The deglaciation of coastal areas of southeast Greenland

Large marine-terminating glaciers around the margins of the Greenland Ice Sheet have retreated, accelerated and thinned over the last two decades. Relatively little is known about the longer term behaviour of the Greenland Ice Sheet, yet this information is valuable for assessing the significance of modern changes. We address this by reporting 11 new beryllium-10 (10Be) exposure ages from previously uninvestigated coastal areas across southeast Greenland. The new ages are combined with existing data from the region to assess the timing of glacier retreat after the Last Glacial Maximum. The results show that deglaciation occurred first in the north of the region (~68°N) and progressed southwards. This north–south progression is attributed to the influence of the warm Irminger Current on the ice margin. Areas in the south of the region were isolated from the warm waters by the shallow bathymetry of the continental shelf. This demonstrates that oceanographic forcing paced the deglaciation of southeast Greenland through the Younger Dryas and early Holocene. In most areas of southeast Greenland bedrock ages are systematically older than their counterpart boulder samples; this offset is likely the result of inherited 10Be content in bedrock surfaces. This suggests that subglacial erosion during the last glacial cycle was insufficient to completely remove pre-existing 10Be content. Alternatively, this pattern may be the signature of a substantial retreat and advance cycle prior to final Holocene deglaciation

Association of Tat with Promoters of PTEN and PP2A Subunits Is Key to Transcriptional Activation of Apoptotic Pathways in HIV-Infected CD4+ T Cells

Apoptosis in HIV-1-infected CD4+ primary T cells is triggered by the alteration of the PI3K and p53 pathways, which converge on the FOXO3a transcriptional activator. Tat alone can cause activation of FOXO3a and of its proapoptotic target genes. To understand how Tat affects this pathway, we carried out ChIP-Chip experiments with Tat. Tat associates with the promoters of PTEN and two PP2A subunit genes, but not with the FOXO3a promoter. PTEN and PP2A encode phosphatases, whose levels and activity are increased when Tat is expressed. They counteract phosphorylation of Akt1 and FOXO3a, and so activate transcriptional activity of FOXO3a. FOXO3a promotes increased transcription of Egr-1, which can further stimulate the transcription of PTEN, thereby reinforcing the pathway that leads to FOXO3a transcriptional activation. RNAi experiments support the role of PTEN and PP2A in the initiation of the Tat-mediated cascade, which is critical to apoptosis. The increased accumulation of PTEN and PP2A subunit mRNAs during Tat expression is more likely to be the result of increased transcription initiation and not relief of promoter-proximal pausing of RNAPII. The Tat-PTEN and -PP2A promoter interactions provide a mechanistic explanation of Tat-mediated apoptosis in CD4+ T cells

Polymorphisms in Anopheles gambiae Immune Genes Associated with Natural Resistance to Plasmodium falciparum

Many genes involved in the immune response of Anopheles gambiae, the main malaria vector in Africa, have been identified, but whether naturally occurring polymorphisms in these genes underlie variation in resistance to the human malaria parasite, Plasmodium falciparum, is currently unknown. Here we carried out a candidate gene association study to identify single nucleotide polymorphisms (SNPs) associated with natural resistance to P. falciparum. A. gambiae M form mosquitoes from Cameroon were experimentally challenged with three local wild P. falciparum isolates. Statistical associations were assessed between 157 SNPs selected from a set of 67 A. gambiae immune-related genes and the level of infection. Isolate-specific associations were accounted for by including the effect of the isolate in the analysis. Five SNPs were significantly associated to the infection phenotype, located within or upstream of AgMDL1, CEC1, Sp PPO activate, Sp SNAKElike, and TOLL6. Low overall and local linkage disequilibrium indicated high specificity in the loci found. Association between infection phenotype and two SNPs was isolate-specific, providing the first evidence of vector genotype by parasite isolate interactions at the molecular level. Four SNPs were associated to either oocyst presence or load, indicating that the genetic basis of infection prevalence and intensity may differ. The validity of the approach was verified by confirming the functional role of Sp SNAKElike in gene silencing assays. These results strongly support the role of genetic variation within or near these five A. gambiae immune genes, in concert with other genes, in natural resistance to P. falciparum. They emphasize the need to distinguish between infection prevalence and intensity and to account for the genetic specificity of vector-parasite interactions in dissecting the genetic basis of Anopheles resistance to human malaria

Consensus guidelines for the use and interpretation of angiogenesis assays

The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference

Supplementary_material – Supplemental material for The deglaciation of coastal areas of southeast Greenland

<p>Supplemental material, Supplementary_material for The deglaciation of coastal areas of southeast Greenland by Laurence M Dyke, Anna LC Hughes, Camilla S Andresen, Tavi Murray, John F Hiemstra, Anders A Bjørk and Ángel Rodés in The Holocene</p