Effects of oral meal feeding on whole body protein breakdown and protein synthesis in cachectic pancreatic cancer patients

Background: Pancreatic cancer is often accompanied by cachexia, a syndrome of severe weight loss and muscle wasting. A suboptimal response to nutritional support may further aggravate cachexia, yet the influence of nutrition on protein kinetics in cachectic patients is poorly understood. Methods: Eight cachectic pancreatic cancer patients and seven control patients received a primed continuous intravenous infusion of l‐[ring‐2H5]phenylalanine and l‐[3,3‐2H2]tyrosine for 8 h and ingested sips of water with l‐[1‐13C]phenylalanine every 30 min. After 4 h, oral feeding was started. Whole body protein breakdown, protein synthesis, and net protein balance were calculated. Results are given as median with interquartile range. Results: Baseline protein breakdown and protein synthesis were higher in cachectic patients compared with the controls (breakdown: 67.1 (48.1–79.6) vs. 45.8 (42.6–46.3) µmol/kg lean body mass/h, P = 0.049; and synthesis: 63.0 (44.3–75.6) vs. 41.8 (37.6–42.5) µmol/kg lean body mass/h, P = 0.021). During feeding, protein breakdown decreased significantly to 45.5 (26.9–51.1) µmol/kg lean body mass/h (P = 0.012) in the cachexia group and to 33.7 (17.4–37.1) µmol/kg lean body mass/h (P = 0.018) in the control group. Protein synthesis was not affected by feeding in cachectic patients: 58.4 (46.5–76.1) µmol/kg lean body mass/h, but was stimulated in controls: 47.9 (41.8–56.7) µmol/kg lean body mass/h (P = 0.018). Both groups showed a comparable positive net protein balance during feeding: cachexia: 19.7 (13.1–23.7) and control: 16.3 (13.6–25.4) µmol/kg lean body mass/h (P = 0.908). Conclusion: Cachectic pancreatic cancer patients have a higher basal protein turnover. Both cachectic patients and controls show a comparable protein anabolism during feeding, albeit through a different pattern of protein kinetics. In cachectic patients, this is primarily related to reduced protein breakdown, whereas in controls, both protein breakdown and protein synthesis alterations are involved

What is the Nature of EUV Waves? First STEREO 3D Observations and Comparison with Theoretical Models

One of the major discoveries of the Extreme ultraviolet Imaging Telescope (EIT) on SOHO were intensity enhancements propagating over a large fraction of the solar surface. The physical origin(s) of the so-called `EIT' waves is still strongly debated. They are considered to be either wave (primarily fast-mode MHD waves) or non-wave (pseudo-wave) interpretations. The difficulty in understanding the nature of EUV waves lies with the limitations of the EIT observations which have been used almost exclusively for their study. Their limitations are largely overcome by the SECCHI/EUVI observations on-board the STEREO mission. The EUVI telescopes provide high cadence, simultaneous multi-temperature coverage, and two well-separated viewpoints. We present here the first detailed analysis of an EUV wave observed by the EUVI disk imagers on December 07, 2007 when the STEREO spacecraft separation was $\approx 45^\circ$. Both a small flare and a CME were associated with the wave cadence, and single temperature and viewpoint coverage. These limitations are largely overcome by the SECCHI/EUVI observations on-board the STEREO mission. The EUVI telescopes provide high cadence, simultaneous multi-temperature coverage, and two well-separated viewpoints. Our findings give significant support for a fast-mode interpretation of EUV waves and indicate that they are probably triggered by the rapid expansion of the loops associated with the CME.Comment: Solar Physics, 2009, Special STEREO Issue, in pres

Comprehensive lung injury pathology induced by mTOR inhibitors

Molecular Targets in Oncology[Abstract] Interstitial lung disease is a rare side effect of temsirolimus treatment in renal cancer patients. Pulmonary fibrosis is characterised by the accumulation of extracellular matrix collagen, fibroblast proliferation and migration, and loss of alveolar gas exchange units. Previous studies of pulmonary fibrosis have mainly focused on the fibro-proliferative process in the lungs. However, the molecular mechanism by which sirolimus promotes lung fibrosis remains elusive. Here, we propose an overall cascade hypothesis of interstitial lung diseases that represents a common, partly underlying synergism among them as well as the lung pathogenesis side effects of mammalian target of rapamycin inhibitors

Photochemically produced SO2 in the atmosphere of WASP-39b

S.-M.T. is supported by the European Research Council advanced grant EXOCONDENSE (no. 740963; principal investigator: R. T. Pierrehumbert). E.K.H.L. is supported by the SNSF Ambizione Fellowship grant (no. 193448). X.Z. is supported by NASA Exoplanet Research grant 80NSSC22K0236. O.V. acknowledges funding from the ANR project ‘EXACT’ (ANR-21-CE49-0008-01), from the Centre National d’Études Spatiales (CNES) and from the CNRS/INSU Programme National de Planétologie (PNP). L.D. acknowledges support from the European Union H2020-MSCA-ITN-2109 under grant no. 860470 (CHAMELEON) and the KU Leuven IDN/19/028 grant Escher. This work benefited from the 2022 Exoplanet Summer Program at the Other Worlds Laboratory (OWL) at the University of California, Santa Cruz, a programme financed by the Heising-Simons Foundation. T.D. is an LSSTC Catalyst Fellow. J.K. is an Imperial College Research Fellow. B.V.R. is a 51 Pegasi b Fellow. L.W. is an NHFP Sagan Fellow. A.D.F. is an NSF Graduate Research Fellow.Photochemistry is a fundamental process of planetary atmospheres that regulates the atmospheric composition and stability1. However, no unambiguous photochemical products have been detected in exoplanet atmospheres so far. Recent observations from the JWST Transiting Exoplanet Community Early Release Science Program2,3 found a spectral absorption feature at 4.05 μm arising from sulfur dioxide (SO2) in the atmosphere of WASP-39b. WASP-39b is a 1.27-Jupiter-radii, Saturn-mass (0.28 MJ) gas giant exoplanet orbiting a Sun-like star with an equilibrium temperature of around 1,100 K (ref. 4). The most plausible way of generating SO2 in such an atmosphere is through photochemical processes5,6. Here we show that the SO2 distribution computed by a suite of photochemical models robustly explains the 4.05-μm spectral feature identified by JWST transmission observations7 with NIRSpec PRISM (2.7σ)8 and G395H (4.5σ)9. SO2 is produced by successive oxidation of sulfur radicals freed when hydrogen sulfide (H2S) is destroyed. The sensitivity of the SO2 feature to the enrichment of the atmosphere by heavy elements (metallicity) suggests that it can be used as a tracer of atmospheric properties, with WASP-39b exhibiting an inferred metallicity of about 10× solar. We further point out that SO2 also shows observable features at ultraviolet and thermal infrared wavelengths not available from the existing observations.Publisher PDFPeer reviewe

Liposomes in Biology and Medicine

Drug delivery systems (DDS) have become important tools for the specific delivery of a large number of drug molecules. Since their discovery in the 1960s liposomes were recognized as models to study biological membranes and as versatile DDS of both hydrophilic and lipophilic molecules. Liposomes--nanosized unilamellar phospholipid bilayer vesicles--undoubtedly represent the most extensively studied and advanced drug delivery vehicles. After a long period of research and development efforts, liposome-formulated drugs have now entered the clinics to treat cancer and systemic or local fungal infections, mainly because they are biologically inert and biocompatible and practically do not cause unwanted toxic or antigenic reactions. A novel, up-coming and promising therapy approach for the treatment of solid tumors is the depletion of macrophages, particularly tumor associated macrophages with bisphosphonate-containing liposomes. In the advent of the use of genetic material as therapeutic molecules the development of delivery systems to target such novel drug molecules to cells or to target organs becomes increasingly important. Liposomes, in particular lipid-DNA complexes termed lipoplexes, compete successfully with viral gene transfection systems in this field of application. Future DDS will mostly be based on protein, peptide and DNA therapeutics and their next generation analogs and derivatives. Due to their versatility and vast body of known properties liposome-based formulations will continue to occupy a leading role among the large selection of emerging DDS

Microflares and the Statistics of X-ray Flares

This review surveys the statistics of solar X-ray flares, emphasising the new views that RHESSI has given us of the weaker events (the microflares). The new data reveal that these microflares strongly resemble more energetic events in most respects; they occur solely within active regions and exhibit high-temperature/nonthermal emissions in approximately the same proportion as major events. We discuss the distributions of flare parameters (e.g., peak flux) and how these parameters correlate, for instance via the Neupert effect. We also highlight the systematic biases involved in intercomparing data representing many decades of event magnitude. The intermittency of the flare/microflare occurrence, both in space and in time, argues that these discrete events do not explain general coronal heating, either in active regions or in the quiet Sun.Comment: To be published in Space Science Reviews (2011

An Observational Overview of Solar Flares

We present an overview of solar flares and associated phenomena, drawing upon a wide range of observational data primarily from the RHESSI era. Following an introductory discussion and overview of the status of observational capabilities, the article is split into topical sections which deal with different areas of flare phenomena (footpoints and ribbons, coronal sources, relationship to coronal mass ejections) and their interconnections. We also discuss flare soft X-ray spectroscopy and the energetics of the process. The emphasis is to describe the observations from multiple points of view, while bearing in mind the models that link them to each other and to theory. The present theoretical and observational understanding of solar flares is far from complete, so we conclude with a brief discussion of models, and a list of missing but important observations.Comment: This is an article for a monograph on the physics of solar flares, inspired by RHESSI observations. The individual articles are to appear in Space Science Reviews (2011

Saturn Atmospheric Structure and Dynamics

2 Saturn inhabits a dynamical regime of rapidly rotating, internally heated atmospheres similar to Jupiter. Zonal winds have remained fairly steady since the time of Voyager except in the equatorial zone and slightly stronger winds occur at deeper levels. Eddies supply energy to the jets at a rate somewhat less than on Jupiter and mix potential vorticity near westward jets. Convective clouds exist preferentially in cyclonic shear regions as on Jupiter but also near jets, including major outbreaks near 35°S associated with Saturn electrostatic discharges, and in sporadic giant equatorial storms perhaps generated from frequent events at depth. The implied meridional circulation at and below the visible cloud tops consists of upwelling (downwelling) at cyclonic (anti-cyclonic) shear latitudes. Thermal winds decay upward above the clouds, implying a reversal of the circulation there. Warm-core vortices with associated cyclonic circulations exist at both poles, including surrounding thick high clouds at the south pole. Disequilibrium gas concentrations in the tropical upper troposphere imply rising motion there. The radiative-convective boundary and tropopause occur at higher pressure in the southern (summer) hemisphere due to greater penetration of solar heating there. A temperature “knee ” of warm air below the tropopause, perhaps due to haze heating, is stronger in the summer hemisphere as well. Saturn’s south polar stratosphere is warmer than predicted by radiative models and enhanced in ethane, suggesting subsidence-driven adiabatic warming there. Recent modeling advances suggest that shallow weather laye