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What can we gain from co-analyzing experimental cultures, regionalization, and disciplinary phenomena of late twentieth century life sciences under our historiographic looking glass? This essay investigates the potential of such a... more
What can we gain from co-analyzing experimental cultures, regionalization, and disciplinary phenomena of late twentieth century life sciences under our historiographic looking glass? This essay investigates the potential of such a strategy for the case of cell biology after 1960. By merging perspectives from historical epistemology inspired by the work of Hans-Jörg Rheinberger with a focus on boundary work in the realm of scientific publishing, community building, and disciplinary norms, a set of understudied scientific practices is exposed. These practices, historically subsumed under the label descriptive, have been as central in cell biology as hypothesis-driven research aiming at mechanistic explanations of cellular function. Against the background of an increasing molecular-mechanistic imperative in cell biology since the late 1960s, knowledge from descriptive practices was often judged as having low value but was nonetheless frequently cited and considered
In den ersten Lebenswochen findet bei Saugferkeln kaum eine eigenständi- ge Antikörperproduktion statt. Die Übertragung von maternalen Antikör- pern (AK) über Kolostrum bzw. Milch ist bei vielen Infektionskrankheiten essentiell für den... more
In den ersten Lebenswochen findet bei Saugferkeln kaum eine eigenständi- ge Antikörperproduktion statt. Die Übertragung von maternalen Antikör- pern (AK) über Kolostrum bzw. Milch ist bei vielen Infektionskrankheiten essentiell für den Schutz der Jungtiere. Inwieweit AK gegen Isospora suis, den Erreger der Saugferkelkokzidiose, auf die Ferkel übertragen werden und ob diese einen Schutz vor der Infektion bieten, ist bisher nur unzulänglich un- tersucht. Daher wurde von 22 am 3. Lebenstag (LT) infizierten und 12 nicht infizierten Ferkeln präkolostral, am 1. LT und dann wöchentlich Blut abge- nommen und die AK-Titer (IgG, IgA, IgM) gegen Merozoiten von I. suis mittels IFAT bestimmt. Parallel wurde Kolostral- bzw. Milchserum der Mut- tersauen getestet. Das Kolostralserum der Sauen zeigte deutliche AK-Titer. Nach der Kolostrumaufnahme hatten infizierte und nicht infizierte Ferkel vergleichbare Titer. Ab LT 14 nahm der IgG-Titer bei allen Tieren kontinu- ierlich ab. Bei infizierten Ferkel...
Die von Isospora suis verursachte Saugferkelkokzidiose kann schwere Durchfälle auslösen und führt zu finanziellen Einbußen in der Schweineproduktion. Die Kolonisation des Darms durch Bakterien könnte durch I. suis beeinflusst oder gestört... more
Die von Isospora suis verursachte Saugferkelkokzidiose kann schwere Durchfälle auslösen und führt zu finanziellen Einbußen in der Schweineproduktion. Die Kolonisation des Darms durch Bakterien könnte durch I. suis beeinflusst oder gestört und damit die Mortalität und die Empfänglichkeit für typische Erkrankungen nach dem Absetzten erhöht werden. Um den Einfluss von I. suis und der Behandlung mit Toltrazuril auf symbiotische und fakultativ pathogene Bakterien zu untersuchen, wurden von Isosporafreien und experimentell infizierten Ferkeln in den ersten 12 Lebenstagen Kotproben untersucht. Die Hälfte der infizierten Tiere wurde mit Toltrazuril behandelt. Die Zahl an aeroben und anaeroben Bakterien, Streptokokken, Enterokokken, Enterobacteriaceen, Laktobazillen und von Clostridium perfringens pro Gramm Kot wurde erhoben. Nicht infizierte Tiere schieden weniger Streptokokken, Enterokokken und Anaerobier aus als infizierte Ferkel. In Stichproben konnten pathogene Stämme von C. perfringens...
Infections of neonatal piglets with Cystoisospora suis are responsible for substantial economic losses in pig production. To investigate kinetics of T-cell populations, which are possibly involved in this infection, lymphocytes from... more
Infections of neonatal piglets with Cystoisospora suis are responsible for substantial economic losses in pig production. To investigate kinetics of T-cell populations, which are possibly involved in this infection, lymphocytes from blood, spleen, mesenteric lymph nodes and the jejunal mucosa of infected and noninfected piglets were investigated by flow cytometry and immunohistochemistry at five time points during the acute phase of primary infection. Additionally, mRNA expression levels of pattern recognition receptors and immunomodulatory cytokines in the jejunum were investigated. T-cell receptor-γδ(+) T cells were found to be increased in the gut mucosa 4 days after infection and were most likely involved in the primary local immune response. Five to eleven days later, cytotoxic T cells peaked in this location, which was preceded by an expansion of this lymphocyte population in the mesenteric lymph nodes. In intestines of infected piglets, mRNA expressions of TLR-2, NOD2 and TNF-α were significantly upregulated, suggesting an involvement in parasite recognition, immune response and possibly also in immunopathology. Taken together, this study identifies cellular and molecular players involved in the early immune responses against C. suis, but their precise role in the pathogenesis and control of this neonatal disease requires further investigation.
Quantification of immunohistochemical results constitutes an important tool in the analysis of cells and tissue that is not readily replaced by other techniques. For reliable quantification, it is essential to consider factors such as... more
Quantification of immunohistochemical results constitutes an important tool in the analysis of cells and tissue that is not readily replaced by other techniques. For reliable quantification, it is essential to consider factors such as tissue fixation and tissue sampling. We report a study on the model of the intestine of Isospora suis-infected piglets, in which we addressed (1) whether the quantity of detectable T cells in the intestinal mucosa is the same in formalin-, HOPE®-, and cryo-conserved material or whether the amounts of T cells at least correlate with one another; and (2) whether single jejunal segments differ in regard to the quantity of mucosal T cells and variability of lymphocyte infiltration. Quantification of T cells in histological sections of different parts of the jejunum of 15-22 day old piglets infected with I. suis was performed using an anti-CD3-antibody and stereological point counting. Area fractions of T-cell profiles per intestinal mucosa profile were higher in cryo-conserved samples than in HOPE®- and formalin-conserved material but no correlation between different fixations could be found. The proximal part of the jejunum contained fewer T cells compared with mid- and end-jejunum. Coefficients of variation did not differ between the intestinal segments. For quantification of T cells in the gut mucosa of piglets infected with I. suis, the cryo-conserved mid jejunum seems most suitable in cases when unbiased sampling of the complete intestine is not feasible. It is generally not possible to compare quantitative results of immunostaining in samples conserved by different methods. Microsc. Res. Tech., 2011. © 2011 Wiley-Liss, Inc.
Research in osteoporosis, which is a complex systemic disease, demands suitable large animal models. In pigs, most research has been done in growing minipigs, which probably are not ideal models for postmenopausal osteoporosis. Therefore,... more
Research in osteoporosis, which is a complex systemic disease, demands suitable large animal models. In pigs, most research has been done in growing minipigs, which probably are not ideal models for postmenopausal osteoporosis. Therefore, our aim was to analyze the effects of ovariectomy (OVX) and nutritive calcium shortage on multiparous Large White sows. 32 animals were randomly assigned to 4 groups in a cross design with OVX vs. sham and physiological calcium supplementation (0.75% calcium) vs. dietary calcium shortage (0.3% calcium). The observation period was 10 months with blood sampling every 2 months for hematological, immunological, and biochemical bone marker measurements. At the termination of the experiment, animals were sacrificed. Samples of trabecular bone of distal radius, proximal tibia, and sixth lumbar vertebra were subjected to micro-computed tomography imaging and ashed afterwards. Dual X-ray absorptiometry scans of the proximal femora were performed with prepared bones being placed in a water bath for mimicking soft tissue. Analyses of bone marker and cytokine profile kinetics, distribution of leukocyte subpopulations, and morphometrical and densitometrical analyses showed no evidence of any impact of OVX or calcium shortage. In conclusion, the skeleton of adult sows of a conventional breed is seemingly protected from effects of OVX and calcium shortage.
Infections of neonatal piglets with Cystoisospora suis are responsible for substantial economic losses in pig production. To investigate kinetics of T-cell populations, which are possibly involved in this infection, lymphocytes from... more
Infections of neonatal piglets with Cystoisospora suis are responsible for substantial economic losses in pig production. To investigate kinetics of T-cell populations, which are possibly involved in this infection, lymphocytes from blood, spleen, mesenteric lymph nodes and the jejunal mucosa of infected and noninfected piglets were investigated by flow cytometry and immunohistochemistry at five time points during the acute phase of primary infection. Additionally, mRNA expression levels of pattern recognition receptors and immunomodulatory cytokines in the jejunum were investigated. T-cell receptor-γδ+ T cells were found to be increased in the gut mucosa 4 days after infection and were most likely involved in the primary local immune response. Five to eleven days later, cytotoxic T cells peaked in this location, which was preceded by an expansion of this lymphocyte population in the mesenteric lymph nodes. In intestines of infected piglets, mRNA expressions of TLR-2, NOD2 and TNF-α were significantly upregulated, suggesting an involvement in parasite recognition, immune response and possibly also in immunopathology. Taken together, this study identifies cellular and molecular players involved in the early immune responses against C. suis, but their precise role in the pathogenesis and control of this neonatal disease requires further investigation.
Bone, Volume 48, Issue null, Pages S198, 7 May 2011, Authors:W. Sipos; E. Kralicek; M. Rauner; CJ Duvigneau; HL Worliczek; D. Schamall; RT Hartl; I. Sommerfeld-Stur; E. Dall'Ara; P. Varga; H. Resch; P. Zysset; P. Pietschmann.
A set of 20 Mollicutes strains representing different lines of descent, including the type species of the genus Mycoplasma, Mycoplasma mycoides, Acholeplasma laidlawii and a strain of Mesoplasma, were subjected to polar lipid and fatty... more
A set of 20 Mollicutes strains representing different lines of descent, including the type species of the genus Mycoplasma, Mycoplasma mycoides, Acholeplasma laidlawii and a strain of Mesoplasma, were subjected to polar lipid and fatty acid analyses in order to evaluate their suitability for classification purposes within members of this group. Complex polar lipid and fatty acid profiles were detected for each examined strain. All strains contained the polar lipids phosphocholine-6′-α-glucopyranosyl-(1′-3)-1, 2-diacyl-glycerol (MfGL-I), 1-O-alkyl/alkenyl-2-O-acyl-glycero-3-phosphocholine (MfEL), sphingomyelin (SphM), 1-O-alkyl/alkenyl-glycero-3-phosphocholine (lysoMfEL), the unknown aminophospholipid APL1 and the cholesterol Chol2. A total of 19 strains revealed the presence of phosphatidylethanolamine (PE) and/or phosphatidylglycerol (PG), and the presence of diphosphatidylglycerol (DPG) was detected in 13 strains. The unknown aminolipid AL1 was found in the extracts of 17 strains. Unbranched saturated and unsaturated compounds predominated in the fatty acid profiles. Major fatty acids were usually C16:0, C18:0, C18:1 ω9c and ‘Summed feature 5’ (C18:2 ω6, 9c/C18:0 anteiso). Our results demonstrated that members of the M. mycoides cluster showed rather homogenous polar lipid and fatty acid profiles. In contrast, each of the other strains was characterized by a unique polar lipid profile and significant quantitative differences in the presence of certain fatty acids. These results indicate that analyses of both polar lipid and fatty acid profiles could be a useful tool for classification of mycoplasmas.
Data from 13 trials involving 124 suckling piglets experimentally infected with Isospora suis were evaluated for the effects of infection dose and age on the clinical and parasitological outcome of infection in four different models,... more
Data from 13 trials involving 124 suckling piglets experimentally infected with Isospora suis were evaluated for the effects of infection dose and age on the clinical and parasitological outcome of infection in four different models, infections with 1,000 oocysts on the 1st day of life (d.o.l.) (model 1; 9 piglets/3 litters), 1,000 oocysts on the 4th d.o.l. (model 2; 25 piglets/11 litters), 1,500 oocysts on the 4th d.o.l. (model 3; 40 piglets/20 litters) and 10,000 oocysts on the 4th d.o.l. (model 4; 50 animals/10 litters). Weights were determined on the day of birth and in weekly intervals. Faecal consistency and quantitative oocysts excretion were evaluated for 2 weeks starting 4 days after infection (d.p.i.). The weight gain depression was most noticeable in model 2 (infection on the 1st d.o.l.), where animals only gained 2.08 x their birth weight until the 22nd d.o.l., compared to 2.31–2.52 x in the other groups. This correlated with the occurrence of watery diarrhoea which was found in 37 % of the samples in the acute phase (4–11 d.p.i.) in model 2 but only in 12–20 % of the samples in the other models. Median oocyst excretion peaked earlier in the models with higher infection doses but reached the highest values in model 2 (early infection). As in previous studies, this cross-sectional analysis of a larger number of animals confirms the influence of age on the outcome of isosporosis in suckling piglets, stressing the need to control the infection at an early life phase.
Porcine neonatal coccidiosis is caused by the protozoan Isospora suis and affects mainly piglets in the first three weeks of life. High morbidity with diarrhoea and reduced weight gain lead to economic losses, affecting pig-breeding... more
Porcine neonatal coccidiosis is caused by the protozoan Isospora suis and affects mainly piglets in the first three weeks of life. High morbidity with diarrhoea and reduced weight gain lead to economic losses, affecting pig-breeding worldwide. Infection causes damage of the mucosal surface in the jejunum and ileum and transient non-haemorhagic diarrhoea. Secondary infections with other enteric pathogens may lead to increased mortality. Despite its economic and veterinary importance, the immunology of porcine isosporosis is still poorly understood. A striking feature of the infection is the rapidly increasing age resistance prohibiting the development of clinical disease in piglets older than 3–4 weeks irrespective of the immune status. It can be hypothesised that the development of the innate immune system in the first weeks of life and subsequently its interplay with the adaptive immune system is closely related to this phenomenon. Infections with I. suis induce migration of TcR-γδ+ cells to the gut during primary infection and lead to induction of IFN-γ production by TcR-γδ+ cells and CD4+ T-helper cells in blood and various lymphoid tissues. Like in other coccidial infections both innate as well as adaptive response mechanisms are activated during infection. They might be both not completely developed in the first weeks of life and therefore leaving a time frame for successful infection.
Isospora suis ist ein einzelliger Parasit des Schweins und der Erreger der Saugferkelkokzidiose. Diese Erkrankung zeigt eine hohe Morbidität in betroffenen Ferkelzuchtbetrieben und ist damit ein wichtiger wirtschaftlicher Faktor in der... more
Isospora suis ist ein einzelliger Parasit des Schweins und der Erreger der Saugferkelkokzidiose. Diese Erkrankung zeigt eine hohe Morbidität in betroffenen Ferkelzuchtbetrieben und ist damit ein wichtiger wirtschaftlicher Faktor in der Schweineproduktion. Im Verlauf der Infektion wird die Schleimhaut des Dünndarmepithels in Jejunum und Ileum stark geschädigt, was zu charakteristischen unblutigen Durchfällen führt. Eine Folge der reduzierten Nährstoffaufnahme im so geschädigten Dünndarm sind verminderte Absetzgewichte und ein starkes Auseinanderwachsen der Würfe, zusätzlich können Sekundärinfektionen mit anderen Darmpathogenen die Mortalitätsrate erhöhen. Trotz der wirtschaftlichen und veterinärmedizinischen Bedeutung der Saugferkelkokzidiose sind die Interaktionen zwischen Wirt und Parasit bislang nur unzureichend aufgeklärt. Dieser Übersichtsartikel befasst sich mit dem Lebenszyklus von I. suis und den klinischen und parasitologischen Charakteristika der Saugferkelkokzidiose. Weiters werden verschiedene Modelle der experimentellen Infektion und etablierte in vitro-Methoden zur Erforschung von I. suis vorgestellt. Er gibt einen Überblick über die natürliche Altersresistenz gegen Infektionen mit I. suis, die Immunantwort verschiedener Wirte bei anderen Kokzidieninfektionen (Eimeria spp., Cryptosporidium muris) und eine Zusammenfassung der Besonderheiten des Immunsystems des Schweins und seiner Entwicklung in den ersten Lebenswochen. Isospora suis, an intestinal protozoan parasite of swine, is the causative agent of neonatal coccidiosis, a disease with high morbidity in affected pig-breeding units and consequently of high economic importance. Infection leads to damage of the mucosal surface in the jejunum and ileum and to non-haemorrhagic diarrhoea. As a result, weight gain of piglets is reduced and secondary infections with other enteric pathogens may lead to increased mortality. Despite its economic and veterinary importance, host-parasite interactions are still poorly understood. To examine these interactions experimental infection models are established using outbred piglets infected with defined numbers of parasites on different days of life. This review discusses the life cycle of Isospora suis and the clinical and parasitological characteristics of porcine neonatal coccidiosis including pathology, and compare the different experimental infection models and the tools for studying Isospora suis in vitro. Moreover, it summarises findings about natural age resistance of pigs against infections with Isospora suis, our current knowledge about immune response to other coccidial infections, e.g. with Eimeria spp. in different hosts, and gives a short overview on peculiarities of the porcine immune system and its development in young animals which may play a role in porcine coccidiosis.
Porcine coccidiosis caused by Isospora suis is one of the leading causes of neonatal diarrhea in suckling piglets. Currently the only registered drug for metaphylaxis is toltrazuril. To evaluate the effect of treatment on piglets from 7... more
Porcine coccidiosis caused by Isospora suis is one of the leading causes of neonatal diarrhea in suckling piglets. Currently the only registered drug for metaphylaxis is toltrazuril. To evaluate the effect of treatment on piglets from 7 Austrian farms without and 8 Austrian farms with toltrazuril application we examined oocyst excretion (including determination of oocysts per gram of feces; OPG), diarrhea (fecal score FS 1–4 with 3 and 4 being diarrhea), and general health (health score HS 1–4 with 3 and 4 describing poor health). Both groups included farms with different levels of hygiene. Samples from 265 litters without treatment, comprising 1588 individual samples, and 1548 samples from 258 treated litters were taken twice (around the 14th and the 21st day of life, respectively), examined by autofluorescence and, if positive, by McMaster counting. In both groups animals had less diarrhea and lower health scores during the second sampling but the treated piglets were always significantly healthier and had less diarrhea. The percentage of weaned piglets was higher in treated animals although this was not significant (p = 0.052). In the first round of sampling 17.8% of the individual samples from untreated piglets were positive for oocysts (with a maximum prevalence on the 12–15th day of life) while in the treated piglets only 0.4% shed oocysts p < 0.001). At the second sampling only 2.1% of the untreated animals and none of treated piglets excreted I. suis (p = 0.083). Positive animals shed up to 8 × 103 OPG. There was an increased risk for infected piglets to develop diarrhea (odds ratio, OR 4.73) and poor health (OR 5.05) in untreated piglets, and poor hygiene without disinfection was identified as a risk factor for poor health (OR 1.90), diarrhea (OR 1.42) and oocyst excretion (OR 1.73). The risk of poor health (OR 2.89) and diarrhea (OR 1.44) was also increased for piglets under poor hygienic conditions receiving toltrazuril, so both metaphylaxis of coccidiosis and good hygiene are necessary to effectively control neonatal diarrhea. The costs of treatment are considerably lower than the estimated financial production losses. Therefore, treatment is recommended for farms where clinical coccidiosis is diagnosed.
Highly purified antigen and appropriate controls are essential for antigen-specific immunoassays. In the case of Isospora suis, the causative agent of neonatal porcine coccidiosis, the only current source of antigen is oocysts isolated... more
Highly purified antigen and appropriate controls are essential for antigen-specific immunoassays. In the case of Isospora suis, the causative agent of neonatal porcine coccidiosis, the only current source of antigen is oocysts isolated from faeces. The aim of this study was to develop a procedure for high-grade purification of I. suis oocysts from piglet faeces to obtain both antigen and representative controls suitable for in vitro re-stimulation of lymphocytes. This was achieved by use of filtration, density-gradient centrifugation and fluorescence-activated cell sorting (FACS). The feasibility for immunological studies was demonstrated with IFN-gamma ELISPOT assays after in vitro re-stimulation of lymphocytes from previously infected swine using the obtained antigen. The developed method allowed the production of highly purified antigen and representative controls from faeces with an oocyst recovery rate of 14%. Regarding the application of the obtained material it could be shown that lymphocytes from I. suis-infected pigs react in an antigen-specific manner in terms of an in vitro recall response by the production of IFN-gamma. This demonstrates the suitability of the developed method for the production of antigen and controls for sensitive immunological readout systems. Moreover, the detected specific IFN-gamma response encourages further functional studies on the cellular immune response to I. suis.
Isospora suis, a common intestinal parasite of piglets, causes neonatal porcine coccidiosis, which results in reduced and uneven weaning weights and economic losses in pig production. Nevertheless, there are no detailed studies available... more
Isospora suis, a common intestinal parasite of piglets, causes neonatal porcine coccidiosis, which results in reduced and uneven weaning weights and economic losses in pig production. Nevertheless, there are no detailed studies available on the immune response to I. suis. The aim of this study was to carry out phenotypical characterization of lymphocytes during primary infections on day 3 after birth. Infected and noninfected piglets were investigated between days 7 and 16 after birth. Lymphocytes from the blood, spleen and mesenteric lymph nodes (flow cytometry) and of the jejunal mucosa (immunohistochemistry) were analysed. A decrease in T cells, especially with the phenotype of resting T-helper cells, T-cell receptor-γδ-T cells, and regulatory T cells in the blood, spleen and mesenteric lymph nodes was noticeable. An increase in cells with the phenotype of natural killer cells in the spleen of infected animals was found, and the subset of TcR-γδ-T cells was strongly increased in the gut mucosa. Our findings suggest an accelerated migration of those cells into the gut. This study provides a strong indication for the involvement of adaptive and innate immune response mechanisms in the primary immune response to I. suis, especially of TcR-γδ-T cells as a linkage between innate and adaptive immunity.
Isospora suis ist ein einzelliger Parasit des Schweins und der Erreger der Saugferkelkokzidiose. Diese Erkrankung zeigt eine hohe Morbidität in betroffenen Ferkelzuchtbetrieben und ist damit ein wichtiger wirtschaftlicher Faktor in der... more
Isospora suis ist ein einzelliger Parasit des Schweins und der Erreger der Saugferkelkokzidiose. Diese Erkrankung zeigt eine hohe Morbidität in betroffenen Ferkelzuchtbetrieben und ist damit ein wichtiger wirtschaftlicher Faktor in der Schweineproduktion. Im Verlauf der Infektion wird die Schleimhaut des Dünndarmepithels in Jejunum und Ileum stark geschädigt, was zu charakteristischen unblutigen Durchfällen führt. Eine Folge der reduzierten Nährstoffaufnahme im so geschädigten Dünndarm sind verminderte Absetzgewichte und ein starkes Auseinanderwachsen der Würfe, zusätzlich können Sekundärinfektionen mit anderen Darmpathogenen die Mortalitätsrate erhöhen. Trotz der wirtschaftlichen und veterinärmedizinischen Bedeutung der Saugferkelkokzidiose sind die Interaktionen zwischen Wirt und Parasit bislang nur unzureichend aufgeklärt. Dieser Übersichtsartikel befasst sich mit dem Lebenszyklus von I. suis und den klinischen und parasitologischen Charakteristika der Saugferkelkokzidiose. Weiters werden verschiedene Modelle der experimentellen Infektion und etablierte in vitro-Methoden zur Erforschung von I. suis vorgestellt. Er gibt einen Überblick über die natürliche Altersresistenz gegen Infektionen mit I. suis, die Immunantwort verschiedener Wirte bei anderen Kokzidieninfektionen (Eimeria spp., Cryptosporidium muris) und eine Zusammenfassung der Besonderheiten des Immunsystems des Schweins und seiner Entwicklung in den ersten Lebenswochen. Isospora suis, an intestinal protozoan parasite of swine, is the causative agent of neonatal coccidiosis, a disease with high morbidity in affected pig-breeding units and consequently of high economic importance. Infection leads to damage of the mucosal surface in the jejunum and ileum and to non-haemorrhagic diarrhoea. As a result, weight gain of piglets is reduced and secondary infections with other enteric pathogens may lead to increased mortality. Despite its economic and veterinary importance, host-parasite interactions are still poorly understood. To examine these interactions experimental infection models are established using outbred piglets infected with defined numbers of parasites on different days of life. This review discusses the life cycle of Isospora suis and the clinical and parasitological characteristics of porcine neonatal coccidiosis including pathology, and compare the different experimental infection models and the tools for studying Isospora suis in vitro. Moreover, it summarises findings about natural age resistance of pigs against infections with Isospora suis, our current knowledge about immune response to other coccidial infections, e.g. with Eimeria spp. in different hosts, and gives a short overview on peculiarities of the porcine immune system and its development in young animals which may play a role in porcine coccidiosis.
Isospora suis, the causative agent of porcine neonatal coccidiosis (isosporosis), was identified as an important pathogen of pigs only in the 1970s with the intensification of pig production in industrialised countries. The parasite is... more
Isospora suis, the causative agent of porcine neonatal coccidiosis (isosporosis), was identified as an important pathogen of pigs only in the 1970s with the intensification of pig production in industrialised countries. The parasite is diagnosed with high prevalences in neonatal piglets and is associated with considerable economic problems due to diarrhoea and subsequent weight loss. While details of the life cycle and the more general features of the parasite have been described in detail, little is known about the host–parasite interplay which determines clinical and pathological outcome as well as the development of immunity. The dynamics of transmission and the pathogenesis of the disease are poorly understood, as are phenomena such as age resistance to the disease in piglets older than 3 weeks. In recent studies infection models mimicking the natural situation have been established for research on the host–parasite interactions and population dynamics of I. suis. The results indicate complex actions of the developing immune system in porcine neonates involving both innate and acquired immunity in the control of the parasite. Interactions of the parasite with the gut flora of the fast-developing neonatal pig are still not resolved, although an increase of clostridiosis is implied in outbreaks of isosporosis with increased mortality. Treatment with coccidiocides considerably improves piglet health; however, sustainable control regimes are still to be developed. New technologies like custom-made species-specific commercial immunological assays, in vitro propagation of I. suis in suitable host cells, genotyping of both host and parasite and the use of germ-free piglets for defined infection models will throw light on the unresolved questions surrounding I. suis and porcine coccidiosis.
The rise and growth of mechanistic thought and explanation has been a central theme in the historiography of biology in the twentieth and twenty first centuries. However, this historiography often treats mechanism and mechanistic thought... more
The rise and growth of mechanistic thought and explanation has been a central theme in the historiography of biology in the twentieth and twenty first centuries. However, this historiography often treats mechanism and mechanistic thought as a distinct and distinguishable element within biology, one which was more or less uniform, and which possessed its own momentum. By contrast, a contextualist approach finds mechanism to have been co-extensive with a host of other developments and practices in biology that were occurring simultaneously. Putting mechanism in its place requires attention to its relationships with other elements of biological practice, theory, and representation. In this panel we particularly reflect on the importance of descriptive biology, narrative science, experimental interventionism, and interdisciplinary cooperation. All four papers speak to mechanism, and by placing it in association with these additional elements, have the capacity to change our appreciation of what mechanism did to and for biology.

Our four cases span molecular, cellular, and organismal mechanistic scales, each addressing biological phenomena that fostered multi-disciplinary attention. All four adopt the approach of integrated history and philosophy of science in order to bring to life the epistemic questions faced by historical actors, and offer more or less appropriate terms in which to understand their philosophical and historical significance. For each of us, the recognition that mechanism and mechanistic thought mattered for our actors is a starting point, one which might then: mask significant differences between approaches to mechanism (Berry); or overshadow elements of research that have been underappreciated (Worliczek); or supply a meeting point for cooperative scientific practices which test biology’s universality (Schürch); or help scientists productively manage partial accounts of unique events (Bonnin); the four papers are discussed by a concluding commentary (Grote).
This paper traces a substantial visual end epistemic change in cell biology, a field strongly associated with evidence from microscopic imaging, during the 1970s. This change was initiated by the adoption of fluorescence microscopy from... more
This paper traces a substantial visual end epistemic change in cell biology, a field strongly associated with evidence from microscopic imaging, during the 1970s. This change was initiated by the adoption of fluorescence microscopy from diagnostic research on infectious diseases. The binding of antibodies to particular molecules made it possible to stain proteins of interest, thereby allowing for a visualisation of the molecular architecture of cell components. In comparison with electron microscopy, the dominant imaging method of the 1950s and 1960s in cell biology, the epistemic qualities of this new technique allowed researchers to acquire different and novel kinds of knowledge. Cell biologists defined what had thus far remained a hypothetical cellular entity using fluorescence microscopy: the cytoskeleton as a network of fibres that was responsible for cell shape and motility. As I will show, the application and establishment of fluorescence microscopy re-defined the cytoskeleton as an evidence-based entity of significance equal to that of canonised structures such as the cell nucleus. Furthermore, this method was mobilised by authors and editors, who soon began using these new images produced by researchers for textbooks, thereby contributing to a re-shaped iconography and canonised picture of the cell. Based on published articles, textbooks, editorial archives, papers of scientific societies, as well as interviews with various actors, I aim to understand and reconstruct how a new kind of image was established as evidence, and how the associated visual knowledge was used to shape the field of cell biology, challenging the dominance of electron microscopy.
Immunofluorescence microscopy (IFM) was established as an epistemic tool for Cell Biology during the 1970s by a relatively small number of researchers, mainly based in the USA and Germany, leading to a substantial transformation of the... more
Immunofluorescence microscopy (IFM) was established as an epistemic tool for Cell Biology during the 1970s by a relatively small number of researchers, mainly based in the USA and Germany, leading to a substantial transformation of the visual culture of the field. In this period, primarily knowledge about subcellular architecture was produced by IFM, ultimately defining the “biochemical anatomy” of the cell. Questions about function and mechanisms, described as being characteristic for Cell Biology after World War II, could not be addressed as such. IFM can be interpreted as a unifying factor between two lines of inquiry: basic and translational research, each having different epistemic interests, but working collaboratively on developing and establishing IFM. From a descriptive and morphological quality of knowledge produced jointly to some extent, motivations for applying IFM parted quickly, leading to a separation after a short phase of unity and collaborative actions. In this paper I aim to explore how the epistemic qualities of IFM-images were utilized differently in research and publication practice, and how their epistemic value was judged: By scientists doing basic research and by those doing translational research, where differentiating the healthy from the pathological was equally important as the characterization of phenotypes of cancer cells. I aim to carve out the dynamics and effects of this alteration of unity and disunity in the field of Cell Biology with regards to the relevance of knowledge producible by the very same technique, that was accompanied by an alteration between morphological and functional epistemic interests.
Today’s Cell Biology is confronted with a dilemma: Descriptive research tends to be excluded from the reward systems in basic biomedical research. But description as an epistemic practice is perceived (again) as essential for heuristic... more
Today’s Cell Biology is confronted with a dilemma: Descriptive research tends to be excluded from the reward systems in basic biomedical research. But description as an epistemic practice is perceived (again) as essential for heuristic processes and innovation in the field. Yet, historical references remain vague and no definitions of descriptive research are provided in recently published opinions on this topic. In this paper I aim to investigate the potential of an integrated HPS-approach to stimulate and enrich current conceptual considerations in Cell Biology. Since the 1970s this field is strongly shaped by an imperative of mechanistic explanation. I will provide two resources for such debates: First, I will analyze and expose descriptive ways of knowing (Pickstone) in their historical context. Second, I will investigate the epistemic impact of descriptive practices for Cell Biology.
I will examine the preconditions for and consequences of a distinctive mode of knowledge production in Cell Biology: the practice of describing the molecular architecture of the cell in the 1970s and 1980s. The adoption of immunofluorescence microscopy in 1974/75, by a small number of researchers based at the Cold Spring Harbor Laboratory, precipitated the focus on molecular architecture. In the following decade, cell biologists produced primarily knowledge about the molecular composition of subcellular structures with this visualization technique. This led to defining the biochemical anatomy of the cell. Along with the stabilization of this visual domain in Cell Biology a new epistemic practice emerged, which I call molecularized morphology. Molecularized morphology was established in a period in which investigating cell structure was considered outdated if it was not directly correlated with mechanistic explanations of cell function. Cell biologists judge this practice in an ambiguous way: It was explicitly valued in the 1970s and its historic importance for the development of Cell Biology is not questioned. But in retrospect some researchers defame historic practitioners of molecularized morphology as having worked “merely descriptive.” My approach is based on the hypothesis that a genuinely descriptive epistemic practice – molecularized morphology – was accepted because of its embedded molecularization and functional knowledge that met with demands for novel morphological approaches.
I aim to carve out implications for recent publishing and funding policies: How can systematic investigations of recurring phases of valuing description in modern biomedical research inspire today’s practices? My considerations resonate with recent calls for “new waves of descriptive research” in Cell Biology. Policies dismissing descriptive knowledge as not eligible for publication in the most prestigious journals challenge this demand. Moreover, researchers who practice descriptive ways of knowing seem to be judged as second tier members of the scientific community. This perspective is based on the – preliminary – hypothesis that modern internal concepts of describing are not openly addressed and discussed. That might be caused by a field-inherent dismissive stance on practices associated with naturalist traditions, as it was shown for Molecular Biology. Investigating such practices epistemologically and historiographically in close interaction with active researchers and policy makers provide valuable resources for current conceptual debates in Cell Biology.
Entangling morphology and physiology – the trajectory of simple and complex systems of cultured cells in 1980’s research on cytoskeleton-environment interactions Hanna Lucia Worliczek Affiliations: University of Vienna, Department of... more
Entangling morphology and physiology – the trajectory of simple and complex systems of cultured cells in 1980’s research on cytoskeleton-environment interactions
Hanna Lucia Worliczek
Affiliations: University of Vienna, Department of History, DK “The Sciences in Historical, Philosophical and Cultural Contexts”; Department of Science Communication and Higher Education Research, Alpen-Adria-Universität Klagenfurt; McDonnel Initiative Scholar at the Marine Biological Laboratory.
Contact: hanna.worliczek@univie.ac.at
In 1956 Honor B. Fell, a major contributor to cell/tissue/organ culture, presented her perspective on the future of tissue culture in relation to morphology. She described an “unnatural divorce between morphology and physiology”, with the former describing the appearance and characteristics of cells and tissues grown in culture, and the latter investigating them biochemically. Fell attested that biochemical approaches had become more and more dominant but that a rapprochement between morphology and physiology has been on its ways in the field of tissue culture research – which she coined “physiological morphology”.  A requirement for scientists working with tissue culture to implement this rapprochement was in her view a thorough knowledge on form and structure as a basis for any physiological and biochemical studies. Taking Fell’s remarks as a conceptual trajectory, I aim to investigate the interplay of morphology and physiology in a field of inquiry that has been strongly depended on various systems of cultured cells/tissues/organs: research on the interaction between the cytoskeleton and the extracellular environment in the 1980s.
In this context, I will: (i) compare how morphological and physiological aspects were brought together by representatives of different laboratories to explain cytoskeleton-environment interactions and phenomena associated with them; (ii) investigate the epistemic possibilities and technical/epistemic limitations of different models used to study cell-environment interactions, with a focus on visualizing morphological characteristics; and (iii) carve out further trajectories of different approaches to investigate cytoskeleton-environment interactions in increasingly specialized fields like focal adhesion-, mechanotransduction-, or tumor microenvironment-research.
I take four perspectives on interactions between the cytoskeleton and the extracellular environment as a starting point, which were presented in 1987 at the 2nd Abercrombie-symposium on “Cell behaviour: shape, adhesion and motility”. In the proceedings of this meeting, two seemingly opposing approaches to these interactions can be identified in review papers from two different research groups: One came from the lab of Mina Bissell, who presented complex 3D systems of cultured cells as an imperative for modelling tissue environment, and who included visual evidence from gene expression studies, phase contrast and electron microscopy in contribution. The other approach came from the lab of Keith Burridge, who promoted a model of cultured fibroblasts monolayers for cell-substratum interactions, and who included micrographs of the cytoskeleton from immunofluorescence and interference reflection microscopy. However, these approaches were not conceived as mutually exclusive. The contributions by Avri Ben-Ze’ev and Benjamin Geiger to the 1987 symposium can be interpreted as a merging zone of these apparently opposing approaches, using methodologies and concepts from and referencing both directions.
By comparing these four positions on cytoskeleton-environment interactions from 1987, and by contrasting them with later published original work, reviews and personal recollections of the same actors, I aim to investigate the trajectory of qualitatively diverging “physiological morphologies” that led to the development of different specialized research fields.
The phrase “Seeing is believing”, used by contemporary cell biologists, highlights the pronounced visual culture of modern cell biology and the importance of visual evidence in this discipline which has been present since its formation in... more
The phrase “Seeing is believing”, used by contemporary cell biologists, highlights the pronounced visual culture of modern cell biology and the importance of visual evidence in this discipline which has been present since its formation in the 1940s. Microscopic visualizations have played and continue to play a crucial role in describing, explaining and understanding cellular structure and function. Historiographic and epistemological accounts of modern cell biology are dominated by questions concerning the development of mechanistic explanations of cellular functions, with a focus on the interrelation of microscopic imaging and experimental-interventional analyses. This perspective marginalizes description as an epistemic practice, and the impact of descriptive knowledge. Consequently, historical trajectories of changing constructions of descriptive qualities as designators for valuing or dismissing research and their impact on contemporary cell biology remain unexplored.

Using changes of cell biology’s visual culture since the 1950s as a heuristic lens, this paper explores descriptive practices and their interrelation with a proposed “mechanistic imperative” which the discipline continues to feel to this day. Mechanistic explanations of cell functions became a designator for research worth publishing in major cell biology journals during the 1970s, in parallel to a decreasing appreciation of “pure” morphology using electron microscopy, observational and qualitative studies, and ultimately “merely descriptive research”. At the same time, and contrary to these developments, some researchers were able to publish detailed molecular-morphological descriptions of the cytoskeleton in the 1970s and 1980s thanks to their application of new imaging techniques. This new descriptive body of knowledge was used simultaneously to inform mechanistic hypotheses about cell motility and their experimental-interventional testing. Based on these findings, this paper asks (i) how interpretations of “description” by cell biologists have changed; (ii) to what extent new imaging techniques promoted phases of valuing and devaluing descriptive practices; (iii) which dichotomies (e.g. observational/experimental, exploratory/hypothesis-driven) have been mobilized when dismissing research as “merely descriptive” and (iv) how researchers evaded such a dismissal.
Panel at the ISHPSSB meeting, Oslo, 7-12 July 2019
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General abstract (NEW) The focus of the panel is on the tradition of organ culture in vitro, as distinct from cell culture. In fact, while cell culture was committed to "observing the activities of cells when freed from the entanglements... more
General abstract (NEW) The focus of the panel is on the tradition of organ culture in vitro, as distinct from cell culture. In fact, while cell culture was committed to "observing the activities of cells when freed from the entanglements of the organism" (Harrison 1912) by means of an unprecedented act of disembodiment (Landecker 2007), involving the complete destruction of tissue architecture, the study of "controlled growth" (Thomson 1914) was rather aimed at identifying and reconstituting the suitable conditions for recapitulating in vitro morphogenetic processes and the maintenance of normal physiological functions (Willmer 1965). On one side, organ culture established new experimental settings for addressing the role of contextual factors in establishing, maintaining and switching cell specification and brought to light the lability of the differentiated state of cells (Harrison 1933; Grobstein 1963; Moscona 1964; Hay 1993). On the other side, these very settings also allowed highlighting the extent of the intrinsic self-organizational capacity of cells in collectively establishing functional higher order 3D structures such as tissues and organs. Organ culture's conceptual framework and technological innovations drove the shift from 2D to 3D culture systems, and can be seen as the common root of current 3D advanced microphysiological systems such as organoids and organs-on-a-chip. As to the first aspect, some contributions will focus on the role of scientists like Aron Moscona and Clifford Grobstein, and their respective insights into the biomechanics and biochemistry of the extracellular matrix in morphogenesis and their underlying philosophical commitments. Furthermore, an analysis on the contribution of Giuseppe Levi to organ culture will draw attention to the relevance of the Italian tradition of these studies. Characteristic of the early organ culture approach was the development of techniques for bridging the "unnatural divorce between morphology and physiology" (Fell 1956), and accounting for the role of the structures and forces emerging at tissue and organ level in setting the stage for specific biochemical and molecular changes. This "physiological morphology" ideal was implemented in a plurality of epistemically and experimentally diverging approaches in the 1980s, as the focus became the interaction between cytoskeleton and the extracellular environment. A comparison between the different approaches as they emerged at the 1987 Abercrombie Symposium will shed light on their respective influence on different specialized research fields, such as focal adhesion, mechanotransduction and tumor-microenvironment interactions. The second of the above-mentioned aspect, the emphasis on the self-organizational capacity of cells will be tackled at the case of the discovery of the unique morphogenetic potential of Madine-Darby canine kidney (MDCK) cells. Later experiments of 3D culture embedment of these cells allow evaluating the extent and limits of such potential, as well as reflecting on the trade-offs involved in mimicking morphogenetic events in vitro. Finally, an update to current debates on the notion of cell type identity and specification will be provided with reference to the latest developments of single-cell genomic analysis. Session I-Chair: Karl S. Matlin
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