A supramolecular assembly mediates lentiviral DNA integration

Retroviral integrase (IN) functions within the intasome nucleoprotein complex to catalyze insertion of viral DNA into cellular chromatin. Using cryo–electron microscopy, we now visualize the functional maedi-visna lentivirus intasome at 4.9 angstrom resolution. The intasome comprises a homo-hexadecamer of IN with a tetramer-of-tetramers architecture featuring eight structurally distinct types of IN protomers supporting two catalytically competent subunits. The conserved intasomal core, previously observed in simpler retroviral systems, is formed between two IN tetramers, with a pair of C-terminal domains from flanking tetramers completing the synaptic interface. Our results explain how HIV-1 IN, which self-associates into higher-order multimers, can form a functional intasome, reconcile the bulk of early HIV-1 IN biochemical and structural data, and provide a lentiviral platform for design of HIV-1 IN inhibitors

A Review of the Occurrence of Bats (Chiroptera) on Islands in the North East Atlantic and on North Sea Installations

The bats recorded from Iceland, the Faroe Islands, the Shetland Islands, the Orkney Islands, and North Sea installations are reviewed to the end of 2012. In total 12 species have been positively identified, while a considerable proportion of all records are sightings of unidentified bats. Eight of the species are European in origin and four originate from the New World. The largest number of species (8) has been recorded in Iceland, but the greatest number of individuals (180) has been found in Orkney. The bat invasion on the Faroe Islands in 2010 is without precedence, when 70 observations of a minimum of 45 individuals were noted. Most bat observations in the study area occurred in the autumn, with fewer in the spring. Most observations were of single animals, but there were also sightings of up to 12 individuals. There has been a marked increase in bat records in the past three decades. We discuss whether this is a real increase, or due to improved communications, increased public awareness, increased shipping, changes in weather patterns and/or the effects of climate change. All factors appear to be involved.© Museum and Institute of Zoology PAS. The attached document is the author(’s’) final accepted/submitted version of the journal article. You are advised to consult the publisher’s version if you wish to cite from it

Discovery and functional prioritization of Parkinson's disease candidate genes from large-scale whole exome sequencing.

BACKGROUND: Whole-exome sequencing (WES) has been successful in identifying genes that cause familial Parkinson's disease (PD). However, until now this approach has not been deployed to study large cohorts of unrelated participants. To discover rare PD susceptibility variants, we performed WES in 1148 unrelated cases and 503 control participants. Candidate genes were subsequently validated for functions relevant to PD based on parallel RNA-interference (RNAi) screens in human cell culture and Drosophila and C. elegans models. RESULTS: Assuming autosomal recessive inheritance, we identify 27 genes that have homozygous or compound heterozygous loss-of-function variants in PD cases. Definitive replication and confirmation of these findings were hindered by potential heterogeneity and by the rarity of the implicated alleles. We therefore looked for potential genetic interactions with established PD mechanisms. Following RNAi-mediated knockdown, 15 of the genes modulated mitochondrial dynamics in human neuronal cultures and four candidates enhanced α-synuclein-induced neurodegeneration in Drosophila. Based on complementary analyses in independent human datasets, five functionally validated genes-GPATCH2L, UHRF1BP1L, PTPRH, ARSB, and VPS13C-also showed evidence consistent with genetic replication. CONCLUSIONS: By integrating human genetic and functional evidence, we identify several PD susceptibility gene candidates for further investigation. Our approach highlights a powerful experimental strategy with broad applicability for future studies of disorders with complex genetic etiologies

Tíðni sjálfsvíga hjá þeim sem áður hafa reynt sjálfsvíg

Neðst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinn View/Open1433 persons who were referred to the psychiatric emergency ward at the Borgarspitalinn Hospital in Reykjavik, in the years 1983-1985, were divided into two groups: parasuicides and others. On the first of december 1991, 11.2% had died in all, which is significantly higher than expected from normal population incidence. The suicide-rate in the parasuicide-group was 3.8%, which is significantly higher than in the other group. Suicide was the most common cause of death in the parasuicide-group, but cardiovascular diseases in the other. The prime method of suicide among males was CO-poisoning, but drowning among females. The highest suicide risk was in the first year after the attempt, where 0.8% of the parasuicide-group committed suicide.Hópi 1433 einstaklinga, sem komu á bráðamóttöku geðdeildar Borgarspítalans á árunum 1983-1985, var skipt í tvennt, eftir því hvort komuástæðan var sjálfsvígstilraun eða ekki. Þann 1. desember 1991 voru 11,2% hópsins látin, sem er marktækt hærri tíðni en í samsvarandi hópi úr almennu þýði. Tíðni sjálfsvíga í sjálfsvígstilraunahópnum var 3,8%, sem var marktækt hærra en í hinum hópnum. Sjálfsvíg var langalgengasta dánarorsökin í sjálfsvígstilraunahópnum en hjarta- og æðasjúkdómar í hinum. Algengustu sjálfsvígsaðferðir voru eitrun með kolmónoxíði hjá körlum og drukknun hjá konum. Úr sjálfsvígstilraunahópnum frömdu 0,8% einstaklinganna sjálfsvíg innan árs

Tíðni sjálfsvíga hjá þeim sem áður hafa reynt sjálfsvíg

Neðst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinn View/Open1433 persons who were referred to the psychiatric emergency ward at the Borgarspitalinn Hospital in Reykjavik, in the years 1983-1985, were divided into two groups: parasuicides and others. On the first of december 1991, 11.2% had died in all, which is significantly higher than expected from normal population incidence. The suicide-rate in the parasuicide-group was 3.8%, which is significantly higher than in the other group. Suicide was the most common cause of death in the parasuicide-group, but cardiovascular diseases in the other. The prime method of suicide among males was CO-poisoning, but drowning among females. The highest suicide risk was in the first year after the attempt, where 0.8% of the parasuicide-group committed suicide.Hópi 1433 einstaklinga, sem komu á bráðamóttöku geðdeildar Borgarspítalans á árunum 1983-1985, var skipt í tvennt, eftir því hvort komuástæðan var sjálfsvígstilraun eða ekki. Þann 1. desember 1991 voru 11,2% hópsins látin, sem er marktækt hærri tíðni en í samsvarandi hópi úr almennu þýði. Tíðni sjálfsvíga í sjálfsvígstilraunahópnum var 3,8%, sem var marktækt hærra en í hinum hópnum. Sjálfsvíg var langalgengasta dánarorsökin í sjálfsvígstilraunahópnum en hjarta- og æðasjúkdómar í hinum. Algengustu sjálfsvígsaðferðir voru eitrun með kolmónoxíði hjá körlum og drukknun hjá konum. Úr sjálfsvígstilraunahópnum frömdu 0,8% einstaklinganna sjálfsvíg innan árs

Movements and site fidelity of killer whales (<i>Orcinus orca</i>) relative to seasonal and long-term shifts in herring (<i>Clupea harengus</i>) distribution

Predators specialising on migratory prey that frequently change migration route face the challenge of finding prey with an unpredictable distribution. Here, we used photo-identification data to investigate whether killer whales observed in herring overwintering and spawning grounds off Iceland follow herring year-round, as previously proposed, and have the ability to adapt to long-term changes in herring distribution. Of 327 identified whales seen more than once, 45% were seen in both grounds, and were thus presumed herring-specialists, likely following herring year-round, while others were only seen on one of the grounds, possibly following herring to unsampled grounds or moving to other locations and exploiting different prey. High seasonal site fidelity to herring grounds, long-term site fidelity to herring spawning grounds, and matches of individual whales between past and recently occupied herring overwintering grounds showed an ability to adapt to long-term changes in prey distribution as well as diversity of movement patterns which are maintained over time, likely as socially-learnt traditions. Such population structuring shows that the movement patterns and foraging ecology of herring-eating killer whales are more complex than previously assumed and must be taken into account in future population assessments. Identifying the factors driving these differences in movements and resource use will be relevant towards our understanding of how prey predictability may drive specialization in this and other top predator species.</p