is solved numerically for parameters relevant to the model. The effect of shear in the lowermost layer of the three-layered model for a Boussinesq fluid is discussed. The results are compared with the earlier studies of Lindzen and Rosenthal, and Sachdev and Satya Narayanan. In the present model, new unstable modes with larger growth rates are obtained and the most unstable gravity wave modes are found to agree closely with the observed ones at various heights. Physics of Fluids is copyrighted by The American Institute of Physics.

Magnetic Field Induced Instabilities In Localized Two-Dimensional Electron Systems

The results of extensive transport studies in localized regime of mesoscopic two-dimensional electron systems (2DES) with varying disorder are presented. A quick overview of previously achieved result is given. The main focus is on the observation of density dependent instabilities manifested by strong resistance oscillations induced by high perpendicular magnetic fields B-perpendicular to. While the amplitude of the oscillations is strongly enhanced with increasing B-perpendicular to, their position in electron density remains unaffected. The temperature dependence of resistivity shows a transition from an activated behaviour at high temperature to a saturated behaviour at low T. In the positions of resistance minima, the T dependence can even become metal-like (d rho/dT > 0). The activation energies obtained from the high T behaviour exhibit a formation of plateaux in connection with the resistance oscillations when analyzed as a function of electron density. We suggest the interplay between a strongly interacting electron phase and the background disorder as a possible explanation for our observation.

The nature of hydrogen induced amorphization of SmNi2 laves compound

Abstract is not available.

Purification of clofibrate-induced carnitine acetyltransferase from rat liver mitochondria

The enzyme carnitine acetyltransferase (acetyl-CoA:carnitine O-acetyltransferase, EC 2.3.1.7) has been purified to homogeneity from hepatic mitochondria of clofibrate-fed rats. It is a protein of molecular weight 56 000 composed of two non-identical subunits of molecular weight 34 000 and 25 000. The enzyme is inhibited by palmityl-CoA as well as acetyl carnitine. The inhibition by fatty acyl-CoA is competitive with respect to both the substrates, carnitine and acetyl-CoA. The inhibition by acetylcarnitine is reversed by carnitine but not by acetyl-CoA.

Metabolite mobilization in the stem galls of Parthenium hysterophorus induced by Epiblema strenuana inferred from the signatures of isotopic carbon and nitrogen and concentrations of total non-structural carbohydrates

Parthenium hysterophorus L. (Asteraceae) is a weed of national significance in Australia. Among the several arthropod agents introduced into Australia to control populations of P. hysterophorus biologically, Epiblema strenuana Walker (Lepidoptera: Tortricidae) is the most widespread and abundant agent. By intercepting the normal transport mechanisms of P. hysterophorus, the larvae of E. strenuana drain nutrients, other metabolic products, and energy, and place the host plant under intense metabolic stress. In this study, determinations of total non-structural carbohydrates (TNC) levels and carbon and nitrogen isotope ratios of fixed products in different parts of the plant tissue, including the gall, have been made to establish the function of gall as a sink for the nutrients. Values of δ13C and δ15N in galls were significantly different than those in proximal and distal stems, whereas the TNC levels were insignificant, when measured in the total population of P. hysterophorus, regardless of plant age. However, carbon, nitrogen, and TNC signatures presented significant results, when assayed in different developmental stages of P. hysterophorus. Carbon isotope ratios in galls were consistently more negative than those from the compared plant organs. Nitrogen isotope ratios in galls, on the contrary, were either similar to or less negative than the compared plant organs, especially within a single host-plant stage population (i.e., either rosette, preflowering, or flowering stage). TNC levels varied within compared plant populations. The stem distal to the gall functioned more efficiently as a nodal channel than the stem proximal to the gall, especially in the translocation of nitrogenous nutrients. Our findings indicate that the gall induced by E. strenuana functions as a sink for the assayed nutrients, although some variations have been observed in the patterns of nutrient mobilization. By creating a sink for the nutrients in the gall, E. strenuana is able to place the overall plant metabolism under stress, and this ability indicates E. strenuana has the necessary potential for use as a biological-control agent.

Stress-induced phase transformation and pseudo-elastic/pseudo-plastic recovery in intermetallic Ni-Al nanowires

Extensive molecular dynamics (MD) simulations have been performed in a B2-NiAl nanowire using an embedded atom method (EAM) potential. We show a stress induced B2 -> body-centered-tetragonal (BCT) phase transformation and a novel temperature and cross-section dependent pseudo-elastic/pseudo-plastic recovery from such an unstable BCT phase with a recoverable strain of similar to 30% as compared to 5-8% in polycrystalline materials. Such a temperature and cross-section dependent pseudo-elastic/pseudo-plastic strain recovery can be useful in various interesting applications of shape memory and strain sensing in nanoscale devices. Effects of size, temperature, and strain rate on the structural and mechanical properties have also been analyzed in detail. For a given size of the nanowire the yield stress of both the B2 and the BCT phases is found to decrease with increasing temperature, whereas for a given temperature and strain rate the yield stress of both the B2 and the BCT phase is found to increase with increase in the cross-sectional dimensions of the nanowire. A constant elastic modulus of similar to 80 GPa of the B2 phase is observed in the temperature range of 200-500 K for nanowires of cross-sectional dimensions in the range of 17.22-28.712 angstrom, whereas the elastic modulus of the BCT phase shows a decreasing trend with an increase in the temperature.

A hexokinase effect in the inhibition of oxidative phosphorylation in heart muscle mitochondria by Adriamycin

The inhibitory action of the anticancer antibiotic, Adriamycin, on succinate-dependent oxidative phosphorylation in heart mitochondria was markedly potentiated by the presence of hexokinase in the reaction medium. This 'hexokinase effect' was not observed in the oxidation of NAD+-linked substrates, or when liver or kidney mitochondria were used in place of heart mitochondria. These results offer a biochemical explanation for the extreme cardiac toxicity of the drug.

Quasi Crystalline A1-Mn Alloys: Pressure Induced Crystallization and Structural Studies

Irreversible, Pressure induced, quasicrystal-to-crystal transitions are observed for the first time in melt spun alloys at 4.9 GPa for Al 78 Mn22 and 9.3 GPa for Al86 Mn14 by monitoring the electrical resistivities of these alloys as a function of pressure. Electron diffraction and x-ray measurements are used to show that these quasicrystalline phases have icosohedral point group symmetry. The crystalline phases which appear at high pressures are identified as h.c.p. for Al78 Mn22 and orthorhombic for Al86 Mn14.

Development and feasibility testing of an education program to improve knowledge and self-care among Aboriginal and Torres Strait Islander patients with heart failure

Background/Aim There is a 70% higher age-adjusted incidence of heart failure (HF) amongst Aboriginal and Torres Strait Islander people, three times more hospitalisations and twice as many deaths than non-Aboriginal people. There is a need to develop holistic yet individualised approaches in accord with the values of Aboriginal community healthcare to support patient education and self-care. The aim of this study was to re-design an existing HF educational resource (Fluid Watchers-Pacific Rim©) to be culturally safe for Aboriginal and Torres Strait Islander peoples, working in collaboration with the local community, and to conduct feasibility testing. Methods This study was conducted in two phases and utilised a mixed methods approach (qualitative and quantitative). Phase 1 of this study used action research methods to develop a culturally safe electronic resource to be provided to Aboriginal HF patients via a tablet computer. A HF expert panel adapted the existing resource to ensure it was evidence-based and contained appropriate language and images that reflects Aboriginal culture. A stakeholder group (which included Aboriginal workers and HF patients, as well as researchers and clinicians) then reviewed the resources and changes were made accordingly. In Phase 2, the new resource was tested on a sample of Aboriginal HF patients to assess feasibility and acceptability. Patient knowledge, satisfaction and self-care behaviours were measured using a before and after design with validated questionnaires. As this was a pilot test to determine feasibility, no statistical comparisons were made. Results - Phase 1: Throughout the process of resource development, two main themes emerged from the stakeholder consultation. These were the importance of identity, meaning that it was important to ensure that the resource accurately reflected the local community, with the appropriate clothing, skin tone and voice. The resource was adapted to reflect this and of the local community voiced the recordings for the resource. The other theme was comprehension; images were important and all text was converted to the first person and used plain language. - Phase 2: Five Aboriginal participants, mean age 61.6 ± 10.0 years, with NYHA Class III and IV heart failure were enrolled. Participants reported a high level of satisfaction with the resource (83.0%). HF knowledge (percentage of correct responses) increased from 48.0 ± 6.7% to 58.0 ± 9.7%, a 20.8% increase and results of the self-care index indicated that the biggest change was in patient confidence for self-care with a 95% increase in confidence score (46.7 ± 16.0 to 91.1 ± 11.5). Changes in management and maintenance scores varied between9275 patients. Conclusion By working in collaboration with HF experts, Aboriginal researchers and patients, a culturally safe HF resource has been developed for Aboriginal and Torres Strait Islander patients. Engaging Aboriginal researchers, capacity-building, and being responsive to local systems and structures enabled this pilot study to be successfully completed with the Aboriginal community and positive participant feedback demonstrated that the methodology used in this study was appropriate and acceptable; participants were able to engage with willingness and confidence.