Can lepton flavor violating interactions explain the LSND results?

If the atmospheric and the solar neutrino problem are both explained by neutrino oscillations, and if there are only three light neutrinos, then all mass-squared differences between the neutrinos are known. In such a case, existing terrestrial neutrino oscillation experiments cannot be significantly affected by neutrino oscillations, but, in principle there could be an anomaly in the neutrino flux due to new neutrino interactions. We discuss how a non-standard muon decay $\mu^+ \to e^+ \bar\nu_e \nu_\ell$ would modify the neutrino production processes of these experiments. Since $SU(2)_L$ violation is small for New Physics above the weak scale one can use related flavor-violating charged lepton processes to constrain these decays in a model independent way. We show that the upper bounds on $\mu \to 3e$, muonium-antimuonium conversion and $\tau \to \mu e e$ rule out any observable effect for the present experiments due to $\mu^+ \to e^+ \bar\nu_e \nu_\ell$ for $\ell=e,\mu,\tau$, respectively. Applying similar arguments to flavor-changing semi-leptonic reactions we exclude the possibility that the "oscillation signals" observed at LSND are due to flavor-changing interactions that conserve total lepton number.Comment: 21 pages, 6 figures, Latex; minor correction

Late Stage Infection in Sleeping Sickness

At the turn of the 19th century, trypanosomes were identified as the causative agent of sleeping sickness and their presence within the cerebrospinal fluid of late stage sleeping sickness patients was described. However, no definitive proof of how the parasites reach the brain has been presented so far. Analyzing electron micrographs prepared from rodent brains more than 20 days after infection, we present here conclusive evidence that the parasites first enter the brain via the choroid plexus from where they penetrate the epithelial cell layer to reach the ventricular system. Adversely, no trypanosomes were observed within the parenchyma outside blood vessels. We also show that brain infection depends on the formation of long slender trypanosomes and that the cerebrospinal fluid as well as the stroma of the choroid plexus is a hostile environment for the survival of trypanosomes, which enter the pial space including the Virchow-Robin space via the subarachnoid space to escape degradation. Our data suggest that trypanosomes do not intend to colonize the brain but reside near or within the glia limitans, from where they can re-populate blood vessels and disrupt the sleep wake cycles

Production of red fluorescent, constitutive monomeric cherry protein expressing trypanosomes for localization and morphological description of Trypanosoma brucei brucei in tissue of CNS

Trypanosoma brucei ist als kausaler Erreger der Schlafkrankheit bekannt und sein Auftreten im Liquor cerebrospinalis im sekundären Stadium der Schlafkrankheit wurde mehrfach beschrieben. Bislang ist es jedoch weitestgehend ungeklärt wie Trypanosomen in das ZNS eindringen und sich dort verhalten. Um Trypanosomen im Gewebe des ZNS zu lokalisieren, wurde ein rot fluoreszierendes Protein (mCherry) in Trypanosoma brucei brucei kloniert und das Gewebe des ZNS von Nagetieren fluoreszenz- und elektronenmikroskopisch untersucht. Die elektronenmikroskopischen Aufnahmen zeigten, dass der Parasit zunächst den Plexus choroideus besiedelt und sich anschließend über den Liqour cerebrospinalis in die Virchow-Robin Räume ausbreitet. Im Parenchym des Gehirns konnten keine Trypanosomen außerhalb von Blutgefäßen nachgewiesen werden. Zudem zeigte sich in Rekultivierungsexperimenten eine morphologisch abweichende Form von Trapanosoma brucei, die morphologisch beschrieben wurde. Die Ergebnisse lassen vermuten, dass Trypanosomen im sekundären Stadium nicht primär in das Parenchym des ZNS eindringen, sondern zunächst den Plexus choroideus besiedeln und sich morphologisch anpassen, um sich von dort über den Liquor cerebrospinalis bis in die Virchow Robin Räume auszubreiten.Trypanosomes are known as the causative agent of sleeping sickness and their presence in the cerebrospinal fluid of late stage sleeping sickness patients was described several times. However it is still unknown how trypanosomes reach the brain. To find out the localization of trypanosomes in the tissue of the CNS, a red fluorescent protein (mCherry) was cloned and expressed in Trypanosoma brucei brucei and fluorescence- and electron micrographs prepared from rodent brains were analyzed. The electron micrographs showed that the parasite first enters the brain via the choroid plexus and migrates to the ventricular system to reach the Virchow-Robin space. No trypanosomes were observed within the parenchyma of the brain outside blood vessels. In addition a new formation of long slender trypanosomes in the tissue of the CNS was morphologically described. The results suggest that trypanosomes do not enter the parenchyma of the CNS at the beginning of the second stage of sleeping sickness. First they colonize the choroid plexus and adapt to the new environment then they migrate to the ventricular system and reach the Virchow-Robin space

Zijn de Gentse wegen klaar voor de bakfiets? Onderzoek UGent naar gevolgen van opkomst van fietsvarianten voor infrastructuur

In Vlaanderen en Brussel is er een enorm potentieel aan extra fietsverplaatsingen want zelfs voor korte verplaatsingen stappen veel mensen nog in de auto. Maar in steeds meer steden krijgen fietsers en het openbaar vervoer meer ruimte dan de auto. In de geleidelijke modal shift die bezig is, kunnen fietsvarianten als de bakfiets of de ligfiets een belangrijke rol spelen. Maar het fietsnetwerk en de fietsinfrastructuur is vaak (nog) niet aangepast aan dit nieuwe type voertuigen, zo blijkt uit een onderzoek van UGent

Prostaglandin E-2 suppresses human group 2 innate lymphoid cell function

Background: Group 2 innate lymphoid cells (ILC2s) are involved in the initial phase of type 2 inflammation and can amplify allergic immune responses by orchestrating other type 2 immune cells. Prostaglandin (PG) E-2 is a bioactive lipid that plays protective roles in the lung, particularly during allergic inflammation. Objective: We set out to investigate how PGE(2) regulates human ILC2 function. Methods: The effects of PGE(2) on human ILC2 proliferation and intracellular cytokine and transcription factor expression were assessed by means of flow cytometry. Cytokine production was measured by using ELISA, and real-time quantitative PCR was performed to detect PGE(2) receptor expression. Results: PGE(2) inhibited GATA-3 expression, as well as production of the type 2 cytokines IL-5 and IL-13, from human tonsillar and blood ILC2s in response to stimulation with a combination of IL-25, IL-33, thymic stromal lymphopoietin, and IL-2. Furthermore, PGE(2) downregulated the expression of IL-2 receptor alpha (CD25). In line with this observation, PGE(2) decreased ILC2 proliferation. These effects were mediated by the combined action of E-type prostanoid receptor (EP) 2 and EP4 receptors, which were specifically expressed on ILC2s. Conclusion: Our findings reveal that PGE(2) limits ILC2 activation and propose that selective EP2 and EP4 receptor agonists might serve as a promising therapeutic approach in treating allergic diseases by suppressing ILC2 function

A human post-mortem brain model for the standardization of multi-centre MRI studies

14sireservedMulti-centre MRI studies of the brain are essential for enrolling large and diverse patient cohorts, as required for the investigation of heterogeneous neurological and psychiatric diseases. However, the multi-site comparison of standard MRI data sets that are weighted with respect to tissue parameters such as the relaxation times (T1, T2) and proton density (PD) may be problematic, as signal intensities and image contrasts depend on site-specific details such as the sequences used, imaging parameters, and sensitivity profiles of the radiofrequency (RF) coils. Water or gel phantoms are frequently used for long-term and/or inter-site quality assessment. However, these phantoms hardly mimic the structure, shape, size or tissue distribution of the human brain. The goals of this study were: (1) to validate the long-term stability of a human post-mortem brain phantom, performing quantitative mapping of T1, T2, and PD, and the magnetization transfer ratio (MTR) over a period of 18. months; (2) to acquire and analyse data for this phantom and the brain of a healthy control (HC) in a multi-centre study for MRI protocol standardization in four centres, while conducting a voxel-wise as well as whole brain grey (GM) and white matter (WM) tissue volume comparison. MTR, T2, and the quotient of PD in WM and GM were stable in the post-mortem brain with no significant changes. T1 was found to decrease from 267/236. ms (GM/WM) to 234/216. ms between 5 and 17. weeks post embedment, stabilizing during an 18-month period following the first scan at about 215/190. ms. The volumetric measures, based on T1-weighted MP-RAGE images obtained at all participating centres, revealed inter- and intra-centre variations in the evaluated GM and WM volumes that displayed similar trends in both the post-mortem brain as well as the HC. At a confidence level of 95%, brain regions such as the brainstem, deep GM structures as well as boundaries between GM and WM tissues were found to be less reproducible than other brain regions in all participating centres. The results demonstrate that a post-mortem brain phantom may be used as a reliable tool for multi-centre MR studies.mixedDroby, Amgad; Lukas, Carsten; Schänzer, Anne; Spiwoks-Becker, Isabella; Giorgio, Antonio; Gold, Ralf; De Stefano, Nicola; Kugel, Harald; Deppe, Michael; Wiendl, Heinz; Meuth, Sven G.; Acker, Till; Zipp, Frauke; Deichmann, RalfDroby, Amgad; Lukas, Carsten; Schänzer, Anne; Spiwoks Becker, Isabella; Giorgio, Antonio; Gold, Ralf; DE STEFANO, Nicola; Kugel, Harald; Deppe, Michael; Wiendl, Heinz; Meuth, Sven G.; Acker, Till; Zipp, Frauke; Deichmann, Ral

Comparison of trypanosome survival times in cerebrospinal-fluid and/or HMI-9 medium.

<p>AnTat1.1 was isolated 11 days <i>p.i.</i> from rat blood, separated from blood cells and adjusted to a cell density of 5*10⁴ parasites in 100 µl of the respective solution. Contamination of csf with blood did not exceed 20%, as judged from the erythrocyte count. <i>Rattus norvegicus</i> csf supported survival of the parasites only for some 30 hours (▴) and could not be prolonged by supplementing 33 mM glucose (data not shown). However, in a mixture of csf and HMI-9 medium (1∶1), trypanosomes survived significantly longer (i.e. approx. 45 h, ▪). As HMI-9 medium (<b>♦</b>) contains all nutrients in excess, it supports growth of trypanosomes for approximately 56 h, even if diluted with saline solution (1∶1, X).</p

Electron micrographs showing the location of trypanosomes more than 20 days after blood infection.

<p><b>a,</b> Trypanosomes (T) are in close proximity to pial cells (PC) within the subarachnoid space (SAS); BP brain parenchyma. <b>b,</b> Trypanosomes (T) are located intimately between pial cells (PC) at the intersection between subarachnoid space and <i>pia mater</i>. <b>c,</b> Area of the <i>pia mater</i> containing densly packed trypanosomes between pial cells. A, astroglial endfeet forming the <i>glia limitans</i>; SAS, subarachnoid space. <b>d,</b> Detail of c. Astrocytes (A) forming the <i>glia limitans</i> (lower line of vertical arrows). The upper line of vertical arrows marks the mesothelium. The horizontal arrow labels a tight junction between two pial cells. Trypanosomes (T) are seen between pial cells. <b>e, </b><i>Glia limitans</i> (labelled by two arrows) marks the border between brain parenchyma (BP) and <i>pia mater</i> (PM); A, foot of an astrocyte. In this image trypanosomes (T) are located within the dilated <i>glial limitans</i> (asterisks). <b>f,</b> A trypanosome located between pial cells (PC). The two arrows point to the two flagella proving that the parasites are capable of cell division at this location.</p