The Single State Dominance Hypothesis and the Two-Neutrino Double Beta Decay of Mo100

The hypothesis of the single state dominance (SSD) in the calculation of the two-neutrino double beta decay of Mo100 is tested by exact consideration of the energy denominators of the perturbation theory. Both transitions to the ground state as well as to the 0+ and 2+ excited states of the final nucleus Ru100 are considered. We demonstrate, that by experimental investigation of the single electron energy distribution and the angular correlation of the outgoing electrons, the SSD hypothesis can be confirmed or ruled out by a precise two-neutrino double beta decay measurement (e.g. by NEMO III collaboration).Comment: 13 pages, RevTex, 1 figur

Regulation of Neuron Survival through an Intersectin-Phosphoinositide 3'-Kinase C2 -AKT Pathway

While endocytosis attenuates signals from plasma membrane receptors, recent studies suggest that endocytosis also serves as a platform for the compartmentalized activation of cellular signaling pathways. Intersectin (ITSN) is a multidomain scaffolding protein that regulates endocytosis and has the potential to regulate various biochemical pathways through its multiple, modular domains. To address the biological importance of ITSN in regulating cellular signaling pathways versus in endocytosis, we have stably silenced ITSN expression in neuronal cells by using short hairpin RNAs. Decreasing ITSN expression dramatically increased apoptosis in both neuroblastoma cells and primary cortical neurons. Surprisingly, the loss of ITSN did not lead to major defects in the endocytic pathway. Yeast two-hybrid analysis identified class II phosphoinositide 3′-kinase C2β (PI3K-C2β) as an ITSN binding protein, suggesting that ITSN may regulate a PI3K-C2β-AKT survival pathway. ITSN associated with PI3K-C2β on a subset of endomembrane vesicles and enhanced both basal and growth factor-stimulated PI3K-C2β activity, resulting in AKT activation. The use of pharmacological inhibitors, dominant negatives, and rescue experiments revealed that PI3K-C2β and AKT were epistatic to ITSN. This study represents the first demonstration that ITSN, independent of its role in endocytosis, regulates a critical cellular signaling pathway necessary for cell survival

Neutrino statistics and big bang nucleosynthesis

Neutrinos may possibly violate the spin-statistics theorem, and hence obey Bose statistics or mixed statistics despite having spin half. We find the generalized equilibrium distribution function of neutrinos which depends on a single fermi-bose parameter, \kappa, and interpolates continuously between the bosonic and fermionic distributions when \kappa changes from -1 to +1. We consider modification of the Big Bang Nucleosynthesis (BBN) in the presence of bosonic or partly bosonic neutrinos. For pure bosonic neutrinos the abundances change (in comparison with the usual Fermi-Dirac case) by -3.2% for 4He (which is equivalent to a decrease of the effective number of neutrinos by \Delta N_\nu = - 0.6), +2.6% for 2H and -7% for 7Li. These changes provide a better fit to the BBN data. Future BBN studies will be able to constrain the fermi-bose parameter to \kappa > 0.5, if no deviation from fermionic nature of neutrinos is found. We also evaluate the sensitivity of future CMB and LSS observations to the fermi-bose parameter.Comment: 11 pages, 3 figures, matches version in JCAP, discussion and references extended slightl

Topographical expression of class IA and class II phosphoinositide 3-kinase enzymes in normal human tissues is consistent with a role in differentiation

BACKGROUND: Growth factor, cytokine and chemokine-induced activation of PI3K enzymes constitutes the start of a complex signalling cascade, which ultimately mediates cellular activities such as proliferation, differentiation, chemotaxis, survival, trafficking, and glucose homeostasis. The PI3K enzyme family is divided into 3 classes; class I (subdivided into IA and IB), class II (PI3K-C2α, PI3K-C2β and PI3K-C2γ) and class III PI3K. Expression of these enzymes in human tissue has not been clearly defined. METHODS: In this study, we analysed the immunohistochemical topographical expression profile of class IA (anti-p85 adaptor) and class II PI3K (PI3K-C2α and PI3K-C2β) enzymes in 104 formalin-fixed, paraffin embedded normal adult human (age 33–71 years, median 44 years) tissue specimens including those from the gastrointestinal, genitourinary, hepatobiliary, endocrine, integument and lymphoid systems. Antibody specificity was verified by Western blotting of cell lysates and peptide blocking studies. Immunohistochemistry intensity was scored from undetectable to strong. RESULTS: PI3K enzymes were expressed in selected cell populations of epithelial or mesenchymal origin. Columnar epithelium and transitional epithelia were reactive but mucous secreting and stratified squamous epithelia were not. Mesenchymal elements (smooth muscle and endothelial cells) and glomerular epithelium were only expressed PI3K-C2α while ganglion cells expressed p85 and PI3K-C2β. All three enzymes were detected in macrophages, which served as an internal positive control. None of the three PI3K isozymes was detected in the stem cell/progenitor compartments or in B lymphocyte aggregates. CONCLUSIONS: Taken together, these data suggest that PI3K enzyme distribution is not ubiquitous but expressed selectively in fully differentiated, non-proliferating cells. Identification of the normal in vivo expression pattern of class IA and class II PI3K paves the way for further analyses which will clarify the role played by these enzymes in inflammatory, neoplastic and other human disease conditions

Health Industries in the Twentieth Century. Introduction

This article is the introduction to the special issue' Health Industries in the Twentieth Century'. It offers a broad literature review of scholarly works about the history of health and medicine, and stresses the opportunities for business historians to tackle the field of healthcare

Two PI 3-Kinases and One PI 3-Phosphatase Together Establish the Cyclic Waves of Phagosomal PtdIns(3)P Critical for the Degradation of Apoptotic Cells

Cyclic oscillations in the level of phosphatidylinositol 3-phosphate in phagosomes, regulated by two phosphoinositide kinases and one phosphatase, are critical for phagosome maturation and degradation of apoptotic cells

Connecting Biology and Mathematics: First Prepare the Teachers

Developing the connection between biology and mathematics is one of the most important ways to shift the paradigms of both established science disciplines. However, adding some mathematic content to biology or biology content to mathematics is not enough but must be accompanied by development of suitable pedagogical models. I propose a model of pedagogical mathematical biological content knowledge as a feasible starting point for connecting biology and mathematics in schools and universities. The process of connecting these disciplines should start as early as possible in the educational process, in order to produce prepared minds that will be able to combine both disciplines at graduate and postgraduate levels of study. Because teachers are a crucial factor in introducing innovations in education, the first step toward such a goal should be the education of prospective and practicing elementary and secondary school teachers

Selective mGluR1 Antagonist EMQMCM Inhibits the Kainate-Induced Excitotoxicity in Primary Neuronal Cultures and in the Rat Hippocampus

Abundant evidence suggests that indirect inhibitory modulation of glutamatergic transmission, via metabotropic glutamatergic receptors (mGluR), may induce neuroprotection. The present study was designed to determine whether the selective antagonist of mGluR1 (3-ethyl-2-methyl-quinolin-6-yl)-(4-methoxy-cyclohexyl)-methanone methanesulfonate (EMQMCM), showed neuroprotection against the kainate (KA)-induced excitotoxicity in vitro and in vivo. In in vitro studies on mouse primary cortical and hippocampal neuronal cultures, incubation with KA (150 μM) induced strong degeneration [measured as lactate dehydrogenase (LDH) efflux] and apoptosis (measured as caspase-3 activity). EMQMCM (0.1–100 μM) added 30 min to 6 h after KA, significantly attenuated the KA-induced LDH release and prevented the increase in caspase-3 activity in the cultures. Those effects were dose- and time-dependent. In in vivo studies KA (2.5 nmol/1 μl) was unilaterally injected into the rat dorsal CA1 hippocampal region. Degeneration was calculated by counting surviving neurons in the CA pyramidal layer using stereological methods. It was found that EMQMCM (5–10 nmol/1 μl) injected into the dorsal hippocampus 30 min, 1 h, or 3 h (the higher dose only) after KA significantly prevented the KA-induced neuronal degeneration. In vivo microdialysis studies in rat hippocampus showed that EMQMCM (100 μM) significantly increased γ-aminobutyric acid (GABA) and decreased glutamate release. When perfused simultaneously with KA, EMQMCM substantially increased GABA release and prevented the KA-induced glutamate release. The obtained results indicate that the mGluR1 antagonist, EMQMCM, may exert neuroprotection against excitotoxicity after delayed treatment (30 min to 6 h). The role of enhanced GABAergic transmission in the neuroprotection is postulated

Structural brain abnormalities in the common epilepsies assessed in a worldwide ENIGMA study

Progressive functional decline in the epilepsies is largely unexplained. We formed the ENIGMA-Epilepsy consortium to understand factors that influence brain measures in epilepsy, pooling data from 24 research centres in 14 countries across Europe, North and South America, Asia, and Australia. Structural brain measures were extracted from MRI brain scans across 2149 individuals with epilepsy, divided into four epilepsy subgroups including idiopathic generalized epilepsies (n =367), mesial temporal lobe epilepsies with hippocampal sclerosis (MTLE; left, n = 415; right, n = 339), and all other epilepsies in aggregate (n = 1026), and compared to 1727 matched healthy controls. We ranked brain structures in order of greatest differences between patients and controls, by meta-Analysing effect sizes across 16 subcortical and 68 cortical brain regions. We also tested effects of duration of disease, age at onset, and age-by-diagnosis interactions on structural measures. We observed widespread patterns of altered subcortical volume and reduced cortical grey matter thickness. Compared to controls, all epilepsy groups showed lower volume in the right thalamus (Cohen's d = \ue2 '0.24 to \ue2 '0.73; P < 1.49 7 10 \ue2 '4), and lower thickness in the precentral gyri bilaterally (d = \ue2 '0.34 to \ue2 '0.52; P < 4.31 7 10 \ue2 '6). Both MTLE subgroups showed profound volume reduction in the ipsilateral hippocampus (d = \ue2 '1.73 to \ue2 '1.91, P < 1.4 7 10 \ue2 '19), and lower thickness in extrahippocampal cortical regions, including the precentral and paracentral gyri, compared to controls (d = \ue2 '0.36 to \ue2 '0.52; P < 1.49 7 10 \ue2 '4). Thickness differences of the ipsilateral temporopolar, parahippocampal, entorhinal, and fusiform gyri, contralateral pars triangularis, and bilateral precuneus, superior frontal and caudal middle frontal gyri were observed in left, but not right, MTLE (d = \ue2 '0.29 to \ue2 '0.54; P < 1.49 7 10 \ue2 '4). Contrastingly, thickness differences of the ipsilateral pars opercularis, and contralateral transverse temporal gyrus, were observed in right, but not left, MTLE (d = \ue2 '0.27 to \ue2 '0.51; P < 1.49 7 10 \ue2 '4). Lower subcortical volume and cortical thickness associated with a longer duration of epilepsy in the all-epilepsies, all-other-epilepsies, and right MTLE groups (beta, b < \ue2 '0.0018; P < 1.49 7 10 \ue2 '4). In the largest neuroimaging study of epilepsy to date, we provide information on the common epilepsies that could not be realistically acquired in any other way. Our study provides a robust ranking of brain measures that can be further targeted for study in genetic and neuropathological studies. This worldwide initiative identifies patterns of shared grey matter reduction across epilepsy syndromes, and distinctive abnormalities between epilepsy syndromes, which inform our understanding of epilepsy as a network disorder, and indicate that certain epilepsy syndromes involve more widespread structural compromise than previously assumed