Aspects of the glacial and postglacial history of North-West Argyll

The Loch Lomond Advance limits and raised marine shorelines in N. W. Argyll have been mapped and surveyed. Radiocarbon dated Lateglacial and Postglacial pollen sites at Salen and Loch Shiel provide the vegetational history and chronology for the area. 14 Loch Lomond Advance glacier termini and associated limits were mapped using the distribution of hummocky and fluted moraine, together with a survey of erratic boulders. 83% of the reconstructed former glaciers had a southerly aspect relating to southerly snow-bearing winds. The average firnline gradient was 7.5m/km increasing in altitude towards the north-east; the average firnline height for the area was 369m. The Main Lateglacial Shoreline, formed during the Loch Lomond Stadial, slopes towards 270 with a gradient of 0.15m/km from 9m in the east to Om in the west of the area. It was formed by freeze-thaw action operating under exceptional conditions, and its formation was influenced by rock type. Two Postglacial shorelines are recognized : the Main Postglacial shoreline that slopes towards 270, from 14m to 8m with a gradient of 0.06m/km, and a lower shoreline at approximately 5m which has no definite gradient. An absolute Lateglacial pollen site at Salen, Ardnamurchan, shows an early pioneer community of Rumex, Salix, Gramineae and Cyperaceae species being replaced by an Empetrum heath during the Lateglacial Interstadial. Subsequent stadial conditions are reflected by open herb communities and the onset of coarse minerogenic sedimentation. This minerogenic influx ceased around 10,000 to 9,700 B.P. with a rapid recolonization of the surrounding area by pioneer herbs, then dwarf shrub and finally deciduous woodland. Middle and Late Postglacial vegetational development is recorded by lacustrine sediments from Loch Shiel where the fossil pollen record shows that a mixed deciduous woodland of Quercus, Alnus, Betula and Corylus was progressively cleared by man. Palaeomagnetic and chemical records were obtained from the site. The Main Postglacial Transgression flooded Loch Shiel resulting in the deposition of shells of the marine bivlave Thyasira flexonosa

Human APOBEC1 cytidine deaminase edits HBV DNA

Retroviruses, hepadnaviruses, and some other retroelements are vulnerable to editing by single stranded DNA cytidine deaminases. Of the eleven human genes encoding such enzymes, eight have demonstrable enzymatic activity. Six of seven human APOBEC3 are able to hyperedit HBV DNA, frequently on both strands. Although human APOBEC1 (hA1) is not generally expressed in normal liver, hA1 can edit single stranded DNA in a variety of experimental assays. The possibility of ectopic expression of hA1 in vivo cannot be ruled out and interestingly, transgenic mice with A1 expressed under a liver specific promoter develop hepatocellular carcinoma. The impact of hA1 on HBV in tissue culture is varied with reports noting either reduced DNA synthesis or not, with cytidine deamination taking a low profile. We sought to examine the hA1 editing activity on replicating HBV. Using highly sensitive 3DPCR it was possible to show that hA1 edits the HBV minus DNA strand as efficiently as hA3G, considered the reference deaminase for HIV and HBV. The dinucleotide specificity of editing was unique among human cytidine deaminases providing a hallmark of use in a posteriori analyses of in vivo edited genomes. Analysis of sequences derived from the serum of two chronic carriers, indicated that hA1 explained only a small fraction of edited HBV genomes. By contrast, several human APOBEC3 deaminases were active including hA3G

Twin gradients in APOBEC3 edited HIV-1 DNA reflect the dynamics of lentiviral replication

The human immunodeficiency virus (HIV) Vif protein blocks incorporation of two host cell cytidine deaminases, APOBEC3F and 3G, into the budding virion. Not surprisingly, on a vif background nascent minus strand DNA can be extensively edited leaving multiple uracil residues. Editing occurs preferentially in the context of TC (GA on the plus strand) and CC (GG) depending on the enzyme. To explore the distribution of APOBEC3F and –3G editing across the genome, a product/substrate ratio (AA + AG)/(GA + GG) was computed for a series of 30 edited genomes present in the data bases. Two highly polarized gradients were noted each with maxima just 5′ to the central polypurine tract (cPPT) and LTR proximal polypurine tract (3′PPT). The gradients are in remarkable agreement with the time the minus strand DNA remains single stranded. In vitro analyses of APOBEC3G deamination of nascent cDNA spanning the two PPTs showed no pronounced dependence on the PPT RNA:DNA heteroduplex ruling out the competing hypothesis of a PPT orientation effect. The degree of hypermutation varied smoothly among genomes indicating that the number of APOBEC3 molecules packaged varied considerably

Tako-Tsubo Cardiomyopathy Triggered by Misdirection

Tako-Tsubo cardiomyopathy (TTC), also known as transient left ventricular apical ballooning syndrome or stress-induced cardiomyopathy, is a novel reversible cardiomyopathy mimicking acute myocardial infarction without epicardial coronary artery disease. The exact physiopathology of TTC remains unclear. It is usually precipitated by acute physical or emotional stress and it most commonly affects postmenopausal women. The growing number of clinical cases of TTC have demonstrated a wide field of possible etiologies beyond the emotional stress. We report a case of a 67-year-old postmenopausal woman who was being supplemented by enteral feeding via a nasogastric tube and who developed TTC due to misdirection, probably favored by the mechanical blockade by the nasogastric tube, while swallowing the drug pills

Genetic Variation of SARS Coronavirus in Beijing Hospital

To characterize genetic variation of severe acute respiratory syndrome–associated coronavirus (SARS-CoV) transmitted in the Beijing area during the epidemic outbreak of 2003, we sequenced 29 full-length S genes of SARS-CoV from 20 hospitalized SARS patients on our unit, the Beijing 302 Hospital. Viral RNA templates for the S-gene amplification were directly extracted from raw clinical samples, including plasma, throat swab, sputum, and stool, during the course of the epidemic in the Beijing area. We used a TA-cloning assay with direct analysis of nested reverse transcription–polymerase chain reaction products in sequence. One hundred thirteen sequence variations with nine recurrent variant sites were identified in analyzed S-gene sequences compared with the BJ01 strain of SARS-CoV. Among them, eight variant sites were, we think, the first documented. Our findings demonstrate the coexistence of S-gene sequences with and without substitutions (referred to BJ01) in samples analyzed from some patients

The Dendritic Cell Receptor DNGR-1 Promotes the Development of Atherosclerosis in Mice.

RATIONALE: Necrotic core formation during the development of atherosclerosis is associated with a chronic inflammatory response and promotes accelerated plaque development and instability. However, the molecular links between necrosis and the development of atherosclerosis are not completely understood. Clec9a (C-type lectin receptor) or DNGR-1 (dendritic cell NK lectin group receptor-1) is preferentially expressed by the CD8α+ subset of dendritic cells (CD8α+ DCs) and is involved in sensing necrotic cells. We hypothesized that sensing of necrotic cells by DNGR-1 plays a determinant role in the inflammatory response of atherosclerosis. OBJECTIVE: We sought to address the impact of total, bone marrow-restricted, or CD8α+ DC-restricted deletion of DNGR-1 on atherosclerosis development. METHODS AND RESULTS: We show that total absence of DNGR-1 in Apoe (apolipoprotein e)-deficient mice (Apoe-/-) and bone marrow-restricted deletion of DNGR-1 in Ldlr (low-density lipoprotein receptor)-deficient mice (Ldlr-/-) significantly reduce inflammatory cell content within arterial plaques and limit atherosclerosis development in a context of moderate hypercholesterolemia. This is associated with a significant increase of the expression of interleukin-10 (IL-10). The atheroprotective effect of DNGR-1 deletion is completely abrogated in the absence of bone marrow-derived IL-10. Furthermore, a specific deletion of DNGR-1 in CD8α+ DCs significantly increases IL-10 expression, reduces macrophage and T-cell contents within the lesions, and limits the development of atherosclerosis. CONCLUSIONS: Our results unravel a new role of DNGR-1 in regulating vascular inflammation and atherosclerosis and potentially identify a new target for disease modulation

Inversing the natural hydrogen bonding rule to selectively amplify GC-rich ADAR-edited RNAs

DNA complementarity is expressed by way of three hydrogen bonds for a G:C base pair and two for A:T. As a result, careful control of the denaturation temperature of PCR allows selective amplification of AT-rich alleles. Yet for the same reason, the converse is not possible, selective amplification of GC-rich alleles. Inosine (I) hydrogen bonds to cytosine by two hydrogen bonds while diaminopurine (D) forms three hydrogen bonds with thymine. By substituting dATP by dDTP and dGTP by dITP in a PCR reaction, DNA is obtained in which the natural hydrogen bonding rule is inversed. When PCR is performed at limiting denaturation temperatures, it is possible to recover GC-rich viral genomes and inverted Alu elements embedded in cellular mRNAs resulting from editing by dsRNA dependent host cell adenosine deaminases. The editing of Alu elements in cellular mRNAs was strongly enhanced by type I interferon induction indicating a novel link mRNA metabolism and innate immunity