Activation of Autophagy in a Rat Model of Retinal Ischemia following High Intraocular Pressure

Acute primary open angle glaucoma is an optic neuropathy characterized by the elevation of intraocular pressure, which causes retinal ischemia and neuronal death. Rat ischemia/reperfusion enhances endocytosis of both horseradish peroxidase (HRP) or fluorescent dextran into ganglion cell layer (GCL) neurons 24 h after the insult. We investigated the activation of autophagy in GCL-neurons following ischemia/reperfusion, using acid phosphatase (AP) histochemistry and immunofluorescence against LC3 and LAMP1. Retinal I/R lead to the appearance of AP-positive granules and LAMP1-positive vesicles 12 and 24 h after the insult, and LC3 labelling at 24 h, and induced a consistent retinal neuron death. At 48 h the retina was negative for autophagic markers. In addition, Western Blot analysis revealed an increase of LC3 levels after damage: the increase in the conjugated, LC3-II isoform is suggestive of autophagic activity. Inhibition of autophagy by 3-methyladenine partially prevented death of neurons and reduces apoptotic markers, 24 h post-lesion. The number of neurons in the GCL decreased significantly following I/R (I/R 12.21±1.13 vs controls 19.23±1.12 cells/500 µm); this decrease was partially prevented by 3-methyladenine (17.08±1.42 cells/500 µm), which potently inhibits maturation of autophagosomes. Treatment also prevented the increase in glial fibrillary acid protein immunoreactivity elicited by I/R. Therefore, targeting autophagy could represent a novel and promising treatment for glaucoma and retinal ischemia

The Spectrum of C9orf72-mediated Neurodegeneration and Amyotrophic Lateral Sclerosis

The discovery that a hexanucleotide repeat expansion in C9orf72 is the most numerous genetic variant of both amyotrophic lateral sclerosis and frontotemporal dementia has opened a rapidly growing field, which may provide long hoped for advances in the understanding and treatment of these devastating diseases. In this review we describe the various phenotypes, clinical and pathological, associated with expansion of C9orf72, which go beyond amyotrophic lateral sclerosis and frontotemporal dementia to include neurodegeneration more broadly. Next we take a step back and summarize the current understanding of the C9orf72 expansion and its protein products at a molecular level. Three mechanisms are prominent: toxicity mediated directly by RNA transcribed from the repeat; toxicity mediated by dipeptide repeat proteins translated from the repeat sequence; and haploinsufficiency resulting from reduced transcription of the C9orf72 exonic sequence. A series of exciting advances have recently described how dipeptide repeat proteins might interfere with the normal role of the nucleolus in maturation of RNA binding proteins and in production of ribosomes. Importantly, these mechanisms are unlikely to be mutually exclusive. We draw attention to the fact that clinical and pathological similarities to other genetic variants without a repeat expansion must not be overlooked in ascribing a pathogenic mechanism to C9orf72-disease. Finally, with a view to impact on patient care, we discuss current practice with respect to genetic screening in patients with and without a family history of disease, and the most promising developments towards therapy that have been reported to date

Normative data on Dutch idiomatic expressions: Native speakers

Item does not contain fulltextIn the context of the research programme ‘Idiomatic Second Language Acquisition’ (for more information see http://isla.ruhosting.nl), we collected normative data of 374 Dutch idiomatic expressions by 390 native speakers. In an online test, we asked participants to judge various dimensions of idiomatic expressions on a five-point scale: Frequency, Usage, Familiarity, Imageability, and Transparency. In addition, we objectively assessed their knowledge of idiom meaning by means of a multiple choice question (Idiom knowledge recognition). The dataset contains the aggregated results per expression for the 5 subjective dimensions (Frequency, Usage, Familiarity, Imageability, and Transparency) and the objective Idiom knowledge recognition (proportion correct). This work is part of the research program Free Competition in the Humanities with project number 23000349 NWO ISLA FdL, which is financed by the Netherlands Organisation for Scientific Research (NWO)

Normative data on Dutch idiomatic expressions: Native speakers

In the context of the research programme ‘Idiomatic Second Language Acquisition’ (for more information see http://isla.ruhosting.nl), we collected normative data of 374 Dutch idiomatic expressions by 390 native speakers. In an online test, we asked participants to judge various dimensions of idiomatic expressions on a five-point scale: Frequency, Usage, Familiarity, Imageability, and Transparency. In addition, we objectively assessed their knowledge of idiom meaning by means of a multiple choice question (Idiom knowledge recognition). The dataset contains the aggregated results per expression for the 5 subjective dimensions (Frequency, Usage, Familiarity, Imageability, and Transparency) and the objective Idiom knowledge recognition (proportion correct). This work is part of the research program Free Competition in the Humanities with project number 23000349 NWO ISLA FdL, which is financed by the Netherlands Organisation for Scientific Research (NWO)

MAGNETOACTIVE P-GE ROD WAVEGUIDE LOSS ANALYSIS ON THE CONCENTRATION OF TWO COMPONENT HOLE CHARGE CARRIERS / CILINDRINIŲ GIROELEKTRINIŲ P-GE BANGOLAIDŽIŲ NUOSTOLIŲ PRIKLAUSOMYBĖS NUO DVIEJŲ RŪŠIŲ KRŪVININKŲ KONCENTRACIJOS TYRIMAS

A new algorithm is utilized to examine the phase and attenuation constants of open dissipative epsilon- and (or) mu-gyrotropic rod waveguides. Our algorithm allows analyzing the waveguides made of materials having very high losses. The dispersion characteristics of p-Ge with a waveguide of two component hole charge carriers are calculated when the ratio of heavy hole concentration in the material is equal to 5%, 50% and 95% of the total free carrier concentration. The effective mass of p-Ge heavy and light holes are 0.279me and 0.043me respectively. The dispersion characteristics of the main and eight higher modes are presented in the paper. The transformation of higher hybrid modes at some heavy hole concentrations can be noticed. Waveguide broad bandwidth can be considerably extended due to the fact that the losses of higher modes are larger in comparison to those of the main mode at certain heavy hole concentration. Santrauka Darbe pateikiami dviejų rūšių krūvininkų (lengvųjų ir sunkiųjų skylučių) puslaidininkinių p-Ge giroelektrinių bangolaidžių, kuriuos veikia B 1 0 = r T indukcijos nuolatinis išilginis magnetinis laukas, dispersinių charakteristikų skaičiavimo rezultatai, įvertinant nuostolius bangolaidyje. Skaičiavimo algoritmas leidžia tirti bangolaidžius, pagamintus iš medžiagų, atnešančių labai didelius nuostolius. Tiriamos 1 mm spindulio bangolaidžių dažninės charakteristikos 5–200 GHz dažnių ruože. Laisvųjų krūvininkų koncentracija bangolaidyje yra N = 5·1019 m–3. Nustatoma nuostolių priklausomybė nuo sunkiųjų skylučių krūvininkų koncentracijos Nh, esant trims skirtingoms sunkiųjų skylučių koncentracijoms, kai Nh sudaro 5 %, 50 % ir 95 % nuo visų krūvininkų koncentracijos N bangolaidyje. Reikšminiai žodžiai: girotropiniai, giroelektriniai bangolaidžiai, p-Ge, puslaidininkių plazma, nuolatinis magnetinis laukas, dielektrinės skvarbos tenzorius, sunkiosios ir lengvosios skylutės, nuostoliai, dispersinės charakteristikos, kompleksinė išilginė sklidimo konstanta