Leukocyte-mimetic liposomes possessing leukocyte membrane proteins pass through inflamed endothelial cell layer by regulating intercellular junctions

Nanoparticles such as liposomes have been applied for the treatment of various diseases such as cancer and inflammatory diseases by utilizing the enhanced permeability and retention effect. However, their entry into inflammation sites is still limited since passive delivery of nanoparticles is often hampered by the presence of endothelial barriers. As leukocytes can pass through the inflamed endothelium via utilizing membrane protein functions, we hypothesized that incorporating leukocyte membrane proteins onto liposomal membranes may impart leukocyte-mimicking functions to liposomes, allowing for their adherence to and active passage through the inflamed endothelium. Herein, we developed leukocyte-mimetic liposomes (LM-Lipo) by leukocyte membrane protein transfer and evaluated their function in vitro. Transfer of membrane proteins from human leukemia cells onto liposomal membranes allowed for significant association of the liposomes with inflamed human endothelial cells, and subsequent passage through inflamed endothelial cell layer. The confocal images showed that LM-Lipo significantly induced vascular endothelial-cadherin displacement. These results indicate that LM-Lipo adhered to and regulated intercellular junctions of inflamed endothelial cell layer, resulting in passage through the layer, by mimicking the function of leukocytes. Furthermore, it is suggested that liposomes possessing leukocyte-like functions could be useful for drug delivery to inflammation sites by overcoming endothelial barriers

Roles of peroxisomal oxidation of fatty acids

ペルオキシソームにおける脂肪酸のβ酸化反応は多様な役割を担っている。本項ではペルオキシソームにおける脂肪酸酸化物を介したオルガネラ間での連携について紹介したい。ミトコンドリアとペルオキシソームはいずれも脂肪酸酸化を司るオルガネラである。両オルガネラにおける脂肪酸β酸化で得られる産物はいずれもアセチルCoAであり、ミトコンドリアではそれが直接エネルギー産生に用いられることから、ペルオキシソームはミトコンドリアのエネルギー産生を補助する役割を担うと考えられてきた。しかし、ペルオキシソーム病の解析から極長鎖脂肪酸やフィタン酸はペルオキシソームでのみ酸化されることが明らかになった。また、胆汁酸やドコサヘキサエン酸(DHA)はペルオキシソームで生合成されることなど、ペルオキシソームの脂肪酸酸化は独自の役割を担っており、脂質の分解と生合成および異物代謝に果たす役割が大きいことが明らかとなっている。本稿ではペルオキシソームにおける脂肪酸の酸化に焦点を当て、様々な脂質がペルオキシソームで酸化される意義や他のオルガネラとの連携について紹介したい

Two new Mesodictyopsis species, M. akitaensis sp. nov. and M. miyatanus sp. nov., from a Late Miocene to Pliocene freshwater sediment, Japan

Two new Mesodictyopsis species, M. akitaensis sp. nov. and M. miyatanus sp. nov., are described from freshwater sediment of the Late Miocene to Pliocene Miyata Formation, northern Honshu, Japan. The species are characterized by small size, veluma on inner side of areolae, one fultoportula (sometimes two in M. akitaensis) on central valve face with two (in rare cases three in M. miyatanus) satellite pores, mantle fultoportulae with three satellite pores located on upper mantle close to valve face/mantle junction. Single rimoportula located in a row of areolae on marginal valve face near valve face/mantle junction in M. akitaensis or valve face/mantle junction on a strip in M. miyatanus. The veluma of M. akitaensis are cribra in inner view and sometimes volae on marginal valve face in outer view while those of M. miyatanus are cribra in both inner and outer view. The two species are compared with two similar reported Mesodictyopsis taxa

Suppressive effect of azithromycin on Plasmodium berghei mosquito stage development and apicoplast replication

<p>Abstract</p> <p>Background</p> <p>Azithromycin (AZM) is a macrolide antibiotic that displays an excellent safety profile even in children and pregnant women and has been shown to have anti-malarial activity against blood stage <it>Plasmodium falciparum</it>. This study evaluated the transmission-blocking effect of AZM using a rodent malaria model.</p> <p>Methods</p> <p>AZM-treated mice infected with <it>Plasmodium berghei </it>were exposed to <it>Anopheles stephensi </it>mosquitoes, followed by the observation of parasite development at different phases in the mosquito, i.e., ookinetes in the midgut, oocysts on the midgut, and sporozoites in the midgut and salivary glands. Furthermore, to evaluate the effect on organelle replication of each stage, quantitative real-time PCR analysis was performed.</p> <p>Results</p> <p>The inhibitory effect of AZM was noticeable in both gametocyte-ookinete transformation in the midgut and sporozoite production in the oocyst, while the latter was most remarkable among all the developmental phases examined. Real-time PCR analysis revealed that AZM suppressed apicoplast replication at the period of sporozoite production in oocysts.</p> <p>Conclusions</p> <p>AZM inhibits parasite development in the mosquito stage, probably through the same mechanism as in the liver and blood stages. Such a multi-targeting anti-malarial, along with its safety, would be ideal for mass drug administration in malaria control programmes.</p

Continuous Observations of the Ground Deformations Related to the Matsushiro Earthquakes

In order to investigate the relations between ground deformations and seismic activities in Matsushiro and neighbouring regions, continuous observations on the ground tilt and strain were carried out at Matsushiro and Suzaka. At Matsushiro, three tiltmeters of horizontal pendulum type and two extensometers of bow-string type were installed in the underground gallery bored into Zozan hill, the western suburb of Matsushiro Town. At Suzaka, two tiltmeters of water tube type and two tiltmeters of horizontal pendulum type were installed in the underground gallery bored halfway up Kamatayama hill, the western suburb of Suzaka City. As to Matsushiro, it was observed that the velocity of the ground tilt sometimes changed before the occurrence of an earthquake. As to Suzaka, it proved that the direction of the ground tilt changed markedly every time an earthquake of a magnitude larger than 5.0 occurred, and an anomalous ground tilt appeared before the occurrence of the earthquakes of Sep. 27, 1966, and Feb. 8, 1967

GIPC-phospholipase D in plants

Previously, we detected an unknown sphingophospholipid in cabbage leaves and identified it as phytoceramide-1-phosphate (PC1P). We also found an enzyme activity that produces PC1P by glycosylinositol phosphoceramide (GIPC)-specific hydrolysis in cabbage leaves. To characterize the GIPC-specific phospholipase D (GIPC-PLD) activity, we investigated distributions of GIPC-PLD activity in 25 tissues of 10 plants. In most plants, the GIPC-PLD activity was the highest in roots. Young leaves of cabbage and Welsh onion had higher activities than corresponding aged outer leaves. The GIPC-PLD activities in leaves, stems and roots of mung bean were higher in the sprouting stage than in more mature stages. We also examined distribution of substrate GIPC and product PC1P, and found that GIPC was ubiquitously distributed at 50-280 nmol/g (wet wt) in tissues of plants, whereas PC1P was detectable (3-60 nmol/g wet wt.) only in tissues showing considerable GIPC-PLD activity. These results suggest a possibility that GIPC-PLD activity is involved in plant growth

The novel functional nucleic acid iRed effectively regulates target genes following cytoplasmic delivery by faint electric treatment

An intelligent shRNA expression device (iRed) contains the minimum essential components needed for shRNA production in cells, and could be a novel tool to regulate target genes. However, general delivery carriers consisting of cationic polymers/lipids could impede function of a newly generated shRNA via electrostatic interaction in the cytoplasm. Recently, we found that faint electric treatment (fET) of cells enhanced delivery of siRNA and functional nucleic acids into the cytoplasm in the absence of delivery carriers. Here, we examined fET of cells stably expressing luciferase in the presence of iRed encoding anti-luciferase shRNA. Transfection of lipofectamine 2000 (LFN)/iRed lipoplexes showed an RNAi effect, but fET-mediated iRed transfection did not, likely because of the endosomal localization of iRed after delivery. However, fET in the presence of lysosomotropic agent chloroquine significantly improved the RNAi effect of iRed/fET to levels that were higher than those for the LFN/iRed lipoplexes. Furthermore, the amount of lipid droplets in adipocytes significantly decreased following fET with iRed against resistin in the presence of chloroquine. Thus, iRed could be a useful tool to regulate target genes following fET-mediated cytoplasmic delivery with endosomal escape devices