Trade-off between transcriptome plasticity and genome evolution in cephalopods

Author Posting. © The Author(s), 2017. This is the author's version of the work. It is posted here by permission of Cell Press for personal use, not for redistribution. The definitive version was published in Cell 169 (2017): 191-202, doi:10.1016/j.cell.2017.03.025.RNA editing, a post-transcriptional process, allows the diversification of proteomes beyond the genomic blueprint; however it is infrequently used among animals. Recent reports suggesting increased levels of RNA editing in squids thus raise the question of their nature and effects in these organisms. We here show that RNA editing is particularly common in behaviorally sophisticated coleoid cephalopods, with tens of thousands of evolutionarily conserved sites. Editing is enriched in the nervous system affecting molecules pertinent for excitability and neuronal morphology. The genomic sequence flanking editing sites is highly conserved, suggesting that the process confers a selective advantage. Due to the large number of sites, the surrounding conservation greatly reduces the number of mutations and genomic polymorphisms in protein coding regions. This trade-off between genome evolution and transcriptome plasticity highlights the importance of RNA recoding as a strategy for diversifying proteins, particularly those associated with neural function.NLB was supported by a post-doctoral scholarship from the Center for Nanoscience and Nanotechnology, Tel-Aviv University. The research of RU is supported by the Israel Science Foundation (772/13). The research of EYL was supported by the European Research Council (311257) and the Israel Science Foundation (1380/14). The research of JJCR was supported by the National Institutes of Health [1R0111223855, 1R01NS64259], the National Science Foundation (HRD- 1137725), and the Frank R. Lillie and Laura and Arthur Colwin Research Fellowships from the Marine Biological Laboratory in Woods Hole. The work of JJCR and EE was supported by grant No 094/2013 from the United States-Israel Binational Science Foundation (BSF).2018-04-0

Species-specific imprint of the phytoplankton assemblage on carbon isotopes and the carbon cycle in Lake Kinneret, Israel

Lakes undergoing major changes in phytoplankton species composition are likely to undergo changes in carbon (C) cycling. In this study we used stable C isotopes to understand how the C cycle of Lake Kinneret, Israel, responded to documented changes in phytoplankton species composition. We compared the annual δ13C cycle of particulate organic matter from surface water (POMsurf) between (1) years in which a massive spring bloom of the dinoflagellate Peridinium gatunense occurred (“Peridinium years”) and (2) years in which it did not (“non-Peridinium years”). In non-Peridinium years, the spring δ13C–POMsurf maxima were lower by 3.3‰. These spring δ13C maxima were even lower in POM sinking into sediment traps and in zooplankton (lower by 6.8 and 6.9‰, respectively). These differences in the isotopic composition of the major organic C components in the lake represent ecosystem-level responses to the presence or absence of the key blooming species P. gatunense . When present, the intensive, almost monospecific bloom lowers the concentrations of CO2(aq), causing a reduction in the isotopic fractionation of the algae (higher δ13C of POMsurf) and massive precipitation of calcium carbonate (CaCO3). In “non-Peridinium years, the phytoplankton cannot deplete CO2(aq) to similar levels; the algae maintain higher isotopic fractionation, leading to lower δ13C maxima. These changes are reflected higher up in the food web (zooplankton) and in sedimenting organic matter. The consequences for the ecosystem in non-Peridinium years are lower export of both organic and inorganic C

Extended Y chromosome haplotypes resolve multiple and unique lineages of the Jewish priesthood

It has been known for over a decade that a majority of men who self report as members of the Jewish priesthood (Cohanim) carry a characteristic Y chromosome haplotype termed the Cohen Modal Haplotype (CMH). The CMH has since been used to trace putative Jewish ancestral origins of various populations. However, the limited number of binary and STR Y chromosome markers used previously did not provide the phylogenetic resolution needed to infer the number of independent paternal lineages that are encompassed within the Cohanim or their coalescence times. Accordingly, we have genotyped 75 binary markers and 12 Y-STRs in a sample of 215 Cohanim from diverse Jewish communities, 1,575 Jewish men from across the range of the Jewish Diaspora, and 2,099 non-Jewish men from the Near East, Europe, Central Asia, and India. While Cohanim from diverse backgrounds carry a total of 21 Y chromosome haplogroups, 5 haplogroups account for 79.5% of Cohanim Y chromosomes. The most frequent Cohanim lineage (46.1%) is marked by the recently reported P58 T->C mutation, which is prevalent in the Near East. Based on genotypes at 12 Y-STRs, we identify an extended CMH on the J-P58* background that predominates in both Ashkenazi and non-Ashkenazi Cohanim and is remarkably absent in non-Jews. The estimated divergence time of this lineage based on 17 STRs is 3,190 ± 1,090 years. Notably, the second most frequent Cohanim lineage (J-M410*, 14.4%) contains an extended modal haplotype that is also limited to Ashkenazi and non-Ashkenazi Cohanim and is estimated to be 4.2 ± 1.3 ky old. These results support the hypothesis of a common origin of the CMH in the Near East well before the dispersion of the Jewish people into separate communities, and indicate that the majority of contemporary Jewish priests descend from a limited number of paternal lineages

A clinical evaluation of an ex vivo organ culture system to predict patient response to cancer therapy

IntroductionEx vivo organ cultures (EVOC) were recently optimized to sustain cancer tissue for 5 days with its complete microenvironment. We examined the ability of an EVOC platform to predict patient response to cancer therapy.MethodsA multicenter, prospective, single-arm observational trial. Samples were obtained from patients with newly diagnosed bladder cancer who underwent transurethral resection of bladder tumor and from core needle biopsies of patients with metastatic cancer. The tumors were cut into 250 μM slices and cultured within 24 h, then incubated for 96 h with vehicle or intended to treat drug. The cultures were then fixed and stained to analyze their morphology and cell viability. Each EVOC was given a score based on cell viability, level of damage, and Ki67 proliferation, and the scores were correlated with the patients’ clinical response assessed by pathology or Response Evaluation Criteria in Solid Tumors (RECIST).ResultsThe cancer tissue and microenvironment, including endothelial and immune cells, were preserved at high viability with continued cell division for 5 days, demonstrating active cell signaling dynamics. A total of 34 cancer samples were tested by the platform and were correlated with clinical results. A higher EVOC score was correlated with better clinical response. The EVOC system showed a predictive specificity of 77.7% (7/9, 95% CI 0.4–0.97) and a sensitivity of 96% (24/25, 95% CI 0.80–0.99).ConclusionEVOC cultured for 5 days showed high sensitivity and specificity for predicting clinical response to therapy among patients with muscle-invasive bladder cancer and other solid tumors

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements