The microbiome of the marine flatworm Macrostomum lignano provides fitness advantages and exhibits circadian rhythmicity

AbstractThe close association between animals and their associated microbiota is usually beneficial for both partners. Here, we used a simple marine model invertebrate, the flatworm Macrostomum lignano, to characterize the host-microbiota interaction in detail. This analysis revealed that the different developmental stages each harbor a specific microbiota. Studies with gnotobiotic animals clarified the physiological significance of the microbiota. While no fitness benefits were mediated by the microbiota when food was freely available, animals with microbiota showed significantly increased fitness with a reduced food supply. The microbiota of M. lignano shows circadian rhythmicity, affecting both the total bacterial load and the behavior of specific taxa. Moreover, the presence of the worm influences the composition of the bacterial consortia in the environment. In summary, the Macrostomum-microbiota system described here can serve as a general model for host-microbe interactions in marine invertebrates.</jats:p

Comments on John D. Keen and James E. Keen, What is the point: will screening mammography save my life? BMC Medical Informatics and Decision Making, 2009

This paper by John D. Keen and James E. Keen addresses a thorny subject. The numerical findings and commentaries in their paper will be disturbing to some readers and seem to defy logic and well established viewpoints. It may well generate angry letters to the editor. However such numerical analysis and reporting including civil discussion should be welcomed and are the basis for informed decision making – something that is highly needed in this field

Characterization of the C-Terminal Nuclease Domain of Herpes Simplex Virus pUL15 as a Target of Nucleotidyltransferase Inhibitors

The natural product α-hydroxytropolones manicol and β-thujaplicinol inhibit replication of herpes simplex viruses 1 and 2 (HSV-1 and HSV-2, respectively) at nontoxic concentrations. Because these were originally developed as divalent metal-sequestering inhibitors of the ribonuclease H activity of HIV-1 reverse transcriptase, α-hydroxytropolones likely target related HSV proteins of the nucleotidyltransferase (NTase) superfamily, which share an “RNase H-like” fold. One potential candidate is pUL15, a component of the viral terminase molecular motor complex, whose C-terminal nuclease domain, pUL15C, has recently been crystallized. Crystallography also provided a working model for DNA occupancy of the nuclease active site, suggesting potential protein–nucleic acid contacts over a region of ∼14 bp. In this work, we extend crystallographic analysis by examining pUL15C-mediated hydrolysis of short, closely related DNA duplexes. In addition to defining a minimal substrate length, this strategy facilitated construction of a dual-probe fluorescence assay for rapid kinetic analysis of wild-type and mutant nucleases. On the basis of its proposed role in binding the phosphate backbone, studies with pUL15C variant Lys700Ala showed that this mutation affected neither binding of duplex DNA nor binding of small molecule to the active site but caused a 17-fold reduction in the turnover rate (kcat), possibly by slowing conversion of the enzyme–substrate complex to the enzyme–product complex and/or inhibiting dissociation from the hydrolysis product. Finally, with a view of pUL15-associated nuclease activity as an antiviral target, the dual-probe fluorescence assay, in combination with differential scanning fluorimetry, was used to demonstrate inhibition by several classes of small molecules that target divalent metal at the active site

A clinical and economic evaluation of Control of Hyperglycaemia in Paediatric intensive care (CHiP): a randomised controlled trial.

BACKGROUND: Early research in adults admitted to intensive care suggested that tight control of blood glucose during acute illness can be associated with reductions in mortality, length of hospital stay and complications such as infection and renal failure. Prior to our study, it was unclear whether or not children could also benefit from tight control of blood glucose during critical illness. OBJECTIVES: This study aimed to determine if controlling blood glucose using insulin in paediatric intensive care units (PICUs) reduces mortality and morbidity and is cost-effective, whether or not admission follows cardiac surgery. DESIGN: Randomised open two-arm parallel group superiority design with central randomisation with minimisation. Analysis was on an intention-to-treat basis. Following random allocation, care givers and outcome assessors were no longer blind to allocation. SETTING: The setting was 13 English PICUs. PARTICIPANTS: Patients who met the following criteria were eligible for inclusion: ≥ 36 weeks corrected gestational age; ≤ 16 years; in the PICU following injury, following major surgery or with critical illness; anticipated treatment > 12 hours; arterial line; mechanical ventilation; and vasoactive drugs. Exclusion criteria were as follows: diabetes mellitus; inborn error of metabolism; treatment withdrawal considered; in the PICU > 5 consecutive days; and already in CHiP (Control of Hyperglycaemia in Paediatric intensive care). INTERVENTION: The intervention was tight glycaemic control (TGC): insulin by intravenous infusion titrated to maintain blood glucose between 4.0 and 7.0 mmol/l. CONVENTIONAL MANAGEMENT (CM): This consisted of insulin by intravenous infusion only if blood glucose exceeded 12.0 mmol/l on two samples at least 30 minutes apart; insulin was stopped when blood glucose fell below 10.0 mmol/l. MAIN OUTCOME MEASURES: The primary outcome was the number of days alive and free from mechanical ventilation within 30 days of trial entry (VFD-30). The secondary outcomes comprised clinical and economic outcomes at 30 days and 12 months and lifetime cost-effectiveness, which included costs per quality-adjusted life-year. RESULTS: CHiP recruited from May 2008 to September 2011. In total, 19,924 children were screened and 1369 eligible patients were randomised (TGC, 694; CM, 675), 60% of whom were in the cardiac surgery stratum. The randomised groups were comparable at trial entry. More children in the TGC than in the CM arm received insulin (66% vs. 16%). The mean VFD-30 was 23 [mean difference 0.36; 95% confidence interval (CI) -0.42 to 1.14]. The effect did not differ among prespecified subgroups. Hypoglycaemia occurred significantly more often in the TGC than in the CM arm (moderate, 12.5% vs. 3.1%; severe, 7.3% vs. 1.5%). Mean 30-day costs were similar between arms, but mean 12-month costs were lower in the TGC than in CM arm (incremental costs -£3620, 95% CI -£7743 to £502). For the non-cardiac surgery stratum, mean costs were lower in the TGC than in the CM arm (incremental cost -£9865, 95% CI -£18,558 to -£1172), but, in the cardiac surgery stratum, the costs were similar between the arms (incremental cost £133, 95% CI -£3568 to £3833). Lifetime incremental net benefits were positive overall (£3346, 95% CI -£11,203 to £17,894), but close to zero for the cardiac surgery stratum (-£919, 95% CI -£16,661 to £14,823). For the non-cardiac surgery stratum, the incremental net benefits were high (£11,322, 95% CI -£15,791 to £38,615). The probability that TGC is cost-effective is relatively high for the non-cardiac surgery stratum, but, for the cardiac surgery subgroup, the probability that TGC is cost-effective is around 0.5. Sensitivity analyses showed that the results were robust to a range of alternative assumptions. CONCLUSIONS: CHiP found no differences in the clinical or cost-effectiveness of TGC compared with CM overall, or for prespecified subgroups. A higher proportion of the TGC arm had hypoglycaemia. This study did not provide any evidence to suggest that PICUs should stop providing CM for children admitted to PICUs following cardiac surgery. For the subgroup not admitted for cardiac surgery, TGC reduced average costs at 12 months and is likely to be cost-effective. Further research is required to refine the TGC protocol to minimise the risk of hypoglycaemic episodes and assess the long-term health benefits of TGC. TRIAL REGISTRATION: Current Controlled Trials ISRCTN61735247. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 18, No. 26. See the NIHR Journals Library website for further project information

Evolution of the Southwest Indian Ridge from 55°45′E to 62°E : changes in plate-boundary geometry since 26 Ma

Author Posting. © American Geophysical Union, 2007. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geochemistry Geophysics Geosystems 8 (2007): Q06022, doi:10.1029/2006GC001559.From 55°45′E to 58°45′E and from 60°30′E to 62°00′E, the ultraslow-spreading Southwest Indian Ridge (SWIR) consists of magmatic spreading segments separated by oblique amagmatic spreading segments, transform faults, and nontransform discontinuities. Off-axis magnetic and multibeam bathymetric data permit investigation of the evolution of this part of the SWIR. Individual magmatic segments show varying magnitudes and directions of asymmetric spreading, which requires that the shape of the plate boundary has changed significantly over time. In particular, since 26 Ma the Atlantis II transform fault grew by 90 km to reach 199 km, while a 45-km-long transform fault at 56°30′E shrank to become an 11 km offset nontransform discontinuity. Conversely, an oblique amagmatic segment at the center of a first-order spreading segment shows little change in orientation with time. These changes are consistent with the clockwise rotation of two ~450-km-wide first-order spreading segments between the Gallieni and Melville transform faults (52–60°E) to become more orthogonal to spreading. We suggest that suborthogonal first-order spreading segments reflect a stable configuration for mid-ocean ridges that maximizes upwelling rates in the asthenospheric mantle and results in a hotter and weaker ridge-axis that can more easily accommodate seafloor spreading.Funding for this work came from a JOI-Schlanger Fellowship to Baines and NSF grant 0352054 to Cheadle and John

Convective storms in closed cyclones in Jupiter's South Temperate Belt: (I) observations

On May 31, 2020 a short-lived convective storm appeared in one of the small cyclones of Jupiter's South Temperate Belt (STB) at planetographic latitude 30.8S. The outbreak was captured by amateur astronomer Clyde Foster in methane-band images, became widely known as Clyde's Spot, and was imaged at very high resolution by the Junocam instrument on board the Juno mission 2.5 days later. Junocam images showed a white two-lobed cyclonic system with high clouds observed in the methane-band at 890 nm. The storm evolved over a few days to become a dark feature that showed turbulence for months, presented oscillations in its drift rate, and slowly expanded, first into a Folded Filamentary Region (FFR), and later into a turbulent segment of the STB over a timescale of one year. On August 7, 2021, a new storm strikingly similar to Clyde's Spot erupted in a cyclone of the STB. The new storm exhibited first a similar transformation into a turbulent dark feature, and later transformed into a dark cyclone fully formed by January 2022. We compare the evolution into a FFR of Clyde's Spot with the formation of a FFR observed by Voyager 2 in 1979 in the South South Temperate Belt (SSTB) after a convective outburst in a cyclone that also developed a two-lobed shape. We also discuss the contemporaneous evolution of an additional cyclone of the STB, which was similar to the one were Clyde's Spot developed. This cyclone did not exhibit visible internal convective activity, and transformed from pale white in 2019, with low contrast with the environment, to dark red in 2020, and thus, was very similar to the outcome of the second storm. This cyclone became bright again in 2021 after interacting with Oval BA. We present observations of these phenomena obtained by amateur astronomers, ground-based telescopes, Hubble Space Telescope and Junocam. This study reveals that short-lived small storms that are active for only a few days can produce complex longterm changes that extend over much larger areas than those initially covered by the storms. In a second paper [In tilde urrigarro et al., 2022] we use the EPIC numerical model to simulate these storms and study moist convection in closed cyclones.We are very thankful to the large community of amateur observers operating small telescopes that submit their Jupiter observations to databases such as PVOL and ALPO-Japan. We are also grateful to two anonymous reviewers for their comments that improved the clarity of this paper. This work has been supported by Grant PID2019-109467GB-I00 funded by MCIN/AEI/10.13039/501100011033/and by Grupos Gobierno Vasco IT1366-19. PI acknowledges a PhD scholarship from Gobierno Vasco. GSO and TM were supported by NASA with funds distributed to the Jet Propulsion Laboratory, California Institute of Technology under contract 80NM0018D0004. C. J. Hansen was sup-ported by funds from NASA, USA to the Juno mission via the Planetary Science Institute. IOE was supported by a contract funded by Europlanet 2024 RI to navigate Junocam images, now available as maps in PVOL at http://pvol2.ehu.eus. Europlanet 2024 RI has received funding from the European Unions Horizon 2020 research and innovation programme under grant agreement No 871149. G.S. Orton, S. R. Brueshaber, T. W. Momary, K. H. Baines and E. K. Dahl were visiting Astronomers at the Infrared Telescope Facility, which is operated by the University of Hawaii under contract 80HQTR19D0030 with the National Aeronautics and Space Administration. In addition, support from NASA Juno Participating Scientist award 80NSSC19K1265 was provided to M.H. Wong. This work has used data acquired from the NASA/ESA Hubble Space Telescope (HST) , which is operated by the Association of 807 Universities for Research in Astronomy, Inc., under NASA contract NAS 5-26555. These HST observations are associated with several HST observing programs: GO/DD 14661 (PI: M.H. Wong) , GO/DD 15665 (PI: I. de Pater) , GO/DD 15159 (PI: M. H. Wong) , GO/DD 15502 (PI: A. Simon) , GO/DD 14661 (PI: M. H. Wong) , GO/DD 16074 (PI: M.H. Wong) , GO/DD 16053 (PI: I. de Pater) , GO/DD 15929 (PI: A. Simon) , GO/DD 16269 (PI: A. Simon) . PlanetCam observations were collected at the Centro Astronomico Hispanico en Andalucia (CAHA) , operated jointly by the Instituto de Astrofisica de Andalucia (CSIC) and the Andalusian Universities (Junta de Andalucia) . This work was enabled by the location of the IRTF and Gemini North telescopes within the Mauakea Science Reserve, adjacent to the summit of Maunakea. We are grateful for the privilege of observing Kaawela (Jupiter) from a place that is unique in both its astronomical quality and its cultural signifi-cance. This research has made use of the USGS Integrated Software for Imagers and Spectrometers (ISIS) . Voyager 2 images were accessed through The PDS Ring-Moon Systems Nodes OPUS search service

The Iceman's Last Meal Consisted of Fat, Wild Meat, and Cereals

The history of humankind is marked by the constant adoption of new dietary habits affecting human physiology, metabolism, and even the development of nutrition-related disorders. Despite clear archaeological evidence for the shift from hunter-gatherer lifestyle to agriculture in Neolithic Europe [1], very little information exists on the daily dietary habits of our ancestors. By undertaking a complementary -omics approach combined with microscopy, we analyzed the stomach content of the Iceman, a 5,300-yearold European glacier mummy [2, 3]. He seems to have had a remarkably high proportion of fat in his diet, supplemented with fresh or dried wild meat, cereals, and traces of toxic bracken. Our multipronged approach provides unprecedented analytical depth, deciphering the nutritional habit, meal composition, and food-processing methods of this Copper Age individual