Background: Cryptochromes (CRY), members of the DNA photolyase/cryptochrome protein family, regulate the circadian clock in animals and plants. Two types of animal CRYs are known, mammalian CRY and Drosophila CRY. Both CRYs participate in the regulation of circadian rhythm, but they have different light dependencies for their reactions and have different effects on the negative feedback loop which generates a circadian oscillation of gene expression. Mammalian CRYs act as a potent inhibitor of transcriptional activator whose reactions do not depend on light, but Drosophila CRY functions as a light-dependent suppressor of transcriptional inhibitor.

We developed infrared laser-evoked gene operator (IR-LEGO), a microscope system optimized for heating cells without photochemical damage. Infrared irradiation causes reproducible temperature shifts of the in vitro microenvironment in a power-dependent manner. When applied to living Caenorhabditis elegans, IR-LEGO induced heat shock-mediated expression of transgenes in targeted single cells in a more efficient and less deleterious manner than a 440-nm dye laser and elicited physiologically relevant phenotypic responses.

Xeroderma pigmentosum (XP) is an autosomal recessive disorder characterized by a high frequency of skin cancer on sun-exposed areas, and neurological complications. XP has a defect in the early step(s) of nucleotide-excision repair (NER) and consists of eight different genetic complementation groups (groups A-G and a variant). We established XPA (group-A XP) gene-deficient mice by gene targeting of mouse embryonic stem (ES) cells. The XPA-deficient mice showed neither obvious physical abnormalities nor pathological alterations, but were defective in NER and highly susceptible to ultraviolet-B- or 9,10-dimethyl-1,2-benz[a]anthracene-induced skin carcinogenesis. These findings provide in vivo evidence that the XPA protein protects mice from carcinogenesis initiated by ultraviolet or chemical carcinogen. The XPA-deficient mice may provide a good in vivo model to study the high incidence of skin carcinogenesis in group A XP patients.

Social familiarity affects mating preference among various vertebrates. Here, we show that visual contact of a potential mating partner before mating (visual familiarization) enhances female preference for the familiarized male, but not for an unfamiliarized male, in medaka fish. Terminal-nerve gonadotropin-releasing hormone 3 (TN-GnRH3) neurons, an extrahypothalamic neuromodulatory system, function as a gate for activating mating preferences based on familiarity. Basal levels of TN-GnRH3 neuronal activity suppress female receptivity for any male (default mode). Visual familiarization facilitates TN-GnRH3 neuron activity (preference mode), which correlates with female preference for the familiarized male. GnRH3 peptides, which are synthesized specifically in TN-GnRH3 neurons, are required for the mode-switching via self-facilitation. Our study demonstrates the central neural mechanisms underlying the regulation of medaka female mating preference based on visual social familiarity.

In Alzheimer disease, amyloid ␤, a 39 -43-residue peptide produced by cleavage from a large amyloid precursor protein, undergoes conformational change to form amyloid fibrils and deposits as senile amyloid plaques in the extracellular cerebral cortices of the brain. However, the mechanism of how the intrinsically linear amyloid fibrils form spherical senile plaques is unknown. With total internal reflection fluorescence microscopy combined with the use of thioflavin T, an amyloid-specific fluorescence dye, we succeeded in observing the formation of the senile plaque-like spherulitic structures with diameters of around 15 m on the chemically modified quartz surface. Realtime observation at a single fibrillar level revealed that, in the absence of tight contact with the surface, the cooperative and radial growth of amyloid fibrils from the core leads to a huge spherulitic structure. The results suggest the underlying physicochemical mechanism of senile plaque formation, essential for obtaining insight into prevention of Alzheimer disease.In Alzheimer disease, amyloid ␤ (A␤) 3 peptide forms amyloid fibrils that deposit in the extracellular space of the brain as senile amyloid plaques, pathological hallmarks of Alzheimer disease, and also in the walls of cerebral blood vessels (1-5). The formation of A␤ amyloid fibrils is considered to be a nucleationdependent process in which A␤ peptides slowly associate to form a nucleus, which then grows via an extension reaction involving the sequential incorporation of A␤ peptides, producing rigid and straight morphology consisting of several layers of cross-␤ sheets (6, 7). This process is influenced by several factors, i.e. peptide concentration, pH, ionic strength, and interactions with other components (8, 9). The interactions with lipid membranes in particular have received attention because the membrane surface might be responsible for both neurotoxicity and senile plaque formation (10 -12).For several proteins including A␤, amyloid fibrils prepared on the solid substrates such as mica or quartz produce radial assemblies (13)(14)(15). Considering that in several neurodegenerative diseases, radial and spherical aggregates of amyloid fibrils are found in tissue deposits (5, 16), surface interaction may play dominant roles in the formation of amyloid fibrils and their deposition in vivo (7,17). Moreover, amyloid deposits are found in a specific tissue region, suggesting that a specific surface chemistry is involved in the fibril formation and deposition processes in general. However, the behavior of amyloid fibrils on solid surfaces is still far from clear. To obtain further insight into the mechanism of senile plaque formation and the effects of surface, direct observations are needed.We previously developed a unique approach to monitoring fibril growth in real time at the single fibril level (18,19), in which TIRFM was combined with the use of thioflavin T, an amyloid-specific fluorescence dye (20). With this approach, we focused on the effects of the physicochemical prope...