The MASSE Project: Applications of Biotechnology for Planetary Exploration

Automated life-detection experiments for solar system exploration have been previously. proposed and used onboard the. Viking, Mars lander,s, although. with ambiguous results. The recent advances in biotechnology such as biosensors, protein microarrays, and microfluidics alongside increased. knowledge in biomarker science have led to vastly improved sophistication and sensitivity for a new approach in life detection. The MASSE project has taken the challenge of integrating all of this knowledge into a new generation of interplanetary flight instrumentation for the main purpose.ot combining several mutually. confirming tests for life, organic/microbial contamination, prebiotic and abiotic chemicals into a small low powered instrument. Although the primary goal is interplanetary exploration, several terrestrial applications have become apparent specifically in point-of-care medical technology, bio-warfare, environmental sensing and microbial monitoring of manned space-flight vehicles

Canvass: a crowd-sourced, natural-product screening library for exploring biological space

NCATS thanks Dingyin Tao for assistance with compound characterization. This research was supported by the Intramural Research Program of the National Center for Advancing Translational Sciences, National Institutes of Health (NIH). R.B.A. acknowledges support from NSF (CHE-1665145) and NIH (GM126221). M.K.B. acknowledges support from NIH (5R01GM110131). N.Z.B. thanks support from NIGMS, NIH (R01GM114061). J.K.C. acknowledges support from NSF (CHE-1665331). J.C. acknowledges support from the Fogarty International Center, NIH (TW009872). P.A.C. acknowledges support from the National Cancer Institute (NCI), NIH (R01 CA158275), and the NIH/National Institute of Aging (P01 AG012411). N.K.G. acknowledges support from NSF (CHE-1464898). B.C.G. thanks the support of NSF (RUI: 213569), the Camille and Henry Dreyfus Foundation, and the Arnold and Mabel Beckman Foundation. C.C.H. thanks the start-up funds from the Scripps Institution of Oceanography for support. J.N.J. acknowledges support from NIH (GM 063557, GM 084333). A.D.K. thanks the support from NCI, NIH (P01CA125066). D.G.I.K. acknowledges support from the National Center for Complementary and Integrative Health (1 R01 AT008088) and the Fogarty International Center, NIH (U01 TW00313), and gratefully acknowledges courtesies extended by the Government of Madagascar (Ministere des Eaux et Forets). O.K. thanks NIH (R01GM071779) for financial support. T.J.M. acknowledges support from NIH (GM116952). S.M. acknowledges support from NIH (DA045884-01, DA046487-01, AA026949-01), the Office of the Assistant Secretary of Defense for Health Affairs through the Peer Reviewed Medical Research Program (W81XWH-17-1-0256), and NCI, NIH, through a Cancer Center Support Grant (P30 CA008748). K.N.M. thanks the California Department of Food and Agriculture Pierce's Disease and Glassy Winged Sharpshooter Board for support. B.T.M. thanks Michael Mullowney for his contribution in the isolation, elucidation, and submission of the compounds in this work. P.N. acknowledges support from NIH (R01 GM111476). L.E.O. acknowledges support from NIH (R01-HL25854, R01-GM30859, R0-1-NS-12389). L.E.B., J.K.S., and J.A.P. thank the NIH (R35 GM-118173, R24 GM-111625) for research support. F.R. thanks the American Lebanese Syrian Associated Charities (ALSAC) for financial support. I.S. thanks the University of Oklahoma Startup funds for support. J.T.S. acknowledges support from ACS PRF (53767-ND1) and NSF (CHE-1414298), and thanks Drs. Kellan N. Lamb and Michael J. Di Maso for their synthetic contribution. B.S. acknowledges support from NIH (CA78747, CA106150, GM114353, GM115575). W.S. acknowledges support from NIGMS, NIH (R15GM116032, P30 GM103450), and thanks the University of Arkansas for startup funds and the Arkansas Biosciences Institute (ABI) for seed money. C.R.J.S. acknowledges support from NIH (R01GM121656). D.S.T. thanks the support of NIH (T32 CA062948-Gudas) and PhRMA Foundation to A.L.V., NIH (P41 GM076267) to D.S.T., and CCSG NIH (P30 CA008748) to C.B. Thompson. R.E.T. acknowledges support from NIGMS, NIH (GM129465). R.J.T. thanks the American Cancer Society (RSG-12-253-01-CDD) and NSF (CHE1361173) for support. D.A.V. thanks the Camille and Henry Dreyfus Foundation, the National Science Foundation (CHE-0353662, CHE-1005253, and CHE-1725142), the Beckman Foundation, the Sherman Fairchild Foundation, the John Stauffer Charitable Trust, and the Christian Scholars Foundation for support. J.W. acknowledges support from the American Cancer Society through the Research Scholar Grant (RSG-13-011-01-CDD). W.M.W.acknowledges support from NIGMS, NIH (GM119426), and NSF (CHE1755698). A.Z. acknowledges support from NSF (CHE-1463819). (Intramural Research Program of the National Center for Advancing Translational Sciences, National Institutes of Health (NIH); CHE-1665145 - NSF; CHE-1665331 - NSF; CHE-1464898 - NSF; RUI: 213569 - NSF; CHE-1414298 - NSF; CHE1361173 - NSF; CHE1755698 - NSF; CHE-1463819 - NSF; GM126221 - NIH; 5R01GM110131 - NIH; GM 063557 - NIH; GM 084333 - NIH; R01GM071779 - NIH; GM116952 - NIH; DA045884-01 - NIH; DA046487-01 - NIH; AA026949-01 - NIH; R01 GM111476 - NIH; R01-HL25854 - NIH; R01-GM30859 - NIH; R0-1-NS-12389 - NIH; R35 GM-118173 - NIH; R24 GM-111625 - NIH; CA78747 - NIH; CA106150 - NIH; GM114353 - NIH; GM115575 - NIH; R01GM121656 - NIH; T32 CA062948-Gudas - NIH; P41 GM076267 - NIH; R01GM114061 - NIGMS, NIH; R15GM116032 - NIGMS, NIH; P30 GM103450 - NIGMS, NIH; GM129465 - NIGMS, NIH; GM119426 - NIGMS, NIH; TW009872 - Fogarty International Center, NIH; U01 TW00313 - Fogarty International Center, NIH; R01 CA158275 - National Cancer Institute (NCI), NIH; P01 AG012411 - NIH/National Institute of Aging; Camille and Henry Dreyfus Foundation; Arnold and Mabel Beckman Foundation; Scripps Institution of Oceanography; P01CA125066 - NCI, NIH; 1 R01 AT008088 - National Center for Complementary and Integrative Health; W81XWH-17-1-0256 - Office of the Assistant Secretary of Defense for Health Affairs through the Peer Reviewed Medical Research Program; P30 CA008748 - NCI, NIH, through a Cancer Center Support Grant; California Department of Food and Agriculture Pierce's Disease and Glassy Winged Sharpshooter Board; American Lebanese Syrian Associated Charities (ALSAC); University of Oklahoma Startup funds; 53767-ND1 - ACS PRF; PhRMA Foundation; P30 CA008748 - CCSG NIH; RSG-12-253-01-CDD - American Cancer Society; RSG-13-011-01-CDD - American Cancer Society; CHE-0353662 - National Science Foundation; CHE-1005253 - National Science Foundation; CHE-1725142 - National Science Foundation; Beckman Foundation; Sherman Fairchild Foundation; John Stauffer Charitable Trust; Christian Scholars Foundation)Published versionSupporting documentatio

Low-Frequency Spectral Energy Distributions of Radio Pulsars Detected with the Murchison Widefield Array

We present low-frequency spectral energy distributions of 60 known radio pulsars observed with the Murchison Widefield Array telescope. We searched the GaLactic and Extragalactic All-sky Murchison Widefield Array survey images for 200-MHz continuum radio emission at the position of all pulsars in the Australia Telescope National Facility (ATNF) pulsar catalogue. For the 60 confirmed detections, we have measured flux densities in 20 × 8 MHz bands between 72 and 231 MHz. We compare our results to existing measurements and show that the Murchison Widefield Array flux densities are in good agreement

Prioritization of knowledge-needs to achieve best practices for bottom trawling in relation to seabed habitats

Management and technical approaches that achieve a sustainable level of fish production while at the same time minimizing or limiting the wider ecological effects caused through fishing gear contact with the seabed might be considered to be ‘best practice’. To identify future knowledge-needs that would help to support a transition towards the adoption of best practices for trawling, a prioritization exercise was undertaken with a group of 39 practitioners from the seafood industry and management, and 13 research scientists who have an active research interest in bottom-trawl and dredge fisheries. A list of 108 knowledge-needs related to trawl and dredge fisheries was developed in conjunction with an ‘expert task force’. The long list was further refined through a three stage process of voting and scoring, including discussions of each knowledge-need. The top 25 knowledge-needs are presented, as scored separately by practitioners and scientists. There was considerable consistency in the priorities identified by these two groups. The top priority knowledge-need to improve current understanding on the distribution and extent of different habitat types also reinforced the concomitant need for the provision and access to data on the spatial and temporal distribution of all forms of towed bottom-fishing activities. Many of the other top 25 knowledge-needs concerned the evaluation of different management approaches or implementation of different fishing practices, particularly those that explore trade-offs between effects of bottom trawling on biodiversity and ecosystem services and the benefits of fish production as food.Fil: Kaiser, Michel J.. Bangor University; Reino UnidoFil: Hilborn, Ray. University of Washington; Estados UnidosFil: Jennings, Simon. Fisheries and Aquaculture Science; Reino UnidoFil: Amaroso, Ricky. University of Washington; Estados UnidosFil: Andersen, Michael. Danish Fishermen; DinamarcaFil: Balliet, Kris. Sustainable Fisheries Partnership; Estados UnidosFil: Barratt, Eric. Sanford Limited; Nueva ZelandaFil: Bergstad, Odd A. Institute of Marine Research; NoruegaFil: Bishop, Stephen. Independent Fisheries Ltd; Nueva ZelandaFil: Bostrom, Jodi L. Marine Stewardship Council; Reino UnidoFil: Boyd, Catherine. Clearwater Seafoods; CanadáFil: Bruce, Eduardo A. Friosur S.A.; ChileFil: Burden, Merrick. Marine Conservation Alliance; Estados UnidosFil: Carey, Chris. Independent Fisheries Ltd.; Estados UnidosFil: Clermont, Jason. New England Aquarium; Estados UnidosFil: Collie, Jeremy S. University of Rhode Island,; Estados UnidosFil: Delahunty, Antony. National Federation of Fishermen; Reino UnidoFil: Dixon, Jacqui. Pacific Andes International Holdings Limited; ChinaFil: Eayrs, Steve. Gulf of Maine Research Institute; Estados UnidosFil: Edwards, Nigel. Seachill Ltd.; Reino UnidoFil: Fujita, Rod. Environmental Defense Fund; Reino UnidoFil: Gauvin, John. Alaska Seafood Cooperative; Estados UnidosFil: Gleason, Mary. The Nature Conservancy; Estados UnidosFil: Harris, Brad. Alaska Pacific University; Estados UnidosFil: He, Pingguo. University of Massachusetts Dartmouth; Estados UnidosFil: Hiddink, Jan G. Bangor University; Reino UnidoFil: Hughes, Kathryn M. Bangor University; Reino UnidoFil: Inostroza, Mario. EMDEPES; ChileFil: Kenny, Andrew. Fisheries and Aquaculture Science; Reino UnidoFil: Kritzer, Jake. Environmental Defense Fund; Estados UnidosFil: Kuntzsch, Volker. Sanford Limited; Estados UnidosFil: Lasta, Mario. Diag. Montegrande N° 7078. Mar del Plata; ArgentinaFil: Lopez, Ivan. Confederacion Española de Pesca; EspañaFil: Loveridge, Craig. South Pacific Regional Fisheries Management Organisation; Nueva ZelandaFil: Lynch, Don. Gorton; Estados UnidosFil: Masters, Jim. Marine Conservation Society; Reino UnidoFil: Mazor, Tessa. CSIRO Marine and Atmospheric Research; AustraliaFil: McConnaughey, Robert A. US National Marine Fisheries Service; Estados UnidosFil: Moenne, Marcel. Pacificblu; ChileFil: Francis. Marine Scotland Science; Reino UnidoFil: Nimick, Aileen M. Alaska Pacific University; Estados UnidosFil: Olsen, Alex. A. Espersen; DinamarcaFil: Parker, David. Young; Reino UnidoFil: Parma, Ana María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Nacional Patagónico; ArgentinaFil: Penney, Christine. Clearwater Seafoods; CanadáFil: Pierce, David. Massachusetts Division of Marine Fisheries; Estados UnidosFil: Pitcher, Roland. CSIRO Marine and Atmospheric Research; AustraliaFil: Pol, Michael. Massachusetts Division of Marine Fisheries; Estados UnidosFil: Richardson, Ed. Pollock Conservation Cooperative; Estados UnidosFil: Rijnsdorp, Adriaan D. Wageningen IMARES; Países BajosFil: Rilatt, Simon. A. Espersen; DinamarcaFil: Rodmell, Dale P. National Federation of Fishermen's Organisations; Reino UnidoFil: Rose, Craig. FishNext Research; Estados UnidosFil: Sethi, Suresh A. Alaska Pacific University; Estados UnidosFil: Short, Katherine. F.L.O.W. Collaborative; Nueva ZelandaFil: Suuronen, Petri. Fisheries and Aquaculture Department; ItaliaFil: Taylor, Erin. New England Aquarium; Estados UnidosFil: Wallace, Scott. The David Suzuki Foundation; CanadáFil: Webb, Lisa. Gorton's Inc.; Estados UnidosFil: Wickham, Eric. Unit four –1957 McNicoll Avenue; CanadáFil: Wilding, Sam R. Monterey Bay Aquarium; Estados UnidosFil: Wilson, Ashley. Department for Environment; Reino UnidoFil: Winger, Paul. Memorial University Of Newfoundland; CanadáFil: Sutherland, William J. University of Cambridge; Reino Unid

Pan-cancer analysis of whole genomes identifies driver rearrangements promoted by LINE-1 retrotransposition

About half of all cancers have somatic integrations of retrotransposons. Here, to characterize their role in oncogenesis, we analyzed the patterns and mechanisms of somatic retrotransposition in 2,954 cancer genomes from 38 histological cancer subtypes within the framework of the Pan-Cancer Analysis of Whole Genomes (PCAWG) project. We identified 19,166 somatically acquired retrotransposition events, which affected 35% of samples and spanned a range of event types. Long interspersed nuclear element (LINE-1; L1 hereafter) insertions emerged as the first most frequent type of somatic structural variation in esophageal adenocarcinoma, and the second most frequent in head-and-neck and colorectal cancers. Aberrant L1 integrations can delete megabase-scale regions of a chromosome, which sometimes leads to the removal of tumor-suppressor genes, and can induce complex translocations and large-scale duplications. Somatic retrotranspositions can also initiate breakage–fusion–bridge cycles, leading to high-level amplification of oncogenes. These observations illuminate a relevant role of L1 retrotransposition in remodeling the cancer genome, with potential implications for the development of human tumors

Fc-Optimized Anti-CD25 Depletes Tumor-Infiltrating Regulatory T Cells and Synergizes with PD-1 Blockade to Eradicate Established Tumors

CD25 is expressed at high levels on regulatory T (Treg) cells and was initially proposed as a target for cancer immunotherapy. However, anti-CD25 antibodies have displayed limited activity against established tumors. We demonstrated that CD25 expression is largely restricted to tumor-infiltrating Treg cells in mice and humans. While existing anti-CD25 antibodies were observed to deplete Treg cells in the periphery, upregulation of the inhibitory Fc gamma receptor (FcγR) IIb at the tumor site prevented intra-tumoral Treg cell depletion, which may underlie the lack of anti-tumor activity previously observed in pre-clinical models. Use of an anti-CD25 antibody with enhanced binding to activating FcγRs led to effective depletion of tumor-infiltrating Treg cells, increased effector to Treg cell ratios, and improved control of established tumors. Combination with anti-programmed cell death protein-1 antibodies promoted complete tumor rejection, demonstrating the relevance of CD25 as a therapeutic target and promising substrate for future combination approaches in immune-oncology

Fc Effector Function Contributes to the Activity of Human Anti-CTLA-4 Antibodies.

With the use of a mouse model expressing human Fc-gamma receptors (FcγRs), we demonstrated that antibodies with isotypes equivalent to ipilimumab and tremelimumab mediate intra-tumoral regulatory T (Treg) cell depletion in vivo, increasing the CD8+ to Treg cell ratio and promoting tumor rejection. Antibodies with improved FcγR binding profiles drove superior anti-tumor responses and survival. In patients with advanced melanoma, response to ipilimumab was associated with the CD16a-V158F high affinity polymorphism. Such activity only appeared relevant in the context of inflamed tumors, explaining the modest response rates observed in the clinical setting. Our data suggest that the activity of anti-CTLA-4 in inflamed tumors may be improved through enhancement of FcγR binding, whereas poorly infiltrated tumors will likely require combination approaches

Study of the B−→Λc+Λˉc−K−B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-} decay

The decay $B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-}$ is studied in proton-proton collisions at a center-of-mass energy of $\sqrt{s}=13$ TeV using data corresponding to an integrated luminosity of 5 $\mathrm{fb}^{-1}$ collected by the LHCb experiment. In the $\Lambda_{c}^+ K^{-}$ system, the $\Xi_{c}(2930)^{0}$ state observed at the BaBar and Belle experiments is resolved into two narrower states, $\Xi_{c}(2923)^{0}$ and $\Xi_{c}(2939)^{0}$, whose masses and widths are measured to be $$m(\Xi_{c}(2923)^{0}) = 2924.5 \pm 0.4 \pm 1.1 \,\mathrm{MeV}, \\ m(\Xi_{c}(2939)^{0}) = 2938.5 \pm 0.9 \pm 2.3 \,\mathrm{MeV}, \\ \Gamma(\Xi_{c}(2923)^{0}) = \phantom{000}4.8 \pm 0.9 \pm 1.5 \,\mathrm{MeV},\\ \Gamma(\Xi_{c}(2939)^{0}) = \phantom{00}11.0 \pm 1.9 \pm 7.5 \,\mathrm{MeV},$$ where the first uncertainties are statistical and the second systematic. The results are consistent with a previous LHCb measurement using a prompt $\Lambda_{c}^{+} K^{-}$ sample. Evidence of a new $\Xi_{c}(2880)^{0}$ state is found with a local significance of $3.8\,\sigma$, whose mass and width are measured to be $2881.8 \pm 3.1 \pm 8.5\,\mathrm{MeV}$ and $12.4 \pm 5.3 \pm 5.8 \,\mathrm{MeV}$, respectively. In addition, evidence of a new decay mode $\Xi_{c}(2790)^{0} \to \Lambda_{c}^{+} K^{-}$ is found with a significance of $3.7\,\sigma$. The relative branching fraction of $B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-}$ with respect to the $B^{-} \to D^{+} D^{-} K^{-}$ decay is measured to be $2.36 \pm 0.11 \pm 0.22 \pm 0.25$, where the first uncertainty is statistical, the second systematic and the third originates from the branching fractions of charm hadron decays.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-028.html (LHCb public pages