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A new thecideide brachiopod species, Thecidellina meyeri, is described from the southern Lesser Antilles (Aruba, Bonaire, Curaçao), Caribbean Sea, with unique morphological characters which clearly separate it from all other described species of Thecidellina in the region. A virtually complete series of ontogenetic stages is recorded, providing insight into the plasticity of shell development during growth in thecideide brachiopods and offering a well-defined standard for comparison with fossil material. Study of the soft tissue suggests that T. meyeri is dioecious, which contradicts the idea of Thecidellina to be hermaphroditic. The limited distribution and the unexpectedly high species diversity within the genus Thecidellina in the Caribbean region support the idea of allopatric speciation due to limited dispersal ability.

background: Mutations of the BCR-ABL tyrosine kinase domain constitute a major cause of resistance to tyrosine kinase inhibitors in patients with chronic myeloid leukemia. We sought to improve the diagnostic armamentarium by screening and to analyze the dynamics of mutated clones in chronic myeloid leukemia patients who experienced hematologic or cytogenetic relapse.Ninety-five patients who relapsed during imatinib therapy were screened for BCR-ABL kinase domain mutations using sensitive denaturing high-performance liquid chromatography (D-HPLC) and direct sequencing. To investigate the dynamics of mutated clones D-HPLC was applied to 453 cDNA samples tracking back from relapse towards the start of imatinib therapy.Twenty-two different point mutations affecting 18 amino acids were detectable in 46/79 (58%) and in 7/16 patients (44%) with hematologic or cytogenetic relapse, respectively. A deletion of 81 nucleotides (del248-274) of ABL exon 4 was observed in two patients. Three patients had exclusively single nucleotide polymorphisms (K247R, T315T, E499E, n=1 each) within the BCR-ABL kinase domain. In patients harboring mutations, hematologic relapse occurred after a median of 12.9 months (range, 0.9-44.2), and BCR-ABL mutations first became detectable at a median of 5.8 months (range, 0-30.5) after starting imatinib therapy (p0.0001). Nine patients showed evidence of BCR-ABL mutations prior to imatinib therapy (T315I, n=4; M351T, n=3; M244V and Y253H, n=1 each).We conclude that: (i) D-HPLC is a sensitive method for screening for BCR-ABL mutations before and during therapy with tyrosine kinase inhibitors; (ii) the occurrence of BCR-ABL mutations during imatinib therapy is predictive of relapse; (iii) mutations may be detectable several months before relapse, and (iv) the sensitive detection of small numbers of mutated clones could provide clinical benefit by triggering early therapeutic interventions.

Background Optimum sample quality is a crucial requirement for molecular monitoring of patients with chronic myeloid leukemia (CML) on therapy. Bedside RNA stabilization systems (e.g., PAXgene) have been developed to inhibit RNA degradation during shipment of samples from the clinical site to the specialized laboratory. In CML, blood but not bone marrow samples have been examined using RNA stabilization in previous studies. Therefore, we sought to investigate the applicability of the PAXgene system for bone marrow samples in CML. Methods Simultaneously stabilized blood and bone marrow samples were obtained from 55 imatinib-resistant CML patients to compare RNA yield and purity, expression of two housekeeping genes (total ABL and beta-glucuronidase; GUS) by quantitative reverse-transcriptase polymerase chain reaction, BCR-ABL expression (ratios BCR-ABL/ABL and BCR-ABL/GUS), and BCR-ABL kinase domain mutations analyzed by denaturing high-performance liquid chromatography and direct sequencing. Results RNA extraction revealed high-quality RNA derived from both stabilized blood and bone marrow samples. RNA yield was significantly higher in bone marrow (median 9.9 microg RNA/mL bone marrow) than in blood (median 4.3 microg RNA/mL blood) (p=0.0005). The number of housekeeping gene transcripts was comparable in blood and bone marrow (median ABL copies/2 microL cDNA 13,260 vs. 25,590; median GUS copies/2 microL cDNA 35,490 vs. 60,200; n.s.). Further, ratios BCR-ABL/ABL (blood vs. bone marrow, median 47% vs. 57%) and ratios BCR-ABL/GUS (blood vs. bone marrow, median 26% vs. 21%) were not significantly different. Results of mutation analysis corresponded in 51 out of 55 patients (93%), whereas moderate differences were observed in four patients. Conclusions We conclude that bone marrow can be effectively stabilized using the PAXgene system and shows concordance with blood in terms of BCR-ABL mRNA quantification and mutation analysis in imatinib-resistant CML patients.

The Young Systematists, in German “Junge Systematiker” (JuSys; www.jusys.gfbs-home.de/), represent a non-profit organisation of early career scientists in the fields of taxonomy and systematics that spans across all groups of organisms. The JuSys were founded in 1998 as a working group of the newly founded German Society for Biological Systematics (GfBS) and have since evolved into an active, autonomous group that is also increasingly attempting to influence the political debate around the situation in taxonomic and systematic research (see the open letter of the JuSys on a debate in the German parliament about supporting taxonomic research by Kaiser et al. 2011). They currently have about 300 members of mainly, but not exclusively, Germanspeaking undergraduate and graduate students as well as postdocs. The JuSys are represented by a spokesperson who is elected by the members on a biannual term and represents the needs of the JuSys. The aim of the organisation is promoting and supporting early career scientists in taxonomy and systematics, primarily through a regular exchange of knowledge on methods and scientific questions through meetings and selforganised workshops. It also serves as an important network for the exchange of ideas and important information, such as scholarships, conferences, and job announcements, through a widely used email list server. The GfBS generously gives financial support for the organisation of the JuSys meetings and workshops as well as supporting individual JuSys members with travel grants for the annual GfBS conference. This current, special volume of ODE both highlights and promotes the high quality, diversity, and impact of the research being performed by early career taxonomists and systematists as represented by the JuSys. The idea of a special volume of ODE including only contributions of early career scientists was discussed by some members of the JuSys and approved by the GfBS board in 2011 under the conditions that at least the first author is a member of the JuSys and that the papers otherwise meet all the normal requirements of the journal (including peer review). We, the guest editors of this volume, are also members of the JuSys and assumed our roles voluntarily. Under the guidance of the former chief editor of ODE, Olaf Bininda-Emonds, we were ultimately responsible for all aspects of the special volume, including issuing the call for papers, organising the review process of all submitted papers, and casting the editorial judgements. We want to thank all JuSys authors for trustfully submitting their manuscripts for this special issue and Olaf Bininda-Emonds for his great support in realising this project. “The Young Systematists special issue” of ODE clearly demonstrates that the current generation of early career scientists in taxonomy and systematics has A. Koch (*) Zoological Research Museum Alexander Koenig, Leibniz Institute for Animal Biodiversity, Section of Herpetology, Adenauerallee 160, 53113 Bonn, Germany e-mail: a.koch@zfmk.de

For the first time thecideide brachiopods have been discovered in the Indonesian Archipelago. All specimens were collected in a water depth of 30 m from an old shipwreck, the "Mutiara", which represents a remarkable habitat for these cryptic brachiopods despite its artificial nature. The thecidellinine species Minutella cf. minuta and the lacazelline species Ospreyella mutiara n. sp. are described and illustrated comprehensively, including their shell ontogeny. The inclusion of the new species O. mutiara in the genus Ospreyella Luter and Worheide, 2003 is based on results of an integrated approach combining morphological, ontogenetic and genetic studies. Relevant morphological characters diagnostic for Ospreyella are established. In addition, all Recent lacazelline brachiopod genera are confirmed as valid taxa using molecular methods. The small body size of 0. mutiara and the weakly developed brachidium in comparison to other Ospreyella species as a consequence of heterochrony is discussed in more detail. O. mutiara is the first species of the exclusively gonochoristic genus Ospreyella for which hermaphroditism is now documented.

Dasatinib (SPRYCEL®) has demonstrated significant efficacy in a high proportion of imatinib-resistant or -intolerant chronic phase CML patients (pts) concerning achievement of hematologic and cytogenetic responses. We sought to establish a relationship between type of preexisting BCR-ABL mutations associated with imatinib resistance and achievement of major molecular response (MMR, BCR-ABL ≤0.1% according to International Scale, IS) after 12 months of dasatinib therapy in pts with chronic phase CML. We have investigated 1,605 peripheral blood samples from 202 pts (n=62 imatinib-intolerant, n=140 imatinib-resistant; 52% male, median age 60 yrs, range 21–78) who had been enrolled in an international phase II study (START-C study, CA180–013) investigating the activity of 70mg dasatinib BID after imatinib failure. Screening for BCR-ABL mutations was performed by D-HPLC combined with DNA sequencing. During follow up, pts were monitored in 3-monthly intervals by RQ-PCR for BCR-ABL mRNA transcripts and by mutation analysis to determine the quantitative course of the preexisting mutation or the emergence of new mutations. Prior to dasatinib therapy, 34 different BCR-ABL mutations involving 29 amino acids were detected in 85/202 pts (42%) with a striking predominance in imatinib-resistant (77/140 pts, 55%) over imatinib-intolerant pts (8/62 pts, 13%). 75 pts showed one, 8 pts two and 2 pts three mutations. RQ-PCR data after 12 months of therapy was available from 154 pts (76%), samples from 48 pts (24%) were not available for monitoring after one year due to progressive disease. MMR was achieved in 28 imatinib-intolerant (45%) and 19 imatinib-resistant pts (14%, p1,000nM). Of 85 pts without sufficient molecular response to dasatinib (BCR-ABL IS >5%) after 12 months (median, range 9–15) mutation analysis revealed the emergence of new mutations in 17 formerly imatinib-resistant pts (T315I, n=2; T315A, n=1; F317L, n=6; V299L, n=2; M351T, n=2; L248V, n=1; G250E, n=1; K271R, n=1; Y320C, n=1). We conclude that dasatinib is capable of inducing high rates of major molecular response after one year treatment particularly in imatinib-intolerant pts. Response dynamics depend on the individual type of mutation which may be a basis for individual dose adjustment according to the mutation pattern.

Dasatinib (BMS-354825) is a novel, oral, multi-targeted kinase inhibitor of BCR-ABL and SRC kinases with preclinical activity against 20/21 imatinib resistant BCR-ABL mutations and clinical phase I/II efficacy in patients with chronic myelogenous leukemia (CML) and BCR-ABL positive acute lymphoblastic leukemia (ALL). We sought to establish a relationship between type of preexisting BCR-ABL mutations associated with imatinib resistance and efficacy of dasatinib in patients (pts) with CML and ALL. We have investigated 872 peripheral blood samples from 394 pts (53% male, median age 60 yrs, range 17–85) who had been enrolled in international phase II studies investigating the activity of 70mg dasatinib BID after imatinib failure (chronic phase, CP, n=198; accelerated phase, AP, n=78; myeloid blast crisis, MyBC, n=53; lymphoid blast crisis, LyBC, or ALL, n=65). Screening for BCR-ABL mutations was performed by D-HPLC combined with DNA sequencing. During follow up, pts were monitored in 3-monthly intervals by RQ-PCR for BCR-ABL mRNA transcripts and by mutation analysis to determine the quantitative course of the preexisting mutation or the emergence of new mutations. Hematologic and cytogenetic response data have been collected sequentially for a median of 8 months (range, 2–11) after start of therapy. Prior to dasatinib, 46 different BCR-ABL mutations involving 36 amino acids were detected in 202/394 pts (51%). 162 pts showed one, 33 pts two, 6 pts three, and 1 pt four mutations. Mutations were observed in 84 pts in CP (42%), 47 pts in AP (60%), 23 pts in MyBC (43%), and 48 pts in LyBC and ALL (74%). In patients with mutations, hematologic response was 91% in CP, 62% in AP, 41% in MyBC, and 34% in LyBC/ALL (p a parallel decrease of the BCR-ABL load and the mutated clone or a decrease of the BCR-ABL load followed by a decrease of the mutated clone after a delay of up to 4–6 months. Up until now 5 pts developed new mutations associated with dasatinib resistance (T315I, n=2, AP and MyBC pts; F317L+F486S, n=2, LyBC and MyBC pts; E507G, n=1, CP pt). We conclude that dasatinib is capable of inducing hematologic and cytogenetic remissions in a significant proportion of imatinib resistant pts harboring BCR-ABL mutations, except T315I. Response dynamics depend on the individual type of mutation which may be a basis for individual dose adaptation according to the mutation pattern.

A full redescription of Griffithsius latipes (Griffiths, 1976) is given. This is necessary because the original description is incomplete and contains inaccuracies.

Nilotinib (AMN107) is a novel, orally active aminopyrimidine-derivative, which selectively inhibits the BCR-ABL tyrosine kinase with greater potency compared with imatinib (Im). In preclinical models, nilotinib was 20–50 times more potent than imatinib in Im-sensitive CML cell lines, and 3–7 times more potent in Im-resistant cell lines. Activity of nilotinib was also demonstrated in 32/33 Im-resistant mutant cell lines. We sought to investigate the efficacy of nilotinib in vivo according to the type of preexisting BCR-ABL mutations. We have investigated peripheral blood samples from 101 CML patients (pts, 63m, 38 f) with a median age of 61 yrs (range, 23–85) who had been enrolled in an international phase II study investigating the efficacy and safety of 400mg nilotinib bid after Im failure (chronic phase, CP, n=64; accelerated phase, AP, n=22; blast crisis, BC, n=15). Screening for BCR-ABL mutations was performed by D-HPLC combined with DNA sequencing. The analysis covered amino acids 207–517 of the BCR-ABL tyrosine kinase domain. The proportion of the mutated clone was estimated from sequencing plots by comparison to plots from serial standard dilutions of Ba/F3 cell lines harboring various concentrations of mutated BCR-ABL. Hematologic and cytogenetic response data are available for a median of 4 mo (range, 1–10) after start of nilotinib therapy. Prior to nilotinib, 28 different BCR-ABL mutations involving 22 amino acids were detected in 61/101 pts (60%). Nine pts showed two, three pts three, and one patient four mutations. Mutations were observed in 37 pts in CP (49%), 15 pts in AP (68%), and 9 pts in BC (60%). In pts with mutations, the overall rate of hematologic response was 70% (78% in CP, 75% in AP, 25% in BC) compared with 88% in pts without mutations. In CP CML, complete cytogenetic response was achieved within 3–6 mo in pts with mutations with high in vitro sensitivity to nilotinib according to O’Hare et al., Cancer Res 2005 and Weisberg et al., Br J Cancer 2006 (M244V, 38nM, n=2; M351T, 15nM; H396R, 41nM; D276G+M351T, 69 and 15nM; E355G+L387F, 47 and 46nM). 4 pts with mutations resulting in relatively higher cellular IC50 to nilotinib had progressed (Y253F+E255K, 125 and 200nM; L248V, 102nM; Y253H, 450nM; F359V, 175nM). 2 pts with small clones (ratio mutated BCR-ABL/ABL 0.14% and 8.6%) harboring the BCR-ABL mutation T315I being highly resistant to Im and nilotinib in vitro did not show signs of relapse after one and 11 mo of nilotinib therapy, respectively. During therapy, novel BCR-ABL mutations (Y253F, E255V, T315I, and F359V) appeared in 4 pts. In conclusion, preliminary data suggest that nilotinib may overcome most of the mutation-associated resistance to Im, and may have an important therapeutic role in Im resistance and in frontline CML therapy to prevent emergence of resistant clones. Response dynamics depend on the individual type of the mutation which may be the basis for individualized dosage of nilotinib according to the mutation pattern. The molecular analysis of the total phase II study population will be reported at the meeting.

For the first time thecideide brachiopods have been discovered in the Indonesian Archipelago. All specimens were collected in a water depth of 30 m from an old shipwreck, the “Mutiara”, which represents a remarkable habitat for these cryptic brachiopods despite its artificial nature. The thecidellinine species Minutella cf. minuta and the lacazelline species Ospreyella mutiara n. sp. are described and illustrated comprehensively, including their shell ontogeny. The inclusion of the new species O. mutiara in the genus Ospreyella Lüter and Wörheide, 2003 is based on results of an integrated approach combining morphological, ontogenetic and genetic studies. Relevant morphological characters diagnostic for Ospreyella are established. In addition, all Recent lacazelline brachiopod genera are confirmed as valid taxa using molecular methods. The small body size of O. mutiara and the weakly developed brachidium in comparison to other Ospreyella species as a consequence of heterochrony is discussed in more detail. O. mutiara is the first species of the exclusively gonochoristic genus Ospreyella for which hermaphroditism is now documented.