Nanopores: maltoporin channel as a sensor for maltodextrin and lambda-phage

BACKGROUND: To harvest nutrition from the outside bacteria e.g. E. coli developed in the outer cell wall a number of sophisticated channels called porins. One of them, maltoporin, is a passive specific channel for the maltodextrin uptake. This channel was also named LamB as the bacterial virus phage Lambda mis-uses this channel to recognise the bacteria. The first step is a reversible binding followed after a lag phase by DNA injection. To date little is known about the binding capacity and less on the DNA injection mechanism. To elucidate the mechanism and to show the sensitivity of our method we reconstituted maltoporin in planar lipid membranes. Application of an external transmembrane electric field causes an ion current across the channel. Maltoporin channel diameter is around a few Angstroem. At this size the ion current is extremely sensitive to any modification of the channels surface. Protein conformational changes, substrate binding etc will cause fluctuations reflecting the molecular interactions with the channel wall. The recent improvement in ion current fluctuation analysis allows now studying the interaction of solutes with the channel on a single molecular level. RESULTS: We could demonstrate the asymmetry of the bacterial phage Lambda binding to its natural receptor maltoporin. CONCLUSION: We suggest that this type of measurement can be used as a new type of biosensors

HLA-J, a Non-Pseudogene as a New Prognostic Marker for Therapy Response and Survival in Breast Cancer

The human leukocyte antigen (HLA) genes are cell-surface proteins, essential for immune cell interaction. HLA-G is known for their high immunosuppressive effect and its potential as predictive marker in breast cancer. However, nothing is known about the HLA-J and its immunosuppressive, prognostic and predictive features, as it is assumed to be a pseudogene by in silico sequence interpretation. HLA-J, ESR1, ERBB2, KRT5 and KRT20 mRNA expression were analysed in 29 fresh frozen breast cancer biopsies and their corresponding resectates obtained from patients treated with neoadjuvant chemotherapy (NACT). mRNA was analysed with gene specific TaqMan-based Primer/Probe sets and normalized to Calmodulin 2. All breast cancer samples did express HLA-J and frequently increased HLA-J mRNA levels after NACT. HLA-J mRNA was significantly associated with overexpression of the ESR1 mRNA status (Spearman ρ 0,5679; p = 0.0090) and KRT5 mRNA (Spearman ρ 0,6121; p = 0.0041) in breast cancer core biopsies and dominated in luminal B subtype. Kaplan Meier analysis revealed that an increase of HLA-J mRNA expression after NACT had worse progression free survival (p = 0,0096), indicating a counterreaction of tumor tissues presumably to prevent elimination by enhanced immune infiltration induced by NACT. This counterreaction is associated with worse prognosis. To our knowledge this is the first study identifying HLA-J as a new predictive marker in breast cancer being involved in immune evasion mechanisms.Humane Leukozyten-Antigene (HLA) sind Proteine auf der Zelloberfläche, die essenziell für die Immunzellinteraktion sind. HLA-G ist für seine hohe immunosuppressive Wirkung sowie als potenzieller prädikativer Marker für Brustkrebs bekannt. Dagegen ist kaum etwas über HLA-J und seine immunosuppressiven, prognostischen und prädiktiven Eigenschaften bekannt, da es basierend auf In-silico-Sequenzanalysen als „Pseudogen“ interpretiert wurde. Die Expression von HLA-J, ESR1, ERBB2, KRT5 und KRT20 mRNA wurde in 29 frisch gefrorenen Brustkrebsbiopsien analysiert und mit den klinisch-pathologischen Daten von Patientinnen, welche mit neoadjuvanter Chemotherapie behandelt wurden, verglichen. Die mRNA-Expression wurde mit genspezifischen TaqMan-basierten Primer/Probe-Sets analysiert und auf Calmodulin 2 normalisiert. Alle Gewebeproben von Patientinnen mit Brustkrebs exprimierten HLA-J, und der HLA-J-mRNA-Spiegel war nach NACT oft erhöht. In den Brustkrebsstanzbiopsien war die HLA-J-mRNA-Expression signifikant mit der Überexpression von ESR1-mRNA (Spearmans ρ 0,5679; p = 0,0090) und KRT5-mRNA (Spearmans ρ 0,6121; p = 0,0041) assoziiert und dominierte im Luminal-B-Subtyp. Die Kaplan-Meier-Analyse zeigte, dass ein Anstieg der HLA-J-mRNA-Expression nach NACT mit einem schlechteren progressionsfreien Überleben einhergeht (p = 0,0096), womöglich als Gegenreaktion des Tumorgewebes, um eine Eliminierung durch tumorinfiltrierende Lymphozyten, welche durch eine NACT induziert wurden, zu verhindern. Diese Gegenreaktion ist mit einer schlechteren Prognose assoziiert. Soweit uns bekannt, handelt es sich hierbei um die erste Studie, die HLA-J als neuen prädiktiven Marker im Brustkrebs identifiziert hat und möglicherweise zur Immunevasion beiträgt

Energetic particle cross-field diffusion: Interaction with Magnetic Decreases (MDs)

International audienceMagnetic field Decreases (MDs) are detected in the heliospheric polar regions. The MDs have minimum spatial scales sizes of 25 proton thermal gyroradii, and are typically bounded by tangential or rotational discontinuities. The distribution of the magnitudes of the decreases within AIDs is a continuum, with the smallest decreases being most frequent in occurrence. The largest decreases can be 80% of the ambient field. The thickness distribution is also a continuum, and is shown to be independent of the field magnitude decrease. Charged particle interactions with the MDs lead to particle guiding center displacements and hence particle cross-held diffusion. We develop a diffusion model to apply to energetic ion interactions with MDs using the MD properties described in this paper. One specific day of data is used to illustrate that the particle cross-field diffusion will be extremely rapid due to such interactions

Kanamycin uptake into Escherichia coli is facilitated by OmpF and OmpC porin channels located in the outer membrane

Despite decades of therapeutic application of aminoglycosides, it is still a matter of debate if porins contribute to the translocation of the antibiotics across the bacterial outer membrane. Here, we quantified the uptake of kanamycin across the major porin channels OmpF and OmpC present in the outer membrane of Escherichia coli. Our analysis revealed that, despite its relatively large size, about 10–20 kanamycin molecules per second permeate through OmpF and OmpC under a 10 μM concentration gradient, whereas OmpN does not allow the passage. Molecular simulations elucidate the uptake mechanism of kanamycin through these porins. Whole-cell studies with a defined set of E. coli porin mutants provide evidence that translocation of kanamycin via porins is relevant for antibiotic potency. The values are discussed with respect to other antibiotics

Negative electrostatic contribution to the bending rigidity of charged membranes and polyelectrolytes screened by multivalent counterions

Bending rigidity of a charged membrane or a charged polyelectrolyte screened by monovalent counterions is known to be enhanced by electrostatic effects. We show that in the case of screening by multivalent counterions the electrostatic effects reduce the bending rigidity. This inversion of the sign of the electrostatic contribution is related to the formation of two-dimensional strongly correlated liquids (SCL) of counterions at the charged surface due to strong lateral repulsion between them. When a membrane or a polyelectrolyte is bent, SCL is compressed on one side and stretched on the other so that thermodynamic properties of SCL contribute to the bending rigidity. Thermodynamic properties of SCL are similar to those of Wigner crystal and are anomalous in the sense that the pressure, compressibility and screening radius of SCL are negative. This brings about substantial negative correction to the bending rigidity. For the case of DNA this effect qualitatively agrees with experiment.Comment: 8 pages, 2 figure

Magnetospheric Emission from Extrasolar Planets

The magnetospheric emissions from extrasolar planets represent a science frontier for the next decade. All of the solar system giant planets and the Earth produce radio emissions as a result of interactions between their magnetic fields and the solar wind. In the case of the Earth, its magnetic field may contribute to its habitability by protecting its atmosphere from solar wind erosion and by preventing energetic particles from reaching its surface. Indirect evidence for at least some extrasolar giant planets also having magnetic fields includes the modulation of emission lines of their host stars phased with the planetary orbits, likely due to interactions between the stellar and planetary magnetic fields. If magnetic fields are a generic property of giant planets, then extrasolar giant planets should emit at radio wavelengths allowing for their direct detection. Existing observations place limits comparable to the flux densities expected from the strongest emissions. Additional sensitivity at low radio frequencies coupled with algorithmic improvements likely will enable a new means of detection and characterization of extrasolar planets within the next decade.Comment: Science white paper for Astro2010; submitted to PSF pane

Plasma Depletion and Mirror Waves Ahead of Interplanetary Coronal Mass Ejections

We find that the sheath regions between fast interplanetary coronal mass ejections (ICMEs) and their preceding shocks are often characterized by plasma depletion and mirror wave structures, analogous to planetary magnetosheaths. A case study of these signatures in the sheath of a magnetic cloud (MC) shows that a plasma depletion layer (PDL) coincides with magnetic field draping around the MC. In the same event, we observe an enhanced thermal anisotropy and plasma beta as well as anti-correlated density and magnetic fluctuations which are signatures of mirror mode waves. We perform a superposed epoch analysis of ACE and Wind plasma and magnetic field data from different classes of ICMEs to illuminate the general properties of these regions. For MCs preceded by shocks, the sheaths have a PDL with an average duration of 6 hours (corresponding to a spatial span of about 0.07 AU) and a proton temperature anisotropy ${T_{\perp p}\over T_{\parallel p}}\simeq 1.2$ -1.3, and are marginally unstable to the mirror instability. For ICMEs with preceding shocks which are not MCs, plasma depletion and mirror waves are also present but at a reduced level. ICMEs without shocks are not associated with these features. The differences between the three ICME categories imply that these features depend on the ICME geometry and the extent of upstream solar wind compression by the ICMEs. We discuss the implications of these features for a variety of crucial physical processes including magnetic reconnection, formation of magnetic holes and energetic particle modulation in the solar wind.Comment: fully refereed, accepted for publication in J. Geophys. Re

Topological magnetic order and superconductivity in EuRbFe4As4

We study single crystals of the magnetic superconductor EuRbFe4As4 by magnetization, electron spin resonance ESR , angle resolved photoemission spectroscopy, and electrical resistance in pulsed magnetic fields up to 63 T. The superconducting state below 36.5 K is almost isotropic and is only weakly affected by the development of Eu2 magnetic order at 15 K. On the other hand, for the external magnetic field applied along the c axis the temperature dependence of the ESR linewidth reveals a Berezinskii Kosterlitz Thouless topological transition below 15 K. This indicates that Eu2 planes are a good realization of a two dimensional XY magnet, which reflects the decoupling of the Eu2 magnetic moments from superconducting FeAs layer

Charge-Fluctuation-Induced Non-analytic Bending Rigidity

In this Letter, we consider a neutral system of mobile positive and negative charges confined on the surface of curved films. This may be an appropriate model for: i) a highly charged membrane whose counterions are confined to a sheath near its surface; ii) a membrane composed of an equimolar mixture of anionic and cationic surfactants in aqueous solution. We find that the charge fluctuations contribute a non-analytic term to the bending rigidity that varies logarithmically with the radius of curvature. This may lead to spontaneous vesicle formation, which is indeed observed in similar systems.Comment: Revtex, 9 pages, no figures, submitted to PR

Detecting the orientation of magnetic fields in galaxy clusters

Clusters of galaxies, filled with hot magnetized plasma, are the largest bound objects in existence and an important touchstone in understanding the formation of structures in our Universe. In such clusters, thermal conduction follows field lines, so magnetic fields strongly shape the cluster's thermal history; that some have not since cooled and collapsed is a mystery. In a seemingly unrelated puzzle, recent observations of Virgo cluster spiral galaxies imply ridges of strong, coherent magnetic fields offset from their centre. Here we demonstrate, using three-dimensional magnetohydrodynamical simulations, that such ridges are easily explained by galaxies sweeping up field lines as they orbit inside the cluster. This magnetic drape is then lit up with cosmic rays from the galaxies' stars, generating coherent polarized emission at the galaxies' leading edges. This immediately presents a technique for probing local orientations and characteristic length scales of cluster magnetic fields. The first application of this technique, mapping the field of the Virgo cluster, gives a startling result: outside a central region, the magnetic field is preferentially oriented radially as predicted by the magnetothermal instability. Our results strongly suggest a mechanism for maintaining some clusters in a 'non-cooling-core' state.Comment: 48 pages, 21 figures, revised version to match published article in Nature Physics, high-resolution version available at http://www.cita.utoronto.ca/~pfrommer/Publications/pfrommer-dursi.pd