Deletion of TRAAK Potassium Channel Affects Brain Metabolism and Protects against Ischemia

Cerebral stroke is a worldwide leading cause of disability. The two-pore domain K(+) channels identified as background channels are involved in many functions in brain under physiological and pathological conditions. We addressed the hypothesis that TRAAK, a mechano-gated and lipid-sensitive two-pore domain K(+) channel, is involved in the pathophysiology of brain ischemia. We studied the effects of TRAAK deletion on brain morphology and metabolism under physiological conditions, and during temporary focal cerebral ischemia in Traak(-/-) mice using a combination of in vivo magnetic resonance imaging (MRI) techniques and multinuclear magnetic resonance spectroscopy (MRS) methods. We provide the first in vivo evidence establishing a link between TRAAK and neurometabolism. Under physiological conditions, Traak(-/-) mice showed a particular metabolic phenotype characterized by higher levels of taurine and myo-inositol than Traak(+/+) mice. Upon ischemia, Traak(-/-) mice had a smaller infarcted volume, with lower contribution of cellular edema than Traak(+/+) mice. Moreover, brain microcirculation was less damaged, and brain metabolism and pH were preserved. Our results show that expression of TRAAK strongly influences tissue levels of organic osmolytes. Traak(-/-) mice resilience to cellular edema under ischemia appears related to their physiologically high levels of myo-inositol and of taurine, an aminoacid involved in the modulation of mitochondrial activity and cell death. The beneficial effects of TRAAK deletion designate this channel as a promising pharmacological target for the treatment against stroke

Magnetic resonance imaging of the neuroprotective effect of xaliproden in rats

RATIONALE AND OBJECTIVES: The neurotrophic effect of Xaliproden has been followed using sequential cerebral magnetic resonance imaging (MRI) in rats with vincristine-induced brain lesion as a model of Alzheimer disease. METHODS: Nineteen rats received an intraseptal injection of vincristine on day 0, followed by a daily gavage with either the vehicle (Tween-20 1%) (n = 10) or Xaliproden (10 mg/kg) (n = 9). Eight sham-operated controls received a daily gavage with either the vehicle (n = 4) or Xaliproden (n = 4). Brain MR imaging was performed at 4.7 T on a Biospec 47/30 MR system before surgery then 3, 7, 10, and 14 days after surgery. RESULTS: At day 3 following vincristine injection, an increase in MR signal intensity in the septum was observed on T2-weighted images. This increase was maximal at day 10, and remained stable until day 14. Daily treatment with Xaliproden delayed the appearance of hypersignals until day 7 and reduced by Ca. 50% the magnitude of the increase in signal intensity from day 10. No changes were observed in the hippocampus. CONCLUSION: Quantitative MRI objectifies noninvasively the neuroprotective effect of Xaliproden on rat brain anatomy

Diffusion-weighted imaging in normal fetal brain maturation

Diffusion-weighted imaging (DWI) provides information about tissue maturation not seen on conventional magnetic resonance imaging. The aim of this study is to analyze the evolution over time of the apparent diffusion coefficient (ADC) of normal fetal brain in utero. DWI was performed on 78 fetuses, ranging from 23 to 37 gestational weeks (GW). All children showed at follow-up a normal neurological evaluation. ADC values were obtained in the deep white matter (DWM) of the centrum semiovale, the frontal, parietal, occipital and temporal lobe, in the cerebellar hemisphere, the brainstem, the basal ganglia (BG) and the thalamus. Mean ADC values in supratentorial DWM areas (1.68 ± 0.05mm2/s) were higher compared with the cerebellar hemisphere (1.25 ± 0.06mm2/s) and lowest in the pons (1.11 ± 0.05mm2/s). Thalamus and BG showed intermediate values (1.25 ± 0.04mm2/s). Brainstem, cerebellar hemisphere and thalamus showed a linear negative correlation with gestational age. Supratentorial areas revealed an increase in ADC values, followed by a decrease after the 30th GW. This study provides a normative data set that allows insights in the normal fetal brain maturation in utero, which has not yet been observed in previous studies on premature babie

Hybrid organo-inorganic materials of the VPO system

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Spectrum of Kidney Involvement in Patients with Myelodysplastic Syndromes.

Myelodysplastic syndromes (MDS) are characterized by a high prevalence of associated autoimmune manifestations. Kidney involvement has been rarely reported in MDS patients. We report on the spectrum of kidney pathological findings in MDS patients. We retrospectively identified MDS patients who had undergone a kidney biopsy between 2001 and 2019 in nine Swiss and French nephrology centres. Nineteen patients (median age 74 years [63-83]) were included. At the time of kidney biopsy, eleven (58%) patients had extra-renal auto-immune manifestations and sixteen (84%) presented with acute kidney injury. Median serum creatinine at diagnosis was 2.8 mg/dL [0.6-8.3] and median urinary protein to creatinine ratio was 1.2 g/g [0.2-11]. Acute tubulo-interstitial nephritis (TIN) was present in seven (37%) patients. Immunofluorescence study in one patient with acute TIN disclosed intense IgG deposits along the tubular basement membrane and Bowman's capsule. Other kidney pathological features included ANCA-negative pauci-immune necrotizing and crescentic glomerulonephritis (n = 3), membranous nephropathy (n = 2), IgA nephropathy (n = 1), IgA vasculitis (n = 1), immunoglobulin-associated membrano-proliferative glomerulonephritis type I (n=1), crescentic C3 glomerulopathy (n = 1), fibrillary glomerulonephritis (n = 1) and minimal change disease (n = 1). Eleven (58%) patients received immunosuppressive treatments, among whom one developed a severe infectious complication. After a median follow-up of 7 month [1-96], nine (47%) patients had chronic kidney disease stage 3 (n = 6) or 4 (n = 3) and five (26%) progressed to end-stage kidney disease. Three patients died. MDS are associated to several autoimmune kidney manifestations, predominantly acute TIN. MDS are to be listed among the potential causes of autoimmune TIN

SUBARU prime focus spectrograph: integration, testing and performance for the first spectrograph

The Prime Focus Spectrograph (PFS) of the Subaru Measurement of Images and Redshifts (SuMIRe) project for Subaru telescope consists in four identical spectrographs fed by 600 fibers each. Each spectrograph is composed by an optical entrance unit that creates a collimated beam and distributes the light to three channels, two visibles and one near infrared. This paper presents the on-going effort for the tests & integration process for the first spectrograph channel: we have developed a detailed Assembly Integration and Test (AIT) plan, as well as the methods, detailed processes and I&T tools. We describe the tools we designed to assemble the parts and to test the performance of the spectrograph. We also report on the thermal acceptance tests we performed on the first visible camera unit. We also report on and discuss the technical difficulties that did appear during this integration phase. Finally, we detail the important logistic process that is require to transport the components from other country to Marseille

Cloning and expression of a complementary DNA encoding a high affinity human neurotensin receptor

AbstractA human neurotensin receptor (hNTR) cDNA was cloned from the colonic adenocarcinoma cell line HT29. The cloned cDNA encodes a putative peptide of 418 amino acids with 7 transmembrane domains. The amino acid sequence of the hNTR is 84% identical to the rat NTR [Neuron, 4 (1990) 847-854]. Transfection of this cDNA into COS cells results in the expression of receptors with pharmacological properties similar to those found with HT29 cells. Northern blot analysis using the hNTR cDNA probe indicated a single transcript of 4 kb in the brain, the small intestine and blood mononuclear cells

The ambivalent shadow of the pre-Wilsonian rise of international law

The generation of American international lawyers who founded the American Society of International Law in 1906 and nurtured the soil for what has been retrospectively called a “moralistic legalistic approach to international relations” remains little studied. A survey of the rise of international legal literature in the U.S. from the mid-19th century to the eve of the Great War serves as a backdrop to the examination of the boosting effect on international law of the Spanish American War in 1898. An examination of the Insular Cases before the US Supreme Court is then accompanied by the analysis of a number of influential factors behind the pre-war rise of international law in the U.S. The work concludes with an examination of the rise of natural law doctrines in international law during the interwar period and the critiques addressed.by the realist founders of the field of “international relations” to the “moralistic legalistic approach to international relation

The 18 kDa Translocator Protein (Peripheral Benzodiazepine Receptor) Expression in the Bone of Normal, Osteoprotegerin or Low Calcium Diet Treated Mice

The presence of the translocator protein (TSPO), previously named as the mitochondrial or peripheral benzodiazepine receptor, in bone cells was studied in vitro and in situ using RT-qPCR, and receptor autoradiography using the selective TSPO ligand PK11195

Prime Focus Spectrograph (PFS) for the Subaru Telescope: Overview, recent progress, and future perspectives

PFS (Prime Focus Spectrograph), a next generation facility instrument on the 8.2-meter Subaru Telescope, is a very wide-field, massively multiplexed, optical and near-infrared spectrograph. Exploiting the Subaru prime focus, 2394 reconfigurable fibers will be distributed over the 1.3 deg field of view. The spectrograph has been designed with 3 arms of blue, red, and near-infrared cameras to simultaneously observe spectra from 380nm to 1260nm in one exposure at a resolution of ~1.6-2.7A. An international collaboration is developing this instrument under the initiative of Kavli IPMU. The project is now going into the construction phase aiming at undertaking system integration in 2017-2018 and subsequently carrying out engineering operations in 2018-2019. This article gives an overview of the instrument, current project status and future paths forward.Comment: 17 pages, 10 figures. Proceeding of SPIE Astronomical Telescopes and Instrumentation 201