Continuous monitoring of near-bottom mesoplankton communities in the East China Sea during a series of typhoons

Author Posting. © The Author(s), 2014. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Journal of Oceanography 71 (2015): 115-124, doi:10.1007/s10872-014-0268-y.Typhoons are a common feature of summer and autumn months in the East China Sea. These events often promote phytoplankton growth in surface waters as a result of upwelling and transport of nutrients, but their effects on sub-surface waters and ecosystems are little known. Furthermore, biological studies tend to focus on phytoplankton (using chlorophyll a assays), rather than on heterotrophic zooplankton. Indeed, measurements of biological and physicochemical changes induced by the storms are difficult to perform and risky, using standard shipboard sampling techniques. Using a camera mounted on an underwater, cabled observatory system in shallow coastal waters of Okinawa, Japan, we collected the first continuous, in-situ observations of the near-bottom, mesoplankton community during a series of typhoons. An increase in diatoms and radiolarians was found during all typhoons, whereas the response of larger zooplankton groups was variable between typhoons. A bloom of Trichodesmium cyanobacteria and diatoms was seen after a series of typhoons, while the total chlorophyll a concentration remained nearly unchanged at the sampling location. These findings shed new light on short-term responses of sub-surface ecosystems during typhoons.This work was funded by the Special Framework budget, Okinawa Promotion for Education and Research Project awarded to OIST for the 2012 fiscal year.2015-12-3

Molecular dissection of the mechanism by which EWS/FLI expression compromises actin cytoskeletal integrity and cell adhesion in Ewing sarcoma.

Ewing sarcoma is the second-most-common bone cancer in children. Driven by an oncogenic chromosomal translocation that results in the expression of an aberrant transcription factor, EWS/FLI, the disease is typically aggressive and micrometastatic upon presentation. Silencing of EWS/FLI in patient-derived tumor cells results in the altered expression of hundreds to thousands of genes and is accompanied by dramatic morphological changes in cytoarchitecture and adhesion. Genes encoding focal adhesion, extracellular matrix, and actin regulatory proteins are dominant targets of EWS/FLI-mediated transcriptional repression. Reexpression of genes encoding just two of these proteins, zyxin and α5 integrin, is sufficient to restore cell adhesion and actin cytoskeletal integrity comparable to what is observed when the EWS/FLI oncogene expression is compromised. Using an orthotopic xenograft model, we show that EWS/FLI-induced repression of α5 integrin and zyxin expression promotes tumor progression by supporting anchorage-independent cell growth. This selective advantage is paired with a tradeoff in which metastatic lung colonization is compromised

Intra-host Symbiont Diversity and Extended Symbiont Maintenance in Photosymbiotic Acantharea (Clade F)

Photosymbiotic protists contribute to surface primary production in low-nutrient, open-ocean ecosystems and constitute model systems for studying plastid acquisition via endosymbiosis. Little is known, however, about host-symbiont dynamics in these important relationships, and whether these symbioses are mutualistic is debated. In this study, we applied single-cell sequencing methods and advanced fluorescent microscopy to investigate host-symbiont dynamics in clade F acantharians, a major group of photosymbiotic protists in oligotrophic subtropical gyres. We amplified the 18S rRNA gene from single acantharian hosts and environmental samples to assess intra-host symbiont diversity and to determine whether intra-host symbiont community composition directly reflects the available symbiont community in the surrounding environment. Our results demonstrate that clade F acantharians simultaneously host multiple species from the haptophyte genera Phaeocystis and Chrysochromulina. The intra-host symbiont community composition was distinct from the external free-living symbiont community, suggesting that these acantharians maintain symbionts for extended periods of time. After selectively staining digestive organelles, fluorescent confocal microscopy showed that symbionts were not being systematically digested, which is consistent with extended symbiont maintenance within hosts. Extended maintenance within hosts may benefit symbionts through protection from grazing or viral lysis, and therefore could enhance dispersal, provided that symbionts retain reproductive capacity. The evidence for extended symbiont maintenance therefore allows that Phaeocystis could glean some advantage from the symbiosis and leaves the possibility of mutualism

Genome-wide analyses identify SCN5A as a susceptibility locus for premature atrial contraction frequency.

Premature atrial contractions (PACs) are frequently observed on electrocardiograms and are associated with increased risks of atrial fibrillation (AF), stroke, and mortality. In this study, we aimed to identify genetic susceptibility loci for PAC frequency. We performed a genome-wide association study meta-analysis with PAC frequency obtained from ambulatory cardiac monitoring in 4,831 individuals of European ancestry. We identified a genome-wide significant locus at the SCN5A gene. The lead variant, rs7373862, located in an intron of SCN5A, was associated with an increase of 0.12 [95% CI 0.08-0.16] standard deviations of the normalized PAC frequency per risk allele. Among genetic variants previously associated with AF, there was a significant enrichment in concordance of effect for PAC frequency (n = 73/106, p = 5.1 × 10-5). However, several AF risk loci, including PITX2, were not associated with PAC frequency. These findings suggest the existence of both shared and distinct genetic mechanisms for PAC frequency and AF

Selective serotonin reuptake inhibitor antidepressant use in first trimester pregnancy and risk of specific congenital anomalies: A European register-based study

Evidence of an association between early pregnancy exposure to selective serotonin reuptake inhibitors (SSRI) and congenital heart defects (CHD) has contributed to recommendations to weigh benefits and risks carefully. The objective of this study was to determine the specificity of association between first trimester exposure to SSRIs and specific CHD and other congenital anomalies (CA) associated with SSRI exposure in the literature (signals). A population-based case-malformed control study was conducted in 12 EUROCAT CA registries covering 2.1 million births 1995-2009 including livebirths, fetal deaths from 20 weeks gestation and terminations of pregnancy for fetal anomaly. Babies/fetuses with specific CHD (n = 12,876) and non-CHD signal CA (n = 13,024), were compared with malformed controls whose diagnosed CA have not been associated with SSRI in the literature (n = 17,083). SSRI exposure in first trimester pregnancy was associated with CHD overall (OR adjusted for registry 1.41, 95% CI 1.07-1.86, fluoxetine adjOR 1.43 95% CI 0.85-2.40, paroxetine adjOR 1.53, 95% CI 0.91-2.58) and with severe CHD (adjOR 1.56, 95% CI 1.02-2.39), particularly Tetralogy of Fallot (adjOR 3.16, 95% CI 1.52-6.58) and Ebstein's anomaly (adjOR 8.23, 95% CI 2.92-23.16). Significant associations with SSRI exposure were also found for ano-rectal atresia/stenosis (adjOR 2.46, 95% CI 1.06-5.68), gastroschisis (adjOR 2.42, 95% CI 1.10-5.29), renal dysplasia (adjOR 3.01, 95% CI 1.61-5.61), and clubfoot (adjOR 2.41, 95% CI 1.59-3.65). These data support a teratogenic effect of SSRIs specific to certain anomalies, but cannot exclude confounding by indication or associated factors

Measurement of the Splitting Function in &ITpp &ITand Pb-Pb Collisions at root&ITsNN&IT=5.02 TeV

Data from heavy ion collisions suggest that the evolution of a parton shower is modified by interactions with the color charges in the dense partonic medium created in these collisions, but it is not known where in the shower evolution the modifications occur. The momentum ratio of the two leading partons, resolved as subjets, provides information about the parton shower evolution. This substructure observable, known as the splitting function, reflects the process of a parton splitting into two other partons and has been measured for jets with transverse momentum between 140 and 500 GeV, in pp and PbPb collisions at a center-of-mass energy of 5.02 TeV per nucleon pair. In central PbPb collisions, the splitting function indicates a more unbalanced momentum ratio, compared to peripheral PbPb and pp collisions.. The measurements are compared to various predictions from event generators and analytical calculations.Peer reviewe

Measurement of nuclear modification factors of gamma(1S)), gamma(2S), and gamma(3S) mesons in PbPb collisions at root s(NN)=5.02 TeV

The cross sections for ϒ(1S), ϒ(2S), and ϒ(3S) production in lead-lead (PbPb) and proton-proton (pp) collisions at √sNN = 5.02 TeV have been measured using the CMS detector at the LHC. The nuclear modification factors, RAA, derived from the PbPb-to-pp ratio of yields for each state, are studied as functions of meson rapidity and transverse momentum, as well as PbPb collision centrality. The yields of all three states are found to be significantly suppressed, and compatible with a sequential ordering of the suppression, RAA(ϒ(1S)) > RAA(ϒ(2S)) > RAA(ϒ(3S)). The suppression of ϒ(1S) is larger than that seen at √sNN = 2.76 TeV, although the two are compatible within uncertainties. The upper limit on the RAA of ϒ(3S) integrated over pT, rapidity and centrality is 0.096 at 95% confidence level, which is the strongest suppression observed for a quarkonium state in heavy ion collisions to date. © 2019 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Funded by SCOAP3.Peer reviewe

Electroweak production of two jets in association with a Z boson in proton-proton collisions root s =13 TeV

A measurement of the electroweak (EW) production of two jets in association with a Z boson in proton-proton collisions at root s = 13 TeV is presented, based on data recorded in 2016 by the CMS experiment at the LHC corresponding to an integrated luminosity of 35.9 fb(-1). The measurement is performed in the lljj final state with l including electrons and muons, and the jets j corresponding to the quarks produced in the hard interaction. The measured cross section in a kinematic region defined by invariant masses m(ll) > 50 GeV, m(jj) > 120 GeV, and transverse momenta P-Tj > 25 GeV is sigma(EW) (lljj) = 534 +/- 20 (stat) fb (syst) fb, in agreement with leading-order standard model predictions. The final state is also used to perform a search for anomalous trilinear gauge couplings. No evidence is found and limits on anomalous trilinear gauge couplings associated with dimension-six operators are given in the framework of an effective field theory. The corresponding 95% confidence level intervals are -2.6 <cwww/Lambda(2) <2.6 TeV-2 and -8.4 <cw/Lambda(2) <10.1 TeV-2. The additional jet activity of events in a signal-enriched region is also studied, and the measurements are in agreement with predictions.Peer reviewe

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Inclusive Search for a Highly Boosted Higgs Boson Decaying to a Bottom Quark-Antiquark Pair

© 2018 CERN. An inclusive search for the standard model Higgs boson (H) produced with large transverse momentum (pT) and decaying to a bottom quark-antiquark pair (bb) is performed using a data set of pp collisions at s=13 TeV collected with the CMS experiment at the LHC. The data sample corresponds to an integrated luminosity of 35.9 fb-1. A highly Lorentz-boosted Higgs boson decaying to bb is reconstructed as a single, large radius jet, and it is identified using jet substructure and dedicated b tagging techniques. The method is validated with Z→bb decays. The Z→bb process is observed for the first time in the single-jet topology with a local significance of 5.1 standard deviations (5.8 expected). For a Higgs boson mass of 125 GeV, an excess of events above the expected background is observed (expected) with a local significance of 1.5 (0.7) standard deviations. The measured cross section times branching fraction for production via gluon fusion of H→bb with reconstructed pT > 450 GeV and in the pseudorapidity range -2.5 < η < 2.5 is 74±48(stat)-10+17(syst) fb, which is consistent within uncertainties with the standard model prediction