Cell-autonomous inhibition of alpha 7-containing nicotinic acetylcholine receptors prevents death of parasympathetic neurons during development

Neurotrophic molecules are key retrograde influences of cell survival in the developing nervous system, but other influences such as activity are also emerging as important factors. In the avian ciliary ganglion, half the neurons are eliminated between embryonic day 8 (E8) and E14, but it is not known how cell death is initiated. Because systemic application of alpha7-nicotinic acetylcholine receptor (nAChR) antagonists prevents this cell loss, we examined differences in receptor densities and responses of intracellular calcium to nicotine using the calcium-sensitive dye fura-2. In addition, we determined whether cell-autonomous inhibition of alpha7 activation in neurons prevented cell death. E8 neurons are heterogeneous with respect to alpha7-nAChR density, which leads to large increases in [Ca2+]i in some neurons; E8 neurons also exhibit a slower rate of Ca2+ decay after nicotinic stimulation than E13 neurons. Expressing alpha-bungarotoxin that is tethered to the membrane by a glycosylphosphatidylinositol linkage (GPIalpha btx) in ciliary ganglion neurons with the retroviral vector RCASBP(A) blocks increases in intracellular calcium induced by nicotine through alpha7-nAChRs and prevents neurons from dying. Expression of GPIalpha btx in surrounding non-neural tissues, but not in neurons, does not prevent cell loss. Furthermore, the GPIalpha btx is not efficiently expressed in the accessory oculomotor neurons, eliminating preganglionic inputs as another site for action of the antagonist. These results support the hypothesis that cholinergic inputs facilitate cell death in the developing autonomic nervous system by activating alpha7-nAChRs, possibly by leading to increases in intracellular calcium that exceed the threshold for cell survival

Electromagnetic Compatibility of a Low Voltage Power Supply for the ATLAS Tile Calorimeter Front-End Electronics

The front-end electronics of the ATLAS Tile Calorimeter is powered by DC/DC converters that sit close to it. The performance of the detector electronics is constrained by the conducted noise emissions of its power supply. A compatibility limit is defined for the system. The noise susceptibility of the front-end electronics is evaluated, and different solutions to reduce the front-end electronics noise are discussed and tested

Prostate stem cell antigen is an endogenous lynx1-like prototoxin that antagonizes α7-containing nicotinic receptors and prevents programmed cell death of parasympathetic neurons

Vertebrate alpha-bungarotoxin-like molecules of the Ly-6 superfamily have been implicated as balancers of activity and survival in the adult nervous system. To determine whether a member of this family could be involved in the development of the avian ciliary ganglion, we identified 6 Gallus genes by their homology in structure to mouse lynx1 and lynx2. One of these genes, an ortholog of prostate stem cell antigen (psca), is barely detectable at embryonic day (E) 8, before neuronal cell loss in the ciliary ganglion, but increases >100-fold as the number of neurons begins to decline between E9 and E14. PSCA is highly expressed in chicken and mouse telencephalon and peripheral ganglia and correlates with expression of alpha7-containing nicotinic acetylcholine receptors (alpha7-nAChRs). Misexpressing PSCA before cell death in the ciliary ganglion blocks alpha7-nAChR activation by nicotine and rescues the choroid subpopulation from dying. Thus, PSCA, a molecule previously identified as a marker of prostate cancer, is a member of the Ly-6 neurotoxin-like family in the nervous system, and is likely to play a role as a modulator of alpha7 signaling-induced cell death during development

Radiation-Tolerant Custom Made Low Voltage Power Supply System for ATLAS/TileCal Detector

This paper describes custom made Low Voltage Power Supply (LVPS) system developed for the ATLAS – TileCal detector of the LHC (The Large Hadron Collider) particle accelerator at CERN, Geneva. The system is based on the use of only COTS (Commercial of The Shelf) components, is qualified to be radiation tolerant up to 40krad, and can operate in external DC magnetic field above 0.02 Tesla. The LVPS design described in this paper has been developed and produced for the ATLAS TileCal detector during the years 2001 – 2007

Coronal mass ejections, magnetic clouds, and relativistic magnetospheric electron events: ISTP

The role of high-speed solar wind streams in driving relativistic electron acceleration within the Earth\u27s magnetosphere during solar activity minimum conditions has been well documented. The rising phase of the new solar activity cycle (cycle 23) commenced in 1996, and there have recently been a number of coronal mass ejections (CMEs) and related “magnetic clouds” at 1 AU. As these CME/cloud systems interact with the Earth\u27s magnetosphere, some events produce substantial enhancements in the magnetospheric energetic particle population while others do not. This paper compares and contrasts relativistic electron signatures observed by the POLAR, SAMPEX, Highly Elliptical Orbit, and geostationary orbit spacecraft during two magnetic cloud events: May 27–29, 1996, and January 10–11, 1997. Sequences were observed in each case in which the interplanetary magnetic field was first strongly southward and then rotated northward. In both cases, there were large solar wind density enhancements toward the end of the cloud passage at 1 AU. Strong energetic electron acceleration was observed in the January event, but not in the May event. The relative geoeffectiveness for these two cases is assessed, and it is concluded that large induced electric fields (∂B/∂t) caused in situ acceleration of electrons throughout the outer radiation zone during the January 1997 event

Two-dimensional photonic crystal slab with embedded silicon nanocrystals: Efficient photoluminescence extraction:

A two-dimensional photonic crystal (PhC) slab was fabricated from a luminescent planar waveguide, formed by a (800 nm thick) layer of silicon nanocrystals (SiNCs) embedded in a polished silica plate. Dimensions of the PhC were designed so that light emitted by SiNCs under excitation with an external UV source can, during its propagation in the layer, interact with the periodicity and be Bragg-diffracted into air. This approach leads to up to 8-fold vertical extraction enhancement of SiNCs luminescence from the PhC slab compared to the bare planar layer. Results of the experiment are supported by the computer simulation. (C) 2013 AIP Publishing LLC

Captive breeding of Margaritifera auricularia (Spengler, 1793) and its conservation importance

Margaritifera auricularia is one of the most endangered freshwater mussels (Bivalvia, Unionida) in the world. Since 2013, the abundance of this species in the Ebro River basin (Spain) has sharply declined, driving the species to the verge of regional extinction. Therefore, any management measures that might facilitate the recovery of this species would be essential for its conservation. During 2014–2016, captive breeding of M. auricularia allowed the production of >106 juveniles, out of which 95% were released into the natural environment, and 5% were grown in the laboratory under controlled conditions. The aim of this experimental work was to establish the best culture conditions for the survival and growth of M. auricularia juveniles in the laboratory. The experiment was divided into two phases: phase I, in which juveniles recently detached from fish gills were cultured in detritus boxes until they reached a shell length of 1 mm; and phase II, in which these specimens were transferred to larger aquaria to grow up to 3–4 mm. The best experimental conditions for juvenile survival and growth corresponded to treatments in glass containers at a density of 0.2 ind. L−1, using river water, with added substrate and detritus, enriched with phytoplankton, and avoiding extra aeration. The highest survival and growth rates attained, respectively, values of c. 60% at 100 days and 2.56 mm in shell length at 30–32 weeks. This is the first study to report on the long‐term survival and growth of juvenile M. auricularia in the laboratory, providing essential information in order to implement future conservation measures addressed at reinforcing the natural populations of this highly threatened species in European water bodies.This project was funded by the Government of Aragón, Department of Rural Development and Sustainability and carried out by the Environmental Service Department of SARGA. Special thanks go to Manuel Alcántara, Miguel Ángel Muñoz, Ester Ginés, Carlos Catalá, and Juan Pablo de la Roche, who were involved in the project. The authors appreciate the work of the reviewer and editor who improved the quality of the manuscript. The Aragón's forest rangers are thanked for their assistance during fieldwork

Development and validation of a repharsed phase- HPLC method for simultaneous determination of rosiglitazone and glimepiride in combined dosage forms and human plasma

<p>Abstract</p> <p>Background</p> <p>Rosiglitazone (ROZ) and glimepiride (GLM) are antidiabetic agents used in the treatment of type 2 diabetes mellitus. A survey of the literature reveals that only one spectrophotometric method has been reported for the simultaneous determination of ROS and GLM in pharmaceutical preparations. However the reported method suffers from the low sensitivity, for this reason, our target was to develop a simple sensitive HPLC method for the simultaneous determination of ROZ and GLM in their combined dosage forms and plasma.</p> <p>Results</p> <p>A simple reversed phase high performance liquid chromatographic (RP-HPLC) method was developed and validated for the simultaneous determination of Rosiglitazone (ROS) and Glimepiride (GLM) in combined dosage forms and human plasma. The separation was achieved using a 150 mm × 4.6 mm i.d., 5 μm particle size Symmetry^®C18 column. Mobile phase containing a mixture of acetonitrile and 0.02 M phosphate buffer of pH 5 (60: 40, V/V) was pumped at a flow rate of 1 mL/min. UV detection was performed at 235 nm using nicardipine as an internal standard. The method was validated for accuracy, precision, specificity, linearity, and sensitivity. The developed and validated method was successfully used for quantitative analysis of Avandaryl™ tablets. The chromatographic analysis time was approximately 7 min per sample with complete resolution of ROS (t_R= 3.7 min.), GLM (t_R= 4.66 min.), and nicardipine (t_R, 6.37 min). Validation studieswas performed according to ICH Guidelines revealed that the proposed method is specific, rapid, reliable and reproducible. The calibration plots were linear over the concentration ranges 0.10-25 μg/mL and 0.125-12.5 μg/mL with LOD of 0.04 μg/mL for both compounds and limits of quantification 0.13 and 0.11 μg/mL for ROS and GLM respectively.</p> <p>Conclusion</p> <p>The suggested method was successfully applied for the simultaneous analysis of the studied drugs in their co-formulated tablets and human plasma. The mean percentage recoveries in Avandaryl™ tablets were 100.88 ± 1.14 and 100.31 ± 1.93 for ROS and GLM respectively. Statistical comparison of the results with those of the reference method revealed good agreement and proved that there were no significant difference in the accuracy and precision between the two methods respectively. The interference likely to be introduced from some co-administered drugs such as glibenclamide, gliclazide, metformine, pioglitazone and nateglinide was investigated.</p

Loss of TDP-43 oligomerization or RNA binding elicits distinct aggregation patterns

Aggregation of the RNA-binding protein TAR DNA-binding protein 43 (TDP-43) is the key neuropathological feature of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). In physiological conditions, TDP-43 is predominantly nuclear, forms oligomers, and is contained in biomolecular condensates assembled by liquid-liquid phase separation (LLPS). In disease, TDP-43 forms cytoplasmic or intranuclear inclusions. How TDP-43 transitions from physiological to pathological states remains poorly understood. Using a variety of cellular systems to express structure-based TDP-43 variants, including human neurons and cell lines with near-physiological expression levels, we show that oligomerization and RNA binding govern TDP-43 stability, splicing functionality, LLPS, and subcellular localization. Importantly, our data reveal that TDP-43 oligomerization is modulated by RNA binding. By mimicking the impaired proteasomal activity observed in ALS/FTLD patients, we found that monomeric TDP-43 forms inclusions in the cytoplasm, whereas its RNA binding-deficient counterpart aggregated in the nucleus. These differentially localized aggregates emerged via distinct pathways: LLPS-driven aggregation in the nucleus and aggresome-dependent inclusion formation in the cytoplasm. Therefore, our work unravels the origins of heterogeneous pathological species reminiscent of those occurring in TDP-43 proteinopathy patients