Theileria annulata promotes Src kinase-dependent host cell polarization by manipulating actin dynamics in podosomes and lamellipodia

Theileria annulata is an intracellular protozoan parasite that infects B cells and macrophages of ruminants. Macrophages infected with T. annulata are de-differentiated and display tumour cell properties and a metastatic behaviour. How parasitized cells adapt their morphology, motility and invasive behaviour has not yet been addressed in detail. In this study, I investigated the regulation of host cell actin dynamics in T. annulata-transformed macrophages and how this affects host cell morphology and motility. T. annulata was found to promote the formation of filamentous-actin-rich podosome-type adhesions (PTAs) and lamellipodia, and to establish a polarized morphology of the infected cell. Characteristic for parasite-dependent host cell polarization is that infected cells display a single, persistent lamellipodium. Src kinases--in particular Hck--are required for the polar extension of this lamellipodium. Hck does so by promoting the clustered assembly of PTAs and accumulation of proteins of the Ezrin, Radixin, Moesin (ERM) family in lamellipodia. Polar accumulation of PTAs and ERM proteins correlates with focal matrix degradation underneath lamellipodia. These findings suggest that T. annulata equips its host cell with properties to adhere and invade. These properties are likely to promote the motile behaviour required for dissemination of infected cells in vivo.

The role of postoperative prophylactic antibiotics in the treatment of facial fractures: a randomised, double-blind, placebo-controlled pilot clinical study. Part 1: orbital fractures in 62 patients

The aim of this study was to evaluate the difference between the effects of a 5-day and a 1-day course of antibiotics on the incidence of postoperative infection after displaced fractures of the orbit. A total of 62 patients with orbital blow-out fractures were randomly assigned to two groups, both of which were given amoxicillin/clavulanic acid 1.2g intravenously every 8h from the time of admission to 24h postoperatively. The 5-day group were then given amoxicillin/clavulanic acid 625mg orally every 8h for 4 further days. The 1-day group were given placebo orally at the same time intervals. Follow up appointments were 1, 2, 4, 6, and 12 weeks, and 6 months, postoperatively. An infection in the orbital region was the primary end point. Sixty of the 62 patients completed the study. Two of the 29 patients in the 5-day group (6.8%) and 1/31 patients in the 1-day group (3.2%) developed local infections. In the 5-day group 1 patient developed diarrhoea. In the 1-day group 1 patient developed a rash on the trunk. There were no significant differences in the incidence of infection or side effects between the groups. We conclude that in displaced orbital fractures a postoperative 1-day course of antibiotics is as effective in preventing infective complications as a 5-day regimen.

Orbital involvement in Pott's puffy tumor: a systematic review of published cases

Pott's puffy tumor (PPT) is a frontal subperiosteal abscess associated with underlying frontal bone osteomyelitis. It represents a well-known source of sinogenic intracranial infection, but the orbital complications related to this entity are rarely reported. The goal of this study was to characterize the orbital involvement in PPT.

Loss of astrocyte polarization upon transient focal brain ischemia as a possible mechanism to counteract early edema formation

Brain edema is the main cause of death from brain infarction. The polarized expression of the water channel protein aquaporin-4 (AQP4) on astroglial endfeet surrounding brain microvessels suggests a role in brain water balance. Loss of astrocyte foot process anchoring to the basement membrane (BM) accompanied by the loss of polarized localization of AQP4 to astrocytic endfeet has been shown to be associated with vasogenic/extracellular edema in neuroinflammation. Here, we asked if loss of astrocyte polarity is also observed in cytotoxic/intracellular edema following focal brain ischemia after transient middle cerebral artery occlusion (tMCAO). Upon mild focal brain ischemia, we observed diminished immunostaining for the BM components laminin α4, laminin α2, and the proteoglycan agrin, in the core of the lesion, but not in BMs in the surrounding penumbra. Staining for the astrocyte endfoot anchorage protein β-dystroglycan (DG) was dramatically reduced in both the lesion core and the penumbra, and AQP4 and Kir4.1 showed a loss of polarized localization to astrocytic endfeet. Interestingly, we observed that mice deficient for agrin expression in the brain lack polarized localization of β-DG and AQP4 at astrocytic endfeet and do not develop early cytotoxic/intracellular edema following tMCAO. Taken together, these data indicate that the binding of DG to agrin embedded in the subjacent BM promotes polarized localization of AQP4 to astrocyte endfeet. Reduced DG protein levels and redistribution of AQP4 as observed upon tMCAO might therefore counteract early edema formation and reflect a beneficial mechanism operating in the brain to minimize damage upon ischemia.

On supercurrent superfields and Fayet–Iliopoulos terms in N=1N=1 gauge theories

We revisit the supermultiplet structure of Noether currents for N=1 supersymmetric gauge theories. Using superfield identities and the field equations we show how to derive a superfield equation for the divergences of the Noether currents in terms of the supercurrent and anomaly superfields containing 16_B+16_F components. We refer to this as the natural supercurrent structure as it is invariant under all local symmetries of the theory. It corresponds to the S-multiplet of Komargodski and Seiberg. We clarify the on/off-shell nature of the currents appearing in this multiplet and we study in detail the effect of specific improvement transformations leading to 1) a Ferrara-Zumino multiplet and to 2) a multiplet containing the new improved energy-momentum tensor of Callan, Coleman and Jackiw. Our methods also apply to supersymmetric gauge theories with a Fayet-Iliopoulos term. We construct the natural supercurrent multiplet for such a theory and show how to improve this to a formally gauge-invariant Ferrara-Zumino multiplet by introducing a non-dynamical chiral superfield S to ensure superfield gauge invariance. Finally we study the coupling of this theory to supergravity and show that S remains non-dynamical if the theory is R-symmetric and that S becomes propagating if the theory is not R-symmetric, leading to non-minimal 16_B+16_F supergravity

Estimating the number of motor units using random sums with independently thinned terms

The problem of estimating the numbers of motor units N in a muscle is embedded in a general stochastic model using the notion of thinning from point process theory. In the paper a new moment type estimator for the numbers of motor units in a muscle is denned, which is derived using random sums with independently thinned terms. Asymptotic normality of the estimator is shown and its practical value is demonstrated with bootstrap and approximative confidence intervals for a data set from a 31-year-old healthy right-handed, female volunteer. Moreover simulation results are presented and Monte-Carlo based quantiles, means, and variances are calculated for N in{300,600,1000}.

Magnetic resonance imaging features of orbital inflammation with intracranial extension in four dogs

This retrospective study describes the clinical and magnetic resonance (MR) imaging features of chronic orbital inflammation with intracranial extension in four dogs (two Dachshunds, one Labrador, one Swiss Mountain). Intracranial extension was observed through the optic canal (n=1), the orbital fissure (n=4), and the alar canal (n=1). On T1-weighted images structures within the affected skull foramina could not be clearly differentiated, but were all collectively isointense to hypointense compared with the contralateral, unaffected side, or compared with gray matter. On T2-, short tau inversion recovery (STIR)-, or fluid-attenuated inversion recovery (FLAIR)-weighted images structures within the affected skull foramina appeared hyperintense compared with gray matter, and extended with increased signal into the rostral cranial fossa (n=1) and middle cranial fossa (n=4). Contrast enhancement at the level of the affected skul foramina as well as at the skull base in continuity with the orbital fissure was observed in all patients. Brain edema or definite meningeal enhancement could not be observed, but a close anatomic relationship of the abnormal tissue to the cavernous sinus was seen in two patients. Diagnosis was confirmed in three dogs (one cytology, two biopsy, one necropsy) and was presumptive in one based on clinical improvement after treatment. This study is limited by its small sample size, but provides evidence for a potential risk of intracranial extension of chronic orbital inflammation. This condition can be identified best by abnormal signal increase at the orbital fissure on transverse T2-weighted images, on dorsal STIR images, or on postcontrast transverse or dorsal images.