Blood ties: ABO is a trans-species polymorphism in primates

The ABO histo-blood group, the critical determinant of transfusion incompatibility, was the first genetic polymorphism discovered in humans. Remarkably, ABO antigens are also polymorphic in many other primates, with the same two amino acid changes responsible for A and B specificity in all species sequenced to date. Whether this recurrence of A and B antigens is the result of an ancient polymorphism maintained across species or due to numerous, more recent instances of convergent evolution has been debated for decades, with a current consensus in support of convergent evolution. We show instead that genetic variation data in humans and gibbons as well as in Old World Monkeys are inconsistent with a model of convergent evolution and support the hypothesis of an ancient, multi-allelic polymorphism of which some alleles are shared by descent among species. These results demonstrate that the ABO polymorphism is a trans-species polymorphism among distantly related species and has remained under balancing selection for tens of millions of years, to date, the only such example in Hominoids and Old World Monkeys outside of the Major Histocompatibility Complex.Comment: 45 pages, 4 Figures, 4 Supplementary Figures, 5 Supplementary Table

The uptake of soluble and nanoparticulate imaging isotope in model liver tumours after intra-venous and intra-arterial administration

Delivery of chemotherapeutic drugs to tumours by reformulation as nanoparticles has often been proposed as a means of facilitating increased selective uptake, exploiting the increased permeability of the tumour vasculature. However realisation of this improvement in drug delivery in cancer patients has met with limited success. We have compared tumour uptake of soluble Tc99m-pertechnetate and a colloid of nanoparticles with a Tc99m core, using both intra-venous and intra-arterial routes of administration in a rabbit liver VX2 tumour model. The radiolabelled nanoparticles were tested both in untreated and cationised form. The results from this tumour model in an internal organ show a marked advantage in intra-arterial administration over the intra-venous route, even for the soluble isotope. Tumour accumulation of nanoparticles from arterial administration was augmented by cationisation of the nanoparticle surface with histone proteins, which consistently facilitated selective accumulation within microvessels at the periphery of tumours.Sources of support for this research: Sirtex Medical Ltd, Sydney Australia

A case of advanced infantile myofibromatosis harboring a novel MYH10‐RET fusion

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137282/1/pbc26377_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137282/2/pbc26377.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137282/3/pbc26377-sup-0002-text.pd

The Prevalence of Natural Health Product Use in Patients with Acute Cardiovascular Disease

Background: Natural health products (NHP) use may have implications with respect to adverse effects, drug interactions and adherence yet the prevalence of NHP use by patients with acute cardiovascular disease and the best method to ascertain this information is unknown. Objective: To identify the best method to ascertain information on NHP, and the prevalence of use in a population with acute cardiovascular disease. Methods: Structured interviews were conducted with a convenience sample of consecutive patients admitted with acute cardiovascular disease to the University of Alberta Hospital during January 2009. NHP use was explored using structured and open-ended questions based on Health Canada’s definition of NHP. The medical record was reviewed, and documentation of NHP use by physicians, nurses, and pharmacists, compared against the gold-standard structured interview. Results: 88 patients were interviewed (mean age 62 years, standard deviation [SD 14]; 80 % male; 41 % admitted for acute coronary syndromes). Common co-morbidities included hypertension (59%), diabetes (26%) and renal impairment (19%). NHP use was common (78 % of patients) and 75 % of NHP users reported daily use. The category of NHP most commonly used was vitamins and minerals (73%) followed by herbal products (20%), traditional medicines including Chines

Precision Measurement of the Ds∗+−Ds+D_s^{*+}- D_s^+ Mass Difference

We have measured the vector-pseudoscalar mass splitting $M(D_s^{*+})-M(D_s^+) = 144.22\pm 0.47\pm 0.37 MeV$, significantly more precise than the previous world average. We minimize the systematic errors by also measuring the vector-pseudoscalar mass difference $M(D^{*0})-M(D^0)$ using the radiative decay $D^{*0}\rightarrow D^0\gamma$, obtaining $[M(D_s^{*+})-M(D_s^+)]-[M(D^{*0})-M(D^0)] = 2.09\pm 0.47\pm 0.37 MeV$. This is then combined with our previous high-precision measurement of $M(D^{*0})-M(D^0)$, which used the decay $D^{*0}\rightarrow D^0\pi^0$. We also measure the mass difference $M(D_s^+)-M(D^+)=99.5\pm 0.6\pm 0.3$ MeV, using the $\phi\pi^+$ decay modes of the $D_s^+$ and $D^+$ mesons.Comment: 18 pages uuencoded compressed postscript (process with uudecode then gunzip). hardcopies with figures can be obtained by sending mail to: [email protected]

Observation of a New Charmed Strange Meson

Using the CLEO-II detector, we have obtained evidence for a new meson decaying to $D^0 K^+$. Its mass is $2573.2^{+1.7}_{-1.6}\pm 0.8\pm 0.5$ {}~MeV/$c^2$ and its width is $16^{+5}_{-4}\pm 3$~MeV/$c^2$. Although we do not establish its spin and parity, the new meson is consistent with predictions for an $L=1$, $S=1$, $J_P=2^+$ charmed strange state.Comment: 9 pages uuencoded compressed postscript (process with uudecode then gunzip). hardcopies with figures can be obtained by sending mail to: [email protected]

Exome sequencing identifies NBEAL2 as the causative gene for gray platelet syndrome.

Gray platelet syndrome (GPS) is a predominantly recessive platelet disorder that is characterized by mild thrombocytopenia with large platelets and a paucity of α-granules; these abnormalities cause mostly moderate but in rare cases severe bleeding. We sequenced the exomes of four unrelated individuals and identified NBEAL2 as the causative gene; it has no previously known function but is a member of a gene family that is involved in granule development. Silencing of nbeal2 in zebrafish abrogated thrombocyte formation

Low Numbers of FOXP3 Positive Regulatory T Cells Are Present in all Developmental Stages of Human Atherosclerotic Lesions

BACKGROUND: T cell mediated inflammation contributes to atherogenesis and the onset of acute cardiovascular disease. Effector T cell functions are under a tight control of a specialized T cell subset, regulatory T cells (Treg). At present, nothing is known about the in situ presence of Treg in human atherosclerotic tissue. In the present study we investigated the frequency of naturally occurring Treg cells in all developmental stages of human atherosclerotic lesions including complicated thrombosed plaques. METHODOLOGY: Normal arteries, early lesions (American Heart Association classification types I, II, and III), fibrosclerotic plaques (types Vb and Vc) and 'high risk' plaques (types IV, Va and VI) were obtained at surgery and autopsy. Serial sections were immunostained for markers specific for regulatory T cells (FOXP3 and GITR) and the frequency of these cells was expressed as a percentage of the total numbers of CD3+ T cells. Results were compared with Treg counts in biopsies of normal and inflammatory skin lesions (psoriasis, spongiotic dermatitis and lichen planus). PRINCIPLE FINDINGS: In normal vessel fragments T cells were virtually absent. Treg were present in the intima during all stages of plaque development (0.5-5%). Also in the adventitia of atherosclerotic vessels Treg were encountered, in similar low amounts. High risk lesions contained significantly increased numbers of Treg compared to early lesions (mean: 3.9 and 1.2%, respectively). The frequency of FOXP3+ cells in high risk lesions was also higher compared to stable lesions (1.7%), but this difference was not significant. The mean numbers of intimal FOXP3 positive cells in atherosclerotic lesions (2.4%) was much lower than those in normal (24.3%) or inflammatory skin lesions (28%). CONCLUSION: Low frequencies of Treg in all developmental stages of human plaque formation could explain the smoldering chronic inflammatory process that takes place throughout the longstanding course of atherosclerosis

Luminescent osmium(II) bi-1,2,3-triazol-4-yl complexes: photophysical characterisation and application in light-emitting electrochemical cells

The series of osmium(II) complexes [Os(bpy)3-n(btz)n][PF6]2 (bpy = 2,2’-bipyridyl, btz = 1,1’-dibenzyl-4,4’-bi-1,2,3-triazolyl, 1 n = 0, 2 n = 1, 3 n = 2, 4 n = 3), have been prepared and characterised. The progressive replacement of bpy by btz leads to blue-shifted UV-visible electronic absorption spectra, indicative of btz perturbation of the successively destabilised bpy-centred LUMO. For 4, a dramatic blue-shift relative to the absorption profile for 3 is observed, indicative of the much higher energy LUMO of the btz ligand over that of bpy, mirroring previously reported data on analogous ruthenium(II) complexes. Unlike the previously reported ruthenium systems, heteroleptic complexes 2 and 3 display intense emission in the far-red/near-infrared (λmax = 724 and 713 nm respectively in aerated acetonitrile at RT) as a consequence of higher lying, and hence less thermally accessible, 3MC states. This assertion is supported by ground state DFT calculations which show that the dσ* orbitals of 1 to 4 are destabilised by between 0.60 and 0.79 eV relative to their Ru(II) analogues. The homoleptic complex 4 appears to display extremely week room temperature emission, but on cooling to 77 K the complex exhibits highly intense blue emission with λmax 444 nm. As complexes 1 to 3 display room temperature luminescent emission and readily reversible Os(II)/(III) redox couples, light-emitting electrochemical cell (LEC) devices were fabricated. All LECs display electroluminescent emission in the deep-red/near-IR (λmax = 695 to 730 nm). Whilst devices based on 2 and 3 show inferior current density and luminance than LECs based on 1, the device utilising 3 shows the highest external quantum efficiency at 0.3 %