Iodinated polystyrene: An ion-millable negative resist

Iodinated polystyrene (IPS) is obtained by direct iodination of polystyrene and its lithographic characteristics are investigated. The sensitivity of the polymer to electron beams is increased as the result of iodination by a factor of about 10 and reaches 1 μC/cm². Coated IPS films are very stable and no changes in exposure characteristics are observed even after pre-baking at 220°C for 10 min. It is found that crosslinking does not proceed in a vacuum after electron beam exposure. The milling rate of IPS under Ar⁺ bombardment is measured to be 0.25 nm/s. This is lower than that of poly(glycidyl methacrylate-co-ethyl acrylate) (0.67 nm/s) and that of permalloy (0.42 nm/s), both obtained under the same conditions. The mechanism of sensitization by iodination is discussed.     

Fatty acid profile, and chemical composition of Longissimus muscle of bovine steers and bulls finished in pasture system

The objective of this work was to evaluate the conjugated linoleic acid content (CLA), the fatty acid profile, and the chemical composition of the Longissimus muscle (LM) of steers and bulls finished in pasture systems. Fourteen 1/2 Nelore×1/2 Aberdeen Angus cattle were studied. The animals were slaughtered at approximately 20 months of age, with an approximate final liveweight of 480kg. Moisture, ash, fat, crude protein, cholesterol, and fatty acid contents of Longissimus muscle were determined. Steer muscle had a higher lipid content (3.38%) than that of bulls (1.71%). Total n-3 fatty acids were higher in bulls. The amounts of CLA in steer and bull fat were similar, but the CLA content in steer muscle was higher (47.99mg100g(-1) in LM) than that in bull muscle (23.24mg100g(-1) in LM).     

Acute Hypercapnia/Ischemia Alters the Esterification of Arachidonic Acid and Docosahexaenoic Acid Epoxide Metabolites in Rat Brain Neutral Lipids

In the brain, approximately 90% of oxylipins are esterified to lipids. However, the significance of this esterification process is not known. In the present study, we (1) validated an aminopropyl solid phase extraction (SPE) method for separating esterified lipids using 100 and 500 mg columns and (2) applied the method to quantify the distribution of esterified oxylipins within phospholipids (PL) and neutral lipids (NL) (i.e. triacylglycerol and cholesteryl ester) in rats subjected to head-focused microwave fixation (controls) or CO₂-induced hypercapnia/ischemia. We hypothesized that oxylipin esterification into these lipid pools will be altered following CO₂-induced hypercapnia/ischemia. Lipids were extracted from control (n = 8) and CO₂-asphyxiated (n = 8) rat brains and separated on aminopropyl cartridges to yield PL and NL. The separated lipid fractions were hydrolyzed, purified with hydrophobic–lipophilic–balanced SPE columns, and analyzed with ultra-high-pressure liquid chromatography coupled to tandem mass spectrometry. Method validation showed that the 500 mg (vs 100 mg) aminopropyl columns yielded acceptable separation and recovery of esterified fatty acid epoxides but not other oxylipins. Two epoxides of arachidonic acid (ARA) were significantly increased, and three epoxides of docosahexaenoic acid (DHA) were significantly decreased in brain NL of CO₂-asphyxiated rats compared to controls subjected to head-focused microwave fixation. PL-bound fatty acid epoxides were highly variable and did not differ significantly between the groups. This study demonstrates that hypercapnia/ischemia alters the concentration of ARA and DHA epoxides within NL, reflecting an active turnover process regulating brain fatty acid epoxide concentrations.     

HDAC Class I Inhibitor Domatinostat Preferentially Targets Glioma Stem Cells over Their Differentiated Progeny

Cancer stem cells (CSCs) are in general characterized by higher resistance to cell death and cancer therapies than non-stem differentiated cancer cells. However, we and others have recently revealed using glioma stem cells (GSCs) as a model that, unexpectedly, CSCs have specific vulnerabilities that make them more sensitive to certain drugs compared with their differentiated counterparts. We aimed in this study to discover novel drugs targeting such Achilles’ heels of GSCs as anti-GSC drug candidates to be used for the treatment of glioblastoma, the most therapy-resistant form of brain tumors. Here we report that domatinostat (4SC-202), a class I HDAC inhibitor, is one such candidate. At concentrations where it showed no or minimal growth inhibitory effect on differentiated GSCs and normal cells, domatinostat effectively inhibited the growth of GSCs mainly by inducing apoptosis. Furthermore, GSCs that survived domatinostat treatment lost their self-renewal capacity. These results suggested that domatinostat is a unique drug that selectively eliminates GSCs not only physically by inducing cell death but also functionally by inhibiting their self-renewal. Our findings also imply that class I HDACs and/or LSD1, another target of domatinostat, may possibly have a specific role in the maintenance of GSCs and therefore could be an attractive target in the development of anti-GSC therapies.     

Electron microscopic observation of photoreceptor cells in directly inserted anesthetized Drosophila into a high‐pressure freezing unit

The high‐pressure freezing (HPF) technique is known to cryofix water‐containing materials with little ice‐crystal formation in deep depths compared with other freezing techniques. In this study, HPF for anesthetized living Drosophila was performed by placing them directly on the carrier of the HPF unit and exposing them to light. Frozen Drosophila were freeze substituted, and their compound eyes were examined by transmission electron microscopy. The ultrastructures of ommatidia composed of photoreceptor cells were well preserved. The location of the cytoplasmic organelles inside the photoreceptor cells was observed. In some photoreceptor cells in ommatidia of the light‐exposed Drosphila, the cytoplasmic small granules were localized nearer the base of rhabdomeres, compared with those of the nonlight‐exposed Drosophila. Thus, HPF with the direct insertion of living Drosophila under light exposure into the HPF machine enabled us to examine changes to functional structures of photoreceptor cells that occur within seconds.     

Dietary PlsEtn Ameliorates Colon Mucosa Inflammatory Stress and ACF in DMH-Induced Colon Carcinogenesis Mice: Protective Role of Vinyl Ether Linkage

Ethanolamine plasmalogen (PlsEtn), a sub-class of ethanolamine glycerophospholipids (EtnGpl), is a universal phospholipid in mammalian membranes. Several researchers are interested in the relationship between colon carcinogenesis and colon PlsEtn levels. Here, we evaluated the functional role of dietary purified EtnGpl from the ascidian muscle (87.3 mol% PlsEtn in EtnGpl) and porcine liver (7.2 mol% PlsEtn in EtnGpl) in 1,2-dimethylhydrazine (DMH)-induced aberrant crypt foci (ACF) in vivo, and elucidated the possible underlying mechanisms behind it. Dietary EtnGpl-suppressed DMH-induced aberrant crypt with one foci (AC1) and total ACF formation (P < 0.05). ACF suppression by dietary ascidian muscle EtnGpl was higher compared with dietary porcine liver EtnGpl. Additionally, dietary EtnGpl decreased DMH-induced oxidative damage, overproduction of TNF-α, and expression of apoptosis-related proteins in the colon mucosa. The effect of dietary ascidian muscle EtnGpl showed superiority compared with dietary porcine liver EtnGpl. Our results demonstrate the mechanisms by which dietary PlsEtn suppress ACF formation and apoptosis. Dietary PlsEtn attained this suppression by reducing colon inflammation and oxidative stress hence a reduction in DMH-induced intestinal impairment. These findings provide new insights about the functional role of dietary PlsEtn during colon carcinogenesis.     

Method of determination of truncation parameters from measured surface profile

The probability density function of the roughness height of a sliding surface is not always Gaussian like that of a truncated surface caused by running-in or mild wear. Therefore, it is important for obtaining contact pressure or frictional characteristics to estimate the truncation level of the non-Gaussian distribution function. This paper presents a method of determination of the two truncation parameters in the truncation model presented by King et al. [Proceedings of the 4th Leeds–Lyon Symposium on Tribology, MEP, London, 1978, p. 333]. The two truncation parameters p and β can be determined by plotting the values of skewness S_k and kurtosis K obtained from a measured profile of surface roughness on the S_k–K diagram calculated with the truncation model for various given values of parameters p and β. The height distributions reproduced by the truncation model with the truncation parameters p and β identified by the present method is in good agreement with the original ones of the measured surfaces.     

Involvement of Histamine H3 Receptor Agonism in Premature Ejaculation Found by Studies in Rats

Several of the drugs currently available for the treatment of premature ejaculation (PE) (e.g., local anesthetics or antidepressants) are associated with numerous safety concerns and exhibit weak efficacy. To date, no therapeutics for PE have been approved in the United States, highlighting the need to develop novel agents with sufficient efficacy and fewer side effects. In this study, we focused on the histamine H₃ receptor (H₃R) as a potential target for the treatment of PE and evaluated the effects of imetit (an H₃R/H₄R agonist), ciproxifan (an H₃R antagonist), and JNJ-7777120 (an H₄R antagonist) in vivo. Our in vivo electrophysiological experiments revealed that imetit reduced mechanical stimuli-evoked neuronal firing in anesthetized rats. This effect was inhibited by ciproxifan but not by JNJ-7777120. Subsequently, we evaluated the effect of imetit using a copulatory behavior test to assess ejaculation latency (EL) in rats. Imetit prolonged EL, although this effect was inhibited by ciproxifan. These findings indicate that H₃R stimulation suppresses mechanical stimuli-evoked neuronal firing in the spinal–penile neurotransmission system, thereby resulting in prolonged EL. To our knowledge, this is the first report to describe the relationship between H₃R and PE. Thus, H₃R agonists may represent a novel treatment option for PE.     

Azide-phenolic resin UV resist (MRL) for microlithography

Poly(4-vinylphenol) sensitized by an aromatic monoazide compound (4-azidochalcone), called MRL (Micro Resist for Longer wavelengths), has been prepared and evaluated as a negative UV resist. The resist is sensitive to radiation in the 300 to 400 nm region. The sensitivity of MRL is comparable to that of a positive quinonediazide photoresist under exposure to unfiltered light from a high pressure Hg lamp. An aqueous base developer removes the unexposed areas of MRL with no evidence of swelling of the exposed areas, indicating its high resolution capability. The main products in the exposure of MRL films are found to be primary and secondary amines. It is concluded that the formation of secondary amines attached to the polymer chain is responsible for the insolubilization of the exposed MRL in the base developer.     

CNS regulation of blood lactate concentration in anesthetized rats

This study evaluated the effect of stimulating the central nervous system (CNS) with neostigmine, an inhibitor of acetylcholinesterase, on the blood lactate concentration in fed rats and in rats fasted for 48 hours. After the rat was anesthetized with pentobarbital, neostigmine was stereotaxically injected into the third cerebral ventricle. In fed rats, the central injection of neostigmine significantly increased the blood lactate level, while concomitantly increasing plasma glucagon, epinephrine and norepinephrine concentrations. Constant infusion of somatostatin throughout the experiments, to inhibit glucagon secretion from the pancreas, did not affect alterations in blood lactate by central injection of neostigmine. In adreno-medullated rats, CNS-stimulation by neostigmine still increased plasma norepinephrine significantly, however, the alteration in blood lactate was only one-third of that in intact rats. Intraperitoneal propranolol, but not phentolamine, prevented the rise in lactate. Neostigmine increased lactate in fasted rats as well as in fed rats. We conclude that in anesthetized rats, stimulation of the CNS by neostigmine increases blood lactate mainly through circulating epinephrine and partially through circulating norepinephrine or direct sympathetic nervous stimulation; glucagon does not appear to be involved in the increase in blood lactate.