(In-)Consistencies in the relativistic description of excited states in the Bethe-Salpeter equation

The Bethe-Salpeter equation provides the most widely used technique to extract bound states and resonances in a relativistic Quantum Field Theory. Nevertheless a thorough discussion how to identify its solutions with physical states is still missing. The occurrence of complex eigenvalues of the homogeneous Bethe-Salpeter equation complicates this issue further. Using a perturbative expansion in the mass difference of the constituents we demonstrate for scalar fields bound by a scalar exchange that the underlying mechanism which results in complex eigenvalues is the crossing of a normal (or abnormal) with an abnormal state. Based on an investigation of the renormalization of one-particle properties we argue that these crossings happen beyond the applicability region of the ladder Bethe-Salpeter equation. The implications for a fermion-antifermion bound state in QED are discussed, and a consistent interpretation of the bound state spectrum of QED is proposed.Comment: 39 pages, 14 figures, LaTeX2e, uses amssymb, minor changes, references added, to appear in Annals Phy

The incretin hormone glucagon-like peptide 1 increases mitral cell excitability by decreasing conductance of a voltage-dependent potassium channel.

KEY POINTS: The gut hormone called glucagon-like peptide 1 (GLP-1) is a strong moderator of energy homeostasis and communication between the peripheral organs and the brain. GLP-1 signalling occurs in the brain; using a newly developed genetic reporter line of mice, we have discovered GLP-synthesizing cells in the olfactory bulb. GLP-1 increases the firing frequency of neurons (mitral cells) that encode olfactory information by decreasing activity of voltage-dependent K channels (Kv1.3). Modifying GLP-1 levels, either therapeutically or following the ingestion of food, could alter the excitability of neurons in the olfactory bulb in a nutrition or energy state-dependent manner to influence olfactory detection or metabolic sensing. The results of the present study uncover a new function for an olfactory bulb neuron (deep short axon cells, Cajal cells) that could be capable of modifying mitral cell activity through the release of GLP-1. This might be of relevance for the action of GLP-1 mimetics now widely used in the treatment of diabetes. ABSTRACT: The olfactory system is intricately linked with the endocrine system where it may serve as a detector of the internal metabolic state or energy homeostasis in addition to its classical function as a sensor of external olfactory information. The recent development of transgenic mGLU-yellow fluorescent protein mice that express a genetic reporter under the control of the preproglucagon reporter suggested the presence of the gut hormone, glucagon-like peptide (GLP-1), in deep short axon cells (Cajal cells) of the olfactory bulb and its neuromodulatory effect on mitral cell (MC) first-order neurons. A MC target for the peptide was determined using GLP-1 receptor binding assays, immunocytochemistry for the receptor and injection of fluorescence-labelled GLP-1 analogue exendin-4. Using patch clamp recording of olfactory bulb slices in the whole-cell configuration, we report that GLP-1 and its stable analogue exendin-4 increase the action potential firing frequency of MCs by decreasing the interburst interval rather than modifying the action potential shape, train length or interspike interval. GLP-1 decreases Kv1.3 channel contribution to outward currents in voltage clamp recordings as determined by pharmacological blockade of Kv1.3 or utilizing mice with Kv1.3 gene-targeted deletion as a negative control. Because fluctuations in GLP-1 concentrations monitored by the olfactory bulb can modify the firing frequency of MCs, olfactory coding could change depending upon nutritional or physiological state. As a regulator of neuronal activity, GLP-1 or its analogue may comprise a new metabolic factor with a potential therapeutic target in the olfactory bulb (i.e. via intranasal delivery) for controlling an imbalance in energy homeostasis.This work was supported by NIH R01 DC013080 and DC003387 from the NIDCD, an American Heart Association (AHA) Postdoctoral Grant Award 14POST20380615, a Creative Research Council (CRC) award from FSU, a grant from the Medical Research Council, UK (MR/J013293/1) and support from the National Health and Medical Research Council of Australia, Project Grant #1025031. PPG-YFP mice, expressing the YFP variant Venus under the control of the mouse proglucagon promoter (mGLU124 line), were generated with grant support from the Wellcome Trus

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Immunoreactivity for the NR1 subunit of the NMDA receptor in spinally-projecting catecholamine and serotonin neurons of the rat ventral medulla

This article appeared in a journal published by Elsevier Ltd. Under Elsevier's copyright, mandated authors are not permitted to make work available in an institutional repository.Bulbospinal neurons in the ventral medulla play important roles in the regulation of sympathetic outflow. Physiological evidence suggests that these neurons are activated by N-methyl-D-aspartate (NMDA) and non-NMDA subtypes of glutamate receptors. In this study, we examined bulbospinal neurons in the ventral medulla for the presence of immunoreactivity for the NMDA NR1 subunit, which is essential for NMDA receptor function. Rats received bilateral injections of cholera toxin B into the tenth thoracic spinal segment to label bulbospinal neurons. Triple immunofluorescent labeling was used to detect cholera toxin B with a blue fluorophore, NR1 with a red fluorophore, and either tyrosine hydroxylase or tryptophan hydroxylase with a green fluorophore. In the rostral ventrolateral medulla, NR1 occurred in all bulbospinal tyrosine hydroxylase-positive neurons and 96% of bulbospinal tyrosine hydroxylase-negative neurons, which were more common in sections containing the facial nucleus. In the raphe pallidus, the parapyramidal region, and the marginal layer, 98% of bulbospinal tryptophan hydroxylase-positive neurons contained NR1 immunoreactivity. NR1 was also present in all of the bulbospinal tryptophan hydroxylase-negative neurons, which comprised 20% of bulbospinal neurons in raphe pallidus and the parapyramidal region. These results show that virtually all bulbospinal tyrosine hydroxylase and non-tyrosine hydroxylase neurons in the rostral ventrolateral medulla and virtually all bulbospinal serotonin and non-serotonin neurons in raphe pallidus and the parapyramidal region express NR1, the obligatory subunit of the NMDA receptor. NMDA receptors on bulbospinal neurons in the rostral ventral medulla likely influence sympathoexcitation in normal and pathological conditions

Interneuronal inputs to sympathetic preganglionic neurons: evidence from transected spinal cord

Boston, US

Neuropeptide Y mRNA expression in interneurons in rat spinal cord

Neuropeptide Y (NPY)-immunoreactive axons are present within the spinal cord. Some of these axons originate from neurons in the brainstem. Other axons arise from within the spinal cord since NPY-immunoreactivity can be detected after complete spinal cord transection. To identify spinal neurons that might express NPY, we localized NPY mRNA in rat spinal cord using in situ hybridization histochemistry. NPY mRNA-containing neurons were localized in the dorsal horn, in medial laminae of the grey matter and in the lateral spinal nucleus in thoracic, lumbar and sacral cord. The location of some of these neurons, and their proximity to sympathetic preganglionic neurons, suggest some NPY-containing interneurons are likely to be involved in spinal as well as supraspinal autonomic reflex pathways