• The incidence of mutations within the MAPK pathway, the CRBN pathway, and TP53 is significantly increased in drug-refractory MM.• Mutations in CRBN might contribute to IMiD resistance in drug-refractory MM.In this study, targeted sequencing to screen 50 multidrug refractory multiple myeloma (rMM) patients was performed by using the Multiple Myeloma Mutation Panel. Patients were pretreated with both immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs), and 88%, 78%, and 68% were refractory to an IMiD, a PI, or both, respectively. The majority of patients had progressive (82%) or refractory (78%) disease immediately before sampling, with 43% being IMiD refractory and 46% being PI refractory in the most recent line of therapy. Compared with newly diagnosed MM, an increased prevalence of mutations in the Ras pathway genes KRAS, NRAS, and/or BRAF (72%), as well as TP53 (26%), CRBN (12%), and CRBN pathway genes (10%) was observed. Longitudinal analyses performed in 3 patients with CRBN mutations at time of IMiD resistance confirmed that these mutations were undetectable at earlier, IMiD-sensitive time points. Furthermore, the functional introduction of these mutations in MM cells conferred lenalidomide resistance in vitro. These data indicate a differential genetic landscape in rMM associated with drug response. (Blood. 2016;128(9):1226-1233
Because the nature, tempo and trajectories of biological changes that follow the cessation of trawling are unknown for seamounts, it is unclear whether closing them to trawling will lead to a recovery of the fauna and, if so, over what time scales. This paper reports on a 'test of recovery' from repeated towed camera surveys on three seamounts off New Zealand in 2001 and 2006 (5 years apart) and three off Australia in 1997 and 2006 (10 years apart). In each region, seamounts where trawling had ceased were compared to adjacent seamounts where trawling was still active, and to seamounts that had never been trawled. If recovery signals existed, the likelihood of detecting them was high because the seamounts were relatively small and topographically simple, and because quantitative survey methods were employed. Multivariate patterns showed no change in the megafaunal assemblage consistent with recovery over a 5-10 year timeframe on seamounts where trawling had ceased. Results based on the number of species and diversity were equivocal, with some cases of increase and decrease on seamounts where trawling had ceased. A few individual taxa were found at significantly higher abundance in the later surveys where trawling had occurred. We suggest this may have resulted from their resistance to the direct impacts of trawling (two chrysogorgid corals and solitary scleractinians), or from protection in natural refuges inaccessible to trawls (unstalked crinoids, two chrysogorgid corals, gorgonians, and urchins). Alternatively, these taxa may represent the earliest stages of seamount recolonisation. They have potential to be dominant for long periods because the pre-trawling composition of benthic assemblages on seamounts includes taxa that grow slowly and ⁄ or have an association with 'thickets' of a single keystone stony coral (Solenosmilia variabilis) that has generated biogenic habitat over millennia. Resilience of seamount ecosystems dominated by corals is low compared to most other marine systems subject to disturbance by bottom trawling because there are no alternative habitats of the same value for supporting associated species, and because trawling typically removes coral habitat from large areas of individual seamounts. Management to conserve seamount ecosystems needs to account for changing oceanographic conditions (ocean acidification), as well as the direct impacts of human activities such as bottom trawling. Networks of spatial closures that include intact habitats over a range of depths, especially <1500 m, and on clusters and isolated seamounts, may be effective by maintaining the resilience of seamount benthic communities.
Seamounts have often been viewed as specialized habitats that support unique communities; this notion has given rise to several hypotheses about how seamount ecosystems are structured. One, the ‘seamount oasis hypothesis’, predicts that invertebrates are more abundant, speciose and attain higher standing stocks on seamounts compared to other deep‐sea habitats. Because this hypothesis has remained untested for biomass, we ask two questions: (i) Do seamounts support a higher benthic biomass than nearby slopes at corresponding depths? (ii) If they do, which particular taxa and trophic groups drive observed difference in biomass? Analysis of more than 5000 sea‐floor images reveals that the mean biomass of epibenthic megafauna on 20 southwest Pacific seamounts was nearly four times greater than on the adjacent continental slope at comparable depths. This difference is largely attributable to the scleractinian coral Solenosmilia variabilis, whose mean biomass was 29 times higher on seamounts. In terms of trophic guilds, filter‐feeders and filter‐feeders/predators made up a significantly greater proportion of biomass on seamounts, whereas deposit feeders and those with mixed feeding modes dominated at slope habitats. Notwithstanding support for the seamount oasis hypothesis provided by this study, the hypothesis needs to be critically tested for seamounts in less productive regions, for seamounts with a greater proportion of soft substratum, and in other parts of the oceans where scleractinian corals are not prevalent. In this context, testing of seamount paradigms should be embedded in a broader ecological context that includes other margin habitats (e.g. canyons) and community metrics (e.g. diversity and body size).
Three species of epiphytic dinoflagellates-Ostreopsis siamensis, O. lenticularis, and O. ovata have recently been found on both the east and west coasts of the upper North Island, New Zealand. The morphological differences of all three Received 29 August 1998; accepted 27 September 1999 Ostreopsis spp. have been studied with both light and scanning electron microscopes. Detailed studies of the inner face of the thecal wall of Ostreopsis siamensis revealed two types of trichocyst pores: small, simple pores and large multipore structures. The multipore structures apparently have not been previously reported. Surveys conducted during the period from November 1995 to April 1997 showed that all three Ostreopsis spp. were fairly widespread in northern New Zealand, and all three species were found to occur south of 35°S latitude. Cell concentrations of Ostreopsis spp. in summer were substantially higher than in early spring. There was also a clear regional difference in distribution; cell concentrations of the dominant species, O. siamensis, were greatest in Rarawa and Tokerau on the north-east coast. Other less abundant epiphytic species recorded during the same period included Prorocentrum lima, P. compressum, and Coolia monotis. These species were generally more sporadic in distribution than Ostreopsis spp. M98061
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