Revisiting the relativistic ejection event in XTE J1550-564 during the 1998 outburst

We revisit the discovery outburst of the X-ray transient XTE J1550−564 during which relativistic jets were observed in 1998 September, and review the radio images obtained with the Australian Long Baseline Array, and light curves obtained with the Molonglo Observatory Synthesis Telescope and the Australia Telescope Compact Array. Based on Hi spectra, we constrain the source distance to between 3.3 and 4.9 kpc. The radio images, taken some 2 d apart, show the evolution of an ejection event. The apparent separation velocity of the two outermost ejecta is at least 1.3c and may be as large as 1.9c; when relativistic effects are taken into account, the inferred true velocity is ≥ 0.8c. The flux densities appear to peak simultaneously during the outburst, with a rather flat (although still optically thin) spectral index of −0.2

No excess of mitochondrial DNA deletions within muscle in progressive multiple sclerosis

BACKGROUND: Mitochondrial dysfunction is an established feature of multiple sclerosis (MS). We recently described high levels of mitochondrial DNA (mtDNA) deletions within respiratory enzyme-deficient (lacking mitochondrial respiratory chain complex IV with intact complex II) neurons and choroid plexus epithelial cells in progressive MS. OBJECTIVES: The objective of this paper is to determine whether respiratory enzyme deficiency and mtDNA deletions in MS were in excess of age-related changes within muscle, which, like neurons, are post-mitotic cells that frequently harbour mtDNA deletions with ageing and in disease. METHODS: In progressive MS cases (n=17), known to harbour an excess of mtDNA deletions in the central nervous system (CNS), and controls (n=15), we studied muscle (paraspinal) and explored mitochondria in single fibres. Histochemistry, immunohistochemistry, laser microdissection, real-time polymerase chain reaction (PCR), long-range PCR and sequencing were used to resolve the single muscle fibres. RESULTS: The percentage of respiratory enzyme-deficient muscle fibres, mtDNA deletion level and percentage of muscle fibres harbouring high levels of mtDNA deletions were not significantly different in MS compared with controls. CONCLUSION: Our findings do not provide support to the existence of a diffuse mitochondrial abnormality involving multiple systems in MS. Understanding the cause(s) of the CNS mitochondrial dysfunction in progressive MS remains a research priority

Ocean temperature and salinity components of the Madden-Julian oscillation observed by Argo floats

New diagnostics of the Madden-Julian Oscillation (MJO) cycle in ocean temperature and, for the first time, salinity are presented. The MJO composites are based on 4 years of gridded Argo float data from 2003 to 2006, and extend from the surface to 1,400 m depth in the tropical Indian and Pacific Oceans. The MJO surface salinity anomalies are consistent with precipitation minus evaporation fluxes in the Indian Ocean, and with anomalous zonal advection in the Pacific. The Argo sea surface temperature and thermocline depth anomalies are consistent with previous studies using other data sets. The near-surface density changes due to salinity are comparable to, and partially offset, those due to temperature, emphasising the importance of including salinity as well as temperature changes in mixed-layer modelling of tropical intraseasonal processes. The MJO-forced equatorial Kelvin wave that propagates along the thermocline in the Pacific extends down into the deep ocean, to at least 1,400 m. Coherent, statistically significant, MJO temperature and salinity anomalies are also present in the deep Indian Ocean

Identifying causes of Western Pacific ITCZ drift in ECMWF System 4 hindcasts

The development of systematic biases in climate models used in operational seasonal forecasting adversely affects the quality of forecasts they produce. In this study, we examine the initial evolution of systematic biases in the ECMWF System 4 forecast model, and isolate aspects of the model simulations that lead to the development of these biases. We focus on the tendency of the simulated intertropical convergence zone in the western equatorial Pacific to drift northwards by between 0.5° and 3° of latitude depending on season. Comparing observations with both fully coupled atmosphere–ocean hindcasts and atmosphere-only hindcasts (driven by observed sea-surface temperatures), we show that the northward drift is caused by a cooling of the sea-surface temperature on the Equator. The cooling is associated with anomalous easterly wind stress and excessive evaporation during the first twenty days of hindcast, both of which occur whether air-sea interactions are permitted or not. The easterly wind bias develops immediately after initialisation throughout the lower troposphere; a westerly bias develops in the upper troposphere after about ten days of hindcast. At this point, the baroclinic structure of the wind bias suggests coupling with errors in convective heating, although the initial wind bias is barotropic in structure and appears to have an alternative origin

To respond or not to respond - a personal perspective of intestinal tolerance

For many years, the intestine was one of the poor relations of the immunology world, being a realm inhabited mostly by specialists and those interested in unusual phenomena. However, this has changed dramatically in recent years with the realization of how important the microbiota is in shaping immune function throughout the body, and almost every major immunology institution now includes the intestine as an area of interest. One of the most important aspects of the intestinal immune system is how it discriminates carefully between harmless and harmful antigens, in particular, its ability to generate active tolerance to materials such as commensal bacteria and food proteins. This phenomenon has been recognized for more than 100 years, and it is essential for preventing inflammatory disease in the intestine, but its basis remains enigmatic. Here, I discuss the progress that has been made in understanding oral tolerance during my 40 years in the field and highlight the topics that will be the focus of future research

Value of prominent flow voids without cord edema in the detection of spinal arteriovenous fistulae

Purpose: To determine the prevalence of spinal dural arteriovenous fistulae (SDAVF) in patients presenting with prominent vascular flow voids on imaging without other imaging findings suggestive of SDAVF. Methods: We retrospectively identified patients from January 1, 2005 to March 1, 2012 who underwent spinal angiography for suspected SDAVF with prominent vascular flow voids on prior imaging. We excluded patients with other major spinal pathology or other imaging findings of SDAVF including cord hyperintensity, enhancement, or expansion. We calculated the proportion of patients with positive findings for SDAVF on angiography and evaluated the prevalence of SDAVF for this finding alone and in correlation with clinical findings. Results: 18 patients underwent spinal angiography for prominent flow voids on imaging without other spinal pathology or imaging findings of SDAVF. Three had a SDAVF detected on angiography. The prevalence of SDAVF in this population was low, only 17% (95% CI 6-39%). All of the patients with positive angiography findings had myelopathy, increasing the prevalence to 100% if the additional clinical finding of myelopathy was present. Conclusions: Prominent flow voids without other imaging findings suggestive of SDAVF is poorly predictive of the presence of a SDAVF, unless myelopathy is present clinically. © 2014 Alhilali et al

Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.

The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition

Deletion of the GABAA α2-subunit does not alter self dministration of cocaine or reinstatement of cocaine seeking

Rationale GABAA receptors containing α2-subunits are highly represented in brain areas that are involved in motivation and reward, and have been associated with addiction to several drugs, including cocaine. We have shown previously that a deletion of the α2-subunit results in an absence of sensitisation to cocaine. Objective We investigated the reinforcing properties of cocaine in GABAA α2-subunit knockout (KO) mice using an intravenous self-administration procedure. Methods α2-subunit wildtype (WT), heterozygous (HT) and KO mice were trained to lever press for a 30 % condensed milk solution. After implantation with a jugular catheter, mice were trained to lever press for cocaine (0.5 mg/kg/infusion) during ten daily sessions. Responding was extinguished and the mice tested for cue- and cocaine-primed reinstatement. Separate groups of mice were trained to respond for decreasing doses of cocaine (0.25, 0.125, 0.06 and 0.03 mg/kg). Results No differences were found in acquisition of lever pressing for milk. All genotypes acquired self-administration of cocaine and did not differ in rates of self-administration, dose dependency or reinstatement. However, whilst WT and HT mice showed a dose-dependent increase in lever pressing during the cue presentation, KO mice did not. Conclusions Despite a reported absence of sensitisation, motivation to obtain cocaine remains unchanged in KO and HT mice. Reinstatement of cocaine seeking by cocaine and cocaine-paired cues is also unaffected. We postulate that whilst not directly involved in reward perception, the α2-subunit may be involved in modulating the “energising” aspect of cocaine’s effects on reward-seeking

Hyponatremia revisited: Translating physiology to practice

The complexity of hyponatremia as a clinical problem is likely caused by the opposite scenarios that accompany this electrolyte disorder regarding pathophysiology (depletional versus dilutional hyponatremia, high versus low vasopressin levels) and therapy (rapid correction to treat cerebral edema versus slow correction to prevent osmotic demyelination, fluid restriction versus fluid resuscitation). For a balanced differentiation between these opposites, an understanding of the pathophysiology of hyponatremia is required. Therefore, in this review an attempt is made to translate the physiology of water balance regulation to strategies that improve the clinical management of hyponatremia. A physiology-based approach to the patient with hyponatremia is presented, first addressing the possibility of acute hyponatremia, and then asking if and if so why vasopressin is secreted non-osmotically. Additional diagnostic recommendations are not to rely too heavily of the assessment of the extracellular fluid volume, to regard the syndrome of inappropriate antidiuresis as a diagnosis of exclusion, and to rationally investigate the pathophysiology of hyponatremia rather than to rely on isolated laboratory values with arbitrary cutoff values. The features of the major hyponatremic disorders are discussed, including diuretic-induced hyponatremia, adrenal and pituitary insufficiency, the syndrome of inappropriate antidiuresis, cerebral salt wasting, and exercise-associated hyponatremia. The treatment of hyponatremia is reviewed from simple saline solutions to the recently introduced vasopressin receptor antagonists, including their promises and limitations. Given the persistently high rates of hospital-acquired hyponatremia, the importance of improving the management of hyponatremia seems both necessary and achievable. Copyrigh