Testing multiple hypotheses on the colour change of treefrogs in response to various external conditions.

Amphibians are famous for their ability to change colours. And a considerable number of studies have investigated the internal and external factors that affect the expression of this phenotypic plasticity. Evidence to date suggests that thermoregulation and camouflage are the main pressures that influence frogs' adaptive colour change responses. However, certain gaps in our knowledge of this phenomenon remain, namely: (i) how do frogs adjust their colour in response to continuously changing external conditions?; (ii) what is the direction of change when two different functions of colour (camouflage and thermoregulation) are in conflict?; (iii) does reflectance in the near-infrared region show thermally adaptive change?; and (iv) is the colour change ability of each frog an individual trait (i.e., consistent within an individual over time)? Using Dryophytes japonicus (Hylidae, Hyla), we performed a series of experiments to answer the above questions. We first showed that frogs' responses to continuously-changing external conditions (i.e., background colour and temperature) were not linear and limited to the range they experience under natural conditions. Second, when a functional conflict existed, camouflage constrained the adaptive response for thermoregulation and vice versa. Third, though both temperature and background colour induced a change in near-infrared reflectance, this change was largely explained by the high correlation between colour (reflectance in the visible spectrum) and near-infrared reflectance. Fourth, within-individual variation in colour change capacity (i.e., the degree of colour change an individual can display) was lower than inter-individual variation, suggesting individuality of colour change capacity; however, we also found that colour change capacity could change gradually with time within individuals. Our results collectively reveal several new aspects of how evolution shapes the colour change process and highlight how variation in external conditions restricts the extent of colour change in treefrogs.

Comparative and experimental studies on the relationship between body size and countershading in caterpillars.

Countershading is a gradient of colouration in which the illuminated dorsal surfaces are darker than the unilluminated ventral surface. It is widespread in the animal kingdom and endows the body with a more uniform colour to decrease the chance of detection by predators. Although recent empirical studies support the theory of survival advantage conferred by countershading, this camouflage strategy has evolved only in some of the cryptic animals, and our understanding of the factors that affect the evolution of countershading is limited. This study examined the association between body size and countershading using lepidopteran larvae (caterpillars) as a model system. Specifically, we predicted that countershading may have selectively evolved in large-sized species among cryptic caterpillars if (1) large size constrains camouflage which facilitates the evolution of a trait reinforcing their crypsis and (2) the survival advantage of countershading is size-dependent. Phylogenetic analyses of four different lepidopteran families (Saturniidae, Sphingidae, Erebidae, and Geometridae) suggest equivocal results: countershading was more likely to be found in larger species in Saturniidae but not in the other families. The field predation experiment assuming avian predators did not support size-dependent predation in countershaded prey. Collectively, we found only weak evidence that body size is associated with countershading in caterpillars. Our results suggest that body size is not a universal factor that has shaped the interspecific variation in countershading observed in caterpillars.

Copper-Catalyzed N-Arylation of 2-Pyridones Employing Diaryliodonium Salts at Room Temperature.

A new and mild synthetic approach for the N-arylation of 2-pyridones with diaryliodonium salts has been developed. Most reactions proceed readily at room temperature in the presence of 10 mol % of copper chloride. As a result, a wide range of N-arylpyridine-2-ones were synthesized in yields of 23% to 99%. With this method, an antifibrotic drug, Pirfenidone, was successfully synthesized in 99% yield within 30 min at room temperature.

Use of a targeted oncolytic poxvirus, JX-594, in patients with refractory primary or metastatic liver cancer: a phase I trial.

BACKGROUND: JX-594 is a targeted oncolytic poxvirus designed to selectively replicate in and destroy cancer cells with cell-cycle abnormalities and epidermal growth factor receptor (EGFR)-ras pathway activation. Direct oncolysis plus granulocyte-macrophage colony-stimulating factor (GM-CSF) expression also stimulates shutdown of tumour vasculature and antitumoral immunity. We aimed to assess intratumoral injection of JX-594 in patients with refractory primary or metastatic liver cancer. METHODS: Between Jan 4, 2006, and July 4, 2007, 14 patients with histologically confirmed refractory primary or metastatic liver tumours (up to 10.9 cm total diameter) that were amenable to image-guided intratumoral injections were enrolled into this non-comparative, open-label, phase I dose-escalation trial (standard 3x3 design; two to six patients for each dose with 12-18 estimated total patients). Patients received one of four doses of intratumoral JX-594 (10(8) plaque-forming units [pfu], 3x10(8) pfu, 10(9) pfu, or 3x10(9) pfu) every 3 weeks at Dong-A University Hospital (Busan, South Korea). Patients were monitored after treatment for at least 48 h in hospital and for at least 4 weeks as out-patients. Adverse event-monitoring according to the National Cancer Institute Common Toxicity Criteria (version 3) and standard laboratory toxicity grading for haematology, liver and renal function, coagulation studies, serum chemistry, and urinalysis were done. The primary aims were to ascertain the maximum-tolerated dose (MTD) and safety of JX-594 treatment. Data were also collected on pharmacokinetics, pharmacodynamics, and efficacy. Analysis was per protocol. This study is registered with ClinicalTrials.gov, number NCT00629759. FINDINGS: Of 22 patients with liver tumours who were assessed for eligibility, eight patients did not meet inclusion criteria. Therefore, 14 patients, including those with hepatocellular, colorectal, melanoma, and lung cancer, were enrolled. Patients were heavily pretreated (5.6 previous treatments, SD 2.8, range 2.0-12.0) and had large tumours (7.0 cm diameter, SD 2.7, range 1.8-10.9). Patients received a mean of 3.4 (SD 2.2, range 1.0-8.0) cycles of JX-594. All patients were evaluable for toxicity. All patients experienced grade I-III flu-like symptoms, and four had transient grade I-III dose-related thrombocytopenia. Grade III hyperbilirubinaemia was dose-limiting in both patients at the highest dose; the MTD was therefore 1x10(9) pfu. JX-594 replication-dependent dissemination in blood was shown, with resultant infection of non-injected tumour sites. GM-CSF expression resulted in grade I-III increases in neutrophil counts in four of six patients at the MTD. Tumour responses were shown in injected and non-injected tumours. Ten patients were radiographically evaluable for objective responses; non-evaluable patients had contraindications to contrast medium (n=2) or no post-treatment scans (n=2). According to Response Evaluation Criteria in Solid Tumors (RECIST), three patients had partial response, six had stable disease, and one had progressive disease. INTERPRETATION: Intratumoral injection of JX-594 into primary or metastatic liver tumours was generally well-tolerated. Direct hyperbilirubinaemia was the dose-limiting toxicity. Safety was acceptable in the context of JX-594 replication, GM-CSF expression, systemic dissemination, and JX-594 had anti-tumoral effects against several refractory carcinomas. Phase II trials are now underway.