Brain state dependent postinhibitory rebound in entorhinal cortex interneurons

Postinhibitory rebound (PIR) is believed to play an important role in the genesis and maintenance of biological rhythms. While it has been demonstrated during several in vitro studies, in vivo evidence for PIR remains scarce. Here, we report that PIR can be observed in the dorsomedial entorhinal cortex of anesthetized rats, mostly between putatively connected GABAergic interneurons, and that it is more prevalent during the theta (4-6 Hz) oscillation state than the slow (0.5-2 Hz) oscillation state. Functional inhibition was also found to be brain state and postsynaptic cell type dependent but that alone could not explain this brain state dependence of PIR. A theoretical analysis, using two Fitzhugh-Nagumo neurons coupled to an external periodic drive, predicted that the modulation of a faster spiking rate by the slower periodic drive could account for the brain state dependence of PIR. Model predictions were verified experimentally. We conclude that PIR is cell type and brain state dependent and propose that this could impact network synchrony and rhythmogenesis.     

A multi-technique study of altered granitic rock from the Krunkelbach Valley uranium deposit,Southern Germany

Herein, a multi-technique study was performed to reveal the elemental speciation and microphase composition in altered granitic rock collected from the Krunkelbach Valley uranium (U) deposit area near an abandoned U mine, Black Forest, Southern Germany. The former Krunkelbach U mine with 1–2 km surrounding area represents a unique natural analogue site with the rich accumulation of secondary U minerals suitable for radionuclide migration studies from a spent nuclear fuel (SNF) repository. Based on a micro-technique analysis using several synchrotron-based techniques such as X-ray fluorescence analysis, X-ray absorption spectroscopy, powder X-ray diffraction and laboratory-based scanning electron microscopy and Raman spectroscopy, the complex mineral assemblage was identified. While on the surface of granite, heavily altered metazeunerite–metatorbernite (Cu(UO₂)₂(AsO₄)_2−x(PO₄)_x·8H₂O) microcrystals were found together with diluted coatings similar to cuprosklodowskite (Cu(UO₂)₂(SiO₃OH)₂·6H₂O), in the cavities of the rock predominantly well-preserved microcrystals close to metatorbernite (Cu(UO₂)₂(PO₄)₂·8H₂O) were identified. The Cu(UO₂)₂(AsO₄)_2−x(PO₄)_x·8H₂O species exhibit uneven morphology and varies in its elemental composition, depending on the microcrystal part ranging from well-preserved to heavily altered on a scale of ∼200 μm. The microcrystal phase alteration could be presumably attributed to the microcrystal morphology, variations in chemical composition, and geochemical conditions at the site. The occurrence of uranyl-arsenate-phosphate and uranyl-silicate mineralisation on the surface of the same rock indicates the signatures of different geochemical conditions that took place after the oxidative weathering of the primary U- and arsenic (As)-bearing ores. The relevance of uranyl minerals to SNF storage and the potential role of uranyl-arsenate mineral species in the mobilization of U and As into the environment is discussed.

A multi-technique elemental and microphase analysis of altered granitic rock from the Krunkelbach Valley uranium deposit, Black Forest, Southern Germany.     

Discovery and structure-activity relationship of (1R)-8-chloro-2,3,4,5-tetrahydro-1-methyl-1H-3-benzazepine (Lorcaserin), a selective serotonin 5-HT2C receptor agonist for the treatment of obesity

The synthesis and SAR of a novel 3-benzazepine series of 5-HT2C agonists is described. Compound 7d (lorcaserin, APD356) was identified as one of the more potent and selective compounds in vitro (pEC50 values in functional assays measuring [(3)H]phosphoinositol turnover: 5-HT2C = 8.1; 5-HT2A = 6.8; 5-HT2B = 6.1) and was potent in an acute in vivo rat food intake model upon oral administration (ED50 at 6 h = 18 mg/kg). Lorcaserin was further characterized in a single-dose pharmacokinetic study in rat (t1/2 = 3.7 h; F = 86%) and a 28-day model of weight gain in growing Sprague-Dawley rat (8.5% decrease in weight gain observed at 36 mg/kg b.i.d.). Lorcaserin was selected for further evaluation in clinical trials for the treatment of obesity.     

Surveillance and molecular characterization of rotavirus strains circulating in Manipur,North-Eastern India: Increasing prevalence of emerging G12 strains

To determine the frequency and genotypes of rotavirus strains, samples were collected from children hospitalized with acute diarrhea at the Regional Institute of Medical Sciences, Manipur. The globally common genotypes G1P[8] and G2P[4] constituted 58% of the total positive strains, while 3% and 8% strains were emerging genotypes, G9P[6] and G12P[6]. This is the first report of genotype G12 in Manipur. The G12 strains clustered with lineage III strains and had >98% identity with corresponding rotaviruses from Bangladesh, Thailand and the USA. Other uncommon G–P combinations including G4P[4], G4P[6], G10P[6] and G9P[19], along with a few strains that could not be typed were also found. The VP7 genes of G4 and G10 strains clustered with porcine and bovine strains, indicating possible zoonotic transmission. High frequency (36–62%) of rotavirus infection and predominance of G1P[8] and G2P[4] among children with acute diarrhea emphasized the need for implementation of currently available vaccines to reduce the burden of rotavirus induced diarrhea in India.     

Percutaneous endobiliary RFA combined with balloon-sweep for re-opening occluded metallic biliary stents

The aim of this report is to discuss the results of percutaneous endobiliary radiofrequency ablation (RFA) combined with balloon-sweep technique in restoring the patency of occluded self-expandable metallic stents (SEMS) secondary to tumor infiltration. A total of eight patients underwent endobiliary RFA for reopening of occluded SEMS at our institute. After endobiliary RFA, all patients showed restoration of stent patency. After a median follow-up of 6.5 months, four patients had succumbed to the underlying disease at 3, 4, 6, and 7 months. Two of these required reinterventions at 2 and 5 months. One patient died of sepsis and aspiration pneumonia at 3 months. Of the remaining three patients, two required re-intervention after 2 months, while the other remained asymptomatic. The mean duration of stent patency after the first session of RFA was 4?±?2.1 months, which was comparable to the primary patency of these stents (4.2 months). Our experience suggests that endobiliary RFA with balloon sweep is a safe and useful technique for re-establishing the patency of occluded SEMS.