Impaired immune evasion in HIV through intracellular delays and multiple infection of cells

With its high mutation rate, HIV is capable of escape from recognition, suppression and/or killing by CD8(+) cytotoxic T lymphocytes (CTLs). The rate at which escape variants replace each other can give insights into the selective pressure imposed by single CTL clones. We investigate the effects of specific characteristics of the HIV life cycle on the dynamics of immune escape. First, it has been found that cells in HIV-infected patients can carry multiple copies of proviruses. To investigate how this process affects the emergence of immune escape, we develop a mathematical model of HIV dynamics with multiple infections of cells. Increasing the frequency of multiple-infected cells delays the appearance of immune escape variants, slows down the rate at which they replace the wild-type variant and can even prevent escape variants from taking over the quasi-species. Second, we study the effect of the intracellular eclipse phase on the rate of escape and show that escape rates are expected to be slower than previously anticipated. In summary, slow escape rates do not necessarily imply inefficient CTL-mediated killing of HIV-infected cells, but are at least partly a result of the specific characteristics of the viral life cycle.

Cultural and Educational Society of Muslims "Narodna Uzdanica" /"National Hope"/ 1923-1941

Ibrahim Kemura. The Muslim Cultural-Educational Society Narodna uzdanica from 1923/4 to 1941 One of the features of the cultural history of the Bosniacs between the two world wars (1918-1941) was a cultural and educational society named Narodna uzdanica, which was a significant institutional and cultural-intellectual centre of the Bosniac people in Bosnia and Herzegovina. Narodna uzdanica expressed the aspirations and needs of the Bosniac citizens who were its main support and axis and was aimed at fulfilling their interests. This was reflected in an ideological-cultural orientation towards the West and the adoption of positive western achievements while at the same time stressing its Slavic origins and individuality, the education of young people and the formation of a European-type civic intelligentsia, adaptation to life in capitalist society, the development of modern trade and crafts, the emancipation of women, and cultural education based on European values. Thus conceived, the programme enjoyed the support of a wider circle of members, the reading public and the cultural consumers of those particular elements such as education and economic prosperity which it sought to achieve. The political involvement of Narodna uzdanica and its use as a platform for the leading Bosniac political party Jugoslovenska muslimanska organizacija (JMO - Yugoslav Muslim Organisation) which had founded the society, played a significant role in the socio-political life and development of Bosniacs. The opposition to the ruling regime, often expressed through close cooperation with similar Croat organisations and through the pro-Croat attitude of some of the society's leading figures, offered both the regime and Narodna uzdanica's political adversaries grounds for describing it as separatist and Croat and served as a pretext for repressive measures to hinder its normal operations. This research proved these accusations to be groundless, showing that the pro-Croat orientation was primarily political and cultural and that throughout its existence Narodna uzdanica was active in the cultural and educational renaissance of Bosniacs, helping to strengthen their national identity.

Scientific Institutions in a Society of Transition: Strategies of Modernisation

Kristina Petkova (Group Leader), Tzocho Boyadgiev, Galin Gornev, Ivan Tcholakov (Bulgaria), Martin Bauer (Switzerland). Scientific Institutions in a Society of Transition: Strategies of Modernisation. Ms. Petkova is involved in teaching and research in the Institute of Sociology of the Bulgarian Academy of Science and led this project, which was carried out between July 1995 and June 1997. The aims of this project were a) to outline the main adaptive strategies of scientific institutions in a situation of social transition, and b) to analyse the opportunities for mobilising public opinion in support scientific work. The group began from the assumption that the social representation of science reflects the historical development of society as a whole. They developed a theoretical model describing the position of science in the three main types of society in the world today (modern, post-modern, totalitarian) and carried out three types of investigation: a representative survey of the public understanding of scientific institutions in Bulgaria; an in-depth cross-national investigation (Bulgarian - Great Britain); and a content analysis of how science is represented in two national newspapers, the "Rabotnichesko Delo" and the "Daily Telegraph". The results showed that Bulgarian public opinion has a more standard view of science and a more optimistic vision of scientific development than do the British, but that there is a certain insensitivity to the risks of scientific results, etc. The group conclude that in order to survive, scientific institutions in Bulgaria should change their passive attitude and adopt active strategies in both their relationships with the state, and in their contacts with private business and with the institutions of civil society.

The quantitative genetic basis of offspring solicitation and parental response in a passerine bird with biparental care

The coevolution of parental investment and offspring solicitation is driven by partly different evolutionary interests of genes expressed in parents and their offspring. In species with biparental care, the outcome of this conflict ma!: be influenced by the sexual conflict over parental investment, Models for the resolution of such family conflicts have made so far untested assumptions about genetic variation and covariation in the parental resource provisioning response and the level of offspring solicitation. Using a combination of cross-fostering and begging playback experiments, we show that, in the great tit (Parus major), (i) the begging call intensity of nestlings depends on their common origin, suggesting genetic variation for this begging display, (ii) only mothers respond to begging calls by increased food provisioning, and (iii! the size of the parental response is positively related to the begging call intensity of nestlings in the maternal but not paternal line. This study indicates that genetic covariation, its differential expression in the maternal and paternal lines and/or early environmental and parental effects need to be taken into account when predicting the phenotypic outcome of the conflict over investment between genes expressed in each parent and the offspring. [References: 36]

Immunocompetence of nestling great tits in relation to rearing environment and parentage

Theoretical models of host-parasite coevolution assume a partially genetic basis to the variability in susceptibility to parasites among hosts, for instance as a result of genetic variation in immune function. However, few empirical data exist for free-living vertebrate hosts to support this presumption. In a cross-fostering experiment with nestling great tits, by comparing nestlings of the same origin we investigated (i) the variance in host resistance against an ectoparasite due to a common genetic origin, (ii) the effect of ectoparasite infestation on cell-mediated immunity and (iii) the variance in cell-mediated immunity due to a common genetic origin. Ectoparasitic hen fleas can impair the growth of nestling great tits and nestling growth was therefore taken as a measure of host susceptibility. A common origin did not account for a significant part of the variation in host susceptibility to fleas. There was no significant overall effect of fleas on nestling growth or cell-mediated immunity, as assessed by a cutaneous hypersensitivity response. A common rearing environment explained a significant part of the variation in cell-mediated immunity among nestlings, mainly through its effect on nestling body mass. The variation in cell-mediated immunity was also related to a common origin. However, the origin-related variation in body mass did not account for the origin-related differences in cell-mediated immunity. The results of the present study thus suggest heritable variation in cell-mediated immunity among nestling great tits. [References: 49]

Benefits of Induced Host Responses against an Ectoparasite

As a consequence of the deleterious effects of parasites on host fitness, hosts have evolved responses to minimize the negative impact of parasite infection. Facultative parasite-induced responses are favoured when the risk of infection is unpredictable and host responses are costly. In vertebrates, induced responses are generally viewed as being adaptive, although evidence for fitness benefits arising from these responses in natural host populations is lacking. Here we provide experimental evidence for direct reproductive benefits in flea-infested great tit nests arising from exposure during egg production to fleas. In the experiment we exposed a group of birds to fleas during egg laying (the exposed group), thereby allowing for induced responses, and kept another group free of parasites (the unexposed group) over the same time period. At the start of incubation, we killed the parasites in both groups and all nests were reinfested with fleas. If induced responses occur and are adaptive, we expect that birds of the exposed group mount earlier responses and achieve higher current reproductive success than birds in the unexposed group. In agreement with this prediction, our results show that birds with nests infested during egg-laying have (i) fewer breeding failures and raise a higher proportion of hatchlings to hedging age; () offspring that reach greater body mass, grow longer feathers, and hedge earlier, and (iii) a higher number of recruits and first-year grandchildren than unexposed birds. Flea reproduction and survival did not differ significantly between the two treatments. These results provide the first evidence for the occurrence and the adaptiveness of induced responses against a common ectoparasite in a wild population of vertebrates. [References: 50]

Practical sources of error in measuring pulmonary artery occlusion pressure: a study in participants of a special intensivist training program of The Scandinavian Society of Anaesthesiology and Intensive Care Medicine (SSAI)

BACKGROUND: Physiological data obtained with the pulmonary artery catheter (PAC) are susceptible to errors in measurement and interpretation. Little attention has been paid to the relevance of errors in hemodynamic measurements performed in the intensive care unit (ICU). The aim of this study was to assess the errors related to the technical aspects (zeroing and reference level) and actual measurement (curve interpretation) of the pulmonary artery occlusion pressure (PAOP). METHODS: Forty-seven participants in a special ICU training program and 22 ICU nurses were tested without pre-announcement. All participants had previously been exposed to the clinical use of the method. The first task was to set up a pressure measurement system for PAC (zeroing and reference level) and the second to measure the PAOP. RESULTS: The median difference from the reference mid-axillary zero level was - 3 cm (-8 to + 9 cm) for physicians and -1 cm (-5 to + 1 cm) for nurses. The median difference from the reference PAOP was 0 mmHg (-3 to 5 mmHg) for physicians and 1 mmHg (-1 to 15 mmHg) for nurses. When PAOP values were adjusted for the differences from the reference transducer level, the median differences from the reference PAOP values were 2 mmHg (-6 to 9 mmHg) for physicians and 2 mmHg (-6 to 16 mmHg) for nurses. CONCLUSIONS: Measurement of the PAOP is susceptible to substantial error as a result of practical mistakes. Comparison of results between ICUs or practitioners is therefore not possible.