The Curious Case of Indian Ocean Warming

Supplemental information related to this paper is available at the Journals Online website: http://dx.doi.org/10.1175/JCLI-D-14-00471.s1International audienceRecent studies have pointed out an increased warming over the IndianOcean warmpool (the central-eastern Indian Ocean characterized by sea surface temperatures greater than 28.08C) during the past half-century, although the reasons behind this monotonous warming are still debated. The results here reveal a larger picture—namely, that the western tropical Indian Ocean has been warming for more than a century, at a rate faster than any other region of the tropical oceans, and turns out to be the largest contributor to the overall trend in the global mean sea surface temperature (SST). During 1901–2012, while the Indian Ocean warm pool went through an increase of 0.78C, the western Indian Ocean experienced anomalous warming of 1.28C in summer SSTs. The warming of the generally cool western Indian Ocean against the rest of the tropical warmpool region alters the zonal SST gradients, and has the potential to change the Asian monsoon circulation and rainfall, as well as alter the marine food webs in this biologically productive region. The current study using observations and global coupled ocean–atmosphere model simulations gives compelling evidence that, besides direct contribution from greenhouse warming, the long-term warming trend over the western Indian Ocean during summer is highly dependent on the asymmetry in the El Niño–Southern Oscillation (ENSO) teleconnection, and the positive SST skewness associated with ENSO during recent decades

Investigation of the DNA damage response to SFOM-0046, a new small-molecule drug inducing DNA double-strand breaks

2-Ethylphenyl 4-(3-ethylureido)benzenesulfonate (SFOM-0046) is a novel anticancer agent that arrests cell cycle in S-phase and causes DNA replication stress leading to the phosphorylation of H2AX into -H2AX. First, using the M21, HT29, HT-1080 and HeLa cell lines, we confirmed that S-phase cell cycle arrest and -H2AX foci induction by SFOM-0046 is a general mechanism occurring in diverse cancer cell lines. In addition to γ-H2AX, SFOM-0046 activates preferentially ATR-Chk1 in M21 and HT29 cells while both ATR-Chk1 and ATM-Chk2 pathways are activated in HCT116 cells. Colocalization of SFOM-0046-induced 53BP1 foci with -H2AX foci validates that the DNA damage generated corresponds to double-strand-breaks (DSBs). Consistent with an S-phase arrest, SFOM-0046 treatment induces RAD51 foci formation but not DNA-PKcs foci, confirming that homologous recombination is the major DSB repair pathway targeted by the drug. Furthermore, using isogenic HCT116 p53+/+ and HCT116 p53-/- cells, we showed that p53 plays a key role in the survival mechanism to SFOM-0046. Finally, SFOM-0046 exhibits a dose-dependent antitumor activity on human fibrosarcoma HT-1080 tumours grafted onto chick chorioallantoic membranes without showing embryo toxicity even at high doses. Altogether, our results highlight SFOM0046 as a very promising drug that induces a replication stress response

Effects of mass transfers and heating rates during bark and wood hydrothermal treatment

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Synthesis and biological evaluation of novel N-phenyl ureidobenzenesulfonate derivatives as potential anticancer agents. Part 2. Modulation of the ring B

DNA double strand-breaks (DSBs) are the most deleterious lesions that can affect the genome of living beings and are lethal if not quickly and properly repaired. Recently, we discovered a new family of anticancer agents designated as N-phenyl ureidobenzenesulfonates (PUB-SOs) that are blocking the cells cycle progression in S-phase and inducing DNA DSBs. Previously, we have studied the effect of several modifications on the molecular scaffold of PUB-SOs on their cytocidal properties. However, the effect of the nature and the position of substituents on the aromatic ring B is still poorly studied. In this study, we report the preparation and the biological evaluation of 45 new PUB-SO derivatives substituted by alkyl, alkoxy, halogen and nitro groups at different positions on the aromatic ring B. All PUB-SOs were active in the submicromolar to low micromolar range (0.24–20 μM). The cell cycle progression analysis showed that PUB-SOs substituted at position 2 by alkyl, halogen or nitro groups or substituted at position 4 by a hydroxyl group arrest the cell cycle progression in S-phase. Interestingly, all others PUB-SOs substituted at positions 3 and 4 arrested the cell cycle in G2/M-phase. PUB-SOs arresting the cell cycle progression in S-phase also induced the phosphorylation of H2AX (γH2AX) which is indicating the generation of DNA DSBs. We evidenced that few modifications on the ring B of PUB-SOs scaffold lead to cytocidal derivatives arresting the cell cycle in S-phase and inducing γH2AX and DSBs. In addition, this study shows that these new anticancer agents are promising and could be used as alternative to circumvent some of the biopharmaceutical complications that might be encountered during the development of PUB-SOs

XAB2 promotes Ku eviction from single-ended DNA double-strand breaks independently of the ATM kinase

Replication-associated single-ended DNA double-strand breaks (seDSBs) are repaired predominantly through RAD51-mediated homologous recombination (HR). Removal of the non-homologous end-joining (NHEJ) factor Ku from resected seDSB ends is crucial for HR. The coordinated actions of MRE11-CtIP nuclease activities orchestrated by ATM define one pathway for Ku eviction. Here, we identify the pre-mRNA splicing protein XAB2 as a factor required for resistance to seDSBs induced by the chemotherapeutic alkylator temozolomide. Moreover, we show that XAB2 prevents Ku retention and abortive HR at seDSBs induced by temozolomide and camptothecin, via a pathway that operates in parallel to the ATM-CtIP-MRE11 axis. Although XAB2 depletion preserved RAD51 focus formation, the resulting RAD51-ssDNA associations were unproductive, leading to increased NHEJ engagement in S/G2 and genetic instability. Overexpression of RAD51 or RAD52 rescued the XAB2 defects and XAB2 loss was synthetically lethal with RAD52 inhibition, providing potential perspectives in cancer therapy.publishedVersio

Colossal Aggregations of Giant Alien Freshwater Fish as a Potential Biogeochemical Hotspot

The ubiquity and fascinating nature of animal aggregations are widely recognised. We report here consistent and previously undocumented occurences of aggregations of a giant alien freshwater fish, the Wels catfish (Silurus glanis). Aggregative groups were on average composed of 25 (±10 SD, ranging from 15 to 44) adults with estimated average total biomass of 651 kg (386 – 1132) and biomass density of 23 kg m−2 (14 – 40). Aggregations always occurred within the same location. No foraging, reproductive or anti-predator behaviour were observed during the aggregations. A mass-balance model estimated that these colossal aggregations of an alien species can locally release, through excretion only, up to 70 mg P m−2 h−1 and 400 mg N m−2 h−1, potentially representing the highest biogeochemical hotspots reported in freshwater ecosystems and another unexpected ecological effect of alien species

Tropical Channel NEMO-OASIS-WRF Coupled Simulations at Very High Resolution

International audienc

Satellite and in situ sampling mismatches: Consequences for the estimation of satellite sea surface salinity uncertainties

Validation of satellite sea surface salinity (SSS) products is typically based on comparisons with in-situ measurements at a few meters’ depth, which are mostly done at a single location and time. The difference in term of spatio-temporal resolution between the in-situ near-surface salinity and the two-dimensional satellite SSS results in a sampling mismatch uncertainty. The Climate Change Initiative (CCI) project has merged SSS from three satellite missions. Using an optimal interpolation, weekly and monthly SSS and their uncertainties are estimated at a 50 km spatial resolution over the global ocean. Over the 2016–2018 period, the mean uncertainty on weekly CCI SSS is 0.13, whereas the standard deviation of weekly CCI minus in-situ Argo salinities is 0.24. Using SSS from a high-resolution model reanalysis, we estimate the expected uncertainty due to the CCI versus Argo sampling mismatch. Most of the largest spatial variability of the satellite minus Argo salinity is observed in regions with large estimated sampling mismatch. A quantitative validation is performed by considering the statistical distribution of the CCI minus Argo salinity normalized by the sampling and retrieval uncertainties. This quantity should follow a Gaussian distribution with a standard deviation of 1, if all uncertainty contributions are properly taken into account. We find that (1) the observed differences between Argo and CCI data in dynamical regions (river plumes, fronts) are mainly due to the sampling mismatch; (2) overall, the uncertainties are well estimated in CCI version 3, much improved compared to CCI version 2. There are a few dynamical regions where discrepancies remain and where the satellite SSS, their associated uncertainties and the sampling mismatch estimates should be further validated

Personalized Risk Assessment for Prevention and Early Detection of Breast Cancer: Integration and Implementation (PERSPECTIVE I&I).

Early detection of breast cancer through screening reduces breast cancer mortality. The benefits of screening must also be considered within the context of potential harms (e.g., false positives, overdiagnosis). Furthermore, while breast cancer risk is highly variable within the population, most screening programs use age to determine eligibility. A risk-based approach is expected to improve the benefit-harm ratio of breast cancer screening programs. The PERSPECTIVE I&I (Personalized Risk Assessment for Prevention and Early Detection of Breast Cancer: Integration and Implementation) project seeks to improve personalized risk assessment to allow for a cost-effective, population-based approach to risk-based screening and determine best practices for implementation in Canada. This commentary describes the four inter-related activities that comprise the PERSPECTIVE I&I project. 1: Identification and validation of novel moderate to high-risk susceptibility genes. 2: Improvement, validation, and adaptation of a risk prediction web-tool for the Canadian context. 3: Development and piloting of a socio-ethical framework to support implementation of risk-based breast cancer screening. 4: Economic analysis to optimize the implementation of risk-based screening. Risk-based screening and prevention is expected to benefit all women, empowering them to work with their healthcare provider to make informed decisions about screening and prevention