Planck scale effects in neutrino physics

We study the phenomenology and cosmology of the Majoron (flavon) models of three active and one inert neutrino paying special attention to the possible (almost) conserved generalization of the Zeldovich-Konopinski-Mahmoud lepton charge. Using Planck scale physics effects which provide the breaking of the lepton charge, we show how in this picture one can incorporate the solutions to some of the central issues in neutrino physics such as the solar and atmospheric neutrino puzzles, dark matter and a 17 keV neutrino. These gravitational effects induce tiny Majorana mass terms for neutrinos and considerable masses for flavons. The cosmological demand for the sufficiently fast decay of flavons implies a lower limit on the electron neutrino mass in the range of 0.1-1 eV.Comment: 24 pages, 1 figure (not included but available upon request), LaTex, IC/92/196, SISSA-140/92/EP, LMU-09/9

Virtual LSPs at e+ e- Colliders

Currently popular search strategies for supersymmetric particles may be significantly affected due to relatively light sneutrinos which decay dominantly into invisible channels. In certain cases the second lightest neutralino may also decay invisibly leading to two extra carriers of missing energy (in addition to the lightest supersymmetric particle (LSP)) -- the virtual LSPs (VLSPs). It is shown that if the sneutrino masses happen to be in the small but experimentally allowed range ~ 45 - 55 GeV, these particles together with neutralino pairs may contribute significantly to the missing energy in the process e+ e- ---> \gamma + missing energy at LEP-2 energies as an enhancement over the Standard Model or the conventional MSSM predictions. It is further shown that a much larger region of the parameter space can be scanned at a high luminosity e+ e- collider at 500 GeV like the proposed NLC machine. Moreover this process can play a complementary role to direct chargino searches at LEP-2 and NLC which may fail due to a near mass degeneracy of the chargino and the sneutrino. Formulae for the cross sections taking into account full mixings of the charginos and the neutralinos are derived. The signal remains observable even in the context of more restricted models based on N=1 SUGRA with common scalar and gaugino masses. The effect of soft photon brehmsstrahlung on the signal is also discussed briefly.Comment: 51 pages, LaTeX plus 13 postscript figures included using epsfig in uuencoded and compressed form, minor comments adde

Clear-PEM: A PET imaging system dedicated to breast cancer diagnostics

The Clear-PEM scanner for positron emission mammography under development is described. The detector is based on pixelized LYSO crystals optically coupled to avalanche photodiodes and readout by a fast low-noise electronic system. A dedicated digital trigger (TGR) and data acquisition (DAQ) system is used for on-line selection of coincidence events with high efficiency, large bandwidth and small dead-time. A specialized gantry allows to perform exams of the breast and of the axilla. In this paper we present results of the measurement of detector modules that integrate the system under construction as well as the imaging performance estimated from Monte Carlo simulated data.http://www.sciencedirect.com/science/article/B6TJM-4M942B5-D/1/e8aea93baa1aeae3538ea200a5a5466

HIF-1 and c-Src Mediate Increased Glucose Uptake Induced by Endothelin-1 and Connexin43 in Astrocytes

In previous work we showed that endothelin-1 (ET-1) increases the rate of glucose uptake in astrocytes, an important aspect of brain function since glucose taken up by astrocytes is used to supply the neurons with metabolic substrates. In the present work we sought to identify the signalling pathway responsible for this process in primary culture of rat astrocytes. Our results show that ET-1 promoted an increase in the transcription factor hypoxia-inducible factor-1α (HIF-1α) in astrocytes, as shown in other cell types. Furthermore, HIF-1α-siRNA experiments revealed that HIF-1α participates in the effects of ET-1 on glucose uptake and on the expression of GLUT-1, GLUT-3, type I and type II hexokinase. We previously reported that these effects of ET-1 are mediated by connexin43 (Cx43), the major gap junction protein in astrocytes. Indeed, our results show that silencing Cx43 increased HIF-1α and reduced the effect of ET-1 on HIF-1α, indicating that the effect of ET-1 on HIF-1α is mediated by Cx43. The activity of oncogenes such as c-Src can up-regulate HIF-1α. Since Cx43 interacts with c-Src, we investigated the participation of c-Src in this pathway. Interestingly, both the treatment with ET-1 and with Cx43-siRNA increased c-Src activity. In addition, when c-Src activity was inhibited neither ET-1 nor silencing Cx43 were able to up-regulate HIF-1α. In conclusion, our results suggest that ET-1 by down-regulating Cx43 activates c-Src, which in turn increases HIF-1α leading to the up-regulation of the machinery required to take up glucose in astrocytes. Cx43 expression can be reduced in response not only to ET-1 but also to various physiological and pathological stimuli. This study contributes to the identification of the signalling pathway evoked after Cx43 down-regulation that results in increased glucose uptake in astrocytes. Interestingly, this is the first evidence linking Cx43 to HIF-1, which is a master regulator of glucose metabolism

Mechanisms of Loss of Functions of Human Angiogenin Variants Implicated in Amyotrophic Lateral Sclerosis

Background: Mutations in the coding region of angiogenin (ANG) gene have been found in patients suffering from Amyotrophic Lateral Sclerosis (ALS). Neurodegeneration results from the loss of angiogenic ability of ANG (protein coded by ANG). In this work, we performed extensive molecular dynamics (MD) simulations of wild-type ANG and disease associated ANG variants to elucidate the mechanism behind the loss of ribonucleolytic activity and nuclear translocation activity, functions needed for angiogenesis. Methodology/Principal Findings: MD simulations were carried out to study the structural and dynamic differences in the catalytic site and nuclear localization signal residues between WT-ANG (Wild-type ANG) and six mutants. Variants K17I, S28N, P112L and V113I have confirmed association with ALS, while T195C and A238G single nucleotide polymorphisms (SNPs) encoding L35P and K60E mutants respectively, have not been associated with ALS. Our results show that loss of ribonucleolytic activity in K17I is caused by conformational switching of the catalytic residue His114 by 99u. The loss of nuclear translocation activity of S28N and P112L is caused by changes in the folding of the residues 31 RRR 33 that result in the reduction in solvent accessible surface area (SASA). Consequently, we predict that V113I will exhibit loss of angiogenic properties by loss of nuclear translocation activity and L35P by loss of both ribonucleolytic activity and nuclear translocation activity. No functional loss was inferred for K60E. The MD simulation results were supported by hydrogen bond interactio

Gas7-Deficient Mouse Reveals Roles in Motor Function and Muscle Fiber Composition during Aging

Background: Growth arrest-specific gene 7 (Gas7) has previously been shown to be involved in neurite outgrowth in vitro; however, its actual role has yet to be determined. To investigate the physiological function of Gas7 in vivo, here we generated a Gas7-deficient mouse strain with a labile Gas7 mutant protein whose functions are similar to wild-type Gas7. Methodology/Principal Findings: Our data show that aged Gas7-deficient mice have motor activity defects due to decreases in the number of spinal motor neurons and in muscle strength, of which the latter may be caused by changes in muscle fiber composition as shown in the soleus. In cross sections of the soleus of Gas7-deficient mice, gross morphological features and levels of myosin heavy chain I (MHC I) and MHC II markers revealed significantly fewer fast fibers. In addition, we found that nerve terminal sprouting, which may be associated with slow and fast muscle fiber composition, was considerably reduced at neuromuscular junctions (NMJ) during aging. Conclusions/Significance: These findings indicate that Gas7 is involved in motor neuron function associated with muscle strength maintenance

Treatment of Rat Spinal Cord Injury with the Neurotrophic Factor Albumin-Oleic Acid: Translational Application for Paralysis, Spasticity and Pain

Sensorimotor dysfunction following incomplete spinal cord injury (iSCI) is often characterized by the debilitating symptoms of paralysis, spasticity and pain, which require treatment with novel pleiotropic pharmacological agents. Previous in vitro studies suggest that Albumin (Alb) and Oleic Acid (OA) may play a role together as an endogenous neurotrophic factor. Although Alb can promote basic recovery of motor function after iSCI, the therapeutic effect of OA or Alb-OA on a known translational measure of SCI associated with symptoms of spasticity and change in nociception has not been studied. Following T9 spinal contusion injury in Wistar rats, intrathecal treatment with: i) Saline, ii) Alb (0.4 nanomoles), iii) OA (80 nanomoles), iv) Alb-Elaidic acid (0.4/80 nanomoles), or v) Alb-OA (0.4/80 nanomoles) were evaluated on basic motor function, temporal summation of noxious reflex activity, and with a new test of descending modulation of spinal activity below the SCI up to one month after injury. Albumin, OA and Alb-OA treatment inhibited nociceptive Tibialis Anterior (TA) reflex activity. Moreover Alb-OA synergistically promoted early recovery of locomotor activity to 50±10% of control and promoted de novo phasic descending inhibition of TA noxious reflex activity to 47±5% following non-invasive electrical conditioning stimulation applied above the iSCI. Spinal L4–L5 immunohistochemistry demonstrated a unique increase in serotonin fibre innervation up to 4.2±1.1 and 2.3±0.3 fold within the dorsal and ventral horn respectively with Alb-OA treatment when compared to uninjured tissue, in addition to a reduction in NR1 NMDA receptor phosphorylation and microglia reactivity. Early recovery of voluntary motor function accompanied with tonic and de novo phasic descending inhibition of nociceptive TA flexor reflex activity following Alb-OA treatment, mediated via known endogenous spinal mechanisms of action, suggests a clinical application of this novel neurotrophic factor for the treatment of paralysis, spasticity and pain