New insights into the long-term evolutionary history of the avian MHC

SummaryGene duplication and neofunctidnalization are important processes in the evolution of phenotypic complexity. They account for important evolutionary novelties that confer ecological adaptation, such as the major histocompatibility complex (MHC), a multigene family with a central role in vertebrates' adaptive immune system. Multigene families, which evolved in large part through duplication, represent promising systems to study the still strongly depbated relative roles of neutral and adaptive processes in the evolution of phenotypic complexity. Detailed knowledge on ecological function and a well-characterized evolutionary history place the mammals' MHC amongst ideal study systems. However mammalian MHCs usually encompass several million base pairs and hold a large number of functional and non-functional duplicate genes, which makes their study complex. Avian MHCs on the other hand are usually way more compact, but the reconstruction of. their evolutionary history has proven notoriously difficult. However, no focused attempt has been undertaken so far to study the avian MHC evolutionary history in a broad phylogenetic context and using adequate gene regions.In the present PhD, we were able to make important contributions to the understanding of the long-term evolution of the avian MHC class II Β (MHCI1B). First, we isolated and characterized MHCIIB genes in barn owl (Tyto alba?, Strigiformes, Tytonidae), a species from an avian lineage in which MHC has not been studied so far. Our results revealed that with only two functional MHCIIB genes the MHC organization of barn owl may be similar to the 'minimal essential' MHC of chicken (Gallus gallus), indicating that simple MHC organization may be ancestral to birds. Taking advantage of the sequence information from barn owl, we studied the evolution of MHCIIB genes in 13 additional species of 'typical' owls (Strigiformes, Strigidae). Phylogenetic analyses revealed that according to their function, in owls the peptide-binding region (PBR) encoding exon 2 and the non-PBR encoding exon 3 evolve by different patterns. Exon 2 exhibited an evolutionary history of positive selection and recombination, while exon 3 traced duplication history and revealed two paralogs evolving divergently from each other in owls, and in a shorebird, the great snipe {Gallinago media). The results from exon 3 were the first ever from birds to demonstrate gene orthology in species that diverged tens of millions of years ago, and strongly questioned whether the taxa studied before provided an adequate picture of avian MHC evolution. In a follow-up study, we aimed at explaining a striking pattern revealed by phylogenetic trees analyzing the owl sequences along with MHCIIB sequences from other birds: One owl paralog (termed DAB1) grouped with sequences of passerines and falcons, while the other (DAB2) grouped with wildfowl, penguins and birds of prey. This could be explained by either a duplication event preceding the evolution of these bird orders, or by convergent evolution of similar sequences in a number of orders. With extensive phylogenetic analyses we were able to show, that indeed a duplication event preceeded the major avian radiation -100 my ago, and that following this duplication, the paralogs evolved under positive selection. Furthermore, we showed that the divergently evolving amino acid residues in the MHCIIB-encoded β-chain potentially interact with the MHCI I α-chain, and that molecular coevolution of the interacting residues may have been involved in the divergent evolution of the MHCIIB paralogs.The findings of this PhD are of particular interest to the understanding of the evolutionary history of the avian MHC and, by providing essential information on long-term gene history in the avian MHC, open promising perspectives for advances in the understanding of the evolution of multigene families in general, and for avian MHC organization in particular. Amongst others I discuss the importance of including protein structure in the phylogenetic study of multigene families, and the roles of ecological versus molecular selection pressures. I conclude by providing a population genomic perspective on avian MHC, which may serve as a basis for future research to investigate the relative roles of neutral processes involving effective population size effects and of adaptation in the evolution of avian MHC diversity and organization.RésuméLa duplication de gènes et leur néo-fonctionnalisation sont des processus importants dans l'évolution de la complexité phénotypique. Ils sont impliqués dans l'apparition d'importantes nouveautés évolutives favorisant l'adaptation écologique, comme c'est le cas pour le complexe majeur d'histocompatibilité

History of offending behavior in first episode psychosis patients: A marker of specific clinical needs and a call for early detection strategies among young offenders.

OBJECTIVES: Previous literature suggests that early psychosis (EP) patients with a history of offending behavior (HOB) have specific clinical needs. The aims of this study were to assess: (1) the prevalence of HOB in a representative sample of EP; (2) the premorbid and baseline characteristics of patients with HOB, and (3) the potential differences in short-term outcome of such patients when compared to patients without HOB. METHODS: The Early Psychosis Prevention and Intervention Centre (EPPIC) admitted 786 EP patients between 1998 and 2000. Data were collected from patients' files using a standardized questionnaire. Data of 647 patients could be analyzed. RESULTS: HOB patients (29% of the sample) were more likely to be male with lower level of premorbid functioning and education, have used illicit substances and have attempted suicide. They presented with a more complex clinical picture and had poorer 18-month outcome. Most importantly, they had a significantly longer duration of untreated psychosis. CONCLUSIONS: On the basis of the high prevalence and specific features of EP patients with HOB, our study confirms a need for additional research in this domain and for the development of specific treatment strategies. Most importantly, it suggests a need for the promotion of early detection strategies among the populations of young offenders, considering that some of them may be going through the early phases of a psychotic disorder and that reduction of treatment delay and provision of well adapted interventions may have a significant impact at numerous levels in such patients.

Contributions to the history of ocular toxoplasmosis in Southern Brazil

The evolution of knowledge regarding ocular toxoplasmosis over the last 30 years is described based on studies and observations performed in Southern Brazil. The isolation ofToxoplasma gondii established the definitive diagnosis of the disease. It was proven that in most cases, the disease was acquired after birth, a concept supported by the description of numerous familial cases and observation of the disease many years after primary infection. Epidemiological studies showed important regional variations in the prevalence of the disease due to different factors, including the types of strains involved, of which type I predominates. The large number of patients also enabled detailed study of the different forms of clinical presentation of the disease and its complications. New parameters have been established for the use of steroids and the management of pregnant women with active lesions. Studies on the epidemiology of toxoplasmic infection in pregnant women and newborns showed a high prevalence of infection. The different factors of exposure to infection have also been studied. Gradually, preventive actions have been developed in the sphere of public health, although they have not been sufficiently effective. Trends for future research over the next few years are also outlined.

A century of research: what have we learned about the interaction of Trypanosoma cruzi with host cells?

Since the discovery of Trypanosoma cruzi and the brilliant description of the then-referred to "new tripanosomiasis" by Carlos Chagas 100 years ago, a great deal of scientific effort and curiosity has been devoted to understanding how this parasite invades and colonises mammalian host cells. This is a key step in the survival of the parasite within the vertebrate host, and although much has been learned over this century, differences in strains or isolates used by different laboratories may have led to conclusions that are not as universal as originally interpreted. Molecular genotyping of the CL-Brener clone confirmed a genetic heterogeneity in the parasite that had been detected previously by other techniques, including zymodeme or schizodeme (kDNA) analysis. T. cruzi can be grouped into at least two major phylogenetic lineages: T. cruzi I, mostly associated with the sylvatic cycle and T. cruzi II, linked to human disease; however, a third lineage, T. cruziIII, has also been proposed. Hybrid isolates, such as the CL-Brener clone, which was chosen for sequencing the genome of the parasite (Elias et al. 2005, El Sayed et al. 2005a), have also been identified. The parasite must be able to invade cells in the mammalian host, and many studies have implicated the flagellated trypomastigotes as the main actor in this process. Several surface components of parasites and some of the host cell receptors with which they interact have been described. Herein, we have attempted to identify milestones in the history of understanding T. cruzi- host cell interactions. Different infective forms of T. cruzi have displayed unexpected requirements for the parasite to attach to the host cell, enter it, and translocate between the parasitophorous vacuole to its final cytoplasmic destination. It is noteworthy that some of the mechanisms originally proposed to be broad in function turned out not to be universal, and multiple interactions involving different repertoires of molecules seem to act in concert to give rise to a rather complex interplay of signalling cascades involving both parasite and cellular components.

Vector biology prospects in dengue research

We argue that using more natural blood feeding methods to study mosquito vector competence for dengue viruses and exploring the effect of viral infection on other mosquito life-history traits that influence vectorial capacity will significantly advance our understanding of dengue epidemiology.

All-cause mortality in the cohorts of the Spanish AIDS Research Network (RIS) compared with the general population: 1997-2010.

BACKGROUND Combination antiretroviral therapy (cART) has produced significant changes in mortality of HIV-infected persons. Our objective was to estimate mortality rates, standardized mortality ratios and excess mortality rates of cohorts of the AIDS Research Network (RIS) (CoRIS-MD and CoRIS) compared to the general population. METHODS We analysed data of CoRIS-MD and CoRIS cohorts from 1997 to 2010. We calculated: (i) all-cause mortality rates, (ii) standardized mortality ratio (SMR) and (iii) excess mortality rates for both cohort for 100 person-years (py) of follow-up, comparing all-cause mortality with that of the general population of similar age and gender. RESULTS Between 1997 and 2010, 8,214 HIV positive subjects were included, 2,453 (29.9%) in CoRIS-MD and 5,761 (70.1%) in CoRIS and 294 deaths were registered. All-cause mortality rate was 1.02 (95% CI 0.91-1.15) per 100 py, SMR was 6.8 (95% CI 5.9-7.9) and excess mortality rate was 0.8 (95% CI 0.7-0.9) per 100 py. Mortality was higher in patients with AIDS, hepatitis C virus (HCV) co-infection, and those from CoRIS-MD cohort (1997-2003). CONCLUSION Mortality among HIV-positive persons remains higher than that of the general population of similar age and sex, with significant differences depending on the history of AIDS or HCV coinfection.

Quantifying quantitative literacy: Age heaping and the history of human capital

Age data frequently display excess frequencies at round or attractive ages, such as even numbers and multiples of five. This phenomenon of age heaping has been viewed as a problem in previous research, especially in demography and epidemiology. We see it as an opportunity and propose its use as a measure of human capital that can yield comparable estimates across a wide range of historical contexts. A simulation study yields methodological guidelines for measuring and interpreting differences in ageheaping, while analysis of contemporary and historical datasets demonstrates the existence of a robust correlation between age heaping and literacy at both the individual and aggregate level. To illustrate the method, we generate estimates of human capital in Europe over the very long run, which support the hypothesis of a major increase in human capital preceding the industrial revolution.

IRELAND AND LATIN AMERICA: A CULTURAL HISTORY

According to Declan Kiberd, “postcolonial writing does not begin only when the occupier withdraws: rather it is initiated at that very moment when a native writer formulates a text committed to cultural resistance.” The Irish in Latin America – a continent emerging from indigenous cultures, colonisation, and migrations – may be regarded as colonised in Ireland and as colonisers in their new home. They are a counterexample to the standard pattern of identities in the major English-speaking destinations of the Irish Diaspora. Using literary sources, the press, correspondence, music, sports, and other cultural representations, in this thesis I search the attitudes and shared values signifying identities among the immigrants and their families. Their fragmentary and wide-ranging cultures provide a rich context to study the protean process of adaptation to, or rejection of, the new countries. Evolving from oppressed to oppressors, the Irish in Latin America swiftly became ingleses. Subsequently, in order to join the local middle classes they became vaqueros, llaneros, huasos, and gauchos so they could show signs of their effective integration to the native culture, as seen by the Latin American elites. Eventually, some Irish groups separated from the English mainstream culture and shaped their own community negotiating among Irishness, Englishness, and local identities in Brazil, Uruguay, Peru, Cuba, and other places in the region. These identities were not only unmoored in the emigrants’ minds but also manoeuvred by the political needs of community and religious leaders. After reviewing the major steps and patterns of Irish migration to Latin America, the thesis analyses texts from selected works, offers a version of how the settlers became Latin Americans or not, and elucidates the processes by which a new Irish-Latin American hybrid was created.

Genetic and environmental effects on the covariation betweencolour polymorphism and a life history trait

Variation in coloration with a strong underlying genetic basis is frequently found within animal populations but little is known about its function. Covariation between colour polymorphism and life-history traits can arise because morphs perform differently among environments or because they possess alternative alleles coding for key life-history traits. To test these two hypotheses, we studied a population of tawny owls Strix aluco, a bird displaying red, brown and grey morphs. We assessed the colour morph of breeding females, swapped eggs or hatchlings between pairs of nests, and examined how body condition in 3-week-old nestlings covaries with coloration of foster and genetic mothers. Redder foster and genetic mothers produced young in better condition. Because in two other years we observed that greyish females produced offspring in better condition than those of red females, the present study suggests that colour polymorphism signals genetic and phenotypic adaptations to cope with a fluctuating environment.

Iowa Highway Research Board TR-423: 1949–1999, 1999

The year 1949 saw the Iowa General Assembly’s establishment of the Iowa Secondary Road Research Fund, which led to the creation of a supervisory board within what was then the Iowa State Highway Commission to oversee the expenditure of that fund. The purpose of the fund and the board was to research road construction topics likely to be beneficial to the working of Iowa’s secondary, or local, road system. The supervisory board—called the Iowa Highway Research Board (the “Board”)—was organized by the highway commission in December 1949 and first met in May 1950. The creation of the fund and of the Iowa Highway Research Board marked the first organized effort in the United States to investigate local road construction problems and placed Iowa in the forefront of this field of engineering research. That Iowa should be a leader in such an effort is not surprising, given the early and sustained emphasis of the Iowa State Highway Commission on both research and the dissemination of information to county authorities. Now, 50 years later, a retrospective is in order. To that end, the Iowa Highway Research Board commissioned the preparation of a commemorative history. This work is the result of that project. Throughout its existence, the Board has funded nearly 450 projects, several of national significance. Many new construction and maintenance techniques have been developed, some of which have evolved into standard practices in highway construction. Innovative new materials and equipment have been tested. Still other projects have considered a wide variety of subjects related to the efficient operation of the highway system. Highway safety, conservation, and law have all come under research scrutiny. While it will not be possible, given the short space available, to consider all the projects financed by the Iowa Highway Research Board, it is well worthwhile to examine the Board’s principal projects and its resulting contributions to the field of highway research.

A LIBRARY IN THE MAKING: Pioneer History of the Territorial and State Library of Iowa,October 1912

The discovery of early manuscript reports of Territorial and State Librarians, buried in the mass of old official papers transferred from the several departments of State to the new Department of Archives in the Historical Building, has suggested the propriety of completing as far as possible, the historical record of Iowa's State Library, "from the earliest period to the present time." After a thorough research through the papers on file in the Archives Department, the published Journals and departmental reports in the State Library and documents and private papers loaned me by Mr. Newton R. Parvin, librarian of the Iowa Masonic Library, Cedar Rapids. I am now able to present the following historical sketch, Supplemented by the hitherto unpublished papers referred to this filling a gap in the history of a State institution which from very small beginnings has grown to large proportions and has made for itself a firm place in the respect and esteem of every citizen of Iowa.

History of the Benton Street Bridge, Iowa City, Iowa, April 7, 2010

Video from the Iowa Department of Transportation about the construction and remodel of the Benton Street Bridge in Iowa City. This video is a interview of Samuel Cartsens interviewed but Hank Zeletel the Librarian of the DOT at the time the video was produced.

A History of Particle-Size Limits, Special Report, HR-99

Soils consist largely of mineral particles in a wide range of sizes. It is advantageous to assign names, such as "sand", etc., to describe particles which lie between certain size limits. These names are convenient to use and give more information than merely stating that the particles fit certain size limitations. Many systems of particle-size limits have been proposed and used, and have many discrepancies. For example, depending on the system used, a term such as "sand" may designate very different materials. Since no clear-cut divisions can be made between members of a continuous series all particle-size limit schemes are arbitrary. The originators of the various systems were influenced by many factors: convenience of investigation, methods and equipment available for analysis, ease of presenting data, convenience for statistical analysis, previous work, and systems in use. The complications were further compounded because of widely varying fields of endeavor with varying background, outlook, and goals. For example, many inconsistencies are found in engineering depending on whether the size limits are used to differentiate soils, or characterize aggregates for concrete. Some of the investigators have tried to place limits to correspond with the various properties of the soil components; others were more interested in the ease and convenience of obtaining and presenting data. The purpose of this paper is to review many of the systems which have been proposed and used, and if possible, to suggest what may have been the reasons for the selection of the particle-size limits.