Fifteen minute consultation: Managing neonatal and childhood herpes encephalitis

Herpes simplex encephalitis (HSE) is the most common single cause of viral encephalitis in infants and children. Treated or untreated, it can be associated with considerable morbidity and mortality, and its presentation is usually insidious and non-specific. Prompt and careful investigation is important in order to establish the diagnosis so that treatment can be optimised. We address some common questions arising when diagnosing and treating presumed HSE throughout childhood

What doesn't kill you makes you stranger: Dipeptidyl peptidase-4 (CD26) proteolysis differentially modulates the activity of many peptide hormones and cytokines generating novel cryptic bioactive ligands

Dipeptidyl peptidase 4 (DPP4) is an exopeptidase found either on cell surfaces where it is highly regulated in terms of its expression and surface availability (CD26) or in a free/circulating soluble constitutively available and intrinsically active form. It is responsible for proteolytic cleavage of many peptide substrates. In this review we discuss the idea that DPP4-cleaved peptides are not necessarily inactivated, but rather can possess either a modified receptor selectivity, modified bioactivity, new antagonistic activity, or even a novel activity relative to the intact parent ligand. We examine in detail five different major DPP4 substrates: glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), peptide tyrosine-tyrosine (PYY), and neuropeptide Y (NPY), and stromal derived factor 1 (SDF-1 aka CXCL12). We note that discussion of the cleaved forms of these five peptides are underrepresented in the research literature, and are both poorly investigated and poorly understood, representing a serious research literature gap. We believe they are understudied and misinterpreted as inactive due to several factors. This includes lack of accurate and specific quantification methods, sample collection techniques that are inherently inaccurate and inappropriate, and a general perception that DPP4 cleavage inactivates its ligand substrates. Increasing evidence points towards many DPP4-cleaved ligands having their own bioactivity. For example, GLP-1 can work through a different receptor than GLP-1R, DPP4-cleaved GIP can function as a GIP receptor antagonist at high doses, and DPP4-cleaved PYY, NPY, and CXCL12 can have different receptor selectivity, or can bind novel, previously unrecognized receptors to their intact ligands, resulting in altered signaling and functionality. We believe that more rigorous research in this area could lead to a better understanding of DPP4’s role and the biological importance of the generation of novel cryptic ligands. This will also significantly impact our understanding of the clinical effects and side effects of DPP4-inhibitors as a class of anti-diabetic drugs that potentially have an expanding clinical relevance. This will be specifically relevant in targeting DPP4 substrate ligands involved in a variety of other major clinical acute and chronic injury/disease areas including inflammation, immunology, cardiology, stroke, musculoskeletal disease and injury, as well as cancer biology and tissue maintenance in aging

Experiments with polarized 3He at MAMI

Experiments with polarized 3He at MAMI have already a long tradition. The A3 collaboration started in 1993 with the aim to measure the electric form factor of the neutron. At this time MAMI was the second accelerator where experiments with 3He were possible. Some years before this pilot experiment the development of the apparatus to polarize 3He in Mainz started. There are two techniques which allow to polarize sufficient large quantities of 3He. Both techniques will be compared and the benefit of 3He for nuclear physics will be discussed. An review of the experiments done so far with 3He at MAMI will be given and the progress in the target development, the detector setup and the electron beam performance will be pointed out.Comment: Contribution to the Symposium "20 Years of Physics at the Mainz Microtron MAMI", to be published in Eur. Phys. Journal

Neutron charge form factor at large q2q^2

The neutron charge form factor $G_{En}(q)$ is determined from an analysis of the deuteron quadrupole form factor $F_{C2}$ data. Recent calculations, based on a variety of different model interactions and currents, indicate that the contributions associated with the uncertain two-body operators of shorter range are relatively small for $F_{C2}$, even at large momentum transfer $q$. Hence, $G_{En}(q)$ can be extracted from $F_{C2}$ at large $q^2$ without undue systematic uncertainties from theory.Comment: 8 pages, 3 figure

Extraction of electromagnetic neutron form factors through inclusive and exclusive polarized electron scattering on polarized 3He target

Inclusive 3He(e,e') and exclusive 3He(e,e'n) processes with polarized electrons and 3He have been theoretically analyzed and values for the magnetic and electric neutron form factors have been extracted. In both cases the form factor values agree well with the ones extracted from processes on the deuteron. Our results are based on Faddeev solutions, modern NN forces and partially on the incorporation of mesonic exchange currents.Comment: 28 pages, 29 Postscript figure

PGE1 stimulation of HEK293 cells generates multiple contiguous domains with different [cAMP]: role of compartmentalized phosphodiesterases

There is a growing appreciation that the cyclic adenosine monophosphate (cAMP)–protein kinase A (PKA) signaling pathway is organized to form transduction units that function to deliver specific messages. Such organization results in the local activation of PKA subsets through the generation of confined intracellular gradients of cAMP, but the mechanisms responsible for limiting the diffusion of cAMP largely remain to be clarified. In this study, by performing real-time imaging of cAMP, we show that prostaglandin 1 stimulation generates multiple contiguous, intracellular domains with different cAMP concentration in human embryonic kidney 293 cells. By using pharmacological and genetic manipulation of phosphodiesterases (PDEs), we demonstrate that compartmentalized PDE4B and PDE4D are responsible for selectively modulating the concentration of cAMP in individual subcellular compartments. We propose a model whereby compartmentalized PDEs, rather than representing an enzymatic barrier to cAMP diffusion, act as a sink to drain the second messenger from discrete locations, resulting in multiple and simultaneous domains with different cAMP concentrations irrespective of their distance from the site of cAMP synthesis

Measurement of the Electric Form Factor of the Neutron at Q^2 = 0.3-0.8 (GeV/c)^2

The electric form factor of the neutron, G_En, has been measured at the Mainz Microtron by recoil polarimetry in the quasielastic D(e_pol,e'n_pol)p reaction. Three data points have been extracted at squared four-momentum transfers Q^2 = 0.3, 0.6 and 0.8 (GeV/c)^2. Corrections for nuclear binding effects have been applied.Comment: 9 pages, 7 figures, 2 tables. Accepted for publication in EPJ

Multiple Quantum NMR Investigations of Structure- Property Relationships in Synthetic and Aged Silicone Elastomers

Complex engineering elastomeric materials are often characterized by a complex network structure obtained by crosslinking network chains with multiple chain lengths. Further, these networks are commonly filled with thixotropic reinforcing agents such as SiO{sub 2} or carbon black. Degradation of such materials often occurs via mechanisms that alter the fundamental network structure. In order to understand the effects of modifications of network structure and filler-polymer interaction on component performance, a series of model compounds have been studied by {sup 1}H multiple quantum NMR analysis and traditional mechanical property assessments. The {sup 1}H NMR data provides insight into the distribution of segmental dynamics that reveals insight into the changes in mechanical properties

Spectral functions of isoscalar scalar and isovector electromagnetic form factors of the nucleon at two-loop order

We calculate the imaginary parts of the isoscalar scalar and isovector electromagnetic form factors of the nucleon up to two-loop order in chiral perturbation theory. Particular attention is paid on the correct behavior of Im $\sigma_N(t)$ and Im $G_{E,M}^V(t)$ at the two-pion threshold $t_0=4 m_\pi^2$ in connection with the non-relativistic 1/M-expansion. We recover the well-known strong enhancement near threshold originating from the nearby anomalous singularity at $t_c = 4m_\pi^2-m_\pi^4/M^2 = 3.98 m_\pi^2$. In the case of the scalar spectral function Im $\sigma_N(t)$ one finds a significant improvement in comparison to the lowest order one-loop result. Higher order $\pi\pi$-rescattering effects are however still necessary to close a remaining 20%-gap to the empirical scalar spectral function. The isovector electric and magnetic spectral functions Im $G_{E,M}^V(t)$ get additionally enhanced near threshold by the two-pion-loop contributions. After supplementing their two-loop results by a phenomenological $\rho$-meson exchange term one can reproduce the empirical isovector electric and magnetic spectral functions fairly well.Comment: 10 pages, 6 figures, submitted to Physical Review

Extended Gari-Krumpelmann model fits to nucleon electromagnetic form factors

Nucleon electromagnetic form factor data (including recent data) is fitted with models that respect the confinement and asymptotic freedom properties of QCD. Gari-Krumpelmann (GK) type models, which include the major vector meson pole contributions and at high momentum transfer conform to the predictions of perturbative QCD, are combined with Hohler-Pietarinen (HP) models, which also include the width of the rho meson and the addition of higher mass vector meson exchanges, but do not evolve into the explicit form of PQCD at high momentum transfer. Different parameterizations of the GK model's hadronic form factors, the effect of including the width of the rho meson and the addition of the next (in mass) isospin 1 vector meson are considered. The quality of fit and the consistency of the parameters select three of the combined HP/GK type models. Projections are made to the higher momentum transfers which are relevant to electron-deuteron experiments. The projections vary little for the preferred models, removing much of the ambiguity in electron-nucleus scattering predictions.Comment: 18pp, 7 figures, using RevTeX with BoxedEPS macros; 1 new figure, minor textual changes; email correspondence to [email protected]