Inter- and intraspecies phylogenetic analyses reveal extensive X-Y gene conversion in the evolution of gametologous sequences of human sex chromosomes.

International audienceIt has long been believed that the male-specific region of the human Y chromosome (MSY) is genetically independent from the X chromosome. This idea has been recently dismissed due to the discovery that X-Y gametologous gene conversion may occur. However, the pervasiveness of this molecular process in the evolution of sex chromosomes has yet to be exhaustively analyzed. In this study, we explored how pervasive X-Y gene conversion has been during the evolution of the youngest stratum of the human sex chromosomes. By comparing about 0.5 Mb of human-chimpanzee gametologous sequences, we identified 19 regions in which extensive gene conversion has occurred. From our analysis, two major features of these emerged: 1) Several of them are evolutionarily conserved between the two species and 2) almost all of the 19 hotspots overlap with regions where X-Y crossing-over has been previously reported to be involved in sex reversal. Furthermore, in order to explore the dynamics of X-Y gametologous conversion in recent human evolution, we resequenced these 19 hotspots in 68 widely divergent Y haplogroups and used publicly available single nucleotide polymorphism data for the X chromosome. We found that at least ten hotspots are still active in humans. Hence, the results of the interspecific analysis are consistent with the hypothesis of widespread reticulate evolution within gametologous sequences in the differentiation of hominini sex chromosomes. In turn, intraspecific analysis demonstrates that X-Y gene conversion may modulate human sex-chromosome-sequence evolution to a greater extent than previously thought

A library of recombinant Babesia microti cell surface and secreted proteins for diagnostics discovery and reverse vaccinology.

Human babesiosis is an emerging tick-borne parasitic disease and blood transfusion-transmitted infection primarily caused by the apicomplexan parasite, Babesia microti. There is no licensed vaccine for B. microti and the development of a reliable serological screening test would contribute to ensuring the safety of the donated blood supply. The recent sequencing of the B. microti genome has revealed many novel genes encoding proteins that can now be tested for their suitability as subunit vaccine candidates and diagnostic serological markers. Extracellular proteins are considered excellent vaccine candidates and serological markers because they are directly exposed to the host humoral immune system, but can be challenging to express as soluble recombinant proteins. We have recently developed an approach based on a mammalian expression system that can produce large panels of functional recombinant cell surface and secreted parasite proteins. Here, we use the B. microti genome sequence to identify 54 genes that are predicted to encode surface-displayed and secreted proteins expressed during the blood stages, and show that 41 (76%) are expressed using our method at detectable levels. We demonstrate that the proteins contain conformational, heat-labile, epitopes and use them to serologically profile the kinetics of the humoral immune responses to two strains of B. microti in a murine infection model. Using sera from validated human infections, we show a concordance in the host antibody responses to B. microti infections in mouse and human hosts. Finally, we show that BmSA1 expressed in mammalian cells can elicit high antibody titres in vaccinated mice using a human-compatible adjuvant but these antibodies did not affect the pathology of infection in vivo. Our library of recombinant B. microti cell surface and secreted antigens constitutes a valuable resource that could contribute to the development of a serological diagnostic test, vaccines, and elucidate the molecular basis of host-parasite interactions. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved

Long-term cardiovascular outcomes after pregnancy in women with heart disease

BACKGROUND: Women with heart disease are at risk for pregnancy complications, but their long-term cardiovascular outcomes after pregnancy are not known. METHODS AND RESULTS: We examined long-term cardiovascular outcomes after pregnancy in 1014 consecutive women with heart disease and a matched group of 2028 women without heart disease. The primary outcome was a composite of mortality, heart failure, atrial fibrillation, stroke, myocardial infarction, or arrhythmia. Secondary outcomes included cardiac procedures and new hypertension or diabetes mellitus. We compared the rates of these outcomes between women with and without heart disease and adjusted for maternal and pregnancy characteristics. We also determined if pregnancy risk prediction tools (CARPREG [Canadian Cardiac Disease in Pregnancy] and World Health Organization) could stratify long-term risks. At 20-year follow-up, a primary outcome occurred in 33.1% of women with heart disease, compared with 2.1% of women without heart disease. Thirty-one percent of women with heart disease required a cardiac procedure. The primary outcome (adjusted hazard ratio, 19.6; 95% CI, 13.8–29.0; P\u3c0.0001) and new hypertension or diabetes mellitus (adjusted hazard ratio, 1.6; 95% CI, 1.4–2.0; P\u3c0.0001) were more frequent in women with heart disease compared with those without. Pregnancy risk prediction tools further stratified the late cardiovascular risks in women with heart disease, a primary outcome occurring in up to 54% of women in the highest pregnancy risk category. CONCLUSIONS: Following pregnancy, women with heart disease are at high risk for adverse long-term cardiovascular outcomes. Current pregnancy risk prediction tools can identify women at highest risk for long-term cardiovascular events

African horse sickness virus dynamics and host responses in naturally infected horses

African horse sickness (AHS) is a life threatening disease of equids caused by African horse sickness virus (AHSV), a member of the genus Orbivirus in the family Reoviridae. The virus is transmitted to horses by midges (Culicoides spp.) and the disease is most prevalent during the time of year, and in areas where the Culicoides spp. are most abundant, namely in late summer in the summer rainfall areas of the country. Whilst the clinical signs and presentation of the disease were well documented by Sir Arnold Theiler (1921), very little is known or documented about AHSV dynamics or the clinical pathological and serological responses of horses to natural infection with AHSV. This dissertation describes the history and current knowledge on AHS, and the methods and results of a prospective study on natural AHSV infection of horses, undertaken between 2009 and 2010 by the Equine Research Centre (ERC) at the University of Pretoria, Faculty of Veterinary Science, Onderstepoort. This study is the first documented study of its nature and included animals of various ages and therefore variable vaccination status. The objectives of the study were to describe the viral dynamics of AHSV infection in horses, to gain a better understanding of the clinical pathological and serological responses to natural AHS infection and to demonstrate early detection of AHS infection in horses under field conditions.Dissertation (MSc)--University of Pretoria, 2010.Veterinary Tropical Diseasesunrestricte

RISK OF HYPERTENSIVE DISORDERS IN PREGNANCY OF LIVING KIDNEY DONORS: A PILOT COHORT STUDY

The majority of living kidney donors is women. Female donors often ask their physicians whether donation will have any effect on their future pregnancies. Previous studies conclude that living donation poses no great harm for women who wish to become pregnant after donation. In Ontario, we are able to study this issue using large health care databases, and data from the Trillium Gift of Life Network. In this pilot study, hypertensive disorders of pregnancy (gestational hypertension, preeclampsia, eclampsia) were compared among kidney donors and healthy women who did not become kidney donors. 55 donors were studied who became pregnant following kidney donation comparing them to 502 matched female controls. Controls were matched on age, income, date of child birth, date of last pregnancy, history of previous pregnancy with hypertensive complications, and current multiple gestations. There was no statistically significant difference in the risk of hypertensive disorders of pregnancy between donors and controls (13% vs. 8%; OR 1.78; 95% Cl 0.75 to 4.19; p-value=0.19). However, the wide confidence interval and small sample size leaves uncertainty on any conclusions to be drawn. The results of this pilot study provide the foundation for a more definitive study, to rule out a smaller yet clinically important risk

Statebuilding – Widerspruch zu politischer Selbstbestimmung?

Statebuilding als Konfliktnachsorge steht unter Legitimationsdruck. Die Kritik entzündet sich an den konzeptionellen Widersprüchen zwischen den Grundideen liberalen statebuildings und ihrer autoritären Durchsetzung durch internationale Akteure. So wurde der eigentlich anzustrebende politische Prozess z. B. in Bosnien untergraben. Staatliche Institutionen werden aufoktroyiert und drücken nicht den Gestaltungs- und Selbstverwaltungswillen der sie tragenden Gesellschaften aus. Dagegen formiert sich z. B. in Afghanistan gewaltsamer Widerstand. Damit steht die Frage im Raum, wie (staats-) ethische Grundpositionen internationaler Akteure im Sinne der Autonomie des Subjekts und Ansprüche politischer Selbstgestaltung vordemokratischer Gesellschaften gegeneinander abgewogen werden können. Hier wird die These vertreten, dass die intervenierenden Akteure sich an den Prinzipien der Subsidiarität und ownership orientieren sowie dem Faktor Zeit eine entscheidendere Rolle gewähren müssen.As a strategy of post conflict treatment, statebuilding is under pressure: The conceptional contradictions criticized are the foundations of liberal statebuilding on one hand and its autocratic implementation by international actors on the other; this was, for instance, how the political process strived for in Bosnia was undermined. State institutions are created against the creative political will of the respective societies that are supposed to be their source; which, for instance, is one strong reason for the violent resistance in Afghanistan. So how to balance the opposing positions of international actors emphasizing the autonomy of the individual on the one hand and the demand for political self-formation of pre-democratic societies on the other? The author argues that the intervening actors should orientate themselves to the principle of subsidiarity and ownership and let time play a more decisive role

State of Reproductive Health In Women Veterans – VA Reproductive Health Diagnoses and Organization of Care

Reproductive health (RH) is a critical part of health. For women, RH encompasses gynecological health throughout life, preconception care, maternity care, cancer care, and the interaction of RH with other mental and medical conditions. Reproductive Health is defined as a state of complete physical, mental, and social well-be­ing and not merely the absence of reproductive disease or infirmity. This definition highlights the importance of taking a health systems approach that integrates RH care issues and services with other aspects of care needed across the life course. The RH needs of women are shaped by their stages of life and life experiences. For women Veterans, their military experiences may influence their RH in important ways. Given the increasing numbers of women in the military and women Veterans, it is critical to understand key aspects of RH in this unique population of women. This first report of the State of Reproductive Health in Women Veterans provides an overview of the RH diagnoses of women Veterans utilizing the Department of Veterans Affairs (VA) health care services, VA delivery of RH care, and a vision for RH in VA