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Supplementary Materials and Methods; Supplementary Tables S1-S4.

Purpose: Inappropriate activation of the Hedgehog (Hh) signaling pathway in skin is critical for the development of basal cell carcinomas (BCC). We have investigated the anti-BCC efficacy of topically-applied CUR61414, an inhibitor of the Hh signal transduction molecule Smoothened.Experimental Design: In preclinical studies, we used a depilatory model to evaluate the ability of topical formulations of CUR61414 to repress Hh responsive cells found at the base of hair follicles in normal skin. We also tested the in vivo effects of topical CUR61414 on murine BCCs developed in Ptch1 +/− K14-CreER2 p53 fl/fl mice. In a phase I clinical study, we evaluated the safety, tolerability, and efficacy of a multidose regimen of CUR61414 (0.09%, 0.35%, 1.1%, and 3.1%) applied topically to human superficial or nodular BCCs for up to 28 days.Results: In mice, topical CUR61414 significantly inhibited skin Hh signaling, blocked the induction of hair follicle anagen, and shrank existing BCCs. However, we observed no clinical activity of this formulation in human superficial or nodular BCCs in a phase I clinical study.Conclusions: Our data highlight some of the challenges of translating preclinical experience into successful human results for a topical anticancer agent. Clin Cancer Res; 17(10); 3378–87. ©2011 AACR.

Larvae of sea urchins, brittle stars, and allies are common, ecologically important, and diverse members of marine ecosystems in all of the world's oceans today. In contrast to modern representatives, the fossil record of echinoderm larvae is poorly known. This study reports the first ophiopluteus skeleton from Cretaceous sediments worldwide, obtained from chalky sediment of the Isle of Wolin, NW Poland. The evidence presented here, that it is possible to isolate fossil echinoderm larval skeletons from rocks, indicates a hidden diversity of such fragile fossils and thus the possibility of direct geological recording.

In an exceptional preservation state, bones conserve the entire pattern of extracellular bone matrix proteins over thousands or sometimes even millions of years. Here we present typical extracellular bone matrix proteins, which were extracted from a 3.0-million-year-old gomphothere proboscidean, and identified with special antibodies. For the first time, osteonectin, osteopontin and BMP-2 were confidently identified from the extinct Anancus arvernensis, based on late Pliocene material from Willershausen, Lower Saxony, Germany. Our study has value in demonstrating that the longevity of original extracellular bone matrix proteins is much greater than formerly expected, and that such materials may be stabilised for distinct geological periods of time, especially in Fossil Lagerstätten.

Cyclocystoids are a poorly known, rare, extinct class of bi-facially flattened, disc shaped echinoderms, ranging from the Middle Ordovician to the Early Carboniferous. Articulated cyclocystoids are relatively common in the Ordovician but are rarer in younger strata. Here we describe Perforocycloides nathaliae new genus and species, from the early Silurian of Anticosti Island, Quebec, Canada, the first articulated cyclocystoid from the Silurian of North America. This taxon is distinguished from other cyclocystoids by the number of variably sized marginal ossicles, the lack of interseptal plates, and the novelty of pores located in the distal part of the sutures between adjacent marginals on the dorsal surface. These dorsal intermarginal sutural pores led to canals which penetrated the contiguous area of the lateral surface of the marginals and emerged on the ventral surface between the cupules of adjacent marginals. These dorsal intermarginal sutural pores/canals appear to be unique to Perforocycloides and whilst their function is speculative, they provided some form of communication between the dorsal disc and the distal side of the ventral marginals/cupules. Perforocycloides most closely resembles the Ordovician–Silurian genus Zygocycloides, suggesting that this genus may have diversified more widely during the Silurian than previously reported. A review of global Silurian cyclocystoid distribution suggests taxa were geographically confined and that greatest diversity appears to have been located within Baltica. However, it also demonstrates our current limited knowledge. No specimens have been recorded from Gondwana (e.g. Africa, Australia, South America), Siberia, and North and South China, nor are any specimens known confidently anywhere from Přidoli strata.

Motivation for this comment Recently, the Society of Vertebrate Paleontology (SVP) has sent around a letter, dated 21st April, 2020 to more than 300 palaeontological journals, signed by the President, Vice President and a former President of the society (Rayfield et al. 2020). The signatories of this letter request significant changes to the common practices in palaeontology. With our present, multi-authored comment, we aim to argue why these suggestions will not lead to improvement of both practice and ethics of palaeontological research but, conversely, hamper its further development. Although we disagree with most contents of the SVP letter, we appreciate this initiative to discuss scientific practices and the underlying ethics. Here, we consider different aspects of the suggestions by Rayfield et al. (2020) in which we see weaknesses and dangers. It is our intent to compile views from many different fields of palaeontology, as our discipline is (and should remain) pluralistic. This contribution deals with the aspects concerning Myanmar amber. Reference is made to Haug et al. (2020a) for another comment on aspects concerning amateur palaeontologists/ citizen scientists/private collectors.

Recently we documented a bilaterally symmetrical, solitary organism, Yanjiahella biscarpa from the early Cambrian (Fortunian) of China1. We interpreted that Y. biscarpa possessed an echinoderm-like plated theca, a muscular stalk similar to hemichordates and a pair of long, feeding appendages. Our interpretation and our phylogenetic analysis suggest that Y. biscarpa is a stem-echinoderm, which would confirm that echinoderms acquired plates before pentaradial symmetry and that their history is firmly rooted in bilateral forms. Zamora et al.2 however, have criticized our interpretation, arguing against an echinoderm affinity, instead suggesting that the phylogenetic placement of Y. biscarpa is dubious and its significance for understanding deuterostome evolution is uncertain. This criticism2 seems to stem from our interpretation of particular morphological features in Y. biscarpa1 and the perceived lack of echinoderm synapomorphies. Echinoderms possess a calcitic skeleton with a distinctive three-dimensional mesh-like microstructure called stereom, that is considered a major synapomorphy of the Echinodermata3. Zamora et al.2 highlighted the absence of stereom in Y. biscarpa, additionally stating that we had omitted appropriate methods, specifically latex casting, that may confirm the presence of stereom in our specimens. We concede that initially we did not latex cast any specimens of Y. biscarpa, predominantly due to the fragile nature and the associated risk of damaging the specimens in question. In lieu of latex casting we employed Scanning Electron Microscopy (SEM) to investigate the surface and the details of Y. biscarpa specimens. SEM has been extensively used in the past to study stereom microstructure4,5,6 and if such a microstructure was preserved in Y. biscarpa it would have been detected using this technique. Artikeln är ett refereegranskat svar på en publicerad kommentar på en tidigare artikel.

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Articulated ophiocistioids are rare as fossils, enigmatic in terms of their phylogenetic position, and have been considered to be an exclusively Palaeozoic echinoderm group. Apart from articulated body fossils, the fossil record of Ophiocistioidea is otherwise dependent on isolated microfossils. However, it has been demonstrated that disarticulated jaw elements (goniodonts) of ophiocistioids can be diagnostic at genus and species level and can be used to fill gaps in the non-articulated fossil record. The Late Triassic Cassian Formation of Italy is regarded as one of the most important strata of early Mesozoic invertebrates worldwide. A fossil assemblage from a locality near Misurina, South Tyrol, yielded various echinoderms, including a stem group echinoid representative and a new ophiocistioid, Linguaserra triassica sp. nov. The new taxon is described and placed within linguaserrid ophiocistioids. The evolutionary history of the group is briefly discussed in relation to other taxa of theOphiocistioidea and Echinoidea. Linguaserra triassica not only represents the first documented occurrence of this Palaeozoic' echinoderm class from Mesozoic strata but also establishes the stratigraphically youngest record of goniodonts or ophiocistioid teeth in the world.

A diverse Permian crinoid fauna is reported from the Taiyuan Formation, Dajian Member (Asselian) at Anyang, northeastern Henan Province of the North China Craton. The specimens are well preserved, including articulated crowns and cups. The fauna contains representatives of each of the major Paleozoic crinoid clades: Cladida (including the Flexibilia), Disparida, and Camerata. Identified genera suggest a greater affinity with North American faunas than with Tethyan faunas. Four new species,Neoprotencrinus anyangensis,Ulocrinus qiaoi,Artichthyocrinus limani, andSynbathocrinus chenae, are proposed herein.UUID:http://zoobank.org/D08DDDCD-485C-45CC-A014-C1CB58C26588

Hornung, J.J., Reich, M. & Frerichs, U., February 2018. The mosasaur fauna (Squamata: Mosasauridae) from the Campanian (Upper Cretaceous) of Hannover, northern Germany. Alcheringa 42, 543-559. ISSN...

Número especial llamado: "Progress in Echinoderm Paleobiology", Moroccodiscus smithi represents a new cyclocystoid genus and species based on moldic specimens from the Middle Ordovician Taddrist Formation (Darriwilian) of SE Morocco. This represents the earliest articulated member of the Cyclocystoidea and is the first complete cyclocystoid described from the Ordovician of Gondwana, as well as the first cyclocystoid ever recorded from Africa. The anatomy and morphology of this new species were studied using a combination of conventional paleontological methods and nondestructive X-ray computed tomography. Because Moroccodiscus differs from other cyclocystoids, in particular by lacking cupules attached to the marginal ossicles, it is assigned to the new family Moroccodiscidae. This new taxon illustrates the relatively poorly known early diversification of these enigmatic extinct echinoderms and sheds light on the mode of life of cyclocystoids, including injuries to plate circlets during early ontogeny and folding of these disk-like specimens at the time of death. The overall thecal shape was very similar in cyclocystoids and many domal edrioasteroids, probably because they were both sessile or attached, benthic, suspension feeders. However, many oral surface, ambulacral, and marginal ring features had become very different, indicating that these two groups had either converged because of similar life modes or were only distantly related sister groups., Bavarian State Collection of Palaeontology and Geology, Alemania, Department of Earth and Environmental Sciences, Division of Palaeontology and Geobiology, Ludwig-Maximilians-Universität München, Alemania, GeoBio-Center, Alemania, Department of Geological Sciences, Jackson School of Geosciences, University of Texas, Estados Unidos, Laboratoire de Géologie de Lyon: Terre, Planète, Environnement, Unitè Mixte de Recherche, Université Lyon 1, 2, Francia, Laboratoire de Géologie de Lyon: Terre, Planète, Environnement, Unitè Mixte de Recherche, Centre National de la Recherche Scientifique, Francia, Unidad de Zaragoza, Instituto Geológico y Minero de España, España

Friedrich von Hagenow is renowned for his seminal inventory of the diverse invertebrate fauna from the lower Maastrichtian chalk (Upper Cretaceous) of the Isle of Rugen, Germany. Tragically, his immense collection at Stettin (today Szczecin, Poland) was almost completely destroyed during World War II, including the type material of hundreds of species established by him during the first half of the 19th century. Seven belemnite specimens from his collection rediscovered at the Museum fur Naturkunde Berlin, as well as 14 belemnites traced at the Museum fur Mineralogie und Geologie at the Senckenberg Naturhistorische Sammlungen Dresden, include syntypes of four Talpina ichnospecies, labelled T. ramosa, T. solitaria, T. foliacea and T. sentiformis. To document this material, a new ‘digital cylinder seal technique’ was applied. The rediscovered material allows lectotype designations for T. ramosa and T. solitaria (now Trypanites solitarius), whereas T. foliacea and T. sentiformis, which where not formally published by von Hagenow, are regarded as nomina nuda. As a consequence, the non-topotypical neotypes of T. ramosa and T. solitaria, as designated by Ehrhard Voigt in 1972, are obsolete.

Objects collected over more than 300 years, and nearly 250 years of museum tradition have led to one of today’s largest palaeontological collections in Germany. About 2.5 million palaeontological objects are kept in the collections of the Geoscience Museum of the Georg August University, among them types and original material regarding several thousand publications. Just before the official inauguration of the university in 1737, first lectures on natural history were given by Samuel Christian Hollman, Gottingen’s first professor. Already in those times, palaeontological objects had a high significance in the studentical education in natural history, which was continuously retained until today.

The Bavarian State Collection of Palaeontology and Geology (BSPG = Bayerische Staatssammlung fur Palaontologie und Geologie) was founded in 1843, and today represents one of the largest palaeontological collections in Germany both with regard to number of specimens and the spectrum of material included. However, the history of most of the materials that are kept in the BSPG goes back to times well before the BSPG was formally established. Here, a brief historical background of our collections, with special attention to its importance for research and public outreach, is provided.

Spines of irregular echinoids occur in very high abundance in each specimen, and display distinct architecture as a result of the specialized functions of the spines; however, studies on spine microstructure in atelostomate echinoids have rarely been carried out. Accordingly, little is known about their specific morphology. This work aims to elaborate differences in the spine morphology of selected Atelostomata (Spatangoida and Holasteroida) in detail, and to discuss spine microstructure for its potential systematic value. Based on 82 atelostomate species (56 spatangoids and 26 holasteroids), we show that the perforation pattern in the internal cylinder of the spine (helicoidal versus horizontal pattern) provides a safe distinction between the Spatangoida and Holasteroida. According to this character we discuss the geological history of atelostomate echinoids, in particular their migration into the deep sea, based on well-preserved records of fossil spines. © 2015 The Linnean Society of London

Two genera of tylosaurine mosasaurs, Tylosaurus and Hainosaurus, are recorded for the first time from Germany. Tylosaurus sp. is represented by two isolated tooth crowns, originally described as Mosasaurus? alseni (here considered a nomen dubium) from the latest Santonian–Early Campanian, which are very similar to T. ivoensis and T. gaudryi. The material of Hainosaurus sp. comprises a maxillary with associated postorbitofrontal, two pterygoid teeth and several indeterminate cranial fragments. The specimen from the Late Campanian is slightly less derived than H. bernardi from the Maastrichtian in retaining labiolingually less compressed anterior maxillary teeth and unserrated pterygoid teeth with only very weak carinae. Despite only minor skeletal differences, the genus Hainosaurus is considered to be distinct from Tylosaurus because of its significant modification of the dental apparatus compared to the plesiomorphic condition in the latter. This dental morphology suggests a phylogenetic trend from a generalised-piercing marginal dentition in Tylosaurus towards the increasingly labiolingually compressed, symmetrical, strongly bicarinate cutting marginal teeth in Hainosaurus spp. from the Early through Late Campanian and Maastrichtian. A similar trend is also present in pterygoid teeth with very indistinct unserrated carinae in the Campanian Hainosaurus sp. towards serrated ones in the Maastrichtian H. bernardi. A short review indicates the presence of Hainosaurus in northern, central and western Europe (Sweden to Spain) since the Early Campanian, and the occurrence of Tylosaurus spp. in the same area until the Late Campanian. Hainosaurus persisted until the end of the Maastrichtian; outside Europe it may have been present in the Late Campanian of the USA and the Maastrichtian of the Democratic Republic of Congo. Judging from a simple, uni- to bicarinate, stoutly conical tooth morphology in aigialosaurs and very basal mosasaurs as well as phylogenetic patterns, the development of blade-like cutting tooth crowns appears to have been convergent in several clades of large-bodied Campanian–Maastrichtian mosasaurids. These include both mosasaurines ('Leiodon' mosasauroides, Prognathodon? sectorius, Prognathodon? kianda, Eremiasaurus heterodontus) and tylosaurines (Hainosaurus spp.).

In Germany, mosasaur remains are very rare and only incompletely known. However, the earliest records date back to the 1830s, when tooth crowns were found in the chalk of the Isle of Rügen. A number of prominent figures in German palaeontology and geosciences of the 19th and 20th centuries focused on these remains, including, among others, Friedrich von Hagenow, Hermann von Meyer, Andreas Wagner, Hanns Bruno Geinitz and Josef Pompeckj. Most of these works were only short notes, given the scant material. However, the discovery of fragmentary cranial remains in Westphalia in 1908 led to a more comprehensive discussion, which is also of historical importance, as it illustrates the discussions on the highly controversial and radical universal phylogenetic theory proposed by Gustav Steinmann in 1908. This theory saw the existence of continuous lines of descent, evolving in parallel, and did not regard higher taxonomic units as monophyletic groups but as intermediate paraphyletic stages of evolution. In this idea, nearly all fossil taxa form part of these lineages, which extend into the present time, and natural extinction occurs very rarely, if ever. In Steinmann's concept, mosasaurs were not closely related to squamates but formed an intermediate member in a anagenetic chain from Triassic thalattosaurs to extant baleen whales. The newly found specimen led Josef Pompeckj to write a vehement rebuttal to Steinmann's theory, published in 1910, showing that his conclusions were conjectural and speculative, being based on convergence and not supported by scientific evidence. This particular specimen, housed in Göttingen, later also inspired a piece of palaeoart by Franz Roubal under the instructions of Othenio Abel.With the exception of a vertebra from the Campanian of former East Prussia (now Russian Federation), and a possible vertebra from the Cenomanian of Dresden, Saxony, all datable material – today partly lost – originated from the northern part of present-day Germany and stratigraphically from the Campanian–Maastrichtian. The purported record from the Cenomanian of Bavaria (southeastern Germany) was most probably an error, based on Upper Jurassic crocodilian material.

The Solling Formation is the most distinctive unit of the Early Triassic Buntsandstein of the epicontinental Central European Basin. The Solling Formation of Bremke and Furstenberg has yielded one of the richest and most diversified plant collections of the Middle Buntsandstein to date, one of the oldest floras in Europe after the end-Permian mass extinction. Based on the plant fossils, the Middle Buntsandstein ecosystem from Bremke and Furstenberg represents not only one of the earliest floras in Europe after the end-Permian extinction but also one of the earliest Triassic occurrences of insect herbivory from any documented flora worldwide and thus provides a rare glimpse into the third pulse of herbivore expansion. Integrated palaeobotanical, palaeontological and sedimentological studies have enabled reconstruction of two different floodplain environmental settings of the Solling Formation, including their vegetation, the plant–insect interactions and revealing how important taphonomy and environmental settings were for the preservation of Middle Buntsandstein plants. At Bremke a levee-crevasse splay complex is reconstructed that tributed into perennial backwsamps and at Furstenberg unconfined subaerial flows formed a sandy aggradational floodplain with ephemeral ponds. A rich plant community was established and became preserved in backswamps and ponds. This suggests that the scarcity of Buntsandstein floras is clearly related to taphonomical processes and not to extreme environmental conditions under arid or semi-arid climates.

From the early Silurian of Gotland, Sweden, the new ophiocistioid goniodont Linguaserra franzenae sp. nov. is described, figured and discussed within the Linguaserridae Reich & Haude, 2004. The evolutionary history of linguaserrid ophiocistioids is briefly discussed in relation to other members of the Ophiocistioidea. This new echinoderm species not only represents the first documented occurrence of this group from the Llandovery but also establishes the stratigraphically oldest record of goniodonts in the world.

Metatetrapous valdensis Nopcsa, 1923 from the late Berriasian of northwestern Germany was the first dinosaur ichnotaxon ever attributed to a thyreophoran trackmaker. However, the subsequent lost of the original material made this identification and the status of the ichnotaxon questionable for many subsequent authors. This situation was aggravated by the fact that there are only very brief original descriptions accompanied by a single drawing. A reconsideration of the original description recognizes M. valdensis as a valid ichnotaxon, which, albeit showing great resemblance in pes morphology to similar ichnotaxa, stands out from them by a tetradactyl manus. It not only holds its original systematic attribution, but also has sparked early hypotheses on the phylogeny of dinosaurs already in 1922, possibly for the first time based upon tracks. Two surviving natural hypichnial casts of ankylosaurian pes imprints from the same stratum cannot be straightforwardly identified with the type material due to a lack ...

A hypichnium of a manus imprint (preserved as plaster cast) indicates for the first time the presence of the large pterosaur ichnotaxon Purbeckopus cf. pentadactylus Delair, 1963 in the late Berriasian of northwest Germany. It is only the second record of Purbeckopus globally and the first pterosaur track from Germany. It provides evidence of a very large pterosaur (wingspan c. 6 m) in this area and from this time period not yet represented by skeletal remains. When compared with the English type material, the specimen exhibits some differences that are related mostly to different properties of the substrate on which both were left. These include, in the German track, an impression of the metacarpo-phalangeal joint of the wing finger, normally not present in pterosaur tracks. Also interesting is the rather blunt termination of the deeply impressed digits I–III, indicating rather short and blunt claws, which seem more suitable for walking than for grasping or climbing. The specimens of Purbeckopus in Engla...

A well-preserved isolated manus impression evidences the presence of derived aquatic adaptations in the forelimb morphology of Berriasian turtles. Size and the abundant co-occurring turtle fauna indicate that the track was left by a large-sized, bottom-walking basal pancryptodiran. The footprint shows an interesting mosaic of primitive and derived features. The basic turtle pattern is reflected by a short and broad autopodium but thin phalanges, claw reduction and extensive webbing enclosing the digits and lateral and medial margins of the distal metapodium are clearly specialized features related to the aquatic environment. Some characters including the proportional elongation of the first digit, which reached as far distally as the other digits and was probably highly mobile at the metacarpal-phalangeal joint, indicate an even higher degree of specialization. The specimen gives evidence on a hitherto unknown range of appendicular modification in Early Cretaceous turtles, and redundantly proves the aquatic habitat and locomotion of large-sized turtles from the Berriasian of northwestern Germany.

The fossil echinoderm Palaeocucumaria, from the early Devonian Hunsruck Slate of southwestern Germany, has been studied using both traditional techniques and X-ray microtomography, and its anatomy clarified. Phylogenetic analysis shows that it is a stem-group holothurian with a combination of characters that help understand how the modern (crown-group) holothurian body plan developed. Echinoids and holothurians have evolved along different paths, by differential growth of the larval- and rudment-derived body regions. Palaeocucumaria shows that late stem-group holothurians had a water vascular organization with a single external madreporite and calcified stone canal leading to the aboral end of the peripharyngeal coelom, and five primary radial water vessels that gave rise to tentacle-like tube-feet. This fossil data, in combination with a molecular phylogeny based on 18 s-like rRNA gene sequence data, is used to order evolutionary steps in the making of the crown-group holothurian body plan. © 2013 The Linnean Society of London, Biological Journal of the Linnean Society, 2013, 109, 670–681.

Sea cucumbers (Holothuroidea) are a morphologically diverse, ecologically important, and economically valued clade of echinoderms; however, the understanding of the overall systematics of the group remains controversial. Here, we present a phylogeny of extant Holothuroidea assessed with maximum parsimony, maximum likelihood, and Bayesian approaches using approximately 4.3kb of mt- (COI, 16S, 12S) and nDNA (H3, 18S, 28S) sequences from 82 holothuroid terminals representing 23 of the 27 widely-accepted family-ranked taxa. Currently five holothuroid taxa of ordinal rank are accepted. We find that three of the five orders are non-monophyletic, and we revise the taxonomy of the groups accordingly. Apodida is sister to the rest of Holothuroidea, here considered Actinopoda. Within Actinopoda, Elasipodida in part is sister to the remaining Actinopoda. This latter clade, comprising holothuroids with respiratory trees, is now called Pneumonophora. The traditional Aspidochirotida is paraphyletic, with representatives from three orders (Molpadida, Dendrochirotida, and Elasipodida in part) nested within. Therefore, we discontinue the use of Aspidochirotida and instead erect Holothuriida as the sister group to the remaining Pneumonophora, here termed Neoholothuriida. We found four well-supported major clades in Neoholothuriida: Dendrochirotida, Molpadida and two new clades, Synallactida and Persiculida. The mapping of traditionally-used morphological characters in holothuroid systematics onto the phylogeny revealed marked homoplasy in most characters demonstrating that further taxonomic revision of Holothuroidea is required. Two time-tree analyses, one based on calibrations for uncontroversial crown group dates for Eleutherozoa, Echinozoa and Holothuroidea and another using these calibrations plus four more from within Holothuroidea, showed major discrepancies, suggesting that fossils of Holothuroidea may need reassessment in terms of placing these forms with existing crown clades.

A comparative systematic survey of fossil Mesozoic laetmogonid sea cucumbers (Elasipodida) and their relatives is presented. A re-examination of the fossil record shows that only 13 fossil taxa can be recognised as belonging to this group. Four further known ‘laetmogonid’ taxa can be regarded as incertae sedis. An analysis of the results supports the following taxonomic changes. Palaeocaudinidae Boczarowski, 2001 represents a junior synonym of the Laetmogonidae Ekman, 1926. The subfamily Staurocaudininae Boczarowski, 1997 is restricted to the type species of Staurocaudina. The new family Palaeolaetmogonidae comprises probable stem group members of the Laetmogonidae. Three new species (Palaeocaudina rugia, Priscolaetmogone oloughlini, Palaeolaetmogone frankwiesei) are described from Late Cretaceous sediments of Europe. Two new genera (Palaeolaetmogone, Priscolaetmogone) are erected. The geographic distribution and phylogenetic relationships of Mesozoic and Cenozoic laetmogonid holothurians are analysed and discussed.

Purpose: Inappropriate activation of the Hedgehog (Hh) signaling pathway in skin is critical for the development of basal cell carcinomas (BCC). We have investigated the anti-BCC efficacy of topically-applied CUR61414, an inhibitor of the Hh signal transduction molecule Smoothened. Experimental Design: In preclinical studies, we used a depilatory model to evaluate the ability of topical formulations of CUR61414 to repress Hh responsive cells found at the base of hair follicles in normal skin. We also tested the in vivo effects of topical CUR61414 on murine BCCs developed in Ptch1 +/− K14-CreER2 p53 fl/fl mice. In a phase I clinical study, we evaluated the safety, tolerability, and efficacy of a multidose regimen of CUR61414 (0.09%, 0.35%, 1.1%, and 3.1%) applied topically to human superficial or nodular BCCs for up to 28 days. Results: In mice, topical CUR61414 significantly inhibited skin Hh signaling, blocked the induction of hair follicle anagen, and shrank existing BCCs. However, we observed no clinical activity of this formulation in human superficial or nodular BCCs in a phase I clinical study. Conclusions: Our data highlight some of the challenges of translating preclinical experience into successful human results for a topical anticancer agent. Clin Cancer Res; 17(10); 3378–87. ©2011 AACR.

Two species of the genus Camponotites (Formicidae, Formicinae) are described from the Late Pliocene deposits of Willershausen, Lower Saxony, northern Germany: C. silvestris Steinbach, 1967, and C. steinbachi n. sp. The generic name Camponotites has been established for fossil (Tertiary) ants independently by Steinbach (Bericht der Naturhistorischen Gesellschaft zu Hannover 111:95–102, 1967) and by Dlussky (Trudy paleontologiceskogo instituta, akademiâ nauk SSSR, 1981), each for materials of different stratigraphical and geographical origin. Though poorly described, Camponotites Steinbach, 1967, and the single included (type) species C. silvestris Steinbach, 1967 (a monotypic species from the Late Pliocene of Willershausen), were based upon indication in the sense of the ICZN. Therefore, both the generic and specific names are valid and available. Camponotites Dlussky, 1981 (and its type species C. macropterus Dlussky, 1981) were certainly introduced correctly and are therefore available, too; but due to its homonymy the generic name is not valid. The revision shows that in this rare case both generic names are not only homonyms but also synonyms.

A succession of clays with thin shell beds from the French Ardennes, dated to the late Early Pliensbachian Davoei Zone and yielding abundant well-preserved remains of all five extant classes of echinoderms, is described here as a new Lagerstatte. The echinoderms occur in the form of isolated ossicles, semi-articulated plate aggregates and abundant intact skeletons with even the most delicate appendices preserved in place and the finest skeletal structures hardly blurred by recrystallisation. The outstandingly good preservation of the echinoderm specimens allows for a morphological assessment of the represented taxa in detail only rarely achievable by fossil material. The material described herein thus significantly contributes to a better understanding of the systematic position and phylogenetic background of many Early Jurassic echinoderm taxa. The echinoderms are considered to have been buried as an autochthonous or at least parautochthonous assemblage among clumps and beds of Modiolus bivalves. The depositional setting most likely represented a relatively shallow, near-shore soft-bottom environment in which conditions repeatedly favoured the settlement and subsequent effective burial of bivalve-echinoderm assemblages, leading to the formation of the thin highly fossiliferous shell beds intercalating the otherwise nearly sterile clays. The new Lagerstatte opens a unique window into the palaeoecology of an extinct shallow-water soft-bottom community closely comparable to recent analogues.

A diverse holothurian fauna from the Upper Turonian of the Isle of Wolin (northwestern Poland), is described and assessed with respect to palaeoecology, palaeobiology and evolutionary diversification. The fauna was recovered from chalk and partly silicified chalk. A stratigraphic re-assessment of all available biostratigraphic literature permits assignment to the Subprionocyclus neptuni ammonite zonal age (late Turonian). The majority of the holothurian fauna consists of apodid, aspidochirotid, and elasipodid species. The part of the fauna described here consists of sclerite species of three different Recent families of the Apodida. Two new forms, Calcancora venusta sp. nov. and Rigaudites ernsti sp. nov. (Synaptidae: Rynkatorpinae), are described, figured and discussed.

Echinoid teeth are without doubt the most com- plex and highly specialized skeletal component to have evolved in echinoderms. They are biomechanically con- structed to be resilient and tough while maintaining a self- sharpening point. Based on SEM analysis of isolated tooth elements collected primarily from the Ordovician and Silu- rian of Gotland, we provide a detailed structural analysis of the earliest echinoderm teeth. Eight distinct constructional designs are recognized encompassing various degrees of sophistication, from a simple vertical battery of tooth spines to advanced teeth with multiple tooth plate series and a rein- forced core of fibres. These provide key data from which we reconstruct the early stages of tooth evolution. The simplest teeth are composed of stacked rod-like elements with solid calcite tips. More advanced teeth underwent continuous replacement of tooth elements, as a simple self-sharpening mechanism. Within echinoids tooth design was refined by evolving thinner, flatter primary plates with buttressing, allowing maintenance of a sharper and stronger biting edge. Despite the obvious homology between the lanterns of ophiocistioids and echinoids, their teeth are very different in microstructural organization, and they have evolved different self-sharpening mechanisms. Whereas echinoid teeth evolved from a biseries of mouth spines, ophiocistioid goniodonts evolved from a single series of mouth spines. Rogeriserra rep- resents the most primitive known battery of tooth elements but its taxonomic affinities remain unknown.

From the Late Permian Zechstein reefs (Lopingian: Wuchiapingian) of eastern Thuringia, Germany, the new ophiocistioid goniodont Linguaserra spandeli sp. nov., is described, figured, and discussed, within the Linguaserridae Reich and Haude, 2004. The (para)genus Linguaserra is redefined; the stratigraphical and regional distribution as well as the phylogenetic position are briefly discussed. Linguaserra spandeli sp. nov. is the stratigraphically youngest record of this echinoderm group (Echinozoa: Ophiocistioidea) worldwide.