TLR4‐mediated skin carcinogenesis is dependent on immune and radioresistant cells

Skin cancers are the most commonly diagnosed cancers. Understanding what are the factors contributing to skin tumour development can be instrumental to identify preventive therapies. The myeloid differentiation primary response gene (MyD)88, the downstream adaptor protein of most Toll‐like receptors (TLR), has been shown to be involved in several mouse tumourigenesis models. We show here that TLR4, but not TLR2 or TLR9, is upstream of MyD88 in skin tumourigenesis. TLR4 triggering is not dependent on lipopolysaccharide associated to skin‐colonizing bacteria, but on the high mobility group box‐1 protein (HMGB1), an endogenous ligand of TLR4. HMGB1 is released by necrotic keratinocytes and is required for the recruitment of inflammatory cells and for the initiation of inflammation. The expression of TLR4 on both bone marrow‐derived and radioresistant cells is necessary for carcinogenesis. Consistently, a human tissue microarray analysis showed that melanoma and colon cancer display an over‐expression of TLR4 and its downstream adaptor protein MyD88 within tumours. Together, our results suggest that the initial release of HMGB1 triggers a TLR4‐dependent inflammatory response that leads to tumour development.     

Effect of Organic Selenium Supplementation on Growth, Se Uptake, and Nutrient Utilization in Guinea Pigs

Forty weaned male guinea pigs (Cavia porcellus) of 152.6?±?7.96 g mean body weight were divided into four equal groups and fed a common basal diet comprised of 25% ground cowpea (Vigna unguiculata) hay, 30% ground maize (Zea mays) grain, 22% ground gram (Cicer arietinum) grain, 9.5% deoiled rice (Oryza sativa) bran, 6% soybean (Glycine max) meal, 6% fish meal, 1.5% mineral mixture (without Se), and ascorbic acid at 200 mg/kg to meet their nutrient requirements along with 0, 0.1, 0.2, and 0.3 ppm of organic selenium (Se) in groups I, II, III, and IV, respectively. Experimental feeding lasted for a period of 10 weeks, during which, daily feed intake and weekly body weights were recorded. Intake and digestibility of dry matter, organic matter, ether extract, crude fiber, and nitrogen-free extract as well as uptake of calcium and phosphorus were similar (P?>?0.05) among the four groups. Feed:gain ratio was also similar (P?>?0.05) in the four groups. However, digestibility of crude protein was significantly (P?<?0.001) higher in group II supplemented with 0.1 ppm organic Se as compared to other three group. Intake and absorption of Se was significantly (P?<?0.001) higher in all the Se supplemented groups as compared to control group. Average daily gain (ADG) was significantly (P?<?0.05) higher in group II (3.16 g/day) and III (3.38 g/day) as compared to group I (2.88 g/day). However, ADG in group IV (supplemented 0.3 ppm organic Se) was significantly (P?<?0.05) lower (2.83 g/day) than group II and III, but comparable (P?>?0.05) to group I. Findings of the present experiment suggests that Se requirements of guinea pigs are ≥0.2 ppm, as supplementation of 0.1 ppm organic Se in the diet (having 0.1 ppm Se) not only enhanced their growth rate but also improved the protein utilization.     

Interaction of Zinc, Ascorbic Acid, and Folic Acid in Glycation with Albumin as Protein Model

Using albumin as model, we conducted series of in vitro glycation experiments to examine role of zinc in glycation using glucose at 4–100 mg/ml, incubations at 37°C or 60°C, duration of 2 or 4 weeks and in presence of zinc or ascorbic acid (AA) or folic acid (FA). Modifications of bovine serum albumin (BSA) were examined by using fluorescence of advanced glycation end products (AGEs) and dityrosine, UV, and Fourier transformed infrared spectroscopy. Adding zinc (0 to 768.5 μmol/l) resulted in significant inhibition of albumin glycation by glucose with a linear fit, $ y = - 0.0{895}x + {23}0.{99}\left( {{R^2} = 0.{7676},p = 0.0{13}} \right) $ . The glycation by fructose was greater than that of glucose with stronger inhibitory effect by zinc in fructose–glycation (t?=??5.8, p?=?0.002). Addition of zinc significantly decreased fluorescence as seen in Zn?+?FA or Zn?+?AA sets as compared to sets of FA alone (p?=?0.00056) or AA alone (p?=?0.037). The fluorescence for dityrosine and AGE had a correlation of 0.897 (p?<?0.01). The data from fluorescence, UV, and FTIR spectra collectively suggested inhibitory effect of zinc in BSA glycation alone or in presence of FA and AA, showing new dimension for the protective action of zinc in hyperglycemic conditions.     

A coupled sharp-interface immersed boundary-finite-element method for flow-structure interaction with application to human phonation

A new flow-structure interaction method is presented, which couples a sharp-interface immersed boundary method flow solver with a finite-element method based solid dynamics solver. The coupled method provides robust and high-fidelity solution for complex flow-structure interaction (FSI) problems such as those involving three-dimensional flow and viscoelastic solids. The FSI solver is used to simulate flow-induced vibrations of the vocal folds during phonation. Both two- and three-dimensional models have been examined and qualitative, as well as quantitative comparisons, have been made with established results in order to validate the solver. The solver is used to study the onset of phonation in a two-dimensional laryngeal model and the dynamics of the glottal jet in a three-dimensional model and results from these studies are also presented.     

Interaction of heavy metal toxicants with brain constitutive nitric oxide synthase

This study was designed to evaluate thein vitro effects of transition heavy metal cations on activity of constitutive isoform of nitric oxide synthase (cNOS) in rat brain. NOS activity was determined in the cytosolic fractions of rat cerebral hemispheres by conversion of³H-L-arginine to³H-L-citrulline. Different concentrations of mercury (Hg²⁺), nickel (Ni²⁺), manganese (Mn²⁺), zinc (Zn²⁺), cadmium (Cd²⁺), lead (Pb²⁺) and calcium (Ca²⁺) were tested on NOS activity. While all the cations caused inhibition, there were differences in the apparent inhibition constants (Ki) among the cations. With the exception of calcium ion no other cation required preincubation with the enzyme preparation. These results indicate that while calcium ion modulate cNOS activity at regulatory site(s), inhibitory influence of toxic heavy metal cations may be exerted on the catalytic site(s) either by direct binding to it or by interfering with the electron transfer during catalysis.     

Mathematical modeling of laser based potato cutting and peeling

A mathematical model is developed and validated to predict the depth of cut in potato tuber slabs as a function of laser power and travel speed. The model considers laser processing parameters such as input power, spot size and exposure time as well as the properties of the material being cut such as specific heat, thermal conductivity, surface reflectance, etc. The model also considers the phase change of water in potato and the ignition temperature of the solid portion. The composition of the potato tuber is assumed to be of water and solid. The model also assumes that the ablation process is accomplished through ejection of liquid water, debris and water vapour, and combustion of solid. A CO₂ laser operating in c.w. mode was chosen for the experimental work because water absorbs laser energy highly at 10.6 μm, and CO₂ laser units with relatively high output power are available. Slabs of potato tuber were chosen to be laser processed since potato contains high moisture and large amounts of relatively homogeneous tissue. The results of the preliminary calculations and experiments concluded that the model is able to predict the depth of cut in potato tuber parenchyma when subjected to a CO₂ laser beam.