Influence of temperature on hatching success of skipjack tuna (Katsuwonus pelamis): Implications for spawning availability of warm habitats.

Exploring the effects of water temperature on egg development in skipjack tuna (Katsuwonus pelamis) has substantial implications for evaluations of wild spawning habitats. In the present study, we examined the hatching success and duration as a function of temperature from 21 to 33°C under captive environments. A high hatching rate of over 50% between 23 and 31°C was observed, with the shortest hatching duration at 31°C. Because the egg period is vulnerable to predators, a shortened hatching duration with warming water would be ecologically advantageous for K. pelamis, as its main spawning grounds are located in tropical areas.

Hydride-ion-conducting K2NiF4-type Ba-Li oxyhydride solid electrolyte.

Hydrogen transport in solids, applied in electrochemical devices such as fuel cells and electrolysis cells, is key to sustainable energy societies. Although using proton (H+) conductors is an attractive choice, practical conductivity at intermediate temperatures (200-400 °C), which would be ideal for most energy and chemical conversion applications, remains a challenge. Alternatively, hydride ions (H-), that is, monovalent anions with high polarizability, can be considered a promising charge carrier that facilitates fast ionic conduction in solids. Here, we report a K2NiF4-type Ba-Li oxyhydride with an appreciable amount of hydrogen vacancies that presents long-range order at room temperature. Increasing the temperature results in the disappearance of the vacancy ordering, triggering a high and essentially temperature-independent H- conductivity of more than 0.01 S cm-1 above 315 °C. Such a remarkable H- conducting nature at intermediate temperatures is anticipated to be important for energy and chemical conversion devices.

Reproductive Ability of Hybrids between Japanese Pond Turtle (Mauremys japonica) and Reeves' Pond Turtle (Mauremys reevesii).

Hybridization induced by human activities, such as crossbreeding between invasive and native species, can adversely affect the natural biodiversity of an ecosystem. In Japan, the endemic turtle species Mauremys japonica is known to hybridize with the alien species Mauremys reevesii, and putative hybrids have been encountered in the wild. If M. japonica × M. reevesii hybrids can readily crossbreed with M. japonica, the hybridization with M. reevesii could lead to the extinction of pure M. japonica populations. However, information on the reproductive ability of M. japonica × M. reevesii hybrids is limited. In this study, we collected wild-caught hybrids from across western Japan to assess their reproductive ability. We investigated the nesting season timing, clutch size, embryonic development, hatching success, and sperm viability. The results showed that female hybrids nested during the same months as the parental species and had similar clutch sizes and hatching success. No embryonic development abnormalities were detected, and viable sperm were observed in all hybrid male semen samples. In conclusion, the fertility of M. japonica × M. reevesii hybrids appears to be similar to the fertilities of the parental species, posing a potential challenge for M. japonica conservation.

Selective and reversible modification of kinase cysteines with chlorofluoroacetamides.

Irreversible inhibition of disease-associated proteins with small molecules is a powerful approach for achieving increased and sustained pharmacological potency. Here, we introduce α-chlorofluoroacetamide (CFA) as a novel warhead of targeted covalent inhibitor (TCI). Despite weak intrinsic reactivity, CFA-appended quinazoline showed high reactivity toward Cys797 of epidermal growth factor receptor (EGFR). In cells, CFA-quinazoline showed higher target specificity for EGFR than the corresponding Michael acceptors in a wide concentration range (0.1-10 µM). The cysteine adduct of the CFA derivative was susceptible to hydrolysis and reversibly yielded intact thiol but was stable in solvent-sequestered ATP-binding pocket of EGFR. This environment-dependent hydrolysis can potentially reduce off-target protein modification by CFA-based drugs. Oral administration of CFA quinazoline NS-062 significantly suppressed tumor growth in a mouse xenograft model. Further, CFA-appended pyrazolopyrimidine irreversibly inhibited Bruton's tyrosine kinase with higher target specificity. These results demonstrate the utility of CFA as a new class warheads for TCI.

Fragment-Based Discovery of Irreversible Covalent Inhibitors of Cysteine Proteases Using Chlorofluoroacetamide Library.

Fragment-based approach combined with electrophilic reactive compounds is a powerful strategy to discover novel covalent ligands for protein target. However, the promiscuous reactivity often interferes with identification of the fragments possessing specific binding affinity to the targeted protein. In our study, we report the fragment-based covalent drug discovery using the chemically tuned weak reactivity of chlorofluoroacetamide (CFA). We constructed a small fragment library composed of 30 CFA-appended compounds and applied it to the covalent ligand screening for cysteine protease papain as a model protein target. Using the fluorescence enzymatic assay, we identified CFA-benzothiazole 30 as a papain inhibitor, which was found to irreversibly inactivate papain upon enzyme kinetic analysis. The formation of the covalent papain-30 adduct was confirmed using electrospray ionization mass spectrometry analysis. The activity-based protein profiling (ABPP) experiment using an alkynylated analog of 30 (i.e., 30-yne) revealed that 30-yne covalently labeled papain with high selectivity. These data demonstrate potential utility of the CFA-fragment library for de novo discovery of target selective covalent inhibitors.

[A case of large cell neuroendocrine carcinoma (LCNEC) of the uterine cervix successfully treated by postoperative CPT-11+CDDP chemotherapy after non-curative surgery].

A 31-year-old woman, gravida 3 para 3, visited a local clinic because of post-coital bleeding. She was diagnosed as having a uterine-cervical tumor and was referred to our hospital. Large cell neuroendocrine carcinoma (LCNEC) of the uterine cervix was pathologically shown by biopsy. The patient was initially treated by radical hysterectomy. Postoperative pathological examination revealed a direct invasion to the parametrium and the positive resection margin. Postoperatively, she was treated by CPT-11+CDDP. One course of treatment was 60mg/m² of CPT-11 administered on day 1, 8 and 15, and 60 mg/m² of CDDP on day 1, with an intermission after administration for 7 days. Six courses were carried out. This treatment resulted in complete remission. A follow-up at the outpatient clinic revealed the patient had been tumor-free for one year and three months after the first treatment. We suggest that postoperative chemotherapy with CPT-11+CDDP might be useful in the treatment of patients with LCNEC of the uterine cervix.

Impact of Na Concentration on the Phase Transition Behavior and H- Conductivities in the Ba-Li-Na-H-O Oxyhydride System.

K2 NiF4 -type Ba-Li oxyhydride (BLHO) transitions to a so-called hydride superionic conductor, exhibiting a high and essentially temperature-independent hydride ion (H- ) conductivity over 0.01 S cm-1 through the disordering of H- vacancies above 300 °C. In this study, a Ba-Li-Na-H-O oxyhydride system synthesized in which lithium is partially substituted with sodium in BLHO and investigated the effects of Na content on the phase transition behavior and the conductivity. Structural refinements and differential scanning calorimetry experiments confirmed a lowering trend in the phase transition temperatures and decreasing enthalpy changes for the transition with increasing Na content. Substitution of not <40% of Li with Na lowered the degree of ordered vacancies at the H- sites at room temperature and improved conductivities by more than two orders of magnitude in the low-temperature region (T < 300 °C) before the phase transition. These findings clearly show that introducing Na into the lattice effectively stabilizes the high-conductive phase of BLHO.

Computed tomographic analysis of internal structures within the nasal cavities of green, loggerhead and leatherback sea turtles.

The morphology of the tetrapod nasal cavity has adapted to the environment in terms of olfaction and respiration. Reports indicate that the internal structure of the nasal cavity of green sea turtles is more complex than that of turtles in general, but whether or not it is similar among sea turtle species remains unknown. The present study aimed to define the internal structures of the nasal cavity of green (Chelonian mydas), loggerhead (Caretta caretta) and leatherback (Dermochelys coriacea) sea turtles using computed tomography. The nasal cavity of green and loggerhead sea turtles contained anterodorsal, anteroventral, posterodorsal diverticula and a posteroventral excavation in the middle. In contrast, the nasal cavity of leatherback sea turtles had more complicated dorsal region comprising anterodorsal and posterodorsal diverticula, and two excavations between the nostril and anterodorsal diverticulum, but no distinct structures at the ventral region. The airway in the nasal cavity was shorter and thicker in the leatherback, than in the green and loggerhead turtles. These species differences might reflect ecological variety and different evolutionary strategies.

Site-directed mutagenesis of rat thioltransferase: effects of essential cysteine residues for the protection against oxidative stress.

A cDNA of rat liver thioltransferase was cloned and then expressed using pMAL-c expression vector in Escherichia coli. Recombinant rat liver thioltransferase was expressed as a fusion protein with maltose-binding protein and then purified by amylose resin column chromatography to be homogeneity on 12.5% SDS-polyacrylamide gel electrophoretic analysis. The expressed proteins were shown as two bands at around 53 and 41 kDa, suggesting that the high molecular one was a fusion protein of recombinant thioltransferase (11.7 plus 41 kDa) and the other (smaller one) was a maltose-binding protein (41 kDa). A recombinant thioltransferase catalyzed a thiol/disulfide exchange reaction in the same way as thioltransferases purified from various sources. Compared with wild type, the mutants C23A, C26A, C79A, and C83A showed 0%, 17%, 82%, and 86% in the enzymatic activity, respectively. In addition, wild-type-transfected bacteria expressed in bacterial cells showed a strong resistance to H(2)O(2) treatment as well as the case of active mutants (C79A and C83A), but inactive mutants (C23A and C26A) showed no resistance to H(2)O(2) treatment as same as mocktransfection. Thioltransferase can be important for survival of bacterial cells under oxidative stress.

Dosimetric analysis of upper gastrointestinal ulcer after carbon-ion radiotherapy for pancreatic cancer.

PURPOSE: The aim of this study was to clarify the incidence, clinical risk factors, and dose-volume relationship of upper gastrointestinal (GI) ulcer after carbon-ion radiotherapy (C-ion RT) for pancreatic cancer. MATERIALS AND METHODS: Fifty-eight pancreatic cancer patients were treated with C-ion RT from April 2014 to December 2015. The total dose was 55.2Gy (RBE) in 12 fractions. D2cm3 of GI tracts were restricted under 46Gy (RBE); RBE-weighted absorbed dose. The association between dosimetric parameters (V10-50, Dmax, D1cm3, D2cm3) and GI ulcer was examined using Spearman's correlation. The incidence of GI ulcer was compared between the two groups divided by the cutoff value. RESULTS: Twelve patients (21%) experienced gastric ulcer including only one (2%) grade 3 ulcer. There was no grade 4/5 toxicity or duodenal ulcer. V10-30 was significantly associated with gastric ulcer. The 1-year estimated risk of gastric ulcer for the determined cutoff values were 51% vs. 10% (V10, ⩾102cm(3) or less), 42% vs. 9% (V20, ⩾24cm(3) or less), 34% vs. 4% (V30, ⩾6cm(3) or less). CONCLUSIONS: The incidence of GI ulcer after C-ion RT was very low with the dose constraint of D2cm3 <46Gy (RBE). To further minimize the risk of GI ulcer, V10-30 should also be reduced.

In vitro study on marginal and internal fit of CAD/CAM all-ceramic crowns.

The purpose of this study was to evaluate the marginal and internal fit of all-ceramic crowns fabricated using the Decsy CAD/CAM system. A master die of maxillary first premolar was measured, and experimental crowns were fabricated. Four conditions were established by combining two convergence angles (4 degrees and 12 degrees) of the abutment with two different luting space settings (15 microm and 55 microm). The results showed that the experimental crowns had a marginal gap of 42 to 56 microm. When the luting space setting was 15 microm, the internal gap was 85-88 microm; when the setting was 55 microm, the internal gap was 126-138 microm. The marginal gap for each experimental crown met the clinically acceptable criterion.