Synthetic biology: ethical ramifications 2009

During 2007 and 2008 synthetic biology moved from the manifesto stage to research programs. As of 2009, synthetic biology is ramifying; to ramify means to produce differentiated trajectories from previous determinations. From its inception, most of the players in synthetic biology agreed on the need for (a) rationalized design and construction of new biological parts, devices, and systems as well as (b) the re-design of natural biological systems for specified purposes, and that (c) the versatility of designed biological systems makes them suitable to address such challenges as renewable energy, the production of inexpensive drugs, and environmental remediation, as well as providing a catalyst for further growth of biotechnology. What is understood by these goals, however, is diverse. Those assorted understandings are currently contributing to different ramifications of synthetic biology. The Berkeley Human Practices Lab, led by Paul Rabinow, is currently devoting its efforts to documenting and analyzing these ramifications as they emerge

The importance of Antarctic krill in biogeochemical cycles

Antarctic krill (Euphausia superba) are swarming, oceanic crustaceans, up to two inches long, and best known as prey for whales and penguins – but they have another important role. With their large size, high biomass and daily vertical migrations they transport and transform essential nutrients, stimulate primary productivity and influence the carbon sink. Antarctic krill are also fished by the Southern Ocean’s largest fishery. Yet how krill fishing impacts nutrient fertilisation and the carbon sink in the Southern Ocean is poorly understood. Our synthesis shows fishery management should consider the influential biogeochemical role of both adult and larval Antarctic krill

Identification of the α\u3csub\u3e1C\u3c/sub\u3e-Adrenoceptor in Rabbit Arteries and the Human Saphenous Vein Using the Polymerase Chain Reaction

The expression of the α1C-adrenoceptor subtype in human and rabbit blood vessels has been analyzed using the reverse transcriptase/polymerase chain reaction technique (RT/PCR). The 20 bp primers employed were designed from the bovine α1C-adrenoceptor and flank a least conserved region - the putative third cytoplasmic loop. RT/PCR products generated from rabbit and human brain mRNA both had 93% homology to the bovine α1C-adrenoceptor and were used as species and subtype specific probes in Southern blot analysis of vascular RT/PCR products. Poly A+ RNA was purified from the human saphenous vein and rabbit aorta, renal, pulmonary and central ear arteries and amplified by RT/PCR. Size analysis by agarose gel electrophoresis, together with Southern hybridization of the resulting cDNA products confirm the expression of the α1C-adrenoceptor in these vessels

Feeding ecology of myctophid fishes in the northern Scotia Sea

The diets of 9 species of myctophid fishes, Electrona carlsbergi, E. antarctica, Gymnoscopelus fraseri, G. nicholsi, G. braueri, Protomyctophum bolini, P. choriodon, Krefftichthys anderssoni and Nannobrachium achirus, were investigated during austral autumn in the northern Scotia Sea. Based on the percent index of relative importance (%IRI), the data suggest dietary specialisation in some species, which may permit resource partitioning. Hierarchical agglomerative cluster analysis of Bray-Curtis similarity (60% threshold) separated the myctophid community into distinct feeding guilds. One group (G. braueri and E. antarctica) fed principally on Themisto gaudichaudii, another (P. choriodon and G. fraseri) primarily on copepods (Metridia spp. and Rhincalanus gigas), and a third group (G. nicholsi and P. bolini) consumed copepods and euphausids (mostly Metridia spp. and Euphausia frigida). The diets of E. carlsbergi and K. anderssoni differed from the other species, with E. carlsbergi being the only species that consumed salps. There was a general switch in diet from copepods to euphausiids and amphipods as the myctophid predator size increased. Dietary specialisation is likely the result of a combination of predator size, gape size, filtering capacity of the gill rakers and the vertical distribution of predators and prey. Antarctic krill were only consumed by the larger myctophids, which represented a numerically minor part of the myctophid community, supporting the concept that myctophids can provide a krill-independent link between secondary production and higher trophic levels. However, the northern Scotia Sea is dominated by adult krill, which are only suitable as prey for larger fish. In the northern Scotia Sea, myctophid predation had a very small impact on copepod production but a higher impact on macrozooplankton, with a best-estimate of 4% of the daily production of Themisto gaudichaudii and 6% of that of Euphausia superba being consumed

Clinical impact of ibrutinib plus R-CHOP in untreated DLBCL co-expressing BCL2 and MYC in the phase 3 PHOENIX trial

Diffuse large B-cell lymphoma (DLBCL), with high coexpression of BCL2 and MYC proteins (DE lymphoma), is considered an adverse prognostic indicator associated mostly with non-germinal center B-cell–like (non-GCB) DLBCL. BCL2/MYC overexpression is associated with B-cell receptor (BCR) pathway activation; consequently, DE DLBCL may be sensitive to BCR inhibitors. We assessed whether high BCL2/MYC coexpression by RNA sequencing could identify a patient subset responsive to ibrutinib using baseline biopsies from the PHOENIX trial, which evaluated the addition of ibrutinib to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in untreated non-GCB DLBCL. BCL2/MYC RNA expression was correlated with lower event-free survival (EFS) and overall survival (OS) using Kaplan–Meier estimates with Cox regression and log-rank testing. In total, 234 of 766 (30.5%) patients had high BCL2/MYC coexpression: 123 of 386 (31.9%) received ibrutinib plus R-CHOP and 111 of 380 (29.2%) received R-CHOP. EFS was superior with ibrutinib plus R-CHOP compared with R-CHOP alone in patients with high BCL2/MYC coexpression, but there was no significant impact on OS. However, EFS and OS showed clinically meaningful improvement with ibrutinib plus R-CHOP over R-CHOP alone in patients aged &lt;60 years with high BCL2/MYC coexpression. We observed a significant association between high BCL2/MYC coexpression and activated B-cell-like and MYD88 L265P/CD79B-mutated subtypes of DLBCL. Consequently, high BCL2/MYC coexpression identified a subset of non-GCB DLBCL that may be preferentially responsive to ibrutinib and warrants further investigation. This trial was registered at www.clinicaltrials.gov as #NCT01855750. </p

The trophodynamics of Southern Ocean Electrona (Myctophidae) in the Scotia Sea

The Scotia Sea is one of the most productive regions of the Southern Ocean, but its surface waters are experiencing a rapid increase in temperature, which may be changing the behaviour and distribution of many myctophids and their prey species. Electrona antarctica and Electrona carlsbergi are two of the most abundant myctophids in the region, but their ecology is poorly understood and their response to ongoing environmental change is difficult to determine. This study investigated spatial and temporal patterns in their abundance, population structure and diets using mid-water trawl nets deployed across the Scotia Sea during spring, summer and autumn. E. antarctica was the most numerically abundant species (0.09–0.21 ind. 1,000 m−3), with greatest concentrations occurring in the sea-ice sectors. E. carlsbergi occurred in more northern regions, comprising densities of 0.02–0.11 ind. 1,000 m−3. There was evidence of seasonal variation in depth distribution, size-related sexual dimorphism and size-specific vertical stratification for both species. Latitudinal trends in sex ratio and female body size were apparent for E. antarctica. Its diet varied between regions, seasons and size classes, but overall, Euphausia superba, Metridia spp. and Themisto gaudichaudii were the dominant prey items. E. carlsbergi appeared not to recruit in the Scotia Sea. Its diet was dominated by copepods, particularly Rhincalanus gigas and Metridia spp., but regional, seasonal and ontogenetic variations were evident. This study contributes to our understanding of how mid-water food webs are structured in the Southern Ocean and their sensitivity to ongoing environmental change

Comparison of immunohistochemistry and gene expression profiling subtyping for diffuse large B-cell lymphoma in the phase III clinical trial of R-CHOP ± ibrutinib

We assessed the concordance between immunohistochemistry (IHC) and gene expression profiling (GEP) for determining diffuse large B-cell lymphoma (DLBCL) cell of origin (COO) in the phase III PHOENIX trial of rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) with or without ibrutinib. Among 910 of 1114 screened patients with non-germinal centre B cell-like (non-GCB) DLBCL by IHC, the concordance with GEP for non-GCB calls was 82·7%, with 691 (75·9%) identified as activated B cell-like (ABC), and 62 (6·8%) as unclassified. Among 746 of 837 enrolled patients with verified non-GCB DLBCL by IHC, the concordance with GEP was 82·8%, with 567 (76·0%) identified as ABC and 51 (6·8%) unclassified; survival outcomes were similar regardless of COO or treatment, whereas among patients with ABC DLBCL aged &lt;60 years, the overall and event-free survival were substantially better with ibrutinib versus placebo plus R-CHOP [hazard ratio (HR) 0·365, 95% confidence interval (CI) 0·147-0·909, P = 0·0305; HR 0·561, 95% CI 0·326-0·967, P = 0·0348, respectively]. IHC and GEP showed high concordance and consistent survival outcomes among tested patients, indicating centralised IHC may be used to enrich populations for response to ibrutinib plus R-CHOP.</p