An siRNA-based functional genomics screen for the identification of regulators of ciliogenesis and ciliopathy genes

Defects in primary cilium biogenesis underlie the ciliopathies, a growing group of genetic disorders. We describe a whole-genome siRNA-based reverse genetics screen for defects in biogenesis and/or maintenance of the primary cilium, obtaining a global resource. We identify 112 candidate ciliogenesis and ciliopathy genes, including 44 components of the ubiquitin-proteasome system, 12 G-protein-coupled receptors, and 3 pre-mRNA processing factors (PRPF6, PRPF8 and PRPF31) mutated in autosomal dominant retinitis pigmentosa. The PRPFs localize to the connecting cilium, and PRPF8- and PRPF31-mutated cells have ciliary defects. Combining the screen with exome sequencing data identified recessive mutations in PIBF1, also known as CEP90, and C21orf2, also known as LRRC76, as causes of the ciliopathies Joubert and Jeune syndromes. Biochemical approaches place C21orf2 within key ciliopathy-associated protein modules, offering an explanation for the skeletal and retinal involvement observed in individuals with C21orf2 variants. Our global, unbiased approaches provide insights into ciliogenesis complexity and identify roles for unanticipated pathways in human genetic disease.

Novel role of androgens in mitochondrial fission and apoptosis

Androgen and androgen receptors (AR) play critical roles in the proliferation of prostate cancer through transcriptional regulation of target genes. Here, we found that androgens upregulated the expression of dynamin-related protein 1 (Drp1), which is involved in the induction of mitochondrial fission, a common event in mitosis and apoptosis. Clinical tissue samples and various prostate cancer cell lines revealed a positive correlation between Drp1 and AR levels. Treatment of androgen-sensitive cells with an AR agonist, R1881, and antagonist, bicalutamide, showed that Drp1 is transcriptionally regulated by androgens, as confirmed by an AR ChIP-seq assay. Live imaging experiments using pAcGFP1-Mito stably transfected LNCaP (mito-green) cells revealed that androgen did not induce significant mitochondrial fission by itself, although Drp1 was upregulated. However, when treated with CGP37157 (CGP), an inhibitor of mitochondrial Ca²⁺ efflux, these cells exhibited mitochondrial fission, which was further enhanced by pretreatment with R1881, suggesting that androgen-induced Drp1 expression facilitated CGP-induced mitochondrial fission. This enhanced mitochondrial fission was correlated with increased apoptosis. Transfection with dominant-negative (DN-Drp1, K38A) rescued cells from increased apoptosis, confirming the role of androgen-induced Drp1 in the observed apoptosis with combination treatment. Furthermore, we found that CGP reduced the expression of Mfn1, a protein that promotes mitochondrial fusion, a process which opposes fission. We suggest that androgen-increased Drp1 enhanced mitochondrial fission leading to apoptosis. The present study shows a novel role for androgens in the regulation of mitochondrial morphology that could potentially be utilized in prostate cancer therapy.

Le routage de l’information dans les réseaux véhiculaires mobiles

Les réseaux véhiculaires mobiles, ou Vehicular Ad-hoc NETworks (VANETs), existent depuis les années 80, mais sont de plus en plus développés depuis quelques années dans différentes villes à travers le monde. Ils constituent un apport d’informations aux réseaux routiers grâce à la mise en place de communications entre ses constituants : principalement les véhicules, mais aussi certaines infrastructures de bords de routes liées directement aux automobilistes (feux de circulation, parcomètres, infrastructures spécialisées pour les VANETs et bien d’autres). L’ajout des infrastructures apporte un support fixe à la dissémination des informations dans le réseau. Le principal objectif de ce type de réseau est d’améliorer la sécurité routière, les conditions de circulations, et d’apporter aux conducteurs et aux passagers quelques applications publicitaires ou de divertissement. Pour cela, il est important de faire circuler l’information de la manière la plus efficace possible entre les différents véhicules. L’utilisation des infrastructures pour la simulation de ces réseaux est bien souvent négligée. En effet, une grande partie des protocoles présentés dans la littérature simulent un réseau ad-hoc avec des noeuds se déplaçant plus rapidement et selon une carte définie. Cependant, ils ne prennent pas en compte les spécificités même d’un réseau véhiculaire mobile. Le routage de l’information dans les réseaux véhiculaires mobiles utilise les infrastructures de façon certes opportuniste, mais à terme, les infrastructures seront très présentes dans les villes et sur les autoroutes. C’est pourquoi nous nous sommes concentrés dans ce mémoire à l’étude des variations des différentes métriques du routage de l’information lors de l’ajout d’infrastructures sur une autoroute avec l’utilisation du protocole de routage AODV. De plus, nous avons modifié le protocole AODV afin d’obliger les messages à emprunter le chemin passant par les infrastructures si celles-ci sont disponibles. Les résultats présentés sont encourageants, et nous montrent qu’il est important de simuler les réseaux VANETs de manière complète, en considérant les infrastructures.

Summer School Band/Summer School Chorus, July 18, 1939

Concert program for Summer School Band/Summer School Chorus, July 18, 1939

University Chorale, March 1, 1977

Concert program for University Chorale, March 1, 1977

Duo Geminiani and the Bach Ensemble, January 7, 1979

Concert program for Duo Geminiani and the Bach Ensemble, January 7, 1979

Violin Recital, June 1, 1937

Concert program for Violin Recital, June 1, 1937

Strings Concerto Competition, November 17, 2015

Concert Program

The battle of Cable Street

This witness seminar on the events in the East End of London of 4 October 1936, traditionally known as the ‘Battle of Cable Street’, was held at the Institute of Historical Research on 1 May 1991. It was chaired by Professor Geoffrey Alderman and introduced by Noreen Branson. The participants were Sid Bailey (former member of the BUF), Dr David Cesarani, Tony Gilbert, Charlie Goodman, Joyce Goodman, Professor Colin Holmes, Frank Lesser, Kevin Morgan (biographer of Harry Pollitt), Phil Piratin (Communist MP for Mile End 1945–50), Michael Quill, Jack Shaw, Harold Smith, Ronald F. Webb (former member of the BUF) and Len Wise (former member of the BUF). Yvonne Kapp was unable to attend but she sent a short account of her recollections of the event and this has been included with this transcript.

Relationship between national culture, democracy and environmental performance: A panel data analysis

This paper demonstrates the significance of culture in examining the relationshipbetween democratic capital and environmental performance.The aim is to examine the relationship among scores on the Environmental Performance Index and the two dimensions of cross cultural variation suggested by Ronald Inglehart and Christian Welzel. Significantional interrelationships among democracy, cultural and environmental sustaintability measures could be found, following the regression results. Firstly, higher levels of democratic capital stock are associated with better environmental performance. Secondly importance to distinguish between cultural groups could be confirmed.

Postglacial paleoecology and effects of European settlement on the environment of Lake Hunger and Lake Lisgar, Southwestern Ontario /

This investigation has three purposes I to make a comparative chemical study on sediment cores collected for Lake Lisgar (man-made lake in an urban center) and Lake Hunger (natural basin in a rural community) encompassing the time since European settlement I to determine the postglacial chemical history of Lake Hunger, and to determine the vegetational history of the Lake Hunger area from postglacial time to the present. The minus 80 mesh fraction of 108 soil samples and 18 stream sediment samples collected in the vicinity of Lakes' Lisgar and Hunger were analyzed for cold hydrochloric acid soluble lead, zinc, nickel, cobalt, copper, aluminum, sodium, potassium, calcium, magnesium, iron and manganese. Lacustrine sediments from 5 boreholes in the Lake Lisgar basin were collected. Boreholes 1, 2, 3, and 4 were analyzed for palynological and chemical information and Borehole 5 was subjected to pollen and ostracode analysis. Lacustrine sediments from 6 boreholes in the Lake Hunger basin were collected. Palyno- -logical and chemical analysis were performed on Boreholes 1, 2, 3, 4, and 6 and Borehole 5 was analyzed for pollen. In addition, radiocarbon dates were obtained on sediment samples from Boreholes 4 and 5. A total of 8 surface samples were collected from the margins of the Lake Hunger basin and these were chemically analyzed in the laboratory. All of the lacustrine sediments were ashed and analyzed for cold hydrochloric acid soluble lead, zinc, nickel, cobalt, copper, aluminum, sodium, potassium, calcium, magnesium, iron and manganese using a Perkin Elmer 40) Atomic Absorption spectrophotometer. The results . obtained for the 12 elements were expressed as parts per million in dry sediments. It was found that man's influence on the element distribution patterns in the sediments of Lake Lisgar appeared to be related to his urbanizing developments within the lake vicinity, whereas, the rural developments in the vicinity of lake Hunger appeared to have had little effect on the element distribution patterns in the lake sediments. The distribution patterns of lead, zinc, nickel, cobalt, aluminum, magnesium, sodium and potassium are similar to the % ash curve throughout postglacial time indicating that the rate of erosion in the drainage basin is the main factor which controls the concentration of these elements in the sediments of Lake Hunger. The vegetational history, from palynological analysis, of Lake Hunger from postglacial time to the present includes the following stages: tundra, open spruce forest, closed boreal forest, deciduous forest and the trend towards the re-establishment of pine following the clearing of land and the subsequent settlement of the Lake Hunger area by European settlers. The concentrations of some elements (cobalt, nickel, iron, manganese, calcium, magnesium, sodium and potassium) in the sediments of Lake Hunger appears to be higher during pre-cultural compared to post-cultural times. At least one complete postglacial record of the chemical history within a lake basin is necessary in order to accurately assess man's effects on his environment.

Study of heat capacity measurement methods for small samples

Methods of measuring specific heats of small samples were studied. Three automated methods were explored, two of which have shown promising results. The adiabatic continuous heating method, has provided smooth well behaved data but further work is presently underway to improve on the results obtained so far . The decay method has been success fully implemented demonstrating reasonable agreement with accepted data for a copper test sample.