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Eel movement patterns have been frequently studied to learn about their movements within the fresh- and brackish waters of the same river before their spawning migrations. Although otolith microchemistry analyses estimated that the eels used fresh-, brackish, and marine water habitats, inter-river movements of Japanese eels via the sea have not been observed. In previous studies silver eels appear to migrate for spawning in October-December, and so eels that migrate to the sea during this period have been considered as migrating for spawning. In the progress of our acoustic telemetry study on eel movement patterns, we found the first evidence that Japanese eels move between distant rivers via the sea. During the study in the Akugawa River, Wakayama Prefecture, Japan, we released 15 acoustically tagged yellow-phase eels on 8 April 2019. Three of the 15 tagged eels released into the Akugawa River were later caught in the ~ 15 km distant Hidari-Aizu River by a local angler during early mid-July 2020. This showed that 2 of 3 tagged eels migrated seaward in October and December. The other tagged eel had been detected only at a releasing point until 30 June 2019 and due to an unknown reason was never detected again before capture in the Hidari-Aizu River. The remaining 12 tagged eels stayed in the Akugawa River during the study period. These findings indicate that Japanese eels may migrate seaward for purposes other than just spawning. This information is valuable for understanding the eels’ life-history diversity and for future conservation plans.

Populations or species exploiting different habitats can differ in sensory perception as a result of divergent adaptation. In bony fish, the water current is perceived via neuromasts, the end organ of the lateral line system. Although fish in different habitats are known to vary in neuromasts, we know little about the genetic basis for such variation. Here, we investigate the genetic basis for variation in supraorbital neuromasts in a hybrid zone between the Japanese gobies Gymnogobius breunigii and Gymnogobius castaneus. The former has supraorbital canal neuromasts with six cephalic pores, whereas the latter has only superficial neuromasts with no canals or pores in the supraorbital region. Our genomic analysis showed that G. breunigii and G. castaneus occur mainly in the lower and mid/upper reaches, respectively. In a river in northern Japan, hybrids were found at the sites between the habitats of the two species. These hybrids exhibited anomalies of cephalic pores. Using this hybrid zone, we conducted genome-wide association studies and identified one locus significantly associated with the number of pores. Genomic cline analysis in the hybrid zone demonstrated that this locus exhibited a higher introgression rate compared with the genomic background, indicating the possibility of adaptive introgression.

This study monitored post-release movements of 20 wild Japanese eels (Anguilla japonica) [mean ± S.D. 520.8 ± 92.3 mm total length (TL), 217.9 ± 146.3 g body mass (BM)] in a brackish water lagoon in northeastern Japan using acoustic telemetry to elucidate how wild Japanese eels use different river, estuary and marine environments. In addition, 12 cultured Japanese eels (TL = 578.9 ± 18.0 mm, BM = 344.9 ± 25.5 g) were released to understand the comparative behaviours of wild and cultured eels. Both types of eels were simultaneously released in the southern inner part of the lagoon in September 2016 where there are freshwater influences from a river. Following release, eight of the wild eels (40%) were largely sedentary near the released point (river mouth) and stayed at the site for overwinter. Nonetheless, several individuals showed behavioural plasticity of habitat use: three wild eels moved towards the northern part of the lagoon with stronger influence from the sea during May-July 2017. Two wild eels showed clear repeated movements from the lagoon to a river at night and returned to the lagoon by dawn for more than a week every day, and one wild eel migrated upstream for overwintering. Signals from 55% of the wild eels could be detected for more than 6 months, whereas those from all of the cultured eels were lost by December 2016, indicating a short resident time of large cultured eels (BM > 200 g) released in a brackish water area. One wild silver eel migrated to the outer sea during the ebb tide at night in November 2016, probably triggered by the decrease in water temperature (from c. 20°C to c. 13°C), and seven cultured eels similarly moved to the outer sea during October-November 2016. The results revealed the similarities (e.g., nocturnal movements) and differences (e.g., stay period and seasonal movements) in the behavioural characteristics of wild and cultured eels and indicated that habitat connectivity among river, estuary and coastal waters is crucial for enabling eels to efficiently utilise these productive habitats through their behavioural plasticity.

Japanese eels (Anguilla japonica) utilize a broad range of habitats along the marine-freshwater ecotone during their growth phase in inland waters. This study aimed to analyze the foraging behavior of yellow-phase Japanese eels in connected fresh- and brackish water habitats and to connect foraging behavior and habitat use through the analysis of carbon (δ13C) and nitrogen (δ15N) stable isotopes. Stomach contents of eels collected in fresh- and brackish waters were analyzed to identify food sources. Values of δ13C and δ15N were analyzed in eels and their potential food sources, and used to predict the recent foraging patterns of eels in the Matsukawa-ura, a brackish water lagoon, and in three freshwater tributaries. Eels preyed on the benthic river community and the mudflat community of the lagoon. Gobiid fishes were found to be an important food source for eels in fresh- and brackish water habitats, while Japanese mitten crabs (Eriocheir japonica) and shore crabs (Hemigrapsus spp.) were major prey in fresh- and brackish waters respectively. δ13C values of potential eel prey differed significantly between fresh- and brackish waters and were used to classify three recent patterns of foraging by the 73 eels included in this study: 1) freshwater foraging, 2) brackish water foraging, and 3) multiple-habitat foraging. The data suggested that some eels recently or frequently moved between fresh- and brackish water habitats while others demonstrated a higher fidelity to either fresh- or brackish waters. Isotopic characteristics of prey in the respective foraging habitats revealed the plasticity of habitat use of yellow eels in the study area. This study demonstrates an integrated approach to study habitat use and foraging behavior of eels. Furthermore, the study underlines the need to consider freshwater and estuarine habitats and the connectivity between them for eel management and conservation.

With only a few absolute geographic barriers in marine environments, the factors maintaining reproductive isolation among marine organisms remain elusive. However, spatial structuring in breeding habitat can contribute to reproductive isolation. This is particularly important for marine organisms that migrate to use fresh- or brackish water environments to breed. The Japanese Gasterosteus stickleback species, the Pacific Ocean three-spined stickleback (G. aculeatus) and the Japan Sea stickleback (G. nipponicus) overwinter in the sea, but migrate to rivers for spawning. Although they co-occur at several locations across the Japanese islands, they are reproductively isolated. Our previous studies in Bekanbeushi River showed that the Japan Sea stickleback spawns in the estuary, while the Pacific Ocean stickleback mainly spawns further upstream in freshwater. Overall genomic divergence was very high with many interspersed regions of introgression. Here, we investigated genomic divergence and introgression between the sympatric species in the much shorter Tokotan River, where they share spawning sites. The levels of genome-wide divergence were reduced and introgression was increased, suggesting that habitat isolation substantially contributes to a reduction in gene flow. We also found that genomic regions of introgression were largely shared between the two systems. Furthermore, some regions of introgression were located near loci with a heterozygote advantage for juvenile survival. Taken together, introgression may be partially driven by adaptation in this system. Although, the two species remain clearly genetically differentiated. Regions with low recombination rates showed especially low introgression. Speciation reversal is therefore likely prevented by barriers other than habitat isolation.

Japanese eel (Anguilla japonica) is a commercially important species; however, its population has declined in recent years. Appropriate conservation management, including habitat protection, is required to reverse this decline. However, their habitat use pattern during the riverine life stage is poorly understood. In this study, we investigated the longitudinal distribution and microhabitat of small-sized (

Although river-crossing structures can have a detrimental effect on the movement and distribution of anguillid eels (genus Anguilla), they have inhabited locations upstream of river-crossing structures in many rivers. However, the growth stage in which the eels start to climb river-crossing structures remains unclear. In this study, we directly observed, using infrared video camera systems, that the Japanese eel (Anguilla japonica) climbs a low-height vertical weir as a migratory barrier, confirming the ability of eels to climb over a low-height weir within a river. All eels climbed the weir at night, between sunset and sunrise. We observed that the total length of Japanese eels that climbed the weir ranged from 60 to 140 mm, suggesting that eels inhabiting the upstream area of a weir climbed it when they were small and then lived and grew upstream. Moreover, the general additive model showed considerable effects of water temperature and precipitation on eel climbing, suggesting that water temperature and precipitation are important for its activation. The results of this study also show the effectiveness of infrared video cameras in monitoring eel climbing, which could be applied to monitor fish migratory behavior through fish passages. The findings of this study are useful for the comprehensive management and conservation of wild eel stocks.

Colonization of new ecological niches has triggered large adaptive radiations. Although some lineages have made use of such opportunities, not all do so. The factors causing this variation among lineages are largely unknown. Here, we show that deficiency in docosahexaenoic acid (DHA), an essential w-3 fatty acid, can constrain freshwater colonization by marine fishes. Our genomic analyses revealed multiple independent duplications of the fatty acid desaturase gene Fads2 in stickleback lineages that subsequently colonized and radiated in freshwater habitats, but not in close relatives that failed to colonize. Transgenic manipulation of Fads2 in marine stickleback increased their ability to synthesize DHA and survive on DHA-deficient diets. Multiple freshwater ray-finned fishes also show a convergent increase in Fads2 copies, indicating its key role in freshwater colonization., This project was supported by JSPS KAKENHI grants 15H02418 and 23113007 (to J.K.), grant 16H06279 (to A.T.), and grants 26870824 and 16K07469 (to A.I.); the Asahi Glass Foundation (to J.K.); the Sumitomo Foundation (to A.I.); and JSPS postdoctoral fellowships 11J04816 to A.I. and 16J06812 to N.K. The work by N.L. and C.J.S. was funded by internal Eawag funds. B.M. was supported by SNF grant 31003A 175614. O.S. was supported by SNSF grant 31003A_163338. D.M. was supported by SNSF grant PDAMP3_123135 (to O.S).

The Mekong giant catfish

Biodiversity is an important parameter for the evaluation of the extant environmental conditions. Here, we used environmental DNA (eDNA) metabarcoding to investigate fish biodiversity in five different estuaries in Japan. Water samples for eDNA were collected from river mouths and adjacent coastal areas of two estuaries with high degrees of development (the Tama and Miya Rivers) and three estuaries with relatively low degrees of development (the Aka, Takatsu, and Sendai Rivers). A total of 182 fish species across 67 families were detected. Among them, 11 species occurred in all the rivers studied. Rare fishes including endangered species were successfully detected in rich natural rivers. Biodiversity was the highest in the Sendai River and lowest in the Tama River, reflecting the degree of human development along each river. Even though nutrient concentration was low in both the Aka and Sendai Rivers, the latter exhibited greater diversity, including many tropical or subtropical species, owing to its more southern location. Species composition detected by eDNA varied among rivers, reflecting the distribution and migration of fishes. Our results are in accordance with the ecology of each fish species and environmental conditions of each river, suggesting the potential of eDNA for non-invasive assessment of aquatic biodiversity.

Biodiversity is an important parameter for the evaluation of the extant environmental conditions. Here, we used environmental DNA (eDNA) metabarcoding to investigate fish biodiversity in five different estuaries in Japan. Water samples for eDNA were collected from river mouths and adjacent coastal areas of two estuaries with high degrees of development (the Tama and Miya Rivers) and three estuaries with relatively low degrees of development (the Aka, Takatsu, and Sendai Rivers). A total of 182 fish species across 67 families were detected. Among them, 11 species occurred in all the rivers studied. Rare fishes including endangered species were successfully detected in rich natural rivers. Biodiversity was the highest in the Sendai River and lowest in the Tama River, reflecting the degree of human development along each river. Even though nutrient concentration was low in both the Aka and Sendai Rivers, the latter exhibited greater diversity, including many tropical or subtropical species, owing to its more southern location. Species composition detected by eDNA varied among rivers, reflecting the distribution and migration of fishes. Our results are in accordance with the ecology of each fish species and environmental conditions of each river.

The coypu (Myocastor coypus) is a semi-aquatic herbivorous rodent that has been suspected to prey on freshwater unionid mussels in Japan. Fecal DNA metabarcoding that targeted bivalves and terrestrial plants was performed to examine the diet of exotic coypu in the Kiso River, central Japan. Thirty-two fecal samples from four floodplain waterbodies were collected seasonally. In one of the waterbodies, live and dead mussels were investigated to examine the possible effects of coypu predation on mussel population structures. Common coypu predation on unionid mussels was confirmed in two waterbodies. Midden surveys showed that medium- to large-sized mussels tended to be consumed by coypu; possibly resulting in population structures with few large-sized individuals. Seasonal diet selection of terrestrial plants was also detected: two perennial plants were consumed throughout the year, whereas some perennial plants were consumed seasonally. The number of terrestrial plant species/taxa as primary food was higher in summer than in winter, which was attributed to the high consumption of annual plants in the summer. Future studies need to examine the exhaustive diet of coypu including other animals and plants, as well as its effects on freshwater ecosystems in invaded regions.

Team-based learning (TBL) is an active learning method which has been designed to help students solve problems both by themselves and as a team. In this study, TBL was introduced in the journal club (gathering to read and discuss medical papers) for pharmacists, and its effectiveness was compared with that of a traditional lecture. The subjects, 29 pharmacists at Kobe University Hospital, were randomly allocated to the lecture group and TBL group. The pre-test was conducted two months before the journal club, and the post-tests were conducted immediately and one month after the journal club. There was no significant difference in the background data of the pharmacists between the lecture group and the TBL group. The score differences between the pre-test and the post-test immediately after the journal club were not significant (11.4 ± 2.3 points (mean ± SD) in the TBL group, 8.8 ± 4.2 points in the lecture group, P = 0.14). The post-test scores immediately after the journal club in the TBL group (19.6 ± 0.5 points) were significantly higher compared with those in the lecture group (17.8 ± 1.5 points) (P < 0.01), and the learning effect provided by TBL tended to be maintained one month after the TBL. In conclusion, TBL was an alternative method of the ordinal lecture and may be a useful learning method for pharmacists to read medical papers critically compared with the ordinal lecture.

Kobe University Hospital created a simplified 14-item protocol for resolving out-of-hospital prescription queries. The protocol was implemented in September 2016 in nine community pharmacies. If prescriptions were changed as per the new protocol or via typical query procedures, we asked community pharmacies to fax the changed prescriptions, and the hospital pharmacists, rather than medical doctors, modified the prescription history. To evaluate the effects of this simplified protocol, we examined the number of changed outpatient prescriptions and administered questionnaire surveys to community pharmacists and hospital-based medical doctors. The ratio of changed to total outpatient prescriptions decreased in January 2017 (4.1％) compared with those in September 2016 (6.4％). Ultimately, more than half of all outpatient prescriptions were changed by the protocol. Drug brand name changes accounted for 52％ of the total changes during both September 2016 and January 2017, but the proportion of residual medicine adjustment increased from 12％ in September 2016 to 26％ in January 2017. Due to the questionnaire survey, 33％ of surveyed medical doctors indicated that they knew or had heard of the protocol, and 54％ responded that the protocol decreased the burden of addressing outpatient prescription queries. The community pharmacies reported that the burden of clarifying outpatient prescription queries decreased. In conclusion, implementation of the simplified protocol for outpatient prescription queries improved medical efficiency and may help promote cooperative streamlining of community patient pharmaceutical care services.

Hand-foot skin reaction is recognized as one of the most common adverse events related to multiple tyrosine kinase inhibitors, but an effective prevention method has not been identified. The chief aim of this study was to find a mechanism-based preventive method for the skin toxicity induced by sorafenib using vitamin C derivatives. The effects of ascorbyl-2-phosphate magnesium (P-VC-Mg) on the molecular and pathological changes induced by sorafenib were investigated in human keratinocyte HaCaT cells. The cell growth inhibition and apoptotic effects of sorafenib were attenuated by P-VC-Mg. Moreover, P-VC-Mg inhibited the decrease of signal transducer and activator of transcription 3 (STAT3) phosphorylation and the expression of apoptosis suppressors treated by sorafenib. HaCaT cells transfected with the STAT3 dominant-negative form (STAT3DN) and STAT3 small interfering RNA (siRNA) combined with P-VC-Mg did not exhibit the attenuation of cell growth inhibition. Interestingly, after exposure to sorafenib in a three dimensional (3D) skin model assay, the basal layer was significantly thickened and the granular and spinous layers became thinner. In contrast, after exposure to sorafenib with P-VC-Mg, the thickness of the basal, granular, and spinous layers was similar to that of the control image. These findings suggest that P-VC-Mg attenuates sorafenib-induced apoptosis and pathological changes in human keratinocyte cells and in the 3D skin model mediated by the maintenance of STAT3 activity.

SummaryWhat is known and objectives The Screening Tool of Older Persons’ Potentially Inappropriate Prescriptions (stopp) criteria were updated in 2014 (stopp criteria ver.2), but few studies have evaluated the usefulness of stopp criteria in elderly patients. This prospective observational study evaluated the prevalence of potentially inappropriate medications (PIMs), and the efficacy of hospital pharmacists’ assessment and intervention based on stopp criteria ver.2. Methods The study was conducted at three medical units of Kobe University Hospital between April 2015 and March 2016. Pharmacists assessed and detected PIMs based on stopp criteria ver.2 and considered the patient's intention to change the prescription at the time of admission of each patient. If the pharmacists judged that benefits outweighed risks of prescription change and the patients consented to change the medications, they recommended the doctor to change the prescription. If there was a risk of exacerbation of disease by the change of medications and the pharmacists judged it to be difficult to adjust medications during hospitalization or the patients did not consent to change the medications, they did not recommend to change it. The pharmacists and the doctors discussed and finally decided whether to change the PIMs or not. The number of patients prescribed PIMs, the number and contents of PIMs, and the number of medications changed after pharmacists’ intervention were calculated. Results Totally, 822 new inpatients aged ≥65 years prescribed ≥1 daily medicine were included. Their median (interquartile range) age was 75·0 (71·0–80·0) years, and 54·9% were male. According to the criteria, 346 patients (42·1%) were prescribed ≥1 PIMs. Patients prescribed PIMs took significantly more medications than others: 10·0 (7·0–13·0) vs. 6·0 (4·0–9·0), P < 0·001. The total number of PIMs was 651%, 47·6% of which (n = 310) were recommended the doctors to change, and 292 of 651 PIMs (44·9%) were finally discontinued/changed after pharmacists’ assessment and intervention. PIMs related to benzodiazepines, including Z-drugs, were most frequent, with a detailed classifications as follows (changed/total): (i) benzodiazepines for 4 or more weeks (75/205), (ii) drugs that predictably increase the risk of falls in older people (benzodiazepines) (30/67) and (iii) drugs that predictably increase the risk of falls in older people (hypnotic Z-drugs) (15/31). Conclusion Over 40% elderly patients were prescribed PIMs, and pharmacists’ assessments and interventions based on stopp criteria ver.2 were useful in detecting and correcting prescription of PIMs.

Estuarine and coastal ecosystems are important habitats for many fish species. Large-scale patterns of estuarine and coastal fish communities can be affected by geographical factors, such as water temperature and latitude, that limit or allow fish dispersal, and/or by environmental factors that select locally adapted species. Furthermore, increased human activity has also altered fish diversity by modifying estuarine/coastal environments. Here, we used environmental DNA metabarcoding to study a large-scale pattern of estuarine/coastal fish communities across 25 watersheds in the Japanese Archipelago, and we assessed the effects of geographical, environmental, and anthropogenic factors in structuring these communities. Of the 290 fish species detected, 47 species were red-listed by the Japanese Ministry of Environment, and nine were alien. Non-metric multidimensional scaling showed that latitude and water temperature affected both river-mouth and coastal-sea fish communities. Although other anthropogenic factors did not affect these communities, bank artificialisation rates influenced both. The relationship between each fish community and ocean currents was weak. The number of red-listed fish affected both fish community structures, whereas that of alien species did not. The numbers of red-listed fish in coastal points and of all fish species were negatively influenced to the human population density. These findings provide useful information that may be used to conserve estuarine and coastal ecosystems.

The Mekong giant catfish Pangasianodon gigas is one of the largest freshwater fish, measuring up to 3 m in total length. This study was designed to determine the feeding habits of P. gigas to better understand how the fish achieve their large body size. We compared the relationship between gut length (GL) and total length (TL) among related species in superfamily Bagroidea, order Siluriformes (Pangasianodon hypophthalmus and Hemibagrus nemurus) in the Kaeng Krachan reservoir, Thailand. The mean relative gut length (RGL = GL / TL) of P. gigas was 3.50, showing that they have relatively long guts, with values more similar to those of omnivorous P. hypophthalmus (RGL = 3.70) than to those of carnivorous H. nemurus (RGL = 0.92). In the allometric relationship (i.e., log10 GL = log10 a + b log10 TL), the slope close to 1 for P. gigas (b = 1.07) has been widely observed in carnivores, while P. gigas has a greater intercept of the linear equation than P. hypophthalmus and H. nemurus, resulting in a similar GL of P. gigas to omnivorous P. hypophthalmus at approximately 35 cm in TL. Moreover, GL of P. gigas at 150 to 250 cm in TL showed great variations (RGL = 1.35-6.32). The variation in RGL for P. gigas seemed to result from a poor nutritional state. In conclusion, P. gigas is suggested to feed on indigestible materials such as plants, algae, and sediments, and potentially experience fasting in a reservoir.

Albumin-bound paclitaxel (Abraxane®, nab-paclitaxel) is not recommended to be administered concurrently or sequentially with other drugs due to concern for instability. The need to administer drugs separately increases infusion time. We evaluated the compatibility and stability of solutions containing nab-paclitaxel and other drugs, including gemcitabine hydrochloride, carboplatin, dexamethasone sodium phosphate, granisetron hydrochloride, and palonosetron hydrochloride. We visually examined changes in appearance, pH, and concentration of the mixed solutions of nab-paclitaxel and other drugs for up to 24 h. Concentration was measured using high-performance liquid chromatography (HPLC). The appearance and pH of the mixed solutions did not change for up to 24 h. The change in concentration up to 24 h was within 2%. The chromatogram did not change until 8 h. The results showed that the physical compatibility and chemical stability of nab-paclitaxel were not influenced when it was combined with other drugs until 8 h. This study suggests that nab-paclitaxel could be administered in a mixture or sequentially with other drugs to reduce administration time.

On March 11, 2011, a large earthquake occurred, causing a tsunami which struck the Pacific coast of northeast Japan. We investigated the ecological and genetic effects of the large tsunami on the threespine stickleback (genus Gasterosteus) populations in Otsuchi Town, which was one of the most severely damaged areas after the tsunami. Our environmental surveys showed that spring water may have contributed to the habitat recovery. Morphological analysis of the stickleback before and after the tsunami showed morphological shifts in the gill raker number, which is a foraging trait. Genetic analyses revealed that the allelic richness of one population was maintained after the tsunami, whereas that of another decreased in 2012 and then started to recover in 2013. Additionally, we found that the large tsunami and ground subsidence created new spring water-fed pools with sticklebacks, suggesting that the tsunami brought sticklebacks into these pools. Genetic analysis of this population showed that this population might be derived from hybridization between freshwater Gasterosteus aculeatus and anadromous G. nipponicus. Overall, our data indicate that tsunamis can influence morphologies and genetic structures of freshwater fishes. Furthermore, spring water may play important roles in the maintenance and creation of fish habitats, faced with environmental disturbance.

This study aimed to determine the antiemetic efficacy and safety of palonosetron, aprepitant and dexamethasone in patients with testicular germ cell tumours (TGCTs) receiving 5-day cisplatin-based combination chemotherapy. In this open-label, single-arm, single-centre study, the antiemetic therapy consisted of palonosetron 0.75 mg on day 1, aprepitant 125 mg on day 1 and 80 mg on days 2–7 and dexamethasone 6.6 mg on days 1–7. The primary endpoint was complete response (CR; no vomiting/retching or rescue medication) in the overall period (0–240 h), and secondary endpoints included complete protection (CP; defined as CR and no more than mild nausea) and total control (TC; defined as CR and no nausea). The incidence and severity of nausea were assessed on the basis of the Common Terminology Criteria for Adverse Events v4.0 and a subjective rating scale completed by patients. Twenty-five patients were enrolled and evaluated for safety, and 24 patients were evaluated for efficacy. CR was achieved in 62.5% of patients (95% confidence interval [CI] = 40.6–81.2, p = 0.043) in the overall period. CP and TC were achieved in 62.5% (95% CI = 40.6–81.2) and 25.0% of patients (95% CI = 9.8–46.7), respectively, in the overall period. The primary adverse drug reaction was hiccups (48.0%). The events were expected, and none was grade 3 or 4. The examined combination antiemetic therapy was effective and well-tolerated in patients with TGCTs receiving 5-day cisplatin-based combination chemotherapy.

Cordyceps militaris (CM) is gaining attention as a traditional medicinal food, but its molecular biological mechanisms for anti-cancer activity are not identified or clarified. We aimed to elucidate the synthesizing apoptotic effects of CM extracts and to determine the biological effects of CM extract against cordycepin alone in a renal cell carcinoma (RCC) cell line. CM extract showed higher effects of growth inhibition, apoptotic effect, and cell cycle arrest than cordycepin alone. Moreover, CM extract activated extracellular signal-regulated kinase (Erk) highly more than cordycepin alone. We suggest that cordycepin and CM extract induced apoptosis via the activation of Erk dominantly and AMP-activated protein kinase slightly; CM extract has more potent effects on apoptotic effects associated with Erk activation than cordycepin alone.

Identification of landscape structures that predict the distribution of aquatic organisms has the potential to provide a practical management tool for species conservation in agricultural drainage channels. We tested the hypothesis that sites with imperiled freshwater mussels have distinct rural landscape structures and are characterized by the presence of diverse fish communities. In central Japan, the proportion of developed land use in surrounding areas was compared among sites with mussel populations (mussel sites) and randomly chosen sites (random sites) across multiple spatial scales (with a radius ranging from 100 to 3,000 m). Mussel sites were characterized by a much lower proportion of developed land (mean 5-18 %) compared with random sites (mean 32-35 %) at a scale of a parts per thousand currency sign300 m. The areas that met the landscape criteria for mussel sites across multiple scales constituted only 0.23 % of the area that was presumed to have suitable slope and elevation as a mussel habitat. Landscape metrics derived from mussel sites to locate unknown populations had a low predictability (16.7 %). Sites with mussels were located close to each other and had fish communities with higher taxonomic diversity than in sites without mussels. In addition, mussel taxonomic richness was a good predictor of fish community diversity. The quantitative measures of landscape structure may serve as a useful tool when prioritizing or identifying areas for conservation of mussels and fish if spatially autocorrelated distribution of habitat and other critical environmental factors such as habitat connectivity are also considered.

Summary Anthropogenically induced reduction in flood inundation frequency often leads to terrestrialisation, which accompanies establishment and expansions of tree cover on areas formerly with little or no trees. We tested hypotheses that terrestrialisation degrades habitat for freshwater mussels (Unionoida: Unio douglasiae nipponensis and Lanceolaria grayana) by changing the organic matter (OM) dynamics in floodplain backwaters. Stable isotope composition of seston, periphyton, fine and coarse benthic particulate OM (FBPOM and CBPOM) and mussel tissues was measured to understand OM dynamics and food webs in 14 backwaters in the middle segment of the Kiso River, Japan. Isotope ratios, C : N ratio and chlorophyll a as a proxy of food resource characteristics and the frequency of hypoxia were related to mussel growth rates. δ13C of seston, periphyton and FBPOM was low at sites with lower inundation frequency (a greater degree of terrestrialisation), whereas such a trend was not observed for CBPOM (i.e. riparian leaf litter). Mussels fed exclusively on seston or mixtures of seston and periphyton with their δ13C tracking fluctuations in food resources. Sestonic δ13C differences were attributed to changes in dominant carbon origin from predominantly river-borne to autochthonous sources, while periphytic δ13C differences were possibly caused by a varying level of dependence on respiratory CO2. FBPOM-δ13C differences were associated with a greater contribution of CBPOM to the FBPOM pool in infrequently flooded backwaters. Variability in mussel growth was more closely related to hypoxia than food resource characteristics. We inferred that terrestrialisation changes quality of seston and benthic detritus and degrades habitat conditions largely by accumulating riparian leaf litter in the benthic detrital pool and increasing the frequency of hypoxia. The removal of riparian trees may temporarily improve habitat condition in backwaters heavily affected by terrestrialisation. However, ecological integrity in the long run requires the recovery of the process that suppresses terrestrialisation, which includes restoration of incised channels and flood pulses.

We examined fish community structures in floodplain backwaters in the Kiso River, Central Japan, in an uncommon drought year. Nine floodplain backwaters with varying levels of flood inundation frequency were surveyed for winter fish communities, and measured for local environmental variables in summer and winter periods. The winter fish community was better represented, with less diverse and physiologically tolerant species in backwaters with a decreasing flood pulse frequency. The temporal frequency of hypoxic conditions (dissolved oxygen of

Although similar patterns of phenotypic diversification are often observed in phylogenetically independent lineages, differences in the magnitude and direction of phenotypic divergence have been also observed among independent lineages, even when exposed to the same ecological gradients. The stickleback family is a good model with which to explore the ecological and genetic basis of parallel and nonparallel patterns of phenotypic evolution, because there are a variety of populations and species that are locally adapted to divergent environments. Although the patterns of phenotypic divergence as well as the genetic and ecological mechanisms have been well characterized in threespine sticklebacks, Gasterosteus aculeatus, we know little about the patterns of phenotypic diversification in other stickleback lineages. In eastern Hokkaido, Japan, there are three species of ninespine sticklebacks, Pungitius tymensis and the freshwater type and the brackish-water type of the P. pungitius-P. sinensis species complex. They utilize divergent habitats along coast-stream gradients of rivers. Here, we investigated genetic, ecological and phenotypic divergence among three species of Japanese ninespine sticklebacks. Divergence in trophic morphology and salinity tolerance occurred in the direction predicted by the patterns observed in threespine sticklebacks. However, the patterns of divergence in armour plate were different from those previously found in threespine sticklebacks. Furthermore, the genetic basis of plate variation may differ from that in threespine sticklebacks. Because threespine sticklebacks are well-established model for evolutionary research, the sympatric trio of ninespine sticklebacks will be an invaluable resource for ecological and genetic studies on both common and lineage-specific patterns of phenotypic diversification.

We tested the hypothesis that globally imperiled freshwater mussels (Order: Unionoida) can be used as an indicator of fish communities in lowland aquatic systems for relatively small geographic areas (i.e.

Summary 1. Understanding mechanisms behind the distribution of organisms along a gradient of hydrological connectivity is crucial for sustainable management of river–floodplain systems. We tested the hypothesis that frequency of flood pulses exerts a direct influence on the distribution of freshwater mussels (Unionoida) by creating a local environment that limits their fitness. 2. Multiscale habitat analyses combined with transplant-rearing experiments were carried out with a focus on abundance, presence/absence, survival rates and growth rates of mussels. Sixty-nine floodplain waterbodies (FWBs) were surveyed within a 15-km lowland segment of the Kiso River in Japan. 3. The abundance of mussels significantly increased with increased frequency of inundation associated with flood pulses at the among-FWB scale, while the probability of occurrence of mussels was negatively predicted by the amount of benthic organic matter at the within-FWB scale. 4. Field-rearing experiments showed that survival rates were low and growth rates nearly zero in infrequently inundated FWBs (these FWBs had no naturally occurring resident mussels). In such FWBs, hypoxia (DO 15 °C). 5. These findings demonstrated that flood pulse frequency was the most important factor in determining mussel distribution in FWBs because it directly limits mussels’ fitness by mediating local environmental factors, possibly dissolved oxygen (DO) levels. Successful restoration efforts for mussel habitat conservation should focus on processes that lead to improved local conditions.

An increasing number of exotic animals are causing ecological problems. Therefore, for better ecosystem management, it is important to understand how exotic species colonize and adapt to novel environments. The threespine sticklebacks (Gasterosteus aculeatus) can be a good vertebrate model system to explore the ecological and genetic mechanisms of adaptation not only in natural populations, but also in non-native populations. Although morphological changes have been documented in several introduced populations of stickleback, little is known about the dietary changes during colonization into novel environments. Here, we investigated the morphological and dietary changes of exotic threespine stickleback populations introduced into three Japanese crater lakes (Lake Towada, Lake Kussharo, and Lake Shikotsu). Sticklebacks were introduced into the crater lakes likely along with salmonids transplanted for aquaculture. The stickleback population in Lake Kussharo had multiple mitochondrial haplotypes and had larger phenotypic variances than other crater lake stickleback populations that had only one mitochondrial haplotype. Compilation of historical data on the morphology and stomach contents of the Lake Towada stickleback population showed that substantial shifts in body size and stomach contents occurred after colonization. Some of these changes may be related to an outbreak of the Schistocephalus parasite. These results suggest that sticklebacks can change their morphology and trophic ecology when they colonize novel environments. Therefore, extreme care should be taken when salmonids are transported between watersheds for aquaculture and that long-term monitoring of exotic species is essential for ecosystem management. In addition, further genetic studies on phenotypic changes in crater lake sticklebacks would help elucidate the genetic mechanisms underlying the adaptation of exotic fishes to novel environments.

Signal transducer and activator of transcription (STAT) 3 is a key factor in multiple tyrosine kinase inhibitor (mTKI)-induced growth inhibition and apoptosis of renal cell carcinoma (RCC) cells. This study aimed to identify associations between single-nucleotide polymorphisms (SNPs) in the STAT3 gene and tumor response to mTKIs in patients with metastatic RCC (mRCC). Seventy-one patients with clear cell RCC treated with any mTKI were retrospectively genotyped to elucidate a potential association between STAT3 SNPs and overall best response to drugs. Of 50 patients included for analysis, a partial or complete response was observed in 17. A significant association was found between rs4796793 alleles and tumor response [G vs. C, odds ratio (OR) 3.25, 95 % confidence interval (CI) 1.30–8.07]. There were a higher percentage of responders with the C/C genotype at rs4796793 than with the G/C + G/G genotypes (OR 4.46, 95 % CI 1.31–15.28). Time-to-event analysis demonstrated a statistically significant difference between patients with the CC genotype and those with G/C + G/G genotypes in time-to-treatment response, but not in progression-free survival or time-to-treatment failure. The rs4796793 genotype is a novel predictive factor of the response to mTKIs in patients with mRCC. However, prospective translational trials with larger patient cohorts are required to confirm these results.