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Ophioculina Rousseau & Thuy gen. nov. urn:lsid:zoobank.org:act: E82E3C6B-7193-4082-9FDD-6549411E1EFB Type species Ophioculina hoybergia Rousseau & Thuy gen. et sp. nov., by original designation. Diagnosis Dorsal disc with numerous, small, thin scales. Well-developed arm comb. Tentacle pores developed as between-plate openings pointing ventro-distalwards until median arm then reduced to within-plate perforations. Etymology From the Latin ‘ culina ’, kitchen, since most of the specimens where discovered accidentally while clearing a surface area for the kitchen tent of the 2010 field camp.

Rousseau, Julie, Gale, Andrew Scott, Thuy, Ben (2018): New articulated asteroids (Echinodermata, Asteroidea) and ophiuroids (Echinodermata, Ophiuroidea) from the Late Jurassic (Volgian / Tithonian) of central Spitsbergen. European Journal of Taxonomy 411: 1-26, DOI: https://doi.org/10.5852/ejt.2018.411

Ophioculina hoybergia Rousseau & Thuy gen. et sp. nov. urn:lsid:zoobank.org:act: 9832EAD6-F33E-4E37-9F38-0ADB944CBE4F Figs 6���7 Diagnosis As for genus. Etymology In honor of Magne H��yberget, who greatly contributed to the collection of the echinoderm fossils from Spitsbergen and to Norwegian palaeontology. Material examined Holotype NORWAY: central Spitsbergen, Konusdalen, 78��19���97.1��� N, 15��52���15.5��� E (PMO 217.930). Paratypes NORWAY: same data as for holotpye (PMO 218.010b, PMO 218.048); central Spitsbergen, Janusfjellet, 78��20���35.4��� N, 15��49���85.2��� E (PMO 218.001c). More than 80 specimens each consisting of an articulated disc and at least the basal portion of one or more arms have been collected from the Janusfjellet and Konusdalen sites. A large amount of intermingled isolated arm fragments were also present in the samples. Type stratum Lower Middle Volgian (Middle Tithonian), Slottsm��ya Member, Agardhfjellet Formation. Description PMO 217.930 (Fig. 6 A���D) is a fragment of an articulated disc preserving the basal portions of three arms. The specimen is split close to the ventral side. The disc is round and has a diameter of 25.3 mm. The oral plates are long, stout and separated into two seemingly unfused halves (Fig. 6D). The adoral shields are insufficiently preserved on the holotype to provide an accurate description. The oral shields have a narrow rectangular distal portion and a much wider proximal portion which is, however, insufficiently preserved for an unambiguous description. Each dental plate bears a cluster of three small, conical apical oral papillae bordered by a seemingly continuous row of similarly small, uniform, pointed lateral oral papillae, most probably six or seven in number. The second oral tentacle pores are superficial and covered by at least three papillae that are slightly larger than the lateral oral papillae and seemingly form a separate row. The interradial areas (Fig. 6D) are not indented and covered by small, thin, rounded scales rather uniform in size. The interradial disc plates are devoid of granules or other spines. The genital slits are bordered on both sides by small (abradial side of slit) to very small (adradial side), block-like papillae which seem to have originally formed a continuous row. The adradial and abradial genital plates are nearly equal in length. The adradial ones are uniformly slender and bar-like while the abradial plates are flat, with a broadened distal portion reminiscent of a hockey stick, and with a longitudinal ridge. The distal edge of the abradial genital plate bears a continuous row of small, blocklike, blunt papillae similar in shape and size to those lining the abradial edge of the genital slit, and forming a well-developed arm comb (Fig. 6C). The six most proximal arm segments are incorporated within the disc. The tentacle pores are enclosed by lateral and ventral arm plates and developed at least until the eighth segment counted from the first segment that is not incorporated into the disc. The pores rapidly decrease in size distalwards. There are at least three very small tentacle scales on the lateral arm plate part of the proximal tentacle pores. The lateral arm plates abut ventrally from the most proximal segments onwards. They are slightly bulging, but not constricted. The ornamentation of the outer surface is not discernible. There are two to three slender spines, the longest of which nearly equals the length of one segment, on each lateral arm plate (Fig. 6C). The outline of the ventral arm plates is not discernible from the holotype. Paratype 218.001c (Fig. 7 A���B) is an articulated disc preserving most of the five arms and exposing the ventral side. Disc diameter is 9.7 mm. Five arm segments are incorporated into the disc. The longest arm is 32 mm long and slowly tapering. It comprises 24 segments counted from the edge of the disc. Proximal segments are wider than long, distalmost segments are clearly elongated. The tentacle openings are developed as pores enclosed by the ventral and lateral arm plates until the eighth segment counted from the disc edge, and developed as perforations within the lateral arm plates in all the following segments, emerging below the ventralmost spine articulation. The lateral arm plates are ventrally abutting in all arm segments. The ventral arm plates are asymmetrically lozenge-shaped and nearly two times wider than long in all segments. Their proximal edge is pointed with an obtuse angle, while their distal edge is slightly convex. The spine articulations are small, sunken into a shallow, dorso-ventral incision of the lateral arm plate outer surface at some distance from the distal edge of the plate. The microstructure of the spine articulations is not discernible. There are at least two spines on each lateral arm plate, but the actual number is not discernible. The outer surface of lateral arm plate is finely meshed stereom devoid of constrictions or conspicuous ornamentation. The presence of spurs on the outer proximal edge of the lateral arm plates cannot be assessed. Paratype PMO 218.048 (Fig. 7C) is an articulated disc with the basal portion of two arms preserved. It is split close to the ventral side and its morphology is in agreement with that of the holotype. The oral plates, the second oral tentacle pores and the rows of papillae bordering the genital slit are better preserved and complement or unambiguously corroborate the observations made on the holotype. The oral shield is arrow-shaped with a right to acute proximal angle and a much narrower rectangular distal portion. The adoral shields are narrow, L-shaped and with pointed, abutting proximal tips. Paratype PMO 218.010b (Fig. 7 D���E) is an articulated, complete dorsal disc preserving basal portion of five arms. The disc diameter is 21.8 mm. The specimen is split closer to the dorsal side than the holotype. The dorsal disc is covered by small, rounded, thin and uniform scales. The radial shields are thicker than the dorsal disc scales, shaped as rounded, isosceles triangles about one and a half times longer than wide. They are about a quarter of the disc radius in length. The radial shields are distally separated from the arm base by the distal portion of the abradial genital plate that bears a continuous row of small, round to square-like papillae. The dorsal arm plates are not visible. The section of the lateral arm plates suggests a rather thin plate architecture. Remarks The combination of an arm comb and superficial second oral tentacle pores unambiguously places the Spitsbergen specimens in the suborder Ophiurina as recently circumscribed by O���Hara et al. (2017). The suborder currently includes the Astrophiuridae with the highly modified, asteroid-like Astrophiura Sladen, 1879 and its relatives, the Ophiuridae with the type taxon Ophiura ophiura Linnaeus, 1758 and the genera Ophiocrossota Clark, 1928, Ophiocten L��tken, 1855, Ophioctenella Tyler et al., 1995 and Ophionotus Bell, 1902, and the Ophiopyrgidae comprising most of the remaining genera of the former subfamily Ophiurinae (Smith et al. 1995). Assignment to the Astrophiuridae can be ruled out as the specimens from Spitsbergen lack the highly diagnostic characters of the group. With the other two families of the suborder, however, matters are more complicated. While the specimens from Spitsbergen resemble recent Ophiura ophiura with respect to disc morphology and arm skeleton, in particular the orientation of the tentacle notch on the inner side of the lateral arm plate, the development of the tentacle pores in median to distal arm segments rule out most members of the Ophiuridae. Ophiura ooplax (H.L. Clark, 1911) is an exception within the Ophiuridae in having tentacle pores developed as within-plate perforations on almost all arm segments. With respect to lateral arm plate morphology, in particular the outer surface ornamentation and the development of the spine articulations, however, it differs significantly from the specimens described herein. The Ophiopyrgidae include the genera Aspidophiura Matsumoto, 1915, Euvondrea Fell, 1961 and Ophioplinthus Lyman, 1878 which combine within-plate tentacle pores and an overall lateral arm plate morphology comparable to that seen in the Spitsbergen specimens. Assignment to any of these genera is nevertheless precluded since they have rudimentary arm combs and within-plate tentacle pores on almost all arm segments outside the disc rather than on median and distal ones only. We therefore propose the new genus Ophioculina gen. nov. to accommodate the here-described material. A definite family-level assignment is hampered by the absence of diagnoses for the clades of O���Hara et al. (2017). Since Ophioculina gen. nov. shares greatest similarities with members of the Ophiopyrgidae, we tentatively place it in this family. Ophioculina hoybergia gen. et sp. nov. likely used its relatively long, flexible arms for locomotion, while the short arm spines might have been used to gather carrion, detritus or prey (see Hess & Meyer 2008). At Janusfjellet, specimens of Ophioculina hoybergia gen. et sp. nov. are found stacked up in multiple monospecific layers which may have originated from gregarious behavior of living individuals as commonly seen in modern members of the Ophiurina (e.g., Fujita & Ohta 1990)., Published as part of Rousseau, Julie, Gale, Andrew Scott & Thuy, Ben, 2018, New articulated asteroids (Echinodermata, Asteroidea) and ophiuroids (Echinodermata, Ophiuroidea) from the Late Jurassic (Volgian / Tithonian) of central Spitsbergen, pp. 1-26 in European Journal of Taxonomy 411 on pages 17-21, DOI: 10.5852/ejt.2018.411, http://zenodo.org/record/3805999, {"references":["O'Hara T. D., Hugall A. F., Thuy B., Stohr S. & Martynov A. 2017. Restructuring higher taxonomy using broad-scale phylogenomics: the living Ophiuroidea. Molecular Phylogenetics and Evolution 107: 415 - 430. https: // doi. org / 10.1016 / j. ympev. 2016.12.006","Smith A. B., Paterson G. L. J. & Lafay B. 1995. Ophiuroid phylogeny and higher taxonomy: morphological, molecular and palaeontological perspectives. Zoological Journal of the Linnean Society 114: 213 - 243. https: // doi. org / 10.1111 / j. 1096 - 3642.1995. tb 00117 c. x","Hess H. & Meyer C. 2008. A new ophiuroid (Geocoma schoentalensis sp. nov.) from the Middle Jurassic of northwestern Switzerland and remarks on the family Aplocomidae Hess, 1965. Swiss Journal of Geosciences 101: 29 - 40. https: // doi. org / 10.1007 / s 00015 - 008 - 1253 - 5","Fujita T. & Ohta S. 1990. Size structure of dense populations of the brittle star Ophiura sarsii (Ophiuroidea: Echinodermata) in the bathyal zone around Japan. Marine Ecology Progress Series 64: 113 - 122."]}

Polarasterias Rousseau & Gale gen. nov. urn:lsid:zoobank.org:act: 6A46CC92-9366-4DCB-94B5-7313D76EB0A1 Type species Polarasterias janusensis Rousseau & Gale gen. et sp. nov., by original designation. Diagnosis Asteriid with elongated arms, small disc, very broad ambulacral grooves with narrow adambulacrals and weakly developed or absent actinals. Abactinals cruciform, numerous, forming a rectilinear grid arranged in regular transverse rows of seven or more plates on each side of the arm. Tube feet strongly quadriserial. Etymology To emphasize the polar situation of the locality and with reference to the North Star Polaris. Polarasterias janusensis Rousseau & Gale gen. et sp. nov. urn:lsid:zoobank.org:act: 8A3128E8-171C-400D-8BEA-CFA29FADBC41 Fig. 2 Diagnosis As for genus. Etymology The specific epithet refers to the Janus mountain (Janusfjellet) locality. Material examined Holotype NORWAY: central Spitsbergen, Janusfjellet, 78��20���35.4��� N, 15��49���85.2��� E (PMO 218.011 a). Paratypes NORWAY: same location as for holotype (PMO 217.936, PMO 217.982, PMO 218.069). More than 50 partial specimens were collected. Type stratum Lower Middle Volgian (Middle Tithonian), Slottsm��ya Member, Agardhfjellet Formation. Description The holotype, PMO 218.011a (Fig. 2 A���C), is a relatively complete specimen showing an articulated disc with five arms, two of which extend to the tip, preserved in a cut-through manner (i.e., split horizontally approximately along the ambitus) and clearly showing the form and arrangement of the ambulacral groove ossicles. The arms are elongated and the disc is very small. The arms taper slowly and the interbrachial angle is acute (major radius = 65 mm, minor radius = 8 mm). The ambulacral groove is very broad (width = 8 mm) and the ambulacrals occupy roughly 80% of the arm width. The inferomarginals are barely visible on the actinal surfaces of the arms. The presence of actinal ossicles cannot be confirmed from the material available, but the very acute interradii cannot have had significant actinal interradial areas and if actinals were present, they must have been restricted to the proximal arms. There are about 70 ambulacrals and adambulacrals in each half radius. The podial openings for tube feet are strongly quadriserial along the total length of the arms (Fig. 2A, C). The ambulacrals have well demarcated heads, shaft and bases and are not very foreshortened (Fig. 2C) as in many asteriids (Gale 2011a). The ambulacral head is angled to the shaft and the base, and strong dentition is present. The ambulacrals are rectangular in actinal view, short and broad, and have a strongly concave proximal surface for a large adambulacral muscle. The adambulacrals have a prominent distal heel contacting the distal ambulacral base. Each adambulacral carried two spines (diplacantid condition), one of which, probably the outer, is significantly larger than the other (Fig. 2C). The conical, elongated, adambulacral spines at the base of the arm are over 4 mm in length and form a distally directed fringe to the arm. Abundant straight pedicellariae are seen in cross section scattered among the adambulacral spines (Fig. 4 B���C). These include ε shaped basal pieces which possess tall median ridges for insertion of the inner longitudinal adductor muscle (Gale 2011a). A partly disarticulated mouth frame seen from the actinal surface is visible on paratype PMO 217.982 (Fig. 2D) and shows the presence of an adoral carina involving two or three adambulacrals. The oral ossicles are well preserved and have a short, rectangular oral surface which bears two spine articulations. The terminal ossicle is well preserved in paratype specimen PMO 217.936 (Fig. 2E), where it is triangular and as broad as long with a strongly convex distal margin. Paratype specimen PMO 218.069 (Fig. 2 F���G) shows the abactinal surface of an arm. The abactinal ossicles are cruciform, with four processes which contacted adjacent rows and columns, and are arranged in well-marked imbricate transverse columns, with up to seven ossicles in each half radius. The largest two abactinals are present adjacent to the adambulacral, and are identified as the infero- and superomarginals (Fig. 2G). Up to five slightly smaller abactinals are also present in each column. However, it is not possible to identify radials and adradials, so the exact numbers of plates present cannot be discerned. The abactinal ossicles formed a rectilinear reticulate structure, with the spaces occupied by papular openings, and the centre of each abactinal plate carried a long spine. Remarks This new asteroid is clearly a forcipulatid neoasteroid as forcipulate pedicellariae are present. It could potentially belong to the Terminasteridae Gale, 2011a, Zoroasteridae Sladen, 1889 or Asteriidae Gray, 1840 which can be difficult to separate in fossil material, because the families have many morphological features in common (Blake 1990). The single most diagnostic feature of the Asteriidae, the presence of both straight and crossed pedicellariae, unfortunately cannot be confirmed in this material. However, various lines of morphological evidence permit assignation to the Asteriidae. These include the form of the terminal ossicle, which is relatively short and broad as in asteriids while markedly elongated in terminasterids and zoroasterids. Moreover, the morphology of the oral ossicle is similar to that in extant asteriids (Gale 2011a), and the shape of the basal piece of the straight pedicellariae, with a tall median ridge, is also typically asteriid. The strongly quadriserial arrangement of the tube feet along the entire length of the groove is also an asteriid character (Blake 1990). The arrangement of the abactinal ossicles in up to seven transverse rectilinear columns is not typical of extant asteriids, in which a more or less irregular network of plates extends between the superomarginals and the radials (e.g., Fisher 1928: pls 67, 44, 61; Gale & Villier 2013). Polarasterias janusensis gen. et sp. nov. differs significantly from other described Jurassic and Cretaceous asteriid genera. Blake (1990) described two new genera and species from the Hettangian (Early Jurassic) of Germany, Germanasterias amplipapularia Blake, 1990 and Hystrixasterias hettangiurnus Blake, 1990, which he assigned to the Asteriidae. These differ from the described species in the presence of relatively broad actinal interareas, the relatively closed ambulacral groove and the more rapidly tapering arms. Additionally, Germanasterias Blake, 1990 is characterized by having very coarse, numerous, adambulacral spines which are not seen in the Janusfjellet material. Argoviaster occultus Hess, 1972 and Dermaster boehmi de Loriol, 1899 were described from the Bajocian of Switzerland (Hess 1972). Both have stout, relatively short, rapidly tapering arms and narrow ambulacral grooves. The species from Spitsbergen also differs from Cretasterias reticulatus Gale & Villier, 2013 in its more strongly quadriserial tube feet, and the more numerous columns of abactinal ossicles, but agrees in the overall shape of the arms of and the rectilinear arrangement of the abactinal ossicles. Modern members of the Asteriidae family are slow-moving, epifaunal carnivores living on the sea bottom. The relatively large body size, small disc size, multi-element arms, quadriserial tube feet and adoral carina present in Polarasterias janusensis gen. et sp. nov. are all features which favor a predatory mode of feeding (Blake 1987, 1990). The wide ambulacral groove, covered with numerous tube feet, provided a strong adhesion force which could have helped Polarasterias janusensis gen. et sp. nov. to grab and hold its prey. Modern predatory asteroids feed mostly on bivalves, gastropods and other echinoderms, including other asteroids, ophiuroids and echinoids, and are known to form large feeding groups (Spencer & Wright 1966). Similarly, it is likely that Polarasterias janusensis gen. et sp. nov. lived gregariously as epifauna on the Spitsbergen muddy seafloor, where it hunted for bivalves and echinoderms., Published as part of Rousseau, Julie, Gale, Andrew Scott & Thuy, Ben, 2018, New articulated asteroids (Echinodermata, Asteroidea) and ophiuroids (Echinodermata, Ophiuroidea) from the Late Jurassic (Volgian / Tithonian) of central Spitsbergen, pp. 1-26 in European Journal of Taxonomy 411 on pages 5-8, DOI: 10.5852/ejt.2018.411, http://zenodo.org/record/3805999, {"references":["Gale A. S. 2011 a. Phylogeny of the Neoasteroidea (post-Palaeozoic Asteroidea, Echinodermata). Special Papers in Palaeontology 85: 1 - 112.","Blake D. B. 1990. Hettangian Asteriidae (Echinodermata: Asteroidea) from southern Germany: taxonomy, phylogeny and life habits. Palaontologische Zeitschrift 64: 103 - 123. https: // doi. org / 10.1007 / BF 02985925","Fisher W. K. 1928. Asteroidea of the North Pacific and adjacent waters, Part 2. Forcipulata. Bulletin of the United States National Museum 76: 1 - 404.","Gale A. S. & Villier L. 2013. Mass mortality of an asteriid starfish (Forcipulatida, Asteroidea, Echinodermata) from the late Maastrichtian (Late Cretaceous) of Morocco. Palaeontology 56: 577 - 588. https: // doi. org / 10.1111 / pala. 12002","Hess H. 1972. Eine Echinodermen-Fauna aus dem mittleren Dogger des Aargauer Juras. Schweizerische Palaontologische Abhandlungen 92: 1 - 87.","Blake D. B. 1987. A classification and phylogeny of post-Paleozoic sea stars (Asteroidea: Echinodermata). Journal of Natural History 21: 481 - 528. https: // doi. org / 10.1080 / 00222938700771141","Spencer W. K. & Wright C. W. 1966. Asterozoans. In: Moore R. C. (ed.) Treatise on invertebrate paleontology. Part U: Echinodermata 3: U 4 - U 107. The Geological Society of America, Washington DC and The University of Kansas Press, Lawrence."]}

Supplemental information. Figure S1. Representative standard curve for absolute quantification qPCR experiments. Table S1. Standard curve parameters. Table S2. PCR Cycling conditions. Table S3. qPCR Cycling conditions. (DOCX 38Â kb)

INTRODUCTION Des réponses thérapeutiques variables aux glucocorticoïdes (GCs) sont observées parmi les patients atteints de la leucémie lymphoblastique aiguë (LLA). Les protéines Bax et Bim ont déjà montré un rôle important dans l’apoptose des cellules leucémiques. L’expression de Bax était plus basse chez les patients leucémiques résistants au médicament, de même une sensibilité diminuée aux GCs a été associée avec une expression réduite de Bim. La différence dans l’expression pourrait être due à des polymorphismes présents dans ces gènes et donc être associés avec la résistance aux GCs. MÉTHODE Dix-huit polymorphismes en régions régulatrices, 2 polymorphismes exoniques et 7 polymorphismes en région 3’UTR de ces gènes ont été analysés chez les témoins (n=50) et ont permis de déterminer un nombre minimal de polymorphismes suffisants pour définir les haplotypes (tagSNPs). Ces 8 polymorphismes ont ensuite été génotypés chez 286 enfants atteints de la LLA et ont été testés pour l’issue de la maladie par l’analyse de survie. RÉSULTATS Une survie sans évènement et une survie sans rechute diminuées ont été observées pour l’haplotype 3 (p=0,03 et p=0,02). Une survie globale diminuée a été associée avec l’homozygotie pour l’allèle exonique T298C>T (p=0,03), de même que pour les haplotypes 1 et 4 (p=0,04 et p=0,02) du gène Bim. CONCLUSION Les polymorphismes ont été associés avec une survie diminuée chez des enfants atteints de LLA. Il reste à tester d’autres polymorphismes présents dans ces deux gènes ainsi qu’à définir leurs fonctions afin de comprendre leurs rôles dans la réponse aux GCs., INTRODUCTION Variable therapeutic responses to glucocorticoids (GCs) are observed for acute lymphoblastic leukemia (ALL) patients. Proteins Bax and Bim have already shown to play a major role in mediating GC-induced apoptosis in leukemia cells. Bax expression was lower in drug-resistant leukemia samples; likewise lower sensitivity to GC was associated with reduced Bim expression. The difference in the expression can be due to polymorphisms in these genes and therefore associated to GC resistance. METHOD Eighteen polymorphisms in the regulatory region, two exonic polymorphisms and seven polymorphisms in 3’UTR of these genes were analysed in controls (n=50) and have permitted to determine a minimal number of polymorphisms sufficient to define haplotypes (tagSNPs). These 8 single nucleotide polymorphisms (SNPs) were then genotyped in 286 LLA children and were tested for disease outcome by survival analysis. RESULTS A diminished event free survival and a diminished relapse free survival were observed for haplotype 3 (p=0,03 and p=0,02). A diminished overall survival was associated with the exonic T298C>T allele (p=0,03) and with haplotypes 1 and 4 (p=004 and p=0,02) of Bim gene. CONCLUSION Bax and Bim were associated with a diminished survival in LLA children. We still have to test other polymorphisms located in these genes and to define their functions in order to understand their roles in GC response.

International audience; Osteosarcoma is the most frequent primary bone tumor that develops mainly during youth, the median age of diagnosis being 18 years. Despite improvement in osteosarcoma treatment, survival rate is only 30% after 5 years for patients with pulmonary metastases at diagnosis. This warrants exploration of new therapeutic options. The anti-bone resorption molecule receptor activator of NF-kappaB (RANK) is very promising, as it may block the vicious cycle between bone resorption and tumor proliferation that takes place during tumor development in bone site. The cDNA encoding murine RANK-Fc (mRANK-Fc) was administered by gene transfer using an amphiphilic polymer in a mouse model of osteolytic osteosarcoma. Clinical and bone microarchitecture variables were assessed by radiography and micro-CT analyses. In vitro experiments were designed to determine the mechanism of action of RANK-Fc on tumor cell proliferation (XTT assays), apoptosis (caspase activation), cell cycle distribution (fluorescence-activated cell sorting analysis), or gene expression (reverse transcription-PCR). RANK-Fc was effective in preventing the formation of osteolytic lesions associated with osteosarcoma development and in reducing the tumor incidence, the local tumor growth, and the lung metastases dissemination leading to a 3.9-fold augmentation of mice survival 28 days after implantation. On the contrary, mRANK-Fc did not prevent the development of nonosseous tumor nodules, suggesting that bone environment is necessary for mRANK-Fc therapeutic efficacy. Furthermore, mRANK-Fc has no direct activity on osteosarcoma cells in vitro. mRANK-Fc exerts an indirect inhibitory effect on osteosarcoma progression through inhibition of bone resorption. [Mol Cancer Ther 2008;7(10):3389-98].