Pre-M Phase-promoting Factor Associates with Annulate Lamellae in Xenopus Oocytes and Egg Extracts

We have used complementary biochemical and in vivo approaches to study the compartmentalization of M phase-promoting factor (MPF) in prophase Xenopus eggs and oocytes. We first examined the distribution of MPF (Cdc2/CyclinB2) and membranous organelles in high-speed extracts of Xenopus eggs made during mitotic prophase. These extracts were found to lack mitochondria, Golgi membranes, and most endoplasmic reticulum (ER) but to contain the bulk of the pre-MPF pool. This pre-MPF could be pelleted by further centrifugation along with components necessary to activate it. On activation, Cdc2/CyclinB2 moved into the soluble fraction. Electron microscopy and Western blot analysis showed that the pre-MPF pellet contained a specific ER subdomain comprising "annulate lamellae" (AL): stacked ER membranes highly enriched in nuclear pores. Colocalization of pre-MPF with AL was demonstrated by anti-CyclinB2 immunofluorescence in prophase oocytes, in which AL are positioned close to the vegetal surface. Green fluorescent protein-CyclinB2 expressed in oocytes also localized at AL. These data suggest that inactive MPF associates with nuclear envelope components just before activation. This association may explain why nuclei and centrosomes stimulate MPF activation and provide a mechanism for targeting of MPF to some of its key substrates

ACOTES project: Advanced compiler technologies for embedded streaming

Streaming applications are built of data-driven, computational components, consuming and producing unbounded data streams. Streaming oriented systems have become dominant in a wide range of domains, including embedded applications and DSPs. However, programming efficiently for streaming architectures is a challenging task, having to carefully partition the computation and map it to processes in a way that best matches the underlying streaming architecture, taking into account the distributed resources (memory, processing, real-time requirements) and communication overheads (processing and delay). These challenges have led to a number of suggested solutions, whose goal is to improve the programmer’s productivity in developing applications that process massive streams of data on programmable, parallel embedded architectures. StreamIt is one such example. Another more recent approach is that developed by the ACOTES project (Advanced Compiler Technologies for Embedded Streaming). The ACOTES approach for streaming applications consists of compiler-assisted mapping of streaming tasks to highly parallel systems in order to maximize cost-effectiveness, both in terms of energy and in terms of design effort. The analysis and transformation techniques automate large parts of the partitioning and mapping process, based on the properties of the application domain, on the quantitative information about the target systems, and on programmer directives. This paper presents the outcomes of the ACOTES project, a 3-year collaborative work of industrial (NXP, ST, IBM, Silicon Hive, NOKIA) and academic (UPC, INRIA, MINES ParisTech) partners, and advocates the use of Advanced Compiler Technologies that we developed to support Embedded Streaming.Peer ReviewedPostprint (published version

Genome-wide association study identifies 30 Loci Associated with Bipolar Disorder

This paper is dedicated to the memory of Psychiatric Genomics Consortium (PGC) founding member and Bipolar disorder working group co-chair Pamela Sklar. We thank the participants who donated their time, experiences and DNA to this research, and to the clinical and scientific teams that worked with them. We are deeply indebted to the investigators who comprise the PGC. The views expressed are those of the authors and not necessarily those of any funding or regulatory body. Analyses were carried out on the NL Genetic Cluster Computer (http://www.geneticcluster.org ) hosted by SURFsara, and the Mount Sinai high performance computing cluster (http://hpc.mssm.edu).Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P<1x10-4 in an additional 9,412 cases and 137,760 controls. Eight of the 19 variants that were genome-wide significant (GWS, p < 5x10-8) in the discovery GWAS were not GWS in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity. In the combined analysis 30 loci were GWS including 20 novel loci. The significant loci contain genes encoding ion channels, neurotransmitter transporters and synaptic components. Pathway analysis revealed nine significantly enriched gene-sets including regulation of insulin secretion and endocannabinoid signaling. BDI is strongly genetically correlated with schizophrenia, driven by psychosis, whereas BDII is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential new biological mechanisms for BD.This work was funded in part by the Brain and Behavior Research Foundation, Stanley Medical Research Institute, University of Michigan, Pritzker Neuropsychiatric Disorders Research Fund L.L.C., Marriot Foundation and the Mayo Clinic Center for Individualized Medicine, the NIMH Intramural Research Program; Canadian Institutes of Health Research; the UK Maudsley NHS Foundation Trust, NIHR, NRS, MRC, Wellcome Trust; European Research Council; German Ministry for Education and Research, German Research Foundation IZKF of Münster, Deutsche Forschungsgemeinschaft, ImmunoSensation, the Dr. Lisa-Oehler Foundation, University of Bonn; the Swiss National Science Foundation; French Foundation FondaMental and ANR; Spanish Ministerio de Economía, CIBERSAM, Industria y Competitividad, European Regional Development Fund (ERDF), Generalitat de Catalunya, EU Horizon 2020 Research and Innovation Programme; BBMRI-NL; South-East Norway Regional Health Authority and Mrs. Throne-Holst; Swedish Research Council, Stockholm County Council, Söderström Foundation; Lundbeck Foundation, Aarhus University; Australia NHMRC, NSW Ministry of Health, Janette M O'Neil and Betty C Lynch

Contributions of common genetic variants to risk of schizophrenia among individuals of African and Latino ancestry

Schizophrenia is a common, chronic and debilitating neuropsychiatric syndrome affecting tens of millions of individuals worldwide. While rare genetic variants play a role in the etiology of schizophrenia, most of the currently explained liability is within common variation, suggesting that variation predating the human diaspora out of Africa harbors a large fraction of the common variant attributable heritability. However, common variant association studies in schizophrenia have concentrated mainly on cohorts of European descent. We describe genome-wide association studies of 6152 cases and 3918 controls of admixed African ancestry, and of 1234 cases and 3090 controls of Latino ancestry, representing the largest such study in these populations to date. Combining results from the samples with African ancestry with summary statistics from the Psychiatric Genomics Consortium (PGC) study of schizophrenia yielded seven newly genome-wide significant loci, and we identified an additional eight loci by incorporating the results from samples with Latino ancestry. Leveraging population differences in patterns of linkage disequilibrium, we achieve improved fine-mapping resolution at 22 previously reported and 4 newly significant loci. Polygenic risk score profiling revealed improved prediction based on trans-ancestry meta-analysis results for admixed African (Nagelkerke’s R2 = 0.032; liability R2 = 0.017; P < 10−52), Latino (Nagelkerke’s R2 = 0.089; liability R2 = 0.021; P < 10−58), and European individuals (Nagelkerke’s R2 = 0.089; liability R2 = 0.037; P < 10−113), further highlighting the advantages of incorporating data from diverse human populations

Population development of the invader ctenophore <i>Mnemiopsis leidyi</i>, in the Black Sea and in other seas of the Mediterranean basin

In the last two decades of the twentieth century, the ctenophore Mnemiopsis leidyi (A. Agassiz) has invaded the Black, Azov, Marmara and Aegean Seas, and, recently, the Caspian Sea. Here, we compare its spatial and temporal distribution, seasonal dynamics and the time and duration of reproduction. We also discuss factors that control its abundance throughout its invasive range and its effect on ecosystems. Observations are based on the long-term field data collected by three research institutes. An analysis of the effects of temperature, salinity, prey (zoo- and ichthyoplankton) availability and predation (by ctenophores of the genus Beroe) on M. leidyi population size, and the effects of M. leidyi on zoo- and ichthyoplankton, and on fish populations in the Black and Azov Seas is also provided. With the Black Sea current, M. leidyi spreads to the upper layers of the Sea of Marmara, where it now occurs around the year. At regular intervals, the Black Sea current also takes it to the northern Aegean Sea. In contrast, it has to re-invade the Sea of Azov every spring or summer, dying out during winter when the temperature drops below 4°C. The warm summer and mild winter temperatures, relatively low salinity and abundance of prey in the Black Sea are close to optimal for M. leidyi, while they are suboptimal in the northern Aegean Sea, where salinity and temperature are often too high. In the Black Sea the absence of gelatinous and other predators led to an enormous ctenophore abundance for a decade, but with the appearance of Beroe ovata in 1999, M. leidyi abundance greatly decreased. Analysis of seasonal dynamics of M. leidyi in the Black Sea and in other seas of the Mediterranean basin indicates similarities in the timing of maximum abundance and biomass, in spite of some differences in the initiation and duration of reproduction. A peak biomass and density occurred in 1989 in the Black and Azov Seas and in 1990 in the other seas. The M. leidyi invasion negatively affected the ecosystems of the Black Sea and the Sea of Azov. The zooplankton, ichthyoplankton and zooplanktivorous fish stocks all underwent profound changes. Similar effects, but less pronounced, were recorded in the Sea of Marmara. Effects on Mediterranean food chains have, so far, remained insignificant. Salinity is probably supraoptimal here, and several predators prevent M. leidyi from reaching outbreak levels