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The Japanese islands represent one of the world’s biodiversity hotspots. Their geological history and present geography resulted in a high number of endemic species in nearly all major metazoan clades. We investigated the phylogeography of three different intertidal mite species from the Ryukyu islands and southern mainland by means of morphometry and molecular genetics. None of the species represents an endemic, nearly all show distributions ranging over at least the southern and central Ryukyus. Two species, Fortuynia shibai and F. churaumi sp. n. clearly represent sister species that are derived from a common Eastern ancestor. Molecular genetic results indicate that these species separated approx. 3 Ma before the opening of the Okinawa trough, whereas F. shibai most likely showed an ancestral distribution stretching from the central Ryukyus across the Tokara strait to Japanese mainland, whereas F. churaumi probably evolved somewhere south of the Tokara strait. Phylogenetic data further indicates that long periods of isolation resulted in heterogeneous genetic structure but subsequent low sea level stands during Pleistocene allowed recent expansion and gene flow between island populations. Comparing these patterns with those of other animals, these tiny wingless mites apparently show better dispersal abilities than partially volant terrestrial organism groups.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The opisthonotal glands of Astigmata contain monoterpenes, aromatics, aliphatics, and other volatile compounds; some of these compounds act as pheromones and have antifungal effects. This study analyzed volatile compounds secreted by mites on three traditional mite-ripened cheeses from producers (Milbenkäse from Germany, Mimolette and Artisou from France). The mites obtained from various traditional ripened French cheeses (Mimolette, Laguiole, Salers, and Cantal vieux) from stores were also investigated. The gas chromatography (GC) profiles of all their hexane extracts, except the Cantal vieux one, showed almost no differences and were identical to that of Tyrolichus casei Oudemans except for trace components. Based on the GC results, the mites of Cantal vieux were identified as Acarus siro L. For the Artisou and Cantal vieux, not studied before, the influence of the mite secretions on their characteristics was investigated by analyzing the headspace volatiles from the cheeses. According to the results, neral secreted from T. casei is the main compound responsible for the lemon-like flavor of the mite-ripened cheeses, which is, hence, due to a component of the mite secretions rather than the fermentation of the cheese itself. Moreover, the compounds secreted by the mites are not directly added to the cheese through ripening as they were not detected in the odors of the Artisou and Cantal vieux after the mites were removed. However, the consumers of the Artisou usually eat also the cheese rind, and thus, can enjoy its lemon-like flavor fully.

To determine whether the mites used in the ripening process of traditional cheeses are genetically unique to cheese factories, we investigated mites from three types of traditional cheeses, that use mites in the ripening process: ‘Würchwitzer Milbenkäse’ from Germany and ‘Mimolette’ and ‘Artisou’ from France. In addition, traditional ripened cheeses were purchased from cheese specialty stores in France (Mimolette) and Japan (‘Laguiole’ from France) as well as stores in temporary markets in France (‘Salers’ and ‘Cantal vieux’) and the mites obtained from those cheeses were analyzed in this study. Partial sequences of the 28S rRNA gene (28S) were determined and used to reconstruct a phylogenetic tree. Tyrolichus casei, the dominant cheese mite species from the ripening cabinets of three traditional cheese producers and two cheese specialty stores in France and Japan, had identical partial 28S sequences. All specimens from Cantal vieux from a store in the temporary market in France had an identical sequence with Acarus siro and Acarus immobilis in the determined region of the 28S sequences. Mite individuals from Salers from a store in the temporary markets in France shared the same haplotype as Acotyledon paradoxa. For the T. casei individuals from five different localities (19 individuals in total), the nuclear loci were obtained using MIG-seq. More than several thousand genomic regions are amplified simultaneously by multiplex PCR, and targeting regions surrounded by inter-simple sequence repeats (ISSRs) in the genome were sequenced using the MiSeq system (Illumina). SNPs extracted from this genome-wide analysis showed that no genetic structure existed in the populations from any region. Among the five samples from the three regions, which were more than 500 km apart and from completely different environments, the mites had no geographic bias, but all mite individuals were genetically nearly identical. Thus, we found no evidence to support the existence of ‘cheese factory-specific’ T. casei mites, at least in terms of genetic analysis.

Although metastatic cancer is a major cause of death for cancer patients, no efficacious treatment for metastasis is available. We previously showed that the growth of a primary tumor could be inhibited by the administration of an anti-angiogenic small interfering RNA (siRNA) that is encapsulated in an RGD peptide-modified lipid nanoparticle (RGD-LNP). We herein report on the delivery of siRNA by an RGD-LNP to the vasculature is also effective for treating metastatic tumors. We compared the RGD-LNP with the polyethylene glycol (PEG)ylated LNP (PEG-LNP) in terms of accumulation in a lung-metastasized model. Despite malformed structure of vasculature in the metastasized lung, the accumulation of the PEG-LNP in the metastasized lung was lower than that for the RGD-LNP, which suggests that the delivery strategy based on vascular permeability is not completely effective for targeting metastasis tumors. The systemic injection of the RGD-LNP induced a significant silencing in the metastasized vasculature, but not in the normal lung. In addition, the continuous injection of the RGD-LNP encapsulating siRNA against a delta-like ligand 4 (DLL4) drastically prolonged the overall survival of metastasized model mice. Accordingly, our current findings suggest that vasculature targeting would be more effective than enhanced permeability and retention effect-based therapy for the treatment of metastatic cancer.

This randomized, open-label, multicenter, parallel study imitating real-world clinical practice assessed the effect of switching to weekly teriparatide in patients with glucocorticoid-induced osteoporosis (GIO) with a lumbar spine/proximal femur bone mineral density (BMD) T-score ≤ −2.0 or ≤−1.0 and a fragility fracture. Forty-four patients were randomized. The mean durations of the corticosteroid and bisphosphonate administrations were 90.0 and 51.3 months. The baseline BMD at L1–L4 was 0.828 and 0.826 g/cm2 in Groups B (bisphosphonate) and T (teriparatide); at the femur (total), these values were 0.689 and 0.661 g/cm2. The mean change in BMD was numerically higher with teriparatide vs. bisphosphonate but not statistically significant. The mean percentage changes from baseline in BMD at L1–L4 after a 72-week treatment were 0.5% and 4.1% in Groups B and T. The incidence of new fractures was higher in the patients taking bisphosphonates vs. those receiving once-weekly teriparatide at 72 weeks (18.2% vs. 11.8%) and 144 weeks (22.7% vs. 17.6%). The mean percentage change in femur (trochanter) BMD (0.035 [0.007–0.063]; p = 0.02) was significantly greater with teriparatide vs. bisphosphonates. Adverse events (AEs) were more frequent with teriparatide vs. bisphosphonates. Switching to once-weekly teriparatide tended to increase lumbar spine BMD and reduce the occurrence of new fractures vs. bisphosphonates.

The drilling of carbon fiber-reinforced plastic (CFRP) has many important aspects, such as collecting the fine cutting chips. Serious problems relating to machining accuracy can arise when the fine cutting chips diffused into the air are deposited or mixed in the sliding surface and spindle unit of a machine tool. Moreover, the environmental aspects of fine cutting chips can seriously affect the health and safety of workers. Our group has developed a new hollow-type drilling device with a cyclone-type dust collection system, which aspirates and ejects fine cutting chips from a penetration hole in the central part of the drill shank to outside the cutting area. We produced the tools with drills both without a point angle for the counter-boring hole processing and with a point angle for general drilling. In this study the effect of the dust collection rate for cutting chip and the drilling hole shape accuracy are evaluated for the hollow-type drill with two different cutting edge shapes. The results demonstrate the possibility of suppressing the occurrence of fine cutting chips when the hollow-type drill edge is similar to the shape of general twist drill edges. The hole-finish surface properties were improved, and we obtained a higher dust collection rate.