Dynamics of a Semiflexible Polymer or Polymer Ring in Shear Flow

Polymers exposed to shear flow exhibit a rich tumbling dynamics. While rigid rods rotate on Jeffery orbits, flexible polymers stretch and coil up during tumbling. Theoretical results show that in both of these asymptotic regimes the tumbling frequency f_c in a linear shear flow of strength \gamma scales as a power law Wi^(2/3) in the Weissenberg number Wi=\gamma \tau, where \tau is a characteristic time of the polymer's relaxational dynamics. For flexible polymers these theoretical results are well confirmed by experimental single molecule studies. However, for the intermediate semiflexible regime the situation is less clear. Here we perform extensive Brownian dynamics simulations to explore the tumbling dynamics of semiflexible polymers over a broad range of shear strength and the polymer's persistence length l_p. We find that the Weissenberg number alone does not suffice to fully characterize the tumbling dynamics, and the classical scaling law breaks down. Instead, both the polymer's stiffness and the shear rate are relevant control parameters. Based on our Brownian dynamics simulations we postulate that in the parameter range most relevant for cytoskeletal filaments there is a distinct scaling behavior with f_c \tau*=Wi^(3/4) f_c (x) with Wi=\gamma \tau* and the scaling variable x=(l_p/L)(Wi)^(-1/3); here \tau* is the time the polymer's center of mass requires to diffuse its own contour length L. Comparing these results with experimental data on F-actin we find that the Wi^(3/4) scaling law agrees quantitatively significantly better with the data than the classical Wi^(2/3) law. Finally, we extend our results to single ring polymers in shear flow, and find similar results as for linear polymers with slightly different power laws.Comment: 17 pages, 14 figure

Empirical evaluation of the inter-relationship of articular elements involved in the pathoanatomy of knee osteoarthritis using Magnetic Resonance Imaging

<p>Abstract</p> <p>Background</p> <p>In this cross-sectional study, we conducted a comprehensive assessment of all articular elements that could be measured using knee MRI. We assessed the association of pathological change in multiple articular structures involved in the pathoanatomy of osteoarthritis.</p> <p>Methods</p> <p>Knee MRI scans from patients over 45 years old were assessed using a semi-quantitative knee MRI assessment form. The form included six distinct elements: cartilage, bone marrow lesions, osteophytes, subchondral sclerosis, joint effusion and synovitis. Each type of pathology was graded using an ordinal scale with a value of zero indicating no pathology and higher values indicating increasingly severe levels of pathology. The principal dependent variable for comparison was the mean cartilage disease score (CDS), which captured the aggregate extent of involvement of articular cartilage. The distribution of CDS was compared to the individual and cumulative distributions of each articular element using the Chi-squared test. The correlations between pathological change in the various articular structures were assessed in a Spearman correlation table.</p> <p>Results</p> <p>Data from 140 patients were available for review. The cohort had a median age of 61 years (range 45-89) and was 61% female. The cohort included a wide spectrum of OA severity. Our analysis showed a statistically significant trend towards pathological change involving more articular elements as CDS worsened (p-value for trend < 0.0001). Comparison of CDS to change in the severity of pathology of individual articular elements showed statistically significant trends towards more severe pathology as CDS worsened for osteophytes (p-value for trend < 0.0001), bone marrow lesions (p = 0.0003), and subchondral sclerosis (p = 0.009), but not joint effusion or synovitis. There was a moderate correlation between cartilage damage, osteophytes and BMLs as well as a moderate correlation between joint effusion and synovitis. However, cartilage damage and osteophytes were only weakly associated with synovitis or joint effusion.</p> <p>Conclusion</p> <p>Our results support an inter-relationship of multiple articular elements in the pathoanatomy of knee OA. Prospective studies of OA pathogenesis in humans are needed to correlate these findings to clinically relevant outcomes such as pain and function.</p

HST/NICMOS Paschen-alpha Survey of the Galactic Center: Overview

We have recently carried out the first wide-field hydrogen Paschen-alpha line imaging survey of the Galactic Center (GC), using the NICMOS instrument aboard the Hubble Space Telescope. The survey maps out a region of 2253 pc^2 around the central supermassive black hole (Sgr A*) in the 1.87 and 1.90 Micron narrow bands with a spatial resolution of 0.01 pc at a distance of 8 kpc. Here we present an overview of the observations, data reduction, preliminary results, and potential scientific implications, as well as a description of the rationale and design of the survey. We have produced mosaic maps of the Paschen-alpha line and continuum emission, giving an unprecedentedly high resolution and high sensitivity panoramic view of stars and photo-ionized gas in the nuclear environment of the Galaxy. We detect a significant number of previously undetected stars with Paschen-alpha in emission. They are most likely massive stars with strong winds, as confirmed by our initial follow-up spectroscopic observations. About half of the newly detected massive stars are found outside the known clusters (Arches, Quintuplet, and Central). Many previously known diffuse thermal features are now resolved into arrays of intriguingly fine linear filaments indicating a profound role of magnetic fields in sculpting the gas. The bright spiral-like Paschen-alpha emission around Sgr A* is seen to be well confined within the known dusty torus. In the directions roughly perpendicular to it, we further detect faint, diffuse Paschen-alpha emission features, which, like earlier radio images, suggest an outflow from the structure. In addition, we detect various compact Paschen-alpha nebulae, probably tracing the accretion and/or ejection of stars at various evolutionary stages.Comment: accepted for publication in MNRAS; a version of higher resolution images may be found at http://www.astro.umass.edu/~wqd/papers/hst/paper1.pd

The role of ADAM17 during liver damage

Abstract A disintegrin and metalloprotease (ADAM) 17 is a membrane bound protease, involved in the cleavage and thus regulation of various membrane proteins, which are critical during liver injury. Among ADAM17 substrates are tumor necrosis factor α (TNFα), tumor necrosis factor receptor 1 and 2 (TNFR1, TNFR2), the epidermal growth factor receptor (EGFR) ligands amphiregulin (AR) and heparin-binding-EGF-like growth factor (HB-EGF), the interleukin-6 receptor (IL-6R) and the receptor for a hepatocyte growth factor (HGF), c-Met. TNFα and its binding receptors can promote liver injury by inducing apoptosis and necroptosis in liver cells. Consistently, hepatocyte specific deletion of ADAM17 resulted in increased liver cell damage following CD95 stimulation. IL-6 trans-signaling is critical for liver regeneration and can alleviate liver damage. EGFR ligands can prevent liver damage and deletion of amphiregulin and HB-EGF can result in increased hepatocyte death and reduced proliferation. All of which indicates that ADAM17 has a central role in liver injury and recovery from it. Furthermore, inactive rhomboid proteins (iRhom) are involved in the trafficking and maturation of ADAM17 and have been linked to liver damage. Taken together, ADAM17 can contribute in a complex way to liver damage and injury

Tumor Necrosis Factor-mediated survival of CD169⁺ cells promotes immune activation during vesicular stomatitis virus infection

Innate immune activation is essential to mount an effective antiviral response and to prime adaptive immunity. Although a crucial role of CD169+ cells during vesicular stomatitis virus (VSV) infections is increasingly recognized, factors regulating CD169+ cells during viral infections remain unclear. Here, we show that tumor necrosis factor is produced by CD11b+ Ly6C+ Ly6G+ cells following infection with VSV. The absence of TNF or TNF receptor 1 (TNFR1) resulted in reduced numbers of CD169+ cells and in reduced type I interferon (IFN-I) production during VSV infection, with a severe disease outcome. Specifically, TNF triggered RelA translocation into the nuclei of CD169+ cells; this translocation was inhibited when the paracaspase MALT-1 was absent. Consequently, MALT1 deficiency resulted in reduced VSV replication, defective innate immune activation, and development of severe disease. These findings indicate that TNF mediates the maintenance of CD169+ cells and innate and adaptive immune activation during VSV infection

A3COSMOS: the dust attenuation of star-forming galaxies at z=2.5-4.0 from the COSMOS-ALMA archive

We present an analysis of the dust attenuation of star-forming galaxies at z = 2.5-4.0 through the relationship between the UV spectral slope (β), stellar mass (M*), and the infrared excess (IRX = LIR/LUV) based on far-infrared continuum observations from the Atacama Large Millimeter/sub-millimeter Array (ALMA). Our study exploits the full ALMA archive over the COSMOS field processed by the A3COSMOS team, which includes an unprecedented sample of ∼1500 galaxies at z ∼ 3 as primary or secondary targets in ALMA band 6 or 7 observations with a median continuum sensitivity of 126 μJybeam−1 (1σ). The detection rate is highly mass dependent, decreasing drastically below log (M*/M⊙) = 10.5. The detected galaxies show that the IRX-β relationship of massive (log M*/M⊙ > 10) main-sequence galaxies at z = 2.5-4.0 is consistent with that of local galaxies, while starbursts are generally offset by ∼0.5dex to larger IRX values. At the low-mass end, we derive upper limits on the infrared luminosities through stacking of the ALMA data. The combined IRX-M* relation at log(M∗/M⊙)>9 exhibits a significantly steeper slope than reported in previous studies at similar redshifts, implying little dust obscuration at log M*/M⊙ < 10. However, our results are consistent with earlier measurements at z ∼ 5.5, indicating a potential redshift evolution between z ∼ 2 and z ∼ 6. Deeper observations targeting low-mass galaxies will be required to confirm this finding.PL, DL, and ES acknowledge funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 694343). SL acknowledge funding from SCHI 536/9-1. EFJA acknowledge support of the Collaborative Research Center 956, subproject A1, funded by the Deutsche Forschungsgemeinschaft (DFG)

The lifecycle of molecular clouds in nearby star-forming disc galaxies

It remains a major challenge to derive a theory of cloud-scale (⁠≲100 pc) star formation and feedback, describing how galaxies convert gas into stars as a function of the galactic environment. Progress has been hampered by a lack of robust empirical constraints on the giant molecular cloud (GMC) lifecycle. We address this problem by systematically applying a new statistical method for measuring the evolutionary timeline of the GMC lifecycle, star formation, and feedback to a sample of nine nearby disc galaxies, observed as part of the PHANGS-ALMA survey. We measure the spatially resolved (∼100 pc) CO-to-H α flux ratio and find a universal de-correlation between molecular gas and young stars on GMC scales, allowing us to quantify the underlying evolutionary timeline. GMC lifetimes are short, typically 10−30Myr⁠, and exhibit environmental variation, between and within galaxies. At kpc-scale molecular gas surface densities ΣH2≥8M⊙pc−2⁠, the GMC lifetime correlates with time-scales for galactic dynamical processes, whereas at ΣH2≤8M⊙pc−2 GMCs decouple from galactic dynamics and live for an internal dynamical time-scale. After a long inert phase without massive star formation traced by H α (75-90 per cent of the cloud lifetime), GMCs disperse within just 1−5Myr once massive stars emerge. The dispersal is most likely due to early stellar feedback, causing GMCs to achieve integrated star formation efficiencies of 4-10 per cent. These results show that galactic star formation is governed by cloud-scale, environmentally dependent, dynamical processes driving rapid evolutionary cycling. GMCs and H II regions are the fundamental units undergoing these lifecycles, with mean separations of 100−300pc in star-forming discs. Future work should characterize the multiscale physics and mass flows driving these lifecycles.MC and JMDK gratefully acknowledge funding from the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) through an Emmy Noether Research Group (grant number KR4801/1-1) and the DFG Sachbeihilfe (grant number KR4801/2-1). JMDK, APSH, SMRJ, and DTH gratefully acknowledge funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme via the ERC Starting Grant MUSTANG (grant agreement number 714907). MC, JMDK, SMRJ, and DTH acknowledge support from the Australia-Germany Joint Research Cooperation Scheme (UA-DAAD, grant number 57387355). APSH, SMRJ, and DTH are fellows of the International Max Planck Research School for Astronomy and Cosmic Physics at the University of Heidelberg (IMPRS-HD). BG gratefully acknowledges the support of the Australian Research Council as the recipient of a Future Fellowship (FT140101202). CNC, AH, and JP acknowledge funding from the Programme National ‘Physique et Chimie du Milieu Interstellaire’ (PCMI) of the Centre national de la recherche scientifique/Institut national des sciences de l’Univers (CNRS/INSU) with the Institut de Chimie/Institut de Physique (INC/INP), co-funded by the Commissariat a l’ ` energie ´ atomique et aux energies alternatives (CEA) and the Centre ´ national d’etudes spatiales (CNES). AH acknowledges support ´ by the Programme National Cosmology et Galaxies (PNCG) of CNRS/INSU with the INP and the Institut national de physique nucleaire et de physique des particules (IN2P3), co-funded by ´ CEA and CNES. PL, ES, CF, DL, and TS acknowledge funding from the ERC under the European Union’s Horizon 2020 research and innovation programme (grant agreement No. 694343). The work of AKL, JS, and DU is partially supported by the National Science Foundation (NSF) under Grants No. 1615105, 1615109, and 1653300. AKL also acknowledges partial support from the National Aeronautics and Space Administration (NASA) Astrophysics Data Analysis Program (ADAP) grants NNX16AF48G and NNX17AF39G. ER acknowledges the support of the Natural Sciences and Engineering Research Council of Canada (NSERC), funding reference number RGPIN-2017-03987. FB acknowledges funding from the ERC under the European Union’s Horizon 2020 research and innovation programme (grant agreement No. 726384). GB is supported by the Fondo de Fomento al Desarrollo Cient´ıfico y Tecnologico of the Comisi ´ on Nacional de ´ Investigacion Cient ´ ´ıfica y Tecnologica (CONICYT/FONDECYT), ´ Programa de Iniciacion, Folio 11150220. SCOG acknowledges ´ support from the DFG via SFB 881 ‘The Milky Way System’ (subprojects B1, B2, and B8) and also via Germany’s Excellence Strategy EXC-2181/1–390900948 (the Heidelberg STRUCTURES Excellence Cluster). KK gratefully acknowledges funding from the DFG in the form of an Emmy Noether Research Group (grant number KR4598/2-1, PI Kreckel). AU acknowledges support from the Spanish funding grants AYA2016-79006-P (MINECO/FEDER) and PGC2018-094671-B-I00 (MCIU/AEI/FEDER)

Fragile X mental retardation protein protects against tumour necrosis factor-mediated cell death and liver injury.

peer reviewed[en] OBJECTIVE: The Fragile X mental retardation (FMR) syndrome is a frequently inherited intellectual disability caused by decreased or absent expression of the FMR protein (FMRP). Lack of FMRP is associated with neuronal degradation and cognitive dysfunction but its role outside the central nervous system is insufficiently studied. Here, we identify a role of FMRP in liver disease. DESIGN: Mice lacking Fmr1 gene expression were used to study the role of FMRP during tumour necrosis factor (TNF)-induced liver damage in disease model systems. Liver damage and mechanistic studies were performed using real-time PCR, Western Blot, staining of tissue sections and clinical chemistry. RESULTS: Fmr1null mice exhibited increased liver damage during virus-mediated hepatitis following infection with the lymphocytic choriomeningitis virus. Exposure to TNF resulted in severe liver damage due to increased hepatocyte cell death. Consistently, we found increased caspase-8 and caspase-3 activation following TNF stimulation. Furthermore, we demonstrate FMRP to be critically important for regulating key molecules in TNF receptor 1 (TNFR1)-dependent apoptosis and necroptosis including CYLD, c-FLIPS and JNK, which contribute to prolonged RIPK1 expression. Accordingly, the RIPK1 inhibitor Necrostatin-1s could reduce liver cell death and alleviate liver damage in Fmr1null mice following TNF exposure. Consistently, FMRP-deficient mice developed increased pathology during acute cholestasis following bile duct ligation, which coincided with increased hepatic expression of RIPK1, RIPK3 and phosphorylation of MLKL. CONCLUSIONS: We show that FMRP plays a central role in the inhibition of TNF-mediated cell death during infection and liver disease