Investigation on the Tachyonic Neutrino

According to the experimental data, it is still controversial whether the neutrinos, especially the electron-neutrino and muon-neutrino, can be considered as the fermionic spinorial tachyons, and there is still no reliable report on the existence of the right-handed neutrinos. In this letter, we show that the neutrinos with the single handedness can not be the tachyons, but only those of the both handedness can be. Several implications of this result are discussed.Comment: 13 pages, latex, no figure

Slower-than-Light Spin-1/2 Particles Endowed with Negative Mass Squared

Extending in a straightforward way the standard Dirac theory, we study a quantum mechanical wave-equation describing free spinning particles --which we propose to call "Pseudotachyons" (PT's)-- which behave like tachyons in the momentum space, but like subluminal particles (v<c) in the ordinary space. This is allowed since, as it happens in every quantum theory for spin-1/2 particles, the momentum operator (that is conserved) and the velocity operator (that is not) are independent operators, which refer to independent quantities. As a consequence, at variance with ordinary Dirac particles, for PT's the average velocity is not equal to the classical velocity, but actually to the velocity "dual" of the classical velocity. The speed of PT's is therefore smaller than the speed of light. Since a lot of experimental data seems to involve a negative mass squared for neutrinos, we suggest that these particles might be PT's, travelling, because of their very small mass, at subluminal speeds very close to c. The present theory is shown to be separately invariant under the C, P, T transformations; the covariance under Lorentz transformations is also proved. Furthermore, we derive the kinematical constraints linking 4-impulse, 4-velocity and 4-polarization of free PT'sComment: LaTeX; 20 page

Conversion of 5-Methylcytosine to 5-Hydroxymethylcytosine in Mammalian DNA by the MLL Partner TET1

DNA cytosine methylation is crucial for retrotransposon silencing and mammalian development. In a computational search for enzymes that could modify 5-methylcytosine (5mC), we identified TET proteins as mammalian homologs of the trypanosome proteins JBP1 and JBP2, which have been proposed to oxidize the 5-methyl group of thymine. We show here that TET1, a fusion partner of the MLL gene in acute myeloid leukemia, is a 2-oxoglutarate (2OG)- and Fe(II)-dependent enzyme that catalyzes conversion of 5mC to 5-hydroxymethylcytosine (hmC) in cultured cells and in vitro. hmC is present in the genome of mouse embryonic stem cells, and hmC levels decrease upon RNA interference–mediated depletion of TET1. Thus, TET proteins have potential roles in epigenetic regulation through modification of 5mC to hmC.Chemistry and Chemical Biolog

Inducible Costimulator Expression Regulates the Magnitude of Th2-Mediated Airway Inflammation by Regulating the Number of Th2 Cells

Inducible Costimulator (ICOS) is an important regulator of Th2 lymphocyte function and a potential immunotherapeutic target for allergy and asthma. A SNP in the ICOS 5' promoter in humans is associated with increased atopy and serum IgE in a founder population and increased ICOS surface expression and Th2 cytokine production from peripheral blood mononuclear cells. However, it is unknown if increased ICOS expression contributes to disease progression or is a result of disease pathology.We developed a mouse model in which ICOS surface expression levels are genetically predetermined to test our hypothesis that genetic regulation of ICOS expression controls the severity of Th2 responses in vivo. Using ICOS+/+ and ICOS+/- mice in a Th2 model of airway inflammation, we found that T cells from the ICOS+/- mice had reduced ICOS expression and decreased Th2-mediated inflammation in vivo. Although the activation status of the T cells did not differ, T cells isolated from the lungs and draining lymph nodes of ICOS+/- mice at the peak of inflammation produced less Th2 cytokines upon stimulation ex vivo. Using 4get mice, which express GFP upon IL-4 transcription, we determined that the decreased Th2 cytokines in ICOS+/- is due to reduced percentage of Th2 cells and not a defect in their ability to produce IL-4.These data suggest that in both mice and humans, the level of ICOS surface expression regulates the magnitude of the in vivo Th2 response, perhaps by influencing Th2 differentiation

Tachyonic Field Theory and Neutrino Mass Running

In this paper three things are done. (i) We investigate the analogues of Cerenkov radiation for the decay of a superluminal neutrino and calculate the Cerenkov angles for the emission of a photon through a W loop, and for a collinear electron-positron pair, assuming the tachyonic dispersion relation for the superluminal neutrino. The decay rate of a freely propagating neutrino is found to depend on the shape of the assumed dispersion relation, and is found to decrease with decreasing tachyonic mass of the neutrino. (ii) We discuss a few properties of the tachyonic Dirac equation (symmetries and plane-wave solutions), which may be relevant for the description of superluminal neutrinos seen by the OPERA experiment, and discuss the calculation of the tachyonic propagator. (iii) In the absence of a commonly accepted tachyonic field theory, and in view of an apparent "running" of the observed neutrino mass with the energy, we write down a model Lagrangian, which describes a Yukawa-type interaction of a neutrino coupling to a scalar background field via a scalar-minus-pseudoscalar interaction. This constitutes an extension of the standard model. If the interaction is strong, then it leads to a substantial renormalization-group "running" of the neutrino mass and could potentially explain the experimental observations.Comment: 13 pages; RevTeX; to appear in Cent. Eur. J. Phy

B Cell Antigen Presentation Promotes Th2 Responses and Immunopathology during Chronic Allergic Lung Disease

Background: The role of B cells in allergic asthma remains undefined. One mechanism by which B cells clearly contribute to allergic disease is via the production of specific immunoglobulin, and especially IgE. Cognate interactions with specific T cells result in T cell help for B cells, resulting in differentiation and immunoglobulin secretion. Proximal to (and required for) T cell-dependent immunoglobulin production, however, is antigen presentation by B cells. While interaction with T cells clearly has implications for B cell function and differentiation, this study investigated the role that B cells have in shaping the T cell response during chronic allergic lung disease. Methodology/Principal Findings: In these studies, we used a clinically relevant mouse model of chronic allergic lung disease to study the role of B cells and B cell antigen presentation in this disease. In these studies we present several novel findings: 1) Lung B cells from chronically allergen challenged mice up-regulated MHC II and costimulatory molecules CD40, CD80 and CD86. 2) Using in vitro studies, B cells from the lungs of allergen challenged mice could present antigen to T cells, as assessed by T cell proliferation and the preferential production of Th2 cytokines. 3) Following chronic allergen challenge, the levels of Th2 cytokines IL-4 and IL-5 in the lungs and airways were significantly attenuated in B cell 2/2 mice, relative to controls. 4) B cell driven Th2 responses and mucus hyper secretion in the lungs were dependent upon MHC II expression by B cells. Conclusions/Significance: Collectively, these results provide evidence for antigen presentation as a novel mechanism b

Epigenetic polypharmacology: from combination therapy to multitargeted drugs

The modern drug discovery process has largely focused its attention in the so-called magic bullets, single chemical entities that exhibit high selectivity and potency for a particular target. This approach was based on the assumption that the deregulation of a protein was causally linked to a disease state, and the pharmacological intervention through inhibition of the deregulated target was able to restore normal cell function. However, the use of cocktails or multicomponent drugs to address several targets simultaneously is also popular to treat multifactorial diseases such as cancer and neurological disorders. We review the state of the art with such combinations that have an epigenetic target as one of their mechanisms of action. Epigenetic drug discovery is a rapidly advancing field, and drugs targeting epigenetic enzymes are in the clinic for the treatment of hematological cancers. Approved and experimental epigenetic drugs are undergoing clinical trials in combination with other therapeutic agents via fused or linked pharmacophores in order to benefit from synergistic effects of polypharmacology. In addition, ligands are being discovered which, as single chemical entities, are able to modulate multiple epigenetic targets simultaneously (multitarget epigenetic drugs). These multiple ligands should in principle have a lower risk of drug-drug interactions and drug resistance compared to cocktails or multicomponent drugs. This new generation may rival the so-called magic bullets in the treatment of diseases that arise as a consequence of the deregulation of multiple signaling pathways provided the challenge of optimization of the activities shown by the pharmacophores with the different targets is addressed

Phylotranscriptomics suggests the jawed vertebrate ancestor could generate diverse helper and regulatory T cell subsets

This study was supported by The Royal Society Research Grant RG130789 awarded to HD, as well as by a University of Aberdeen Centre for Genome-Enabled Biology and Medicine PhD studentship and Marine Alliance for Science and Technology for Scotland (MASTS) research grant SG363 awarded to AKR.Peer reviewedPublisher PD