Bicarbonate-responsive “soluble” adenylyl cyclase defines a nuclear cAMP microdomain

Bicarbonate-responsive “soluble” adenylyl cyclase resides, in part, inside the mammalian cell nucleus where it stimulates the activity of nuclear protein kinase A to phosphorylate the cAMP response element binding protein (CREB). The existence of this complete and functional, nuclear-localized cAMP pathway establishes that cAMP signals in intracellular microdomains and identifies an alternate pathway leading to CREB activation

The effect of distance on reaction time in aiming movements

Target distance affects movement duration in aiming tasks but its effect on reaction time (RT) is poorly documented. RT is a function of both preparation and initiation. Experiment 1 pre-cued movement (allowing advanced preparation) and found no influence of distance on RT. Thus, target distance does not affect initiation time. Experiment 2 removed pre-cue information and found that preparing a movement of increased distance lengthens RT. Experiment 3 explored movements to targets of cued size at non-cued distances and found size altered peak speed and movement duration but RT was influenced by distance alone. Thus, amplitude influences preparation time (for reasons other than altered duration) but not initiation time. We hypothesise that the RT distance effect might be due to the increased number of possible trajectories associated with further targets: a hypothesis that can be tested in future experiments

Recruitment, augmentation and apoptosis of rat osteoclasts in 1,25-(OH)2D3 response to short-term treatment with 1,25-dihydroxyvitamin D3in vivo

Background Although much is known about the regulation of osteoclast (OC) formation and activity, little is known about OC senescence. In particular, the fate of of OC seen after 1,25-(OH)2D3 administration in vivo is unclear. There is evidence that the normal fate of OC is to undergo apoptosis (programmed cell death). We have investigated the effect of short-term application of high dose 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) on OC apoptosis in an experimental rat model. Methods OC recruitment, augmentation and apoptosis was visualised and quantitated by staining histochemically for tartrate resistant acid phosphatase (TRAP), double staining for TRAP/ED1 or TRAP/DAPI, in situ DNA fragmentation end labelling and histomorphometric analysis. Results Short-term treatment with high-dose 1,25-(OH)2D3 increased the recruitment of OC precursors in the bone marrow resulting in a short-lived increase in OC numbers. This was rapidly followed by an increase in the number of apoptotic OC and their subsequent removal. The response of OC to 1,25-(OH)2D3 treatment was dose and site dependent; higher doses producing stronger, more rapid responses and the response in the tibiae being consistently stronger and more rapid than in the vertebrae. Conclusions This study demonstrates that (1) after recruitment, OC are removed from the resorption site by apoptosis (2) the combined use of TRAP and ED1 can be used to identify OC and their precursors in vivo (3) double staining for TRAP and DAPI or in situ DNA fragmentation end labelling can be used to identify apoptotic OC in vivo

Towards a framework for critical citizenship education

Increasingly countries around the world are promoting forms of "critical" citizenship in the planned curricula of schools. However, the intended meaning behind this term varies markedly and can range from a set of creative and technical skills under the label "critical thinking" to a desire to encourage engagement, action and political emancipation, often labelled "critical pedagogy". This paper distinguishes these manifestations of the "critical" and, based on an analysis of the prevailing models of critical pedagogy and citizenship education, develops a conceptual framework for analysing and comparing the nature of critical citizenship

Stent placement compared with balloon angioplasty for obstructed coronary bypass grafts. Saphenous Vein De Novo Trial Investigators.

BACKGROUND: Treatment of stenosis in saphenous-vein grafts after coronary-artery bypass surgery is a difficult challenge. The purpose of this study was to compare the effects of stent placement with those of balloon angioplasty on clinical and angiographic outcomes in patients with obstructive disease of saphenous-vein grafts. METHODS: A total of 220 patients with new lesions in aortocoronary-venous bypass grafts were randomly assigned to placement of Palmaz-Schatz stents or standard balloon angioplasty. Coronary angiography was performed during the index procedure and six months later. RESULTS: As compared with the patients assigned to angioplasty, those assigned to stenting had a higher rate of procedural efficacy, defined as a reduction in stenosis to less than 50 percent of the vessel diameter without a major cardiac complication (92 percent vs. 69 percent, P\u3c0.001), but they had more frequent hemorrhagic complications (17 percent vs. 5 percent, P\u3c0.01). Patients in the stent group had a larger mean (+/-SD) increase in luminal diameter immediately after the procedure (1.92+/-0.30 mm, as compared with 1.21+/-0.37 mm in the angioplasty group; P\u3c0.001) and a greater mean net gain in luminal diameter at six months (0.85+/-0.96 vs. 0.54+/-0.91 mm, P=0.002). Restenosis occurred in 37 percent of the patients in the stent group and in 46 percent of the patients in the angioplasty group (P=0.24). The outcome in terms of freedom from death, myocardial infarction, repeated bypass surgery, or revascularization of the target lesion was significantly better in the stent group (73 percent vs. 58 percent, P = 0.03). CONCLUSIONS: As compared with balloon angioplasty, stenting of selected venous bypass-graft lesions resulted in superior procedural outcomes, a larger gain in luminal diameter, and a reduction in major cardiac events. However, there was no significant benefit in the rate of angiographic restenosis, which was the primary end point of the study

Evaluación integral de la calidad seminal bovina: valor agregado para la inseminación artificial a tiempo fijo.

La inseminación artificial bovina ha sido la técnica de reproducción asistida de mayor difusión por las ventajas que presenta en el mejoramiento genético, la prevención y control de enfermedades de transmisión sexual, la posibilidad de emplear toros con facilidad de parto y la optimización del manejo reproductivo del rodeo. La Inseminación Artificial a Tiempo Fijo (IATF) suma beneficios tales como evitar la detección de celo, acortar el período de anestro post-parto y concentrar los partos en un período breve. El éxito de la IATF depende de múltiples factores entre los que se encuentra la calidad seminal. Ningún examen de semen in vitro presenta una correlación alta con la fertilidad, por lo cual debe desarrollarse un protocolo de control de calidad que estudie el mayor número posible de características de los espermatozoides. La selección de mejores muestras para IATF permitiría evitar la repetición en las inseminaciones o el repaso con monta natural. El objetivo del presente trabajo es encontrar indicadores seminales, a través de los análisis de rutina y del núcleo espermático, que estén asociados con tasas de preñez elevadas para IATF y permitan predecir el comportamiento de las dosis a campo.Se tomarán muestras aleatorias de cada partida de las dosis seminales congeladas ad hoc y se realizará el control de calidad espermático de rutina y el control nuclear. Se evaluarán: parámetros de motilidad espermática obtenidos por análisis computarizado (CASA), morfología, viabilidad, integridad acrosómica y funcionalidad de la membrana espermática. La evaluación del núcleo espermático incluirá: morfología nuclear, maduración de la cromatina, decondensación y fragmentación nuclear. Esta última, se realizará a través de una prueba desarrollada en nuestro laboratorio (FCV-UBA). Los responsables del CIAVT seleccionarán los establecimientos donde se realizarán los protocolos de IATF, así como los profesionales responsables de implementarlos, quienes recolectarán los resultados de preñez a campo. Sobre la base de estos resultados preliminares de nuestro grupo de trabajo y la experiencia de campo de los responsables del CIAVT, se espera encontrar asociación entre algunos de los parámetros seminales analizados y los porcentajes de preñez obtenidos por la técnica de IATF. Este proyecto intenta encontrar la existencia deindicadores de clasificación de fertilidad y de pérdidas embrionarias tempranas, lo que permitiría realizar una selección de los individuos más aptos para ser empleados como donantes para IATF. De esta forma, se podrían comercializar muestras de semen especialmente seleccionadas, con el valor agregado que esto conlleva.publishedVersio

Body distribution of 11C-methionine and 18FDG in rat measured by microPET

Compounds 18F-fluorodeoxyglucose (18FDG) and 11C-methionine (11C-MET) are radiodiagnostics frequently used in clinical Positron Emission Tomography (PET) as well in preclinical studies of various pathologies. The present study was focused on the comparison of biodistribution of both radiotracers in intact Wistar rats. The animals were scanned by microPET twice. The first scanning was done after 11C-MET administration, the second scan followed 5–7 days later using 18FDG. The radiotracers were injected into the tail vein of animals in isoflurane anesthesia. After a redistribution period, whole body scans were obtained using eXplore Vista SrT GE tomograph. Accumulation of the drugs in tissues was expressed in relative values (% ID/g) in selected regions of interest. As arbitrary reference tissue for drug accumulation, the sternoclavicular area was used. 18C-MET was found remarkably cumulating especially in the liver, spleen and distal part of the gastrointestinal tract. The compound was accumulated in the liver 6.9±0.92 (mean±SEM) times more intensively than in the reference tissue. The respective value for spleen and cecum/colon was 5.62±0.81 and 3.56±0.14 times. Accumulation of 11C-MET in other body parts including the brain and heart was very low and was apparently equal to the arbitrary tissue (0.13±0.01% ID/g). In the same animals 18FDG (biontFDG) was remarkably cumulated especially in Harderian glands compared to arbitrary tissue background (11.02±1.00 times), heart (7.52±1.70 times), brain (6.14±0.37 times), and colon (5.68±0.31 times). 18FDG accumulation in the liver, spleen and other organs was apparently not different from that found in the background (0.14±0.02% ID/g). The data obtained may serve as reference values in further microPET preclinical studies with 11C-MET and 18FDG under the given conditions

Visualising rave music in Virtual Reality: symbolic and interactive approaches

In 2019 the virtual reality experience Cyberdream VR was presented at various events including the Event Two exhibition of computer art held at the Royal College of Art. This short demo for Oculus Gear VR provided a c.5 minute sonic journey, in which the user moves through a series of symbolic environments based on the futuristic techno-utopian or dystopian imagery of 90s rave fliers. These environments accompanied an original soundtrack of rave music and vaporwave, allowing users to enjoy the music whilst feeling as though they are inside synaesthetic virtual spaces related to the symbolic imagery of rave culture. This paper will discuss the subsequent development of this project, which is now being adapted for the Oculus Quest VR headset. Rajmil Fischman’s concept of ‘Music in the Holodeck’; the fictional ’holophonor’ instrument from the TV series Futurama; or the video game Rez Infinite, are among those that suggest paradigms for performing sound and visuals in VR. Drawing upon these ideas, the current iteration of Cyberdream allows the user to trigger ‘sound instruments’ with the Oculus Quest Touch controllers. This is conceived as a means through which the user can ‘paint with sound’ in 3D space, improvising with the music, whilst also generating synaesthetic imagery. The design of these sound instruments presents interesting challenges, in order for sound to be generated in correspondence with visual imagery, where these materials may complement both the music and spatial environments. Drawing on the author’s VJ work, at the macro level of compositional structure, the latest version of the project also seeks ways to provide a more continuous experience analogous to a DJ or VJ set, through blending of music tracks between scenes. This paper will discuss on-going work on this project, advancing the discourse regarding the visualisation of hardcore rave music in virtual reality

Test-retest variability of high resolution positron emission tomography (PET) imaging of cortical serotonin (5HT2A) receptors in older, healthy adults

<p>Abstract</p> <p>Background</p> <p>Position emission tomography (PET) imaging using [¹⁸F]-setoperone to quantify cortical 5-HT_2Areceptors has the potential to inform pharmacological treatments for geriatric depression and dementia. Prior reports indicate a significant normal aging effect on serotonin 5HT_2Areceptor (5HT_2AR) binding potential. The purpose of this study was to assess the test-retest variability of [¹⁸F]-setoperone PET with a high resolution scanner (HRRT) for measuring 5HT_2AR availability in subjects greater than 60 years old. Methods: Six healthy subjects (age range = 65–78 years) completed two [¹⁸F]-setoperone PET scans on two separate occasions 5–16 weeks apart.</p> <p>Results</p> <p>The average difference in the binding potential (BP_ND) as measured on the two occasions in the frontal and temporal cortical regions ranged between 2 and 12%, with the lowest intraclass correlation coefficient in anterior cingulate regions.</p> <p>Conclusion</p> <p>We conclude that the test-retest variability of [¹⁸F]-setoperone PET in elderly subjects is comparable to that of [¹⁸F]-setoperone and other 5HT_2AR radiotracers in younger subject samples.</p

Genome Sequences of Mycobacteriophages Amgine, Amohnition, Bella96, Cain, DarthP, Hammy, Krueger, LastHope, Peanam, PhelpsODU, Phrank, SirPhilip, Slimphazie, and Unicorn

We report the genome sequences of 14 cluster K mycobacteriophages isolated using Mycobacterium smegmatis mc2155 as host. Four are closely related to subcluster K1 phages, and 10 are members of subcluster K6. The phage genomes span considerable sequence diversity, including multiple types of integrases and integration sites