159 research outputs found
Entire curves avoiding given sets in C^n
Let be a proper closed subset of and
at most countable (). We give conditions
of and , under which there exists a holomorphic immersion (or a proper
holomorphic embedding) with .Comment: 10 page
A Carleman type theorem for proper holomorphic embeddings
In 1927, Carleman showed that a continuous, complex-valued function on the
real line can be approximated in the Whitney topology by an entire function
restricted to the real line. In this paper, we prove a similar result for
proper holomorphic embeddings. Namely, we show that a proper \cC^r embedding
of the real line into \C^n can be approximated in the strong \cC^r topology
by a proper holomorphic embedding of \C into \C^n
Pseudomonas aeruginosa Expresses a Functional Human Natriuretic Peptide Receptor Ortholog: Involvement in Biofilm Formation
This is the final version of the article. Available from the publisher via the DOI in this record.Considerable evidence exists that bacteria detect eukaryotic communication molecules and modify their virulence accordingly. In previous studies, it has been demonstrated that the increasingly antibiotic-resistant pathogen Pseudomonas aeruginosa can detect the human hormones brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) at micromolar concentrations. In response, the bacterium modifies its behavior to adapt to the host physiology, increasing its overall virulence. The possibility of identifying the bacterial sensor for these hormones and interfering with this sensing mechanism offers an exciting opportunity to directly affect the infection process. Here, we show that BNP and CNP strongly decrease P. aeruginosa biofilm formation. Isatin, an antagonist of human natriuretic peptide receptors (NPR), prevents this effect. Furthermore, the human NPR-C receptor agonist cANF(4-23) mimics the effects of natriuretic peptides on P. aeruginosa, while sANP, the NPR-A receptor agonist, appears to be weakly active. We show in silico that NPR-C, a preferential CNP receptor, and the P. aeruginosa protein AmiC have similar three-dimensional (3D) structures and that both CNP and isatin bind to AmiC. We demonstrate that CNP acts as an AmiC agonist, enhancing the expression of the ami operon in P. aeruginosa. Binding of CNP and NPR-C agonists to AmiC was confirmed by microscale thermophoresis. Finally, using an amiC mutant strain, we demonstrated that AmiC is essential for CNP effects on biofilm formation. In conclusion, the AmiC bacterial sensor possesses structural and pharmacological profiles similar to those of the human NPR-C receptor and appears to be a bacterial receptor for human hormones that enables P. aeruginosa to modulate biofilm expression. IMPORTANCE: The bacterium Pseudomonas aeruginosa is a highly dangerous opportunist pathogen for immunocompromised hosts, especially cystic fibrosis patients. The sites of P. aeruginosa infection are varied, with predominance in the human lung, in which bacteria are in contact with host molecular messengers such as hormones. The C-type natriuretic peptide (CNP), a hormone produced by lung cells, has been described as a bacterial virulence enhancer. In this study, we showed that the CNP hormone counteracts P. aeruginosa biofilm formation and we identified the bacterial protein AmiC as the sensor involved in the CNP effects. We showed that AmiC could bind specifically CNP. These results show for the first time that a human hormone could be sensed by bacteria through a specific protein, which is an ortholog of the human receptor NPR-C. The bacterium would be able to modify its lifestyle by favoring virulence factor production while reducing biofilm formation.We thank Magalie Barreau and Olivier Maillot for technical assistance.
We thank Christine Farmer for linguistic insight for the manuscript.
T. Rosay is a recipient of a doctoral fellowship from the French Ministry
of Research (MRE). This work was supported by grants from the
CommunautĂ© dâAgglomĂ©ration dâEvreux, the Conseil GĂ©nĂ©ral de lâEure,
European Union (FEDER no. 31970), the French Association âVaincre la
Mucoviscidoseâ and the InterReg IVA PeReNE project
Different Dose-Dependent Modes of Action of C-Type Natriuretic Peptide on Pseudomonas aeruginosa Biofilm Formation.
We have previously shown that the C-type Natriuretic Peptide (CNP), a peptide produced by lungs, is able to impact Pseudomonasaeruginosa physiology. In the present work, the effect of CNP at different concentrations on P. aeruginosa biofilm formation was studied and the mechanisms of action of this human hormone on P. aeruginosa were deciphered. CNP was shown to inhibit dynamic biofilm formation in a dose-dependent manner without affecting the bacterial growth at any tested concentrations. The most effective concentrations were 1 and 0.1 µM. At 0.1 µM, the biofilm formation inhibition was fully dependent on the CNP sensor protein AmiC, whereas it was only partially AmiC-dependent at 1 µM, revealing the existence of a second AmiC-independent mode of action of CNP on P. aeruginosa. At 1 µM, CNP reduced both P. aeruginosa adhesion on glass and di-rhamnolipid production and also increased the bacterial membrane fluidity. The various effects of CNP at 1 µM and 0.1 µM on P. aeruginosa shown here should have major consequences to design drugs for biofilm treatment or prevention
High field dynamic nuclear polarizationâthe renaissance
Sensitivity is a critical issue in NMR spectroscopy, microscopy and imaging, and the factor that often limits the success of various applications. The origin of low sensitivity in NMR is well known to be due to the small magnetic moment of nuclear spins, which yields small Boltzmann polarizations and weak absorption signals. Historically, each advance in technology and methodology that has increased the signal-to-noise in NMR has shifted the boundary of what is achievable, often opening new areas of application and directions of research. The archetypal example of this phenomenon was the introduction of Fourier transform spectroscopy which led to increases of ~10[superscript 2]-fold in signal-to-noise, revolutionizing NMR and many other forms of spectroscopy. More recent technological developments of note include the continuing development of higher field superconducting magnets which increases polarization, and cryoprobes in which the excitation/detection coil is maintained at low temperatures increasing sensitivity through a higher probe Q and decreasing receiver noise. In addition, innovations in NMR methodology have improved sensitivity, classic examples being HartmannâHahn cross polarization, and J-coupling meditated transfer methods, and the introduction of 1H detection of [superscript 13]C/[superscript 15]N resonances. Furthermore, techniques for non-inductive detection of resonance, such as the AFM-based technique of magnetic resonance force microscopy (MRFM), have recently allowed observation of a single electron spin, and ~100 nuclear spins/âHz[superscript 8]
Abstract basins of attraction
Abstract basins appear naturally in different areas of several complex
variables. In this survey we want to describe three different topics in which
they play an important role, leading to interesting open problems
Solid-State Dynamic Nuclear Polarization at 263 GHz: Spectrometer Design and Experimental Results
Dynamic Nuclear Polarization (DNP) experiments transfer polarization from electron spins to nuclear spins with microwave irradiation of the electron spins for enhanced sensitivity in nuclear magnetic resonance (NMR) spectroscopy. Design and testing of a spectrometer for magic angle spinning (MAS) DNP experiments at 263 GHz microwave frequency, 400 MHz 1H frequency is described. Microwaves are generated by a novel continuous-wave gyrotron, transmitted to the NMR probe via a transmission line, and irradiated on a 3.2 mm rotor for MAS DNP experiments. DNP signal enhancements of up to 80 have been measured at 95 K on urea and proline in waterâglycerol with the biradical polarizing agent TOTAPOL. We characterize the experimental parameters affecting the DNP efficiency: the magnetic field dependence, temperature dependence and polarization build-up times, microwave power dependence, sample heating effects, and spinning frequency dependence of the DNP signal enhancement. Stable system operation, including DNP performance, is also demonstrated over a 36 h period.National Institutes of Health (U.S.) (NIH grant EB-002804)National Institutes of Health (U.S.) (NIH grant EB-002026
Affine modifications and affine hypersurfaces with a very transitive automorphism group
We study a kind of modification of an affine domain which produces another
affine domain. First appeared in passing in the basic paper of O. Zariski
(1942), it was further considered by E.D. Davis (1967). The first named author
applied its geometric counterpart to construct contractible smooth affine
varieties non-isomorphic to Euclidean spaces. Here we provide certain
conditions which guarantee preservation of the topology under a modification.
As an application, we show that the group of biregular automorphisms of the
affine hypersurface given by the equation
where acts transitively on the
smooth part reg of for any We present examples of such
hypersurfaces diffeomorphic to Euclidean spaces.Comment: 39 Pages, LaTeX; a revised version with minor changes and correction
An embedding of â in â 2 with hyperbolic complement
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46249/1/208_2005_Article_BF01445264.pd
Pseudomonas aeruginosa Biofilm Dispersion by the Human Atrial Natriuretic Peptide
This is the final version. Available on open access from Wiley via the DOI in this recordData Availability Statement:
The data that support the findings of this study are available from the corresponding author upon reasonable request.Pseudomonas aeruginosa biofilms cause chronic, antibiotic tolerant infections in wounds and lungs. Numerous recent studies demonstrate that bacteria can detect human communication compounds through specific sensor/receptor tools that modulate bacterial physiology. Consequently, interfering with these mechanisms offers an exciting opportunity to directly affect the infection process. It is shown that the human hormone Atrial Natriuretic Peptide (hANP) both prevents the formation of P. aeruginosa biofilms and strongly disperses established P. aeruginosa biofilms. This hANP action is dose-dependent with a strong effect at low nanomolar concentrations and takes effect in 30-120 min. Furthermore, although hANP has no antimicrobial effect, it acts as an antibiotic adjuvant. hANP enhances the antibiofilm action of antibiotics with diverse modes of action, allowing almost full biofilm eradication. The hANP effect requires the presence of the P. aeruginosa sensor AmiC and the AmiR antiterminator regulator, indicating a specific mode of action. These data establish the activation of the ami pathway as a potential mechanism for P. aeruginosa biofilm dispersion. hANP appears to be devoid of toxicity, does not enhance bacterial pathogenicity, and acts synergistically with antibiotics. These data show that hANP is a promising powerful antibiofilm weapon against established P. aeruginosa biofilms in chronic infections.Normandy RegionFrench Ministry of Research (MRE
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