The phase behavior of three N-alkyl-substituted perylene diimide derivatives is examined by differential scanning calorimetry and polarized optical microscopy. The occurrence of multiple phase transitions indicates several crystalline and several liquid crystalline phases. X-ray diffraction measurements show that the liquid crystalline phases display high structural ordering in all three dimensions: smectic layers are formed, and within these smectic layers an additional ordering in columns is observed. Molecular modeling confirms this result and substantiates smectic ordering with interdigitating alkyl chains that determine the distance between the smectic layers. The ordering in columns is favored by π-π interactions between the cofacially oriented perylene molecules and by the elliptic shape of the molecule. Finally, intermolecular dipole-dipole interactions between the carbonyl groups of the imide moieties cause the perylene molecules to orient on average with a slight rotation between neighboring molecules within a columnar stack. Following the determination of the electronic transition dipole moment, this orientation, which still involves substantial π-π interactions, could be confirmed by UV/vis spectroscopy of perylene aggregates. To gauge the potential of these materials as organic semiconductors, the charge carrier mobility of one of the perylene derivatives has been measured by pulse-radiolysis time-resolved microwave conductivity. A value in excess of 0.1 cm 2 V -1 s -1 is found in the liquid crystalline phase, and a value in excess of 0.2 cm 2 V -1 s -1 is found for the crystalline phase. These values are comparable with the highest values previously found for other discotic materials.

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BackgroundAnorexia is a common symptom among cancer patients and contributes to malnutrition and strongly impinges on quality of life. Cancer-induced anorexia is thought to be caused by an inability of food intake-regulating systems in the hypothalamus to respond adequately to negative energy balance during tumour growth. Here, we show that this impaired response of food-intake control is likely to be mediated by altered serotonin signalling and by failure in post-transcriptional neuropeptide Y (NPY) regulation.MethodsTwo tumour cachectic mouse models with different food intake behaviours were used: a C26-colon adenocarcinoma model with increased food intake and a Lewis lung carcinoma model with decreased food intake. This contrast in food intake behaviour between tumour-bearing (TB) mice in response to growth of the two different tumours was used to distinguish between processes involved in cachexia and mechanisms that might be important in food intake regulation. The hypothalamus was used for transcriptomics (affymetrix chips).ResultsIn both models, hypothalamic expression of orexigenic NPY was significantly higher compared with controls, suggesting that this change does not directly reflect food intake status but might be linked to negative energy balance in cachexia. Expression of genes involved in serotonin signalling showed to be different between C26-TB mice and Lewis lung carcinoma-TB mice and was inversely associated with food intake. In vitro, using hypothalamic cell lines, serotonin repressed neuronal hypothalamic NPY secretion while not affecting messenger NPY expression, suggesting that serotonin signalling can interfere with NPY synthesis, transport, or secretion.ConclusionsAltered serotonin signalling is associated with changes in food intake behaviour in cachectic TB mice. Serotonins' inhibitory effect on food intake under cancer cachectic conditions is probably via affecting the NPY system. Therefore, serotonin regulation might be a therapeutic target to prevent the development of cancer-induced eating disorders.

BackgroundAppetite is frequently affected in cancer patients leading to anorexia and consequently insufficient food intake. In this study, we report on hypothalamic gene expression profile of a cancer-cachectic mouse model with increased food intake. In this model, mice bearing C26 tumour have an increased food intake subsequently to the loss of body weight. We hypothesise that in this model, appetite-regulating systems in the hypothalamus, which apparently fail in anorexia, are still able to adapt adequately to changes in energy balance. Therefore, studying changes that occur on appetite regulators in the hypothalamus might reveal targets for treatment of cancer-induced eating disorders. By applying transcriptomics, many appetite-regulating systems in the hypothalamus could be taken into account, providing an overview of changes that occur in the hypothalamus during tumour growth.MethodsC26-colon adenocarcinoma cells were subcutaneously inoculated in 6 weeks old male CDF1 mice. Body weight and food intake were measured three times a week. On day 20, hypothalamus was dissected and used for transcriptomics using Affymetrix chips.ResultsFood intake increased significantly in cachectic tumour-bearing mice (TB), synchronously to the loss of body weight. Hypothalamic gene expression of orexigenic neuropeptides NPY and AgRP was higher, whereas expression of anorexigenic genes CCK and POMC were lower in TB compared to controls.In addition, serotonin and dopamine signalling pathways were found to be significantly altered in TB mice. Serotonin levels in brain showed to be lower in TB mice compared to control mice, while dopamine levels did not change. Moreover, serotonin levels inversely correlated with food intake.ConclusionsTranscriptomic analysis of the hypothalamus of cachectic TB mice with an increased food intake showed changes in NPY, AgRP and serotonin signalling. Serotonin levels in the brain showed to correlate with changes in food intake. Further research has to reveal whether targeting these systems will be a good strategy to avoid the development of cancer-induced eating disorders.Electronic supplementary materialThe online version of this article (doi:10.1007/s13539-013-0121-y) contains supplementary material.

BackgroundIn rodent models, caloric restriction (CR) with maintenance of adequate micronutrient supply has been reported to increase lifespan and to reduce age-induced muscle loss (sarcopenia) during ageing. In the present study, we further investigated effects of CR on the onset and severity of sarcopenia in ageing male C57BL/6 J mice. The aim of this study was to investigate whether CR induces changes in behaviour of the animals that could contribute to the pronounced health-promoting effects of CR in rodents. In addition, we aimed to investigate in more detail the effects of CR on the onset and severity of sarcopenia.MethodsThe mice received either an ad libitum diet (control) or a diet matching 70 E% of the control diet (C). Daily activity, body composition (dual energy X-ray absorptiometry), grip strength, insulin sensitivity, and general agility and balance were determined at different ages. Mice were killed at 4, 12, 24, and 28 months. Skeletal muscles of the hind limb were dissected, and the muscle extensor digitorum longus muscle was used for force-frequency measurements. The musculus tibialis was used for real-time quantitative PCR analysis.ResultsFrom the age of 12 months, CR animals were nearly half the weight of the control animals, which was mainly related to a lower fat mass. In the control group, the hind limb muscles showed a decline in mass at 24 or 28 months of age, which was not present in the CR group. Moreover, insulin sensitivity (oral glucose tolerance test) was higher in this group and the in vivo and ex vivo grip strength did not differ between the two groups.In the hours before food was provided, CR animals were far more active than control animals, while total daily activity was not increased. Moreover, agility test indicated that CR animals were better climbers and showed more climbing behaviours.ConclusionsOur study confirms earlier findings that in CR animals less sarcopenia is present. The mice on the CR diet, however, showed specific behavioural changes characterized by higher bursts of activity within a short time frame before consumption of a 70 E% daily meal. We hypothesize that the positive effects of CR on muscle maintenance in rodents are not merely a direct consequence of a lower energy intake but also related to a more active behaviour in a specific time frame. The burst of activity just before immediate start of eating, might lead to a highly effective use of the restricted protein sources available.

A series of phthalimide-and 1,12-benzoperylene-1′,2′-dicarboxylic imido-linked alkynes were prepared and analyzed by UV, FT-IR, optical microscopy, and differential scanning calorimetry. The possibility to convert ω-alkynes (R-(CH 2)n-CtCH) to diacetylenic compounds (R-(CH2)nCtC-CtC-(CH2)n-R) was investigated for R ) phthalimide and 1,12-benzoperylene-1′,2′-dicarboxylic imide with n ) 1, 3, and 9. Formation of the diacetylenic compound is usually straightforward (as checked by comparison with independently synthesized diacetylenes), and in some cases heat-induced polymerization of the thusformed diacetylenes proceeds directly. For the perylene imide-linked materials with n ) 1 and n ) 3 1,2-polymerization occurs, while for n ) 9 1,4-polymerization occurs. The 1,4-polymerization is also observed for the phthalimide-linked materials. For R ) phthalimide and n ) 1 this 1,4-polymerization can only be induced by further heating, while for the analogous n ) 9 compound 1,4-polymerization is already induced by UV-vis irradiation at room temperature. This is related to the flexibility of the methylene spacer in the crystal.

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