Ciliopathy is differentially distributed in the brain of a Bardet-Biedl syndrome mouse model

Bardet-Biedl syndrome (BBS) is a genetically heterogeneous inherited human disorder displaying a pleotropic phenotype. Many of the symptoms characterized in the human disease have been reproduced in animal models carrying deletions or knock-in mutations of genes causal for the disorder. Thinning of the cerebral cortex, enlargement of the lateral and third ventricles, and structural changes in cilia are among the pathologies documented in these animal models. Ciliopathy is of particular interest in light of recent studies that have implicated primary neuronal cilia (PNC) in neuronal signal transduction. In the present investigation, we tested the hypothesis that areas of the brain responsible for learning and memory formation would differentially exhibit PNC abnormalities in animals carrying a deletion of the Bbs4 gene (Bbs4-/-). Immunohistochemical localization of adenylyl cyclase-III (ACIII), a marker restricted to PNC, revealed dramatic alterations in PNC morphology and a statistically significant reduction in number of immunopositive cilia in the hippocampus and amygdala of Bbs4-/- mice compared to wild type (WT) littermates. Western blot analysis confirmed the decrease of ACIII levels in the hippocampus and amygdala of Bbs4-/- mice, and electron microscopy demonstrated pathological alterations of PNC in the hippocampus and amygdala. Importantly, no neuronal loss was found within the subregions of amygdala and hippocampus sampled in Bbs4-/- mice and there were no statistically significant alterations of ACIII immunopositive cilia in other areas of the brain not known to contribute to the BBS phenotype. Considered with data documenting a role of cilia in signal transduction these findings support the conclusion that alterations in cilia structure or neurochemical phenotypes may contribute to the cognitive deficits observed in the Bbs4-/- mouse mode. © 2014 Agassandian et al

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Apparatus to study crystal channeling and volume reflection phenomena at the SPS H8 beamline

none52A high performance apparatus has been designed and built by the H8-RD22 collaboration for the study of channeling and volume reflection phenomena in the interaction of 400 GeV/c protons with bent silicon crystals, during the 2006 data taking in the external beamline H8 of the CERN SPS. High-quality silicon short crystals were bent by either anticlastic or quasimosaic effects. Alignment with the highly parallel (8 µrad divergence) proton beam was guaranteed through a submicroradian goniometric system equipped with both rotational and translational stages. Particle tracking was possible by a series of silicon microstrip detectors with high-resolution and a parallel plate gas chamber, triggered by various scintillating detectors located along the beamline. Experimental observation of volume reflection with 400 GeV/c protons proved true with a deflection angle of (10.4±0.5) µrad with respect to the unperturbed beam, with a silicon crystal whose (111) planes were parallel to the beam.noneW. Scandale; I. Efthymiopoulos; D. A. Still; A. Carnera; G. Della Mea; D. De Salvador; R. Milan; A. Vomiero; S. Baricordi; S. Chiozzi; P. Dalpiaz; C. Damiani; M. Fiorini; V. Guidi;G. Martinelli; A. Mazzolari; E. Milan; G. Ambrosi; P. Azzarello; R. Battiston; B. Bertucci; W. J. Burger; M. Ionica; P. Zuccon; G. Cavoto; R. Santacesaria; P. Valente; E. Vallazza;A. G. Afonin; V. T. Baranov; Y. A. Chesnokov; V. I. Kotov; V. A. Maisheev; I. A. Yazynin; S. V. Afanasiev; A. D. Kovalenko; A. M. Taratin; N. F. Bondar; A S. Denisov; Y. A. Gavrikov; Y. M. Ivanov; V. G. Ivochkin; S. V. Kosyanenko; L. P. Lapina; P. M. Levtchenko; A. A. Petrunin; V. V. Skorobogatov; V. M. Suvorov; D. Bolognini; L. Foggetta; S. Hasan; M. PrestW., Scandale; I., Efthymiopoulos; D. A., Still; A., Carnera; G., Della Mea; D., De Salvador; R., Milan; A., Vomiero; Baricordi, Stefano; S., Chiozzi; Dalpiaz, Pietro; Damiani, Chiara; Fiorini, Massimiliano; Guidi, Vincenzo; Martinelli, Giuliano; Mazzolari, Andrea; Milan, Emiliano; G., Ambrosi; P., Azzarello; R., Battiston; B., Bertucci; W. J., Burger; M., Ionica; P., Zuccon; G., Cavoto; R., Santacesaria; P., Valente; E., Vallazza; A. G., Afonin; V. T., Baranov; Y. A., Chesnokov; V. I., Kotov; V. A., Maisheev; I. A., Yazynin; S. V., Afanasiev; A. D., Kovalenko; A. M., Taratin; N. F., Bondar; A. S., Denisov; Y. A., Gavrikov; Y. M., Ivanov; V. G., Ivochkin; S. V., Kosyanenko; L. P., Lapina; P. M., Levtchenko; A. A., Petrunin; V. V., Skorobogatov; V. M., Suvorov; D., Bolognini; L., Foggetta; S., Hasan; M., Pres

A decade of the Super Dual Auroral Radar Network (SuperDARN): scientific achievements, new techniques and future directions

The Super Dual Auroral Radar Network (SuperDARN) has been operating as an international co-operative organisation for over 10 years. The network has now grown so that the fields of view of its 18 radars cover the majority of the northern and southern hemisphere polar ionospheres. SuperDARN has been successful in addressing a wide range of scientific questions concerning processes in the magnetosphere, ionosphere, thermosphere, and mesosphere, as well as general plasma physics questions. We commence this paper with a historical introduction to SuperDARN. Following this, we review the science performed by SuperDARN over the last 10 years covering the areas of ionospheric convection, field-aligned currents, magnetic reconnection, substorms, MHD waves, the neutral atmosphere, and E-region ionospheric irregularities. In addition, we provides an up-to-date description of the current network, as well as the analysis techniques available for use with the data from the radars. We conclude the paper with a discussion of the future of SuperDARN, its expansion, and new science opportunities