Evaluation of corneal damage caused by the anticancer drug S-1 in human corneal epithelial cells

The combination drug S-1, which contains tegafur, gimeracil, and oteracil potassium, is a fluoropyrimidine-based oral antineoplastic agent in which the principal drug tegafur is a prodrug of fluorouracil （5-FU）. In recent years, many studies have reported eye problems, especially corneal damage, as an adverse effect of S-1 treatment. In this study, we investigated the cytotoxic effects of each of the constituents of S-1 on corneal epithelial cells by measuring viable cell counts and lactate dehydrogenase （LDH） release. Experimental chemosensitivity study for 5-FU and the constituents of S-1 （i.e., tegafur, gimeracil, and oteracil） using a human cell line. We used immortalized human corneal epithelial （HCE-T） cells to estimate viable cell counts （expressed as a percentage of the control cells） and the activity of LDH in a culture medium （expressed as a percentage of the total LDH activity）. Decreases in viable cell counts were noted with 5-FU and tegafur, but a significant elevation in LDH activity was noted only with tegafur. The incidence of damage in cells exposed to tegafur significantly decreased on adding tranylcypromine, an inhibitor of CYP2A6 that metabolizes tegafur to 5-FU. In addition, 5-FU did not elevate LDH activity, which is an indicator of cell membrane disruption, and concentration-dependence was not observed when cells were treated with 5-FU doses of up to 1,000ng/ml. These findings suggest that the disruption of the metabolic activity of the corneal epithelium by 5-FU is involved in the corneal injury mechanism of S-1

Integrating Cancer Patients’ Satisfaction with Rescue Medication in Pain Assessments

A patient’s pain intensity rating alone is insufficient grounds for determining the pain medication and dosage to administer daily. This study aimed to investigate whether a convenient assessment method could be developed that would reflect the effectiveness of an opioid analgesic on cancer patients’ pain management. We investigated pain intensity （worst, least, average, current） and the effectiveness of the opioid rescue medication in terms of patient satisfaction. This study used Spearman’s rank correlation coefficients to evaluate the relationships between patient satisfaction with rescue medication and both pain intensity and the medication’s perceived effectiveness. Data from 60 participants with a mean age of 60.5±11.4 years （range: 31-79 years） were analyzed. Thirty-eight （63.3%） participants were male, and 22 （36.7%） were female. The correlations found between rescue medication satisfaction and both the worst numerical rating scale （NRS） rating （r＝−0.15, P＝0.16） and the average NRS rating （r＝−0.13, P＝0.13） were not statistically significant. A significant positive correlation was observed between rescue medication satisfaction and the medication’s perceived effectiveness （r＝0.79, P＜0.0001）. Patient satisfaction with their rescue medication can be routinely assessed without imposing a significant burden on the patient. A new assessment method incorporating rescue medication satisfaction and pain intensity measures could allow routine pain assessments to reflect both pain intensity and the effectiveness of opioid analgesics. This new assessment method is potentially preferable to self-reported pain intensity and can identify patients for whom treatment is a priority. It also facilitates rapid dose adjustments and reduces the side effects of overdose due to unnecessary increases in opioid analgesics

Lattice-matched HfN buffer layers for epitaxy of GaN on Si

Gallium nitride is grown by plasma-assisted molecular-beam epitaxy on (111) and (001) silicon substrates using sputter-deposited hafnium nitride buffer layers. Wurtzite GaN epitaxial layers are obtained on both the (111) and (001) HfN/Si surfaces, with crack-free thickness up to 1.2 (mu)m. Initial results for GaN grown on the (111) surface show a photoluminescence peak width of 17 meV at 11 K, and an asymmetric x-ray rocking curve width of 20 arcmin. Wurtzite GaN on HfN/Si(001) shows reduced structural quality and peculiar low-temperature luminescence features. However, growth on the (001) surface results in nearly stress-free films, suggesting that much thicker crack-free layers could be obtained

Feminizing Wolbachia endosymbiont disrupts maternal sex chromosome inheritance in a butterfly species

Wolbachia is a maternally inherited ubiquitous endosymbiotic bacterium of arthropods that displays a diverse repertoire of host reproductive manipulations. For the first time, we demonstrate that Wolbachia manipulates sex chromosome inheritance in a sexually reproducing insect. Eurema mandarina butterfly females on Tanegashima Island, Japan, are infected with the wFem Wolbachia strain and produce all‐female offspring, while antibiotic treatment results in male offspring. Fluorescence in situ hybridization (FISH) revealed that wFem‐positive and wFem‐negative females have Z0 and WZ sex chromosome sets, respectively, demonstrating the predicted absence of the W chromosome in wFem‐infected lineages. Genomic quantitative polymerase chain reaction (qPCR) analysis showed that wFem‐positive females lay only Z0 eggs that carry a paternal Z, whereas females from lineages that are naturally wFem‐negative lay both WZ and ZZ eggs. In contrast, antibiotic treatment of adult wFem females resulted in the production of Z0 and ZZ eggs, suggesting that this Wolbachia strain can disrupt the maternal inheritance of Z chromosomes. Moreover, most male offspring produced by antibiotic‐treated wFem females had a ZZ karyotype, implying reduced survival of Z0 individuals in the absence of feminizing effects of Wolbachia. Antibiotic treatment of wFem‐infected larvae induced male‐specific splicing of the doublesex (dsx) gene transcript, causing an intersex phenotype. Thus, the absence of the female‐determining W chromosome in Z0 individuals is functionally compensated by Wolbachia‐mediated conversion of sex determination. We discuss how Wolbachia may manipulate the host chromosome inheritance and that Wolbachia may have acquired this coordinated dual mode of reproductive manipulation first by the evolution of female‐determining function and then cytoplasmically induced disruption of sex chromosome inheritance

Frequent loss of HLA alleles associated with copy number-neutral 6pLOH in acquired aplastic anemia

Idiopathic aplastic anemia (AA) is a common cause of acquired BM failure. Although autoimmunity to hematopoietic progenitors is thought to be responsible for its pathogenesis, little is known about the molecular basis of this autoimmunity. Here we show that a substantial proportion of AA patients harbor clonal hematopoiesis characterized by the presence of acquired copy number-neutral loss of heterozygosity (CNN-LOH) of the 6p arms (6pLOH). The 6pLOH commonly involved the HLA locus, leading to loss of one HLA haplotype. Loss of HLA-Aexpression from multiple lineages of leukocytes was confirmed by flow cytometry in all 6pLOH(+) cases. Surprisingly, the missing HLAalleles in 6pLOH(+) clones were conspicuously biased to particular alleles, including HLA-A*02:01, A*02:06, A*31:01, and B*40:02. A large-scale epidemiologic study on the HLA alleles of patients with various hematologic diseases revealed that the 4 HLA alleles were over-represented in the germline of AA patients. These findings indicate that the 6pLOH(+) hematopoiesis found in AA represents "escapes"hematopoiesis from the autoimmunity, which is mediated by cytotoxic T cells that target the relevant autoantigens presented on hematopoietic progenitors through these class I HLAs. Our results provide a novel insight into the genetic basis of the pathogenesis of AA. © 2011 by The American Society of Hematology

Glycosphingolipid-enriched microdomain中でGb3と会合する分子の探索

Silurus asotus (catfish) egg lectin (SAL) is a member of rhamnose-binding lectin family, and binds to globotriaosylceramide (Gb3) localized in a glycosphingolipid-enriched microdomain (GEM) on several tumor cell lines. It is known that GEM is involved in cell adhesion and has the capability of sending signals. We report here about proteins involved in GEM associating with Gb3 and mediating signal transduction system in Burkitt\u27s lymphoma Raji cells via SAL binding to Gb3. Although Gb3 molecule was sprinkled over the surface of Raji cells, SAL uniformly bound to the Raji cell surface. Sucrose density-gradient centrifugation method and fluorescence microscopic analysis revealed that not only CD20 and CD81 but also Lyn and Csk were distributed in GEM of Raji cells. The distribution of these molecules was not altered by the treatment with SAL at 4℃ for 30 ruin. Because CD20 was not co-precipitated with the anti-Gb3 antibody, CD20 was not associated with Gb3 on Raji cells. However, there was a 47kDa protein, which was specifically co-precipitated with anti-Gb3 antibody. These results suggest that the 47kDa protein is a candidate for Gb3-associating protein in Raji cells

Genome Sequence of Striga asiatica Provides Insight into the Evolution of Plant Parasitism

Parasitic plants in the genus Striga, commonly known as witchweeds, cause major crop losses in sub-Saharan Africa and pose a threat to agriculture worldwide. An understanding of Striga parasite biology, which could lead to agricultural solutions, has been hampered by the lack of genome information. Here, we report the draft genome sequence of Striga asiatica with 34,577 predicted protein-coding genes, which reflects gene family contractions and expansions that are consistent with a three-phase model of parasitic plant genome evolution. Striga seeds germinate in response to host-derived strigolactones (SLs) and then develop a specialized penetration structure, the haustorium, to invade the host root. A family of SL receptors has undergone a striking expansion, suggesting a molecular basis for the evolution of broad host range among Striga spp. We found that genes involved in lateral root development in non-parasitic model species are coordinately induced during haustorium development in Striga, suggesting a pathway that was partly co-opted during the evolution of the haustorium. In addition, we found evidence for horizontal transfer of host genes as well as retrotransposons, indicating gene flow to S. asiatica from hosts. Our results provide valuable insights into the evolution of parasitism and a key resource for the future development of Striga control strategies.Peer reviewe

The Ganymede Laser Altimeter (GALA) for the Jupiter Icy Moons Explorer (JUICE): Mission, science, and instrumentation of its receiver modules

The Jupiter Icy Moons Explorer (JUICE) is a science mission led by the European Space Agency, being developed for launch in 2023. The Ganymede Laser Altimeter (GALA) is an instrument onboard JUICE, whose main scientific goals are to understand ice tectonics based on topographic data, the subsurface structure by measuring tidal response, and small-scale roughness and albedo of the surface. In addition, from the perspective of astrobiology, it is imperative to study the subsurface ocean scientifically. The development of GALA has proceeded through an international collaboration between Germany (the lead), Japan, Switzerland, and Spain. Within this framework, the Japanese team (GALA-J) is responsible for developing three receiver modules: the Backend Optics (BEO), the Focal Plane Assembly (FPA), and the Analog Electronics Module (AEM). Like the German team, GALA-J also developed software to simulate the performance of the entire GALA system (performance model). In July 2020, the Proto-Flight Models of BEO, FPA, and AEM were delivered from Japan to Germany. This paper presents an overview of JUICE/GALA and its scientific objectives and describes the instrumentation, mainly focusing on Japan’s contribution