Modulation of neurosteroid potentiation by protein kinases at synaptic- and extrasynaptic-type GABAA receptors.

GABAA receptors are important for inhibition in the CNS where neurosteroids and protein kinases are potent endogenous modulators. Acting individually, these can either enhance or depress receptor function, dependent upon the type of neurosteroid or kinase and the receptor subunit combination. However, in vivo, these modulators probably act in concert to fine-tune GABAA receptor activity and thus inhibition, although how this is achieved remains unclear. Therefore, we investigated the relationship between these modulators at synaptic-type α1β3γ2L and extrasynaptic-type α4β3δ GABAA receptors using electrophysiology. For α1β3γ2L, potentiation of GABA responses by tetrahydro-deoxycorticosterone was reduced after inhibiting protein kinase C, and enhanced following its activation, suggesting this kinase regulates neurosteroid modulation. In comparison, neurosteroid potentiation was reduced at α1β3(S408A,S409A)γ2L receptors, and unaltered by PKC inhibitors or activators, indicating that phosphorylation of β3 subunits is important for regulating neurosteroid activity. To determine whether extrasynaptic-type GABAA receptors were similarly modulated, α4β3δ and α4β3(S408A,S409A)δ receptors were investigated. Neurosteroid potentiation was reduced at both receptors by the kinase inhibitor staurosporine. By contrast, neurosteroid-mediated potentiation at α4(S443A)β3(S408A,S409A)δ receptors was unaffected by protein kinase inhibition, strongly suggesting that phosphorylation of α4 and β3 subunits is required for regulating neurosteroid activity at extrasynaptic receptors. Western blot analyses revealed that neurosteroids increased phosphorylation of β3(S408,S409) implying that a reciprocal pathway exists for neurosteroids to modulate phosphorylation of GABAA receptors. Overall, these findings provide important insight into the regulation of GABAA receptors in vivo, and into the mechanisms by which GABAergic inhibitory transmission may be simultaneously tuned by two endogenous neuromodulators

Raviart Thomas Petrov-Galerkin Finite Elements

The general theory of Babu\v{s}ka ensures necessary and sufficient conditions for a mixed problem in classical or Petrov-Galerkin form to be well posed in the sense of Hadamard. Moreover, the mixed method of Raviart-Thomas with low-level elements can be interpreted as a finite volume method with a non-local gradient. In this contribution, we propose a variant of type Petrov-Galerkin to ensure a local computation of the gradient at the interfaces of the elements. The in-depth study of stability leads to a specific choice of the test functions. With this choice, we show on the one hand that the mixed Petrov-Galerkin obtained is identical to the finite volumes scheme "volumes finis \`a 4 points" ("VF4") of Faille, Gallo\"uet and Herbin and to the condensation of mass approach developed by Baranger, Maitre and Oudin. On the other hand, we show the stability via an inf-sup condition and finally the convergence with the usual methods of mixed finite elements.Comment: arXiv admin note: text overlap with arXiv:1710.0439

The forward kinematics of doubly-planar Gough-Stewart platforms and the position analysis of strips of tetrahedra

The final publication is available at link.springer.comA strip of tetrahedra is a tetrahedron-tetrahedron truss where any tetrahedron has two neighbors except those in the extremes which have only one. The problem of finding all the possible lengths for an edge in the strip compatible with a given distance imposed between the strip end-points has been revealed of relevance due to the large number of possible applications. In this paper, this is applied to solve the forward kinematics of 6-6 Gough-Stewart platforms with planar base and moving platform, a problem which is known to have up to 40 solutions (20 if we do not consider mirror configurations with respect to the base as different solutions).Peer ReviewedPostprint (author's final draft

Tuberculosis: the implications for anaesthesia

Tuberculosis is a common problem in South Africa, and provides a number of challenges for the anaesthetist. Patients may present in a variety of ways. Constitutional and pulmonary symptoms are the most common. These may impact on fitness for surgery and choice of anaesthesia. Tuberculosis treatment has the potential for a number of significant drug interactions. These are primarily mediated through induction of the cytochrome P450 enzyme system by rifampicin. Guidelines for the prevention of tuberculosis in the theatre environment need to be followed to avoid placing staff and other patients in danger.Keywords: tuberculosis, antitubercular agents, drug interactions, transmission, bacterial filte

Anaesthetic management of laparoscopic assisted bilateral adrenalectomy in a five-year-old child with Cushing’s disease

A five-year-old girl, weighing 42 kg and with a diagnosis of Cushing’s disease, presented for bilateral, laparoscopic adrenalectomy.South Afr J Anaesth Analg 2011;17(6):396-39

Use of the sitting position for pineal tumour surgery in a five-year-old child

The sitting position provides almost ideal access to several areas within the cranium. The high risk of air embolism has led to decreased use of the sitting position. However, improved identification of patients at risk of paradoxical embolism may allow a more calculated, safer use thereof. Despite an improved understanding of the risks, many neurosurgical centres seldom use this position, and the occasional use of a complex patient position can then create additional challenges. This case report of a child requiring pineal surgery in the sitting position includes a review of the use of this position in children, and highlights the current emphasis on assessing the risk of paradoxical embolism before proceeding to the use of such a position.South Afr J Anaesth Analg, 2011;17(6):388-39

Diseases of red deer introduced to Patagonia and implications for native ungulates

The red deer (Cervus elaphus) invasion in Patagonia has been continuing for nearly a century, with occurrence in all habitats between 34-55°S. Their distribution, movement patterns and locally high densities raise concerns over their potential epidemiological role in maintaining disease reservoirs or transmitting diseases like foot-and-mouth disease or tuberculosis, with potential severe health and economical impact at the interface of humans, livestock or native wildlife.  Among adult females collected by rifle and radiocollared deer that died naturally, no ectoparasites were found (n=73). Fasciola hepatica was encountered in three surveys at prevalences ranging from  9 to 50% (n=108). Taenia ovis krabbei was identified, and Cysticerus tenuicollis was found at a prevalence of 8% (n=12). Ostertagia sp., Bunostomum sp., and Dictyocaulus sp. had a prevalence of 75%, 25% and 13% (n=9), respectively. Several gastrointestinal parasites reported at low prevalence in endangered Patagonian huemul (Hippocamelus bisulcus), are common in livestock and considered commensals in domestic ruminants. Sympatry of huemul with livestock is commonplace, whereas with red deer it occurs in 100 years in Argentina, both red deer and livestock play epidemiological roles for shared diseases. Research, conservation and management efforts should be directed towards livestock herd health programs or restriction of free livestock movements, particularly if diseases are shown to have impact on recruitment of endangered natives. Livestock are routinely researched and inspected at slaughter and thus provide a proxy for diseases afflicting co-existing ungulates.Testing for antibodies to foot-and-mouth disease viral antigen was negative (n=41). A tentative diagnosis of mycobacterial infection  was based on typical visceral  lesions. Antler damage occurred on 73% of shed antlers, with 36% having major breaks of tines and main beams, possibly indicating mineral imbalances. One male had both antlers, including pedicles with portions of frontal, parietal and occipital bones broken off the skull, causing his death. The prevalence of 0.9% of campylognathia (n=776) indicates that the disease unlikely is inheritable, because the founding stock of 20 animals would have had a prevalence of at least 5%. Among deer, handedness of scoliosis related significantly to the hemisphere where specimens originated (p <0.001, n=131). Coriolis forces are known to affect early stages of development such as the innervation pattern of the mammalian vestibular system, or the plane of bilateral symmetry. It is therefore conceivable that the networks processing these environmental cues, or the mechanisms responsible for compensation, are malfunctioning and thus result in a preponderance of facial scoliosis in accordance to the earth´s rotation.Fil: Fluck, Werner Thomas. Universidad de Basilea; Suiza. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata; ArgentinaFil: Smith Flueck, Jm. Universidad Atlantida Argentina; Argentin

The changing immunology of organ transplantation

The engrafted organ becomes a chimera as the recipient's leukocytes station themselves in the transplant. Remarkably, the recipient becomes chimeric as well, in a reverse migration involving immune cells from the graft. Interactions between donor and recipient cells are tolerogenic-a process with implications for the goal of graft acceptance with minimal immunosuppression

Determination of the strange nucleon form factors

The strange contribution to the electric and magnetic form factors of the nucleon is determined at a range of discrete values of $Q^2$ up to $1.4$ GeV$^2$. This is done by combining recent lattice QCD results for the electromagnetic form factors of the octet baryons with experimental determinations of those quantities. The most precise result is a small negative value for the strange magnetic moment: $G_M^s(Q^2=0) = -0.07\pm0.03\,\mu_N$. At larger values of $Q^2$ both the electric and magnetic form factors are consistent with zero to within $2$-sigma