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Character of spoken dialogue systems is important not only for giving a positive impression of the system but also for gaining rapport from users. We have proposed a character expression model for spoken dialogue systems. The model expresses three character traits (extroversion, emotional instability, and politeness) of spoken dialogue systems by controlling spoken dialogue behaviors: utterance amount, backchannel, filler, and switching pause length. One major problem in training this model is that it is costly and time-consuming to collect many pair data of character traits and behaviors. To address this problem, semi-supervised learning is proposed based on a variational auto-encoder that exploits both the limited amount of labeled pair data and unlabeled corpus data. It was confirmed that the proposed model can express given characters more accurately than a baseline model with only supervised learning. We also implemented the character expression model in a spoken dialogue system for an autonomous android robot, and then conducted a subjective experiment with 75 university students to confirm the effectiveness of the character expression for specific dialogue scenarios. The results showed that expressing a character in accordance with the dialogue task by the proposed model improves the user's impression of the appropriateness in formal dialogue such as job interview. [ABSTRACT FROM AUTHOR]

Abstract: The natriuretic peptide (NP) family consists of at least seven members; cardiac ANP, BNP and VNP and brain CNPs (CNP1–4). Phylogenetic and comparative genomic analyses showed that CNP4 is the ancestral molecule of the family, from which CNP3 and CNP1/2 were duplicated in this order, and that the three cardiac NPs were generated from CNP3 by tandem duplication. Seven members existed at the divergence of ray-finned fishes and lobe-finned fishes (tetrapods), but some of the NP genes have disappeared during the course of evolution. In ray-finned fishes, all three cardiac NPs exist in chondrostei and some migratory teleost species, but VNP is generally absent and ANP is absent in a group of teleosts (Beloniformes). In tetrapods, ANP and BNP are present in mammals and amphibians, but ANP is usually absent in reptiles and birds. Thus, BNP is a ubiquitous cardiac NP in bony fishes and tetrapods though elasmobranchs and cyclostomes have only CNP3/4 as a cardiac NP. Functional studies indicate that cardiac NPs are essential Na+-extruding hormones throughout vertebrates; they play critical roles in seawater (SW) adaptation in teleosts, while they are important volume-depleting hormones in mammals as water and Na+ are regulated in parallel in terrestrial animals. In mammals, cardiac NPs become prominent in pathological conditions such as heart failure where they are used in diagnosis and treatment. Although the functional role of BNP has not yet been fully elucidated compared with ANP in non-mammalian vertebrates, it appears that BNP plays pivotal roles in the cardiovascular and body fluid regulation as shown in mammals. ANP has previously been recognized as the principal cardiac NP in mammals and teleosts, but comparative studies have revealed that BNP is the only cardiac NP that exists in all tetrapods and teleosts. This is an excellent example showing that comparative studies have created new insights into the molecular and functional evolution of a hormone family. [Copyright &y& Elsevier]

Abstract: The renin–angiotensin system is an enzyme-linked hormonal cascade that plays an important role in body fluid and cardiovascular regulation. The system is initiated by the action of renin on the precursor protein, angiotensinogen (AGT), whose sequence information is scarce because of its high variability among species. In the present study, we cloned AGT in chondrichthyans (elasmobranchs: Triakis scyllium, Dasyatis akajei, Leucoraja erinacea and a holocephalan: Callorhinchus milii). Homology was low among AGTs thus far identified; 25–28% between elasmobranchs and tetrapods and 33–61% even within chondrichthyans. All chondrichthyan angiotensin (ANG) II’s have a unique Pro3 instead of Val3 as seen in all other species. In addition, holocephalan ANG II has an unusual His4 instead of Tyr4. In addition, and the N-terminal amino acid, which is usually Asp1 in tetrapods and Asn1 in fishes, was highly variable (Asp, Asn or Tyr) in chondrichthyans. Molecular phylogenetic analysis showed that chondrichthyan AGT precursors are clustered into a group separated from those of tetrapods and teleosts. The AGT gene was most abundantly expressed in the liver, followed by the kidney, interrenal tissue and rectal gland of Triakis where biological actions of ANG II have been demonstrated. Collectively, we identified diversified AGT genes for the first time in chondrichthyes and showed that their ANG II’s have unique amino acid residues at positions 1, 3 and 4. High variability of ANG II sequences in chondrichthyans is discussed in relation to their unique regulatory mechanisms such as urea-based osmoregulation. [Copyright &y& Elsevier]

Adrenomedullin (AM) is a multifunctional peptide known to form a hormone family with calcitonin gene-related peptide (CGRP) and amylin. We have cloned five distinct AM cDNAs from the pufferfish, Takifugu rubripes, and named them TrAM-1, -2, -3, -4, and -5. Judging from the deduced precursor sequences and processing pattern of the C-terminal mature peptides, TrAMs may be divided into at least two groups; AM-2 and -3, and AM-1, -4, and possibly -5. Phylogenetic analysis of the mature peptides, exon–intron structure of their genes, and tissue distribution of their mRNA also support this classification. TrAM-1 and -4 were ubiquitously expressed in various tissues including the kidney and interrenal (adrenal homolog) as in the case of mammalian AM, while TrAM-2 and -3 were expressed most abundantly in the brain followed by the vascular tissues. Synteny of the genes around AM gene showed that TrAM-1 is the ortholog of mammalian AM. The presence of a PAMP-like sequence in the prosegment of TrAM-1 also supports this notion. Multiple AMs were also detected in another pufferfish, Tetraodon nigroviridis, and in zebrafish, Danio rerio. The present study shows for the first time the presence of a novel AM family in teleost fish that is independent from CGRP and amylin, which further suggests the possible existence of multiple AMs in mammals. [Copyright &y& Elsevier]

The four-spine sculpin Cottus kazika is a euryhaline teleost, in which faster growth in seawater (SW) and freshwater (FW) has been reported. In this study, cDNA clones encoding growth hormone (GH) and insulin-like growth factor I (IGF-I) were isolated from this species to examine the involvement of the GH/IGF-I axis in osmotic adaptation. The amino acid sequence of GH predicted from cDNA was highly similar to those of other fish species, 92% to Sparus aurata, 67% to Paralichthys olivaceus, and 63% to Oncorhynchus keta. The predicted sequence of IGF-I was also exhibited high similarity to those of other fishes, 97% to Myxocephalus scorpius, 95% to P. olivaceus, and 81% to O. keta. Tissue distribution of GH and IGF-I mRNA in fish reared in FW and SW was examined by reverse transcription-polymerase chain reaction (RT-PCR). The GH mRNA was detected only in the pituitary gland. The major site of IGF-I mRNA expression was the liver while minor signals were detected in various tissues including the pituitary, gill, fin, heart, spleen, intestine, and kidney. The expression level of GH mRNA in the pituitary was not different between FW- and SW-reared fish. However, the level of IGF-I mRNA in the liver of SW-reared fish was significantly higher than that of FW-reared fish. These results suggest the possible involvement of hepatic IGF-I in SW adaptation of this species. [Copyright &y& Elsevier]

Natriuretic peptides (NPs) play important roles in osmoregulatory and cardiovascular systems of vertebrates. For functional studies of NPs, rainbow trout (Oncorhynchus mykiss), a euryhaline fish, is an interesting model. The information on homologous NPs of salmonid fish is, however, still incomplete with respect to C-type NP (CNP). In this study, we isolated cDNAs encoding the precursor of CNP from the brain of trout. Predicted mature CNP (CNP-22) sequence was identical to that of killifish Fundulus heteroclitus, and only one amino acid was different from that of the eel Anguilla japonica, demonstrating a greater conservation among different teleost species than is found with atrial NP (ANP) and ventricular NP (VNP). While the preprosegment of trout CNP retained 57% similarity to the eel sequence, similarities were low to those of sharks and tetrapods. The major site of expression identified by RT-PCR was the brain with minor expression in the atrium. The putative mature CNP-22 was synthesized and its biological activity was compared with other trout NPs (ANP and VNP) using trout ventral aorta, efferent branchial and celiacomesenteric arteries and anterior cardinal vein in vitro. Synthetic trout CNP-22 relaxed all pre-contracted vessels with potencies comparable to trout ANP and VNP. [Copyright &y& Elsevier]

Abstract: Vertebrates expanded their habitats from aquatic to terrestrial environments during the course of evolution. In parallel, osmoregulatory and cardiovascular systems evolved to counter the problems of desiccation and gravity on land. In our physiological studies on body fluid and blood pressure regulation in various vertebrate species, we found that osmoregulatory and cardiovascular hormones have changed their structure and function during the transition from aquatic to terrestrial life. In fact, Na+-regulating and vasodepressor hormones play essential roles in fishes, while water-regulating and vasopressor hormones are dominant in tetrapods. Accordingly, Na+-regulating and vasodepressor hormones, such as natriuretic peptide (NP) and adrenomedullin (AM), are much diversified in teleost fishes compared with mammals. Based on this finding, new NPs and AMs were identified in mammals and other tetrapods. These hormones have only minor roles in the maintenance of normal blood volume and pressure in mammals, but their importance seems to increase when homeostasis is disrupted. Therefore, such hormones can be used for diagnosis and treatment of body fluid and cardiovascular disorders such as cardiac/renal failure and hypertension. In this review, we introduce a new approach for identification of novel Na+-regulating and vasodepressor hormones in mammals based on fish studies. Until recently, new hormones were first discovered in mammals, and then identified and applied in fishes. However, chances are increasing in recent years to identify new hormones first in fishes then in mammals, based on the difference in the regulatory systems between fishes and tetrapods. As the direction is opposite from the traditional phylogenetic approach, we added ‘reverse’ to its name. The ‘reverse’ phylogenetic approach offers a typical example of how comparative fish studies can contribute to the general and clinical endocrinology. [Copyright &y& Elsevier]

Abstract: C-type natriuretic peptide (CNP) cDNA was cloned from the tilapia brain and its inferred mature sequence was chemically synthesized together with previously cloned tilapia A-type and B-type natriuretic peptides (ANP and BNP). The cloned CNP belongs to the CNP-1 type of teleosts. Reverse-transcription polymerase chain reaction showed that the ANP and BNP genes were hardly expressed in the tilapia brain and pituitary, whereas the CNP gene was expressed strongly in the brain and slightly in the pituitary. Effects of homologous natriuretic peptides (100nM each) on growth hormone (GH) and prolactin (PRL) release were examined using dispersed tilapia pituitary cells. Tilapia ANP and BNP stimulated GH and PRL release during 4–8, and 8–24h of incubation. BNP appeared to be more potent than ANP, also stimulating GH and PRL release during 0–4h of incubation. CNP stimulated GH release only during 4–8h of incubation; CNP was without effect on PRL release. All three NPs stimulated GH and PRL mRNA expression in dispersed pituitary cells following 24h of incubation. ANP and BNP significantly elevated intracellular cGMP accumulation in dispersed pituitary cells after 15min of exposure, whereas no effect of CNP was observed. These results indicate a long-lasting stimulation of GH and PRL release by ANP and BNP that is mediated, at least in part, by the guanylyl cyclase-linked NP receptor. [Copyright &y& Elsevier]

Abstract: Guanylyl cyclase C (GC-C) is a single transmembrane receptor for a family of intestinal hormones, guanylins. In the eel, we previously identified three guanylins, whose gene expression was enhanced in the intestine after transfer from fresh water to seawater. However, only limited information is available about the structure and function of their receptor(s). In the present study, we cloned full-length cDNAs encoding two isoforms of GC-C, named GC-C1 and GC-C2, from eel intestine. The predicted GC-C proteins consisted of extracellular ligand-binding domain, membrane-spanning domain, kinase-like domain and cyclase catalytic domain, in which GC-C-specific sequences were largely conserved. Phylogenetic analyses showed that the cloned membrane GCs are grouped with the GC-C of other vertebrates but not with GC-A and GC-B. However, eel GC-Cs appear to have undergone unique structural evolution compared with other GC-Cs. The three eel guanylins (guanylin, uroguanylin and renoguanylin), but not eel atrial natriuretic peptide, stimulated cGMP production dose-dependently in COS cells expressing either of the cloned cDNAs, providing functional support for assignment as eel guanylin receptors. The potency order for cGMP production was uroguanylin>guanylin⩾renoguanylin for GC-C1; guanylin⩾renoguanylin>uroguanylin for GC-C2. The distinctive ligand selectivity was consistent with the low homology (53%) of the extracellular domain of the two GC-Cs compared with that observed for other domains (74–90%). Both GC-C genes were expressed in the alimentary tract (esophagus, stomach and intestine) and kidney, and their expression was higher in the intestine of seawater-adapted eels than that of freshwater eels just as observed with the guanylin genes. However, the expression of the receptor genes was unchanged for 24h after transfer of eels from fresh water to seawater or vice versa, showing slower response of the receptors to salinity changes than their ligands. Collectively, the multiple guanylin—GC-C system may be involved as a paracrine factor in seawater adaptation at the intestine and kidney of the eel. [Copyright &y& Elsevier]

Abstract: Natriuretic peptides (NPs) have diversified from a single NP in cyclostomes and elasmobranchs to multiple NPs in ray-finned fishes where ANP, BNP, VNP, and/or up to four CNPs (CNP-1, 2, 3, and/or 4) have been identified. To trace the evolutionary diversification of NPs in fishes, we analyzed the bichir (Polypterus endlicheri), believed to be the most primitive extant ray-finned fish, for the presence of any NPs by a PCR-based method using primers that amplify all NP cDNAs identified to date. We have cloned cDNAs encoding ANP, BNP, VNP from the heart and three CNPs (CNP-1, 3, and 4) from the brain. An extensive search for CNP-2 from the brain was not successful. The C-terminus of bichir ANP presented an amidation signal as in ray-finned fish ANP. The bichir BNP mRNA had AUUUA repeats in the 3′-untranslated region as observed in all BNP cDNAs of vertebrates. The bichir VNP had a long C-terminal ‘tail’ sequence extending from the intramolecular ring as does teleost VNP. The three bichir CNPs are structurally similar to each teleost counterpart and are grouped after molecular phylogenetic analyses. ANP was most abundantly expressed in the atrium, BNP in the ventricle, and VNP was expressed in both atrium and ventricle. The three CNPs are most abundantly expressed in the brain, and CNP-4 transcripts were found in small amounts in the ventricle and kidney. Taken together, it is clear that all major NPs exist prior to the whole genome duplication that occurred in the teleost lineage. Furthermore, this is the first observation that CNP-3, ANP, BNP, and VNP, whose genes are colocalized in the same chromosome, coexist in a single fish species including teleosts, thereby confirming that CNP-3 is not an ortholog of VNP, and that ANP, BNP, and VNP genes were generated by tandem duplication from the CNP-3 gene. [Copyright &y& Elsevier]

Abstract: Cigarette smoking is the most crucial factor responsible for chronic obstructive pulmonary disease (COPD). The precise mechanisms of the development of the disease have, however, not been fully understood. Recently, impairment of pulmonary endothelial cells has been increasingly recognized as a critical pathophysiological process in COPD. To verify this hypothesis, we examined how cigarette smoke extract (CSE) damages human umbilical vein endothelial cells (HUVECs). CSE activated c-Jun N-terminal kinase (JNK), and treatment of HUVECs with SP600125, a specific inhibitor of the JNK pathway, significantly suppressed endothelial cell damage by CSE. In contrast, inhibition of the extracellular-regulated kinase or the p38 pathway did not affect the cytotoxicity of CSE. Furthermore, anti-oxidants superoxide dismutase and catalase reduced CSE-induced JNK phosphorylation and endothelial cell injury. These results indicate that CSE damages vascular endothelial cells through the JNK pathway activated, at least partially, by oxidative stress. [Copyright &y& Elsevier]

In symbiotic systems in which symbionts are transmitted horizontally, hosts must accept symbionts from the environment while defending themselves against invading pathogenic microorganisms. How they distinguish pathogens from symbionts and how the latter evade host immune defences are not clearly understood. Recognition of foreign materials is one of the most critical steps in stimulating immune responses, and pattern recognition receptors (PRRs) play vital roles in this process. In this study, we focused on a group of highly conserved PRRs, peptidoglycan recognition proteins (PGRPs), in the deep-sea mussel, Bathymodiolus septemdierum , which harbours chemosynthetic bacteria in their gill epithelial cells. We isolated B. septemdierum PGRP genes BsPGRP-S and BsPGRP-L , which encode a short- and a long-type PGRP, respectively. The short-type PGRP has a signal peptide and was expressed in the asymbiotic goblet mucous cells in the gill epithelium, whereas the long-type PGRP was predicted to include a transmembrane domain and was expressed in gill bacteriocytes. Based on these findings, we hypothesize that the secreted and transmembrane PGRPs are engaged in host defence against pathogenic bacteria and/or in the regulation of symbiosis via different cellular localizations and mechanisms. • We isolated two PGRPs from the deep-sea mussel, Bathymodiolus septemdierum. • Short-type PGRP is likely secreted; long-type PGRP is likely a transmembrane protein. • Both PGRPs are primarily expressed in the gill. • In the gill, the short-type PGRP is expressed in asymbiotic goblet mucous cells. • The long-type PGRP is expressed in gill bacteriocytes. [ABSTRACT FROM AUTHOR]

Abstract: Theophylline has been used in the management of bronchial asthma and chronic obstructive pulmonary disease for over 50 years. It has not only a bronchodilating effect, but also an anti-inflammatory one conducive to the inhibition of airway remodeling, including subepithelial fibrosis. To date however, whether theophylline has a direct inhibitory effect on airway fibrosis has not been established. To clarify this question, we examined whether theophylline affected the function of lung fibroblasts. Theophylline suppressed TGF-β-induced type I collagen (COL1) mRNA expression in lung fibroblasts and also inhibited fibroblast proliferation stimulated by FBS and TGF-β-induced α-SMA protein. A cAMP analog also inhibited TGF-β-induced COL1 mRNA expression in lung fibroblasts. A PKA inhibitor reduced the inhibitory effect of theophylline on TGF-β-induced COL1 mRNA expression. These results indicate that theophylline exerts anti-fibrotic effects, at least partly, through the cAMP-PKA pathway. [Copyright &y& Elsevier]