153 research outputs found
Induction of podoplanin by transforming growth factor-β in human fibrosarcoma
AbstractPodoplanin/aggrus is increased in tumors and its expression was associated with tumor malignancy. Podoplanin on cancer cells serves as a platelet-aggregating factor, which is associated with the metastatic potential. However, regulators of podoplanin remain to be determined. Transforming growth factor-β (TGF-β) regulates many physiological events, including tumorigenesis. Here, we found that TGF-β induced podoplanin in human fibrosarcoma HT1080 cells and enhanced the platelet-aggregating-ability of HT1080. TGF-β type I receptor inhibitor (SB431542) and short hairpin RNAs for Smad4 inhibited the podoplanin induction by TGF-β. These results suggest that TGF-β is a physiological regulator of podoplanin in tumor cells
Platelets Strongly Induce Hepatocyte Proliferation with IGF-1 and HGF In Vitro
Background. It is well known that platelets have athrombotic effect. However, platelets play an importantrole not only in hemostasis but also in woundhealing and tissue regeneration. Platelets have beenreported to accumulate in the liver and promote liverregeneration after an extended hepatectomy, but themechanism is unclear. The present study was designedto clarify the mechanism by which plateletshave a direct proliferative effect on hepatocytes invitro.Materials and methods. Hepatocytes obtained frommale BALB/c mice by collagenase digestion and immortalizedhepatocytes (TLR2) were used. To elucidatethe mechanism of the proliferative effect of platelets,DNA synthesis of hepatocytes was measuredunder various conditions and the related cellular signalswere analyzed. Chromatographic analysis wasalso performed to clarify which elements of plateletshave mitogenic activity.Results. DNA synthesis significantly increased in thehepatocytes cultured with platelets (P < 0.001). However,when the platelets and hepatocytes were separated,the platelets did not have a proliferative effect.Whole disrupted platelets, the supernatant fraction,and fresh isolated platelets had a similar proliferativeeffect, while the membrane fraction did not. After theaddition of platelets, both Akt and extracellularsignal-regulated kinases ERK1/2 were activated, butextracellular signal-regulated kinase STAT3 was not activated. Some mitogenic fractions were obtainedfrom the platelet extracts by gel exclusion chromatography;the fractions were rich in hepatocyte growthfactor and IGF-1.Conclusions. Direct contact between platelets andhepatocytes was necessary for the proliferative effect.The direct contact initiated signal transduction involvedin growth factor activation. Hepatocyte growthfactor, vascular endothelial growth factor, and insulin-like growth factor-1, rather than platelet-derivedgrowth factor, mainly contributed to hepatocyteproliferation
Postnatal lethality and chondrodysplasia in mice lacking both chondroitin sulfate N-acetylgalactosaminyltransferase-1 and -2
Chondroitin sulfate (CS) is a sulfated glycosaminoglycan (GAG) chain. In cartilage, CS plays important roles as the main component of the extracellular matrix (ECM), existing as side chains of the major cartilage proteoglycan, aggrecan. Six glycosyltransferases are known to coordinately synthesize the backbone structure of CS; however, their in vivo synthetic mechanism remains unknown. Previous studies have suggested that two glycosyltransferases, Csgalnact1 (t1) and Csgalnact2 (t2), are critical for initiation of CS synthesis in vitro. Indeed, t1 single knockout mice (t1 KO) exhibit slight dwarfism and a reduction in CS content in cartilage compared with wild-type (WT) mice. To reveal the synergetic roles of t1 and t2 in CS synthesis in vivo, we generated systemic single and double knockout (DKO) mice and cartilage-specific t1 and t2 double knockout (Col2-DKO) mice. DKO mice exhibited postnatal lethality, whereas t2 KO mice showed normal size and skeletal development. Col2-DKO mice survived to adulthood and showed severe dwarfism compared with t1 KO mice. Histological analysis of epiphyseal cartilage from Col2-DKO mice revealed disrupted endochondral ossification, characterized by drastic GAG reduction in the ECM. Moreover, DKO cartilage had reduced chondrocyte proliferation and an increased number of apoptotic chondrocytes compared with WT cartilage. Conversely, primary chondrocyte cultures from Col2-DKO knee cartilage had the same proliferation rate as WT chondrocytes and low GAG expression levels, indicating that the chondrocytes themselves had an intact proliferative ability. Quantitative RT-PCR analysis of E18.5 cartilage showed that the expression levels of Col2a1 and Ptch1 transcripts tended to decrease in DKO compared with those in WT mice. The CS content in DKO cartilage was decreased compared with that in t1 KO cartilage but was not completely absent. These results suggest that aberrant ECM caused by CS reduction disrupted endochondral ossification. Overall, we propose that both t1 and t2 are necessary for CS synthesis and normal chondrocyte differentiation but are not sufficient for all CS synthesis in cartilage
Enhancement of metastatic ability by ectopic expression of ST6GalNAcI on a gastric cancer cell line in a mouse model
ST6GalNAcI is a sialyltransferase responsible for the synthesis of sialyl Tn (sTn) antigen which is expressed in a variety of adenocarcinomas including gastric cancer especially in advanced cases, but the roles of ST6GalNAcI and sTn in cancer progression are largely unknown. We generated sTn-expressing human gastric cancer cells by ectopic expression of ST6GalNAcI to evaluate metastatic ability of these cells and prognostic effect of ST6GalNAcI and sTn in a mouse model, and identified sTn carrier proteins to gain insight into the function of ST6GalNAcI and sTn in gastric cancer progression. A green fluorescent protein-tagged human gastric cancer cell line was transfected with ST6GalNAcI to produce sTn-expressing cells, which were transplanted into nude mice. STn-positive gastric cancer cells showed higher intraperitoneal metastatic ability in comparison with sTn-negative control, resulting in shortened survival time of the mice, which was mitigated by anti-sTn antibody administration. Then, sTn-carrying proteins were immunoprecipitated from culture supernatants and lysates of these cells, and identified MUC1 and CD44 as major sTn carriers. It was confirmed that MUC1 carries sTn also in human advanced gastric cancer tissues. Identification of sTn carrier proteins will help understand mechanisms of metastatic phenotype acquisition of gastric cancer cells by ST6GalNAcI and sTn
BioHackathon series in 2011 and 2012: penetration of ontology and linked data in life science domains
The application of semantic technologies to the integration of biological data and the interoperability of bioinformatics analysis and visualization tools has been the common theme of a series of annual BioHackathons hosted in Japan for the past five years. Here we provide a review of the activities and outcomes from the BioHackathons held in 2011 in Kyoto and 2012 in Toyama. In order to efficiently implement semantic technologies in the life sciences, participants formed various sub-groups and worked on the following topics: Resource Description Framework (RDF) models for specific domains, text mining of the literature, ontology development, essential metadata for biological databases, platforms to enable efficient Semantic Web technology development and interoperability, and the development of applications for Semantic Web data. In this review, we briefly introduce the themes covered by these sub-groups. The observations made, conclusions drawn, and software development projects that emerged from these activities are discussed
Serum Wisteria Floribunda Agglutinin-Positive Mac-2 Binding Protein Values Predict the Development of Hepatocellular Carcinoma among Patients with Chronic Hepatitis C after Sustained Virological Response
Measurement of Wisteria floribundaagglutinin-positive human Mac-2 binding protein (WFA+-M2BP) in serum was recently shown to be a noninvasive method to assess liver fibrosis. The aim of this study was to evaluate the utility of serum WFA+-M2BP values to predict the development of hepatocellular carcinoma (HCC) in patients who achieved a sustained virological response (SVR) by interferon treatment. For this purpose, we retrospectively analyzed 238 patients with SVR who were treated with interferon in our department. Serum WFA+-M2BP values were measured at pre-treatment (pre-Tx), post-treatment (24 weeks after completion of interferon; post-Tx), the time of HCC diagnosis, and the last clinical visit. Of 238 patients with SVR, HCC developed in 16 (6.8%) patients. The average follow-up period was 9.1 years. The cumulative incidence of HCC was 3.4% at 5 years and 7.5% at 10 years. The median pre-Tx and post-Tx WFA+-M2BP values were 1.69 (range: 0.28 to 12.04 cutoff index (COI)) and 0.80 (range: 0.17 to 5.29 COI), respectively. The WFA+-M2BP values decreased significantly after SVR (P 60 years), sex (male), pre-Tx platelet count ( 2.0 COI) were associated with the development of HCC after SVR. Conclusion: Post-Tx WFA+-M2BP (> 2.0 COI) is associated with the risk for development of HCC among patients with SVR. The WFA+-M2BP values could be a new predictor for HCC after SVR
Lycenchelys albomaculata Toyoshima 1983
<i>Lycenchelys albomaculata</i> Toyoshima, 1983 <p>(Japanese name: Shirobuchi-hebigenge)</p> <p>(Figs. 1–4; Table 1)</p> <p> <i>Lycenchelys albomaculatus</i> Toyoshima, 1983: 141, 269, 333, figs. 16–19, pl. 92, 156 (original description, type locality: off Kamaishi, Iwate Prefecture, Pacific coast of Honshu, Japan); Toyoshima, 1984: 293, pl. 274-C (brief description); Toyoshima, 1985: 159, figs. 6–7, 16–19, 31, table 1 (description); Hatooka, 1993: 904, unnumbered fig. (key to species); Amaoka <i>et al.</i>, 1995: 241, pl. 404 (brief description); Imamura, 1997: 60 (species list); Koyanagi, 1997: 538, fig. 1 (brief description); Imamura, 1998: 30, fig. 7 (brief description); Zama, 2001: 86, 133 (species list).</p> <p> <i>Lycenchelys albomaculata</i>: Anderson, 1994: 112, 117 (species list); Shinohara <i>et al.</i>, 1996: 180 (species list); Hatooka, 2000: 1035, unnumbered fig. (keys to species); Hatooka, 2002: 1035, unnumbered fig. (key to species); Anderson & Fedorov, 2004: 15 (species list); Shiogaki <i>et al.</i>, 2004: 71 (species list); Shinohara & Anderson, 2007: 64 (key to species); Kitagawa <i>et al.</i>, 2008: 95, unnumbered fig. (brief description); Shinohara <i>et al.</i>, 2009: 723 (species list); Amaoka <i>et al.</i>, 2011: 319, unnumbered fig. (brief description); Balushkin <i>et al.</i>, 2011: 978 (catalog of specimens); Hatooka, 2013: 1229, unnumbered fig. (key to species); Nakabo & Hirashima, 2015: 217 (species list and etymology of scientific name).</p> Material examined <p> <b>Holotype</b>: HUMZ 59531, male, 406.6 mm SL, off Kamaishi, Iwate Prefecture, Tohoku District, northwestern Pacific, 14 Oct. 1976.</p> <p> <b>Paratypes</b> (19 specimens, 326.8–438.5 mm SL, all from Tohoku District, northwestern Pacific): HUMZ 72538– 39, 1 male and 1 female, 356.0– 356.4 mm SL, off Fukushima Prefecture (38°00’N, 142°10.05’E), 800–810 m depth, 6 Feb. 1978; HUMZ 72645–46, 2 males, 389.5–390.9 mm SL, off Fukushima Prefecture (37°26.5’N, 142°09.5’E), 900 m depth, 20 Jan. 1978; HUMZ 72656–57, 1 male and 1 female, 326.9–397.0 mm SL, off Miyagi Prefecture (38°02’N, 142°29’E), 1100–1150 m depth, 7 Feb. 1978; HUMZ 72708, 1 female, 326.8 mm SL, off Fukushima Prefecture (36°58.8’N, 141°47.5’E), 800 m depth, 19 Jan. 1978; HUMZ 72723, 1 male, 387.4 mm SL, off Fukushima Prefecture (37°11’N, 141°57’E), 810–820 m depth, 18 Jan. 1978; HUMZ 72734, 1 female, 358.2 mm SL, off Miyagi Prefecture (38°04’N, 142°12.2’E), 815–820 m depth, 30 Jan. 1978; HUMZ 78063, 1 male, 413.6 mm SL, off Iwate Prefecture (40°21.6’N, 142°25.6’E to 40°26.8’N, 142°22.1’E), 915–945 m depth, 25 Sep. 1978; HUMZ 78074, 1 male, 405.2 mm SL, off Iwate Prefecture (39°22.7’N, 142°36.5’E to 39°27.9’N, 142°40.2’E), 1290– 1300 m depth, 21 Sep. 1978; HUMZ 78082–83, 2 females, 365.0– 371.2 mm SL, off Iwate Prefecture (39°42.6’N, 142°47.5’E to 39°36.4’N, 142°44.2’E), 1120–1130 m depth, 23 Sep. 1978; HUMZ 78087, 1 female, 393.2 mm SL, off Iwate Prefecture (40°04.5’N, 142°43.5’E to 40°10.0’N, 142°39.3’E), 1095–1100 m depth, 25 Sep. 1978; HUMZ 78142, 1 female, 370.6 mm SL, off Iwate Prefecture (39°04.5’N, 142°22.7’E to 39°10.3’N, 142°25.0’E), 980–1000 m depth, 19 Sep. 1978; HUMZ 78200, 1 male, 436.0 mm SL, off Iwate Prefecture (39°40’N, 142°48.4’E to 39°45.3’N, 142°53’E), 1180–1230 m depth, 23 Sep. 1978; HUMZ 78262, 1 male, 434.5 mm SL, off Aomori Prefecture (40°48.9’N, 142°26.2’E to 40°44.4’N, 142°30.5’E), 1120–1165 m depth, 11 Sep. 1978; HUMZ 78269, 1 female, 413.0 mm SL, off Aomori Prefecture (40°47.6’N, 142°16.7’E to 40°41.5’N, 142°19.2’E), 920–948 m depth, 11 Sep. 1978; HUMZ 78322, 1 male, 438.5 mm SL, off Aomori Prefecture (41°02.4’N, 142°11.9’E to 41°08.1’N, 142°12.2’E), 1200–1205 m depth, 8 Sep. 1978.</p> <p> <b>Other specimens</b> (40 specimens, 141.4–508.0 mm SL): HUMZ 72495, 72537, 72610–11, 72648, 72704, 72733, 72738, 180859, 180870, 180879, 180883, 180900, 182282, 182314, 182316, 182318–19, 182326, 209261, 214430–31, 214626, 226944, 12 males and 12 females, 141.1–386.4 mm SL, Tohoku District, northwestern Pacific; HUMZ 119854–55, 120153, 123913, 126048, 126353–55, 4 males and 4 females, 195.3– 508.0 mm SL, eastern Hokkaido Island, northwestern Pacific; HUMZ 133184, 196387–88, 205185, 205192, 205194, 215072, 228077, 4 males and 4 females, 397.5–454.1 mm SL, northeastern Hokkaido Island, Okhotsk Sea.</p> <p> <b>Diagnosis.</b> Vertebrae 22–25 + 99–105 = 122–128; head length 14.3–20.4% SL; interorbital pore 1; occipital pores 3; postorbital pores 4; suborbital pores 7–9 + 2–3; preoperculomandibular pores usually 9; vomerine teeth 2–10; palatine teeth 2–18, arranged in 1 or 1–2 rows; opercular flap well developed; pelvic-fin base positioned posterior to lower edge of gill opening; lateral line complete and positioned ventrally; scales present on pectoral fin and its base; body blackish brown when fresh; 6–10 white blotches present above upper edge of gill opening and on dorsal fin extending onto dorsal part of body.</p> <p> <b>Description.</b> Counts and proportional measurements in Table 1.</p> <p>Body elongate, cross section oval anteriorly, compressed posteriorly; its width at anal-fin origin 3.1–6.0 (5.6)% SL. Head moderately long, ovoid, dorsal profile of head sloping extremely gently to dorsal-fin origin. Cheek swol- len in large males (including holotype), more so than in females and small males. Head of adults longer in males than in females. Snout short, 72.5–219.1 (145.1)% of eye diameter. Eye ovoid, relatively large. Interorbital space relatively narrow in adults, wide in juveniles; its width 8.9–29.6 (17.5)% of eye diameter. Nostril tube short, not reaching upper lip when depressed. Mouth subterminal. Posterior edge of upper jaw reaching vertical through posterior margin of eye in adult males (including holotype), reaching below middle or posterior part of eye in females and juveniles. Labial lobe of lower jaw developed in adults (including holotype). Teeth on jaws, vomer and palatine small and conical; upper jaw with single row, sometimes having some additional teeth behind anterior teeth (including holotype); lower jaw with 2–4 irregular rows anteriorly and 1–2 rows posteriorly; vomerine teeth irregularly arranged; palatine teeth in 1 or 1–2 rows (1). Lower edge of gill opening below lower end of pectoral-fin base. Opercular flap well developed. Gill rakers short; those on upper limb triangular, many triangular and some blunt on lower limb (Fig. 2). Pseudobranch filaments long. Lateral line deciduous, complete and positioned ventrally; originating posterior to last postorbital pore and terminating on tail. Scales small and cycloid, present on body, pectoral axilla, about basal half of pectoral fin, pectoral-fin base, tail and most of vertical fins except margins. Scales covering nape in adults (including holotype), but not in some juveniles. Head without scales.</p> <p>....Continued next page</p> <p>Dorsal-fin origin above middle of pectoral fin; 1st dorsal-fin pterygiophore between neural spines of 3rd to 5th (unknown for holotype) vertebrae. Anal-fin origin below 17th to 20th (unknown for holotype) dorsal-fin ray; 1st anal-fin pterygiophore posterior to parapophysis of ultimate or penultimate abdominal vertebra (unknown for holotype). Last dorsal-fin pterygiophore between neural spines of 2nd to 5th (unknown for holotype) preural vertebrae. Last anal-fin pterygiophore between hemal spines of 2nd to 4th (unknown for holotype) preural vertebrae. Caudal fin with 1–2 epural, 4–5 upper hypural and 3–5 lower hypural rays (unknown for holotype). Pectoral fin moderately long in juveniles, becoming relatively short in adults (including holotype); tip reaching or over middle of abdomen in juveniles, not quite reaching middle portion of abdomen in adults (including holotype); its posterior margin rounded. Upper end of pectoral-fin base on about lateral midline of body. Pelvic fin short; its base posterior to lower edge of gill opening; its posterior margin not reaching pectoral-fin base in adults (including holotype), reaching pectoral-fin base in some juveniles.</p> <p>Head pores small and distinct. Usually 2 nasal pores (including holotype); anterior pore in front of nostril tube, posterior pore about above 1st suborbital pore; third pore present above nostril tube on left side in HUMZ 78087 and on both sides in HUMZ 214430 (Fig. 4A, B). Postorbital pores 4; distance between 1st and 2nd pores longest of those between adjacent pores (Fig. 4A, B). Suborbital pores 9–11 (10); 7–9 (8) pores located below eye and remaining 2 or 3 (2) pores on ascending part of suborbital canal behind eye; 5th pore about below anterior margin of pupil; last pore below eye located posterior to vertical through posterior margin of eye (Fig. 4A). Preoperculomandibular pores usually 9 (including holotype), 4 on lower jaw, 2 on junction of lower jaw and preopercle, and 3 on preopercle; some specimens with 8 pores having only 1 pore on junction of lower jaw and preopercle; HUMZ 72734 having 10 pores with 4 pores on preopercle of right side; last preoperculomandibular pore located posterior to lower part of eye (Fig. 4A, C). One interorbital pore located anterior to center of eyes (Fig. 4B). Occipital pores 3; 1 on midline of occiput, and remaining 2 on left and right sides; middle pore located slightly posterior to other two; all pores located anterior to 3rd postorbital pore (Fig. 4B).</p> <p> <b>Color in alcohol.</b> Holotype (Fig. 3) with head, body and vertical fins brown, opercular region and pectoral fin darker; nine white blotches present dorsally, 1 above upper edge of gill opening and 8 on dorsal fin extending onto dorsal part of body. Paratypes and long preserved non-type specimens with coloration similar to holotype but more recently preserved specimens darker than holotype with one white blotch above upper edge of gill opening and another 5–9 on dorsal fin and dorsal part of body. Juveniles having narrower white blotches than adults.</p> <p> <b>Color when fresh</b> (based on color photograph of HUMZ 228077; Fig. 1). Head, body, pectoral-fin base and vertical fins blackish brown, pectoral fin and margin of vertical fins darker. Ten white blotches; 1 above upper edge of gill opening, 9 on dorsal fin extending onto dorsal part of body.</p> <p> <b>Distribution.</b> The Okhotsk Sea and off the northwestern Pacific coast of the Kuril Islands, and the eastern side of Hokkaido Island to the Ibaraki Prefecture, at depths of 400–1505 m (Toyoshima, 1983, 1984, 1985; Hatooka, 1993, 2000, 2002, 2013; Anderson, 1994; Amaoka <i>et al.</i>, 1995, 2011; Shinohara <i>et al.</i>, 1996; Imamura, 1997, 1998; Koyanagi, 1997; Zama, 2001; Anderson & Fedorov, 2004; Shiogaki <i>et al.</i>, 2004; Shinohara & Anderson, 2007; Kitagawa <i>et al.</i>, 2008; Shinohara <i>et al.</i>, 2009; Balushkin <i>et al.</i>, 2011; this study).</p> <p> <b>Size.</b> The largest specimen recorded during this study was 508.0 mm SL (518.6 mm TL), exceeding the previously recorded maximum length of 50 cm TL (Amaoka <i>et al.</i>, 1995, 2011; Koyanagi, 1997; Imamura, 1998).</p> <p> <b>Remarks.</b> <i>Lycenchelys albomaculata</i> is characterized by the presence of white blotches on the body. Although <i>Lycenchelys bachmanni</i> Gosztonyi, 1977 also has paler blotches on the body (vs. paler blotches absent in other species of <i>Lycenchelys</i>), its blotches are yellowish (Gosztonyi, 1977; Nakamura, 1986). In addition, <i>L. albomaculata</i> is easily separable from <i>L. bachmanni</i> in having a scaled and dark pectoral fin (vs. naked and yellowish white in <i>L. bachimanni</i>) (Gosztonyi, 1977; Nakamura, 1986). Furthermore, <i>L. albomaculata</i> has a higher number of gill rakers (1–3 + 11–14 = 13–17 in <i>L. albomaculata</i> vs. 2 + 8 = 10 in <i>L. bachimanni</i>) (Gosztonyi, 1977; Nakamura, 1986; this study).</p> <p> Toyoshima (1983, 1985) described the occipital pores of <i>L. albomaculata</i> to be “absent”. However, this study found 3 occipital pores in all specimens of <i>L. albomaculata</i>, including the holotype (Fig. 4B).</p>Published as part of <i>Kawarada, Shumpei, Imamura, Hisashi, Narimatsu, Yoji & Shinohara, Gento, 2020, Taxonomic revision of the genus Lycenchelys (Osteichthyes: Zoarcidae) in Japanese waters, pp. 1-66 in Zootaxa 4762 (1)</i> on pages 6-10, DOI: 10.11646/zootaxa.4762.1.1, <a href="http://zenodo.org/record/3743698">http://zenodo.org/record/3743698</a>
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