Background: Exosome is a membrane vesicle released from several types of cells, including neurons. Results: Neuronal exosomes accelerate A␤ fibril formation, and the exosome-associated A␤ is taken into microglia to degrade it. Conclusion: Exosomes promote A␤ clearance. Significance: These findings provide a new function of exosome in the brain and also suggest its involvement in the development of Alzheimer disease.

Background: Exosome, a type of extracellular vesicles, can associate with A␤ in vitro. Results: Intracerebrally injected exosomes trapped A␤ on surface glycosphingolipids and transported it into microglia in AD mouse brains, resulting in reductions in A␤ pathology. Conclusion: Exogenous exosomes act as potent scavengers for A␤ in mouse brains. Significance: The findings provide a novel therapeutic approach for AD.

a b s t r a c tElevated amyloid-b peptide (Ab) in brain contributes to Alzheimer's disease (AD) pathogenesis. We demonstrated the presence of exosome-associated Ab in the cerebrospinal fluid (CSF) of cynomolgus monkeys and APP transgenic mice. The levels of exosome-associated Ab notably decreased in the CSF of aging animals. We also determined that neuronal exosomes, but not glial exosomes, had abundant glycosphingolipids and could capture Ab. Infusion of neuronal exosomes into brains of APP transgenic mice decreased Ab and amyloid depositions, similarly to what reported previously on neuroblastoma-derived exosomes. These findings highlight the role of neuronal exosomes in Ab clearance, and suggest that their downregulation might relate to Ab accumulation and, ultimately, the development of AD pathology.

Laser trapping has served as a useful tool in physics and biology, but, before our work, chemists had not paid much attention to this technique because molecules are too small to be trapped in solution at room temperature. In late 1980s, we demonstrated laser trapping of micrometer-sized particles, developed various methodologies for their manipulation, ablation, and patterning in solution, and elucidated their dynamics and mechanism. In the 1990s, we started laser trapping studies on polymers, micelles, dendrimers, and gold, as well as polymer nanoparticles. Many groups also reported laser trapping studies of nanoclusters, DNA, colloidal suspensions, etc. Following these research streams, we have explored new molecular phenomena induced by laser trapping. Gradient force leading to trapping, mass transfer by local heating, and molecular reorientation following laser polarization are intimately coupled with molecular cluster and aggregate formation due to their intermolecular interactions, which depend on whether the trapping position is at the interface/surface or in solution. In this Account, we summarize our systematic studies on laser trapping chemistry and present some new advances and our future perspectives. We describe the laser trapping of nanoparticles, polymers, and amino acid clusters in solution by focusing a continuous wave 1064 nm laser beam on the molecules of interest and consider their dynamics and mechanism. In dilute solution, nanoparticles with weak mutual interactions are individually trapped at the focal point, while laser trapping of nanoparticles in concentrated solution assembles and confines numerous particles at the focal spot. The assembly of polymers during their laser trapping extends out from the focal point because of the interpolymer interactions, heat transfer, and solvent flow. When the trapping laser is focused at an interface between a thin heavy water solution film of glycine and a glass substrate, the assembled molecules nucleate and evolve to a liquid-liquid phase separation, or they will crystallize if the trapping laser is focused on the solution surface. Laser trapping can induce spatiotemporally the liquid and solid nucleation of glycine, and the dense liquid droplet or crystal formed can grow to a bulk scale. We can control the polymorph of the formed glycine crystal selectively by tuning trapping laser polarization and power. These results provide a new approach to elucidate dynamics and mechanism of crystallization and are the fundamental basis for studying not only enantioselective crystallization but also confined polymerization, trapping dynamics by ultrashort laser pulses, and resonance effect in laser trapping.

Objective:Recent studies indicate that sphingolipids, sphingomyelin (SM) and ceramide (Cer) are associated with the development of metabolic syndrome. However, detailed profiles of serum sphingolipids in the pathogenesis of this syndrome are lacking. Here we have investigated the relationship between the molecular species of sphingolipids in serum and the clinical features of metabolic syndrome, such as obesity, insulin resistance, fatty liver disease and atherogenic dyslipidemia.Subjects:We collected serum from obese (body mass index, BMI⩾35, n=12) and control (BMI=20−22, n=11) volunteers (18−27 years old), measured the levels of molecular species of SM and Cer in the serum by liquid chromatography-mass spectrometry and analyzed the parameters for insulin resistance, liver function and lipid metabolism by biochemical blood test.Results:The SM C18:0 and C24:0 levels were higher, and the C20:0 and C22:0 levels tended to be higher in the obese group than in the control group. SM C18:0, C20:0, C22:0 and C24:0 significantly correlated with the parameters for obesity, insulin resistance, liver function and lipid metabolism, respectively. In addition, some Cer species tended to correlate with these parameters. However, SM species containing unsaturated acyl chains and most of the Cer species were not associated with these parameters.Conclusions:The present results demonstrate that the high levels of serum SM species with distinct saturated acyl chains (C18:0, C20:0, C22:0 and C24:0) closely correlate with the parameters of obesity, insulin resistance, liver function and lipid metabolism, suggesting that these SM species are associated with the development of metabolic syndrome and serve as novel biomarkers of metabolic syndrome and its associated diseases.

The crystallization of glycine in unsaturated solution is made possible by laser trapping of its molecular clusters due to photon pressure of a focused continuous wave near-infrared laser beam. Always one single crystal is spatiotemporally formed at a focal spot, and then it undergoes dissolution, eventually leading to repetitive crystallization and dissolution. The polymorph characterization of the crystal formed in unsaturated solution confirmed the γ-form, which is not obtainable by conventional crystallization methods. The preparation probability of the γ-form compared to the α-form is much higher than that in the supersaturated solution.

We report optical trapping and assembling of colloidal particles at a glass/solution interface with a tightly focused laser beam of high intensity. It is generally believed that the particles are gathered only in an irradiated area where optical force is exerted on the particles by laser beam. Here we demonstrate that, the propagation of trapping laser from the focus to the outside of the formed assembly leads to expansion of the assembly much larger than the irradiated area with sticking out rows of linearly aligned particles like horns. The shape of the assembly, its structure, and the number of horns can be controlled by laser polarization. Optical trapping study utilizing the light propagation will open a new avenue for assembling and crystallizing quantum dots, metal nanoparticles, molecular clusters, proteins, and DNA.

A millimeter-scale dense liquid droplet of glycine is prepared by focusing a CW near-infrared laser beam at the glass/solution interface of a thin film of its supersaturated heavy water solution. The formation process is investigated by direct observation with CCD and by measuring temporal change of the surface height with a displacement meter. The droplet becomes much larger than a focal spot size, a few mm width and ∼150 μm height, and observable with the naked eye. Interestingly, the droplet remains for a few tens of seconds even after switching off the laser beam. Whereas the droplet is kept during laser irradiation, the crystallization is immediately attained by shifting the laser beam to the air/droplet surface. It is considered that the droplet is possibly the early stage of the multistep crystallization process and plays an important role in photon pressure-induced crystallization of glycine.SECTION Nanoparticles and Nanostructures P hoton pressure, which is a gradient force toward a focal spot generated by a focused CW laser beam, has been widely employed as an optical tweezers technique to trap and to manipulate micrometer-sized objects in many fields of physics, optics, and biology. 1-3 Over the past decades, the study on photon pressure in solution has progressed with the size reduction of target materials from microscale to nanoscale, 4-6 and actually, we have extended a series of experiments on the dynamics of photon pressure-induced association of nanoparticles, polymers, micelles, and J-aggregates in their solutions at room temperature. [7][8][9][10][11] As an example, polystyrene latex nanoparticles with 24 nm diameter were trapped and gathered by photon pressure, leading to their assemblies in a focal spot. 11 In single-molecule level, Osborne et al. and Chirico et al. separately reported that the diffusion of Rhodamine 6G molecules in the focal spot were suppressed under photon pressure, although no stable trapping was achieved. 12,13 These results imply that photon pressure efficiently works even on small clusters or molecules, which have the sizes much smaller than the wavelength of the trapping laser.In 2007, we applied photon pressure of a focused CW nearinfrared laser beam to a supersaturated heavy water solution of glycine, and for the first time succeeded in inducing the crystallization, which we call "laser trapping crystallization". 14 This novel phenomenon was explained by assuming that glycine molecules form aggregates under a supersaturated condition before irradiation because the optical gradient force in our experiment is too small to trap the single molecule.Indeed, the presence of small liquid-like clusters of glycine under a supersaturated condition has been experimentally demonstrated. 15 Such clusters, which are associated with each other through weak hydrogen bonds without forming nucleus, should be gathered in the focal spot and reorganized into ordered structures by photon pressure. In 2005, Myerson et al. reported the direct confirmation on the cluster structure...