The spectral function of the omega meson in nuclear matter from a coupled-channel resonance model

We calculate the spectral function of the omega meson in nuclear matter at zero temperature by means of the low-density theorem. The omega N forward scattering amplitude is calculated within a unitary coupled-channel effective Lagrangian model that has been applied successfully to the combined analysis of pion- and photon-induced reactions. While the peak of the omega spectral distribution is shifted only slightly, we find a considerable broadening of the omega meson due to resonance-hole excitations. For omega mesons at rest with respect to the surrounding nuclear medium, we find an additional width of about 60 MeV at saturation density.Comment: 26 pages, 10 figures, added short discussio

Collective modes of asymmetric nuclear matter in Quantum HadroDynamics

We discuss a fully relativistic Landau Fermi liquid theory based on the Quantum Hadro-Dynamics ($QHD$) effective field picture of Nuclear Matter ({\it NM}). From the linearized kinetic equations we get the dispersion relations of the propagating collective modes. We focus our attention on the dynamical effects of the interplay between scalar and vector channel contributions. A beautiful ``mirror'' structure in the form of the dynamical response in the isoscalar/isovector degree of freedom is revealed, with a complete parallelism in the role respectively played by the compressibility and the symmetry energy. All that strongly supports the introduction of an explicit coupling to the scalar-isovector channel of the nucleon-nucleon interaction. In particular we study the influence of this coupling (to a $\delta$-meson-like effective field) on the collective response of asymmetric nuclear matter ($ANM$). Interesting contributions are found on the propagation of isovector-like modes at normal density and on an expected smooth transition to isoscalar-like oscillations at high baryon density. Important ``chemical'' effects on the neutron-proton structure of the mode are shown. For dilute $ANM$ we have the isospin distillation mechanism of the unstable isoscalar-like oscillations, while at high baryon density we predict an almost pure neutron wave structure of the propagating sounds.Comment: 18 pages (LATEX), 8 Postscript figures, uses "epsfig

Membrane permeation of arginine-rich cell-penetrating peptides independent of transmembrane potential as a function of lipid composition and membrane fluidity

Cell-penetrating peptides (CPPs) are prominent delivery vehicles to confer cellular entry of (bio-) macromolecules. Internalization efficiency and uptake mechanism depend, next to the type of CPP and cargo, also on cell type. Direct penetration of the plasma membrane is the preferred route of entry as this circumvents endolysosomal sequestration. However, the molecular parameters underlying this import mechanism are still poorly defined. Here, we make use of the frequently used HeLa and HEK cell lines to address the role of lipid composition and membrane potential. In HeLa cells, at low concentrations, the CPP nona-arginine (R9) enters cells by endocytosis. Direct membrane penetration occurs only at high peptide concentrations through a mechanism involving activation of sphingomyelinase which converts sphingomyelin into ceramide. In HEK cells, by comparison, R9 enters the cytoplasm through direct membrane permeation already at low concentrations. This direct permeation is strongly reduced at room temperature and upon cholesterol depletion, indicating a complex dependence on membrane fluidity and microdomain organisation. Lipidomic analyses show that in comparison to HeLa cells HEK cells have an endogenously low sphingomyelin content. Interestingly, direct permeation in HEK cells and also in HeLa cells treated with exogenous sphingomyelinase is independent of membrane potential. Membrane potential is only required for induction of sphingomyelinase-dependent uptake which is then associated with a strong hyperpolarization of membrane potential as shown by whole-cell patch clamp recordings. Next to providing new insights into the interplay of membrane composition and direct permeation, these results also refute the long-standing paradigm that transmembrane potential is a driving force for CPP uptake

Modified Quark-Meson Coupling Model for Nuclear Matter

The quark-meson coupling model for nuclear matter, which describes nuclear matter as non-overlapping MIT bags bound by the self-consistent exchange of scalar and vector mesons, is modified by introducing medium modification of the bag constant. We model the density dependence of the bag constant in two different ways: one invokes a direct coupling of the bag constant to the scalar meson field, and the other relates the bag constant to the in-medium nucleon mass. Both models feature a decreasing bag constant with increasing density. We find that when the bag constant is significantly reduced in nuclear medium with respect to its free-space value, large canceling isoscalar Lorentz scalar and vector potentials for the nucleon in nuclear matter emerge naturally. Such potentials are comparable to those suggested by relativistic nuclear phenomenology and finite-density QCD sum rules. This suggests that the reduction of bag constant in nuclear medium may play an important role in low- and medium-energy nuclear physics.Comment: Part of the text is reordered, revised version to appear in Phys. Rev. C. 19 pages, ReVTeX, 4 figures embedde

The angiotensin II type 2 receptor activates flow-mediated outward remodelling through T cells-dependent interleukin-17 production

AIMS: The angiotensin II type 1 receptor (AT1R) through the activation of immune cells plays a key role in arterial inward remodelling and reduced blood flow in cardiovascular disorders. On the other side, flow (shear stress)-mediated outward remodelling (FMR), involved in collateral arteries growth in ischaemic diseases, allows revascularization. We hypothesized that the type 2 receptor (AT2R), described as opposing the effects of AT1R, could be involved in FMR. METHODS AND RESULTS: We studied FMR using a model of ligation of feed arteries supplying collateral pathways in the mouse mesenteric arterial bed in vivo. Seven days after ligation, diameter increased by 30% in high flow (HF) arteries compared with normal flow vessels. FMR was absent in mice lacking AT2R. At Day 2, T lymphocytes expressing AT2R were present preferentially around HF arteries. FMR did not occur in athymic (nude) mice lacking T cells and in mice treated with anti-CD3ε antibodies. AT2R activation induced interleukin-17 production by memory T cells. Treatment of nude mice or AT2R-deficient mice with interleukin-17 restored diameter enlargement in HF arteries. Interleukin-17 increased NO-dependent relaxation and matrix metalloproteinases activity, both important in FMR. Remodelling of feeding arteries in the skin flap model of ischaemia was also absent in AT2R-deficient mice and in anti-interleukin-17-treated mice. Finally, remodelling, absent in 12-month-old mice, was restored by a treatment with the AT2R non-peptidic agonist C21. CONCLUSION:AT2R-dependent interleukin-17 production by T lymphocyte is necessary for collateral artery growth and could represent a new therapeutic target in ischaemic disorders

Decreased Numbers of Blood Dendritic Cells and Defective Function of Regulatory T Cells in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis

BACKGROUND: Dendritic cells (DC) and regulatory cells (Treg) play pivotal roles in controlling both normal and autoimmune adaptive immune responses. DC are the main antigen-presenting cells to T cells, and they also control Treg functions. In this study, we examined the frequency and phenotype of DC subsets, and the frequency and function of Treg from patients with ANCA-associated vasculitis (AAV). METHODOLOGY/PRINCIPAL FINDINGS: Blood samples from 19 untreated patients with AAV during flares and before any immunosuppressive treatment were analyzed, along with 15 AAV patients in remission and 18 age-matched healthy controls. DC and Treg numbers, and phenotypes were assessed by flow cytometry, and in vitro suppressive function of Treg was determined by co-culture assay. When compared to healthy volunteers, absolute numbers of conventional and plasmacytoid DC were decreased in AAV patients. During the acute phase this decrease was significantly more pronounced and was associated with an increased DC expression of CD62L. Absolute numbers of Treg (CD4(+)CD25(high)CD127(low/-) Tcells) were moderately decreased in patients. FOXP3 and CD39 were expressed at similar levels on Treg from patients as compared to controls. The suppressive function of Treg from AAV patients was dramatically decreased as compared to controls, and this defect was more pronounced during flares than remission. This Treg functional deficiency occurred in the absence of obvious Th17 deviation. CONCLUSION: In conclusion, these data show that AAV flares are associated with both a decrease number and altered phenotype of circulating DC and point to a role for Treg functional deficiency in the pathogenesis of AAV

Corrigendum to 'Editor's Choice - European Society for Vascular Surgery (ESVS) 2020 Clinical Practice Guidelines on the Management of Vascular Graft and Endograft Infections' [European Journal of Vascular & Endovascular Surgery 59/3 (2020) 339-384]

peer reviewe

Expanding the clinical spectrum of hereditary fibrosing poikiloderma with tendon contractures, myopathy and pulmonary fibrosis due to <i>FAM111B </i>mutations

BACKGROUND: Hereditary Fibrosing Poikiloderma (HFP) with tendon contractures, myopathy and pulmonary fibrosis (POIKTMP [MIM 615704]) is a very recently described entity of syndromic inherited poikiloderma. Previously by using whole exome sequencing in five families, we identified the causative gene, FAM111B (NM_198947.3), the function of which is still unknown. Our objective in this study was to better define the specific features of POIKTMP through a larger series of patients. METHODS: Clinical and molecular data of two families and eight independent sporadic cases, including six new cases, were collected. RESULTS: Key features consist of: (i) early-onset poikiloderma, hypotrichosis and hypohidrosis; (ii) multiple contractures, in particular triceps surae muscle contractures; (iii) diffuse progressive muscular weakness; (iv) pulmonary fibrosis in adulthood and (v) other features including exocrine pancreatic insufficiency, liver impairment and growth retardation. Muscle magnetic resonance imaging was informative and showed muscle atrophy and fatty infiltration. Histological examination of skeletal muscle revealed extensive fibroadipose tissue infiltration. Microscopy of the skin showed a scleroderma-like aspect with fibrosis and alterations of the elastic network. FAM111B gene analysis identified five different missense variants (two recurrent mutations were found respectively in three and four independent families). All the mutations were predicted to localize in the trypsin-like cysteine/serine peptidase domain of the protein. We suggest gain-of-function or dominant-negative mutations resulting in FAM111B enzymatic activity changes. CONCLUSIONS: HFP with tendon contractures, myopathy and pulmonary fibrosis, is a multisystemic disorder due to autosomal dominant FAM111B mutations. Future functional studies will help in understanding the specific pathological process of this fibrosing disorder