Development and Heredity in the Interwar Period: Hans Spemann and Fritz Baltzer on Organizers and Merogones.

This article explores the collaborative research of the Nobel laureate Hans Spemann (1869-1941) and the Swiss zoologist Fritz Baltzer (1884-1974) on problems at the intersection of development and heredity and raises more general questions concerning science and politics in Germany in the interwar period. It argues that Spemann and Baltzer's collaborative work made a significant contribution to the then ongoing debates about the relation between developmental physiology and hereditary studies, although Spemann distanced himself from Drosophila genetics because of his anti-reductionist position. The article analyzes how Spemann framed the issues of heredity in terms of an epigenetic principle in the context of his work on the "organizer," and it explores the experimental dynamics of research on newt merogones carried out by Baltzer in a methodological development of Spemann's constriction experiments. Finally, these research attempts are discussed as part of a broader "prehistory" of the mid-twentieth century cell nuclear transplantation experiments, which provided the basis for later animal cloning.

Vitalism, Holism, and Metaphorical Dynamics of Hans Spemann's "Organizer" in the Interwar Period.

This paper aims to provide a fresh historical perspective on the debates on vitalism and holism in Germany by analyzing the work of the zoologist Hans Spemann (1869-1941) in the interwar period. Following up previous historical studies, it takes the controversial question about Spemann's affinity to vitalistic approaches as a starting point. The focus is on Spemann's holistic research style, and on the shifting meanings of Spemann's concept of an organizer. It is argued that the organizer concept unfolded multiple layers of meanings (biological, philosophical, and popular) during the 1920s and early 1930s. A detailed analysis of the metaphorical dynamics in Spemann's writings sheds light on the subtle vitalistic connotations of his experimental work. How Spemann's work was received by contemporary scientists and philosophers is analyzed briefly, and Spemann's holism is explored in the broader historical context of the various issues about reductionism and holism and related methodological questions that were so prominently discussed not only in Germany in the 1920s.

Fast MPI reconstruction with non-smooth priors by stochastic optimization and data-driven splitting.

Magnetic particle images are currently most often reconstructed using classical Tikhonov regularization (i.e. anℓ2regularization term) combined with Kaczmarz method. Quality enhancing choices like sparsity promotingℓ1-regularization or TV regularization lead to problems that cannot be solved by standard Kaczmarz method. We propose to use stochastic primal-dual hybrid gradient method to gain more flexibility concerning the choice of data fitting term and regularization, respectively, and still obtain an algorithm which is at least as fast as Kaczmarz method. The proposed algorithm performs comparably to the current state-of-the-art method in terms of run time. The quality of reconstructions can be significantly improved as different regularization terms can be easily integrated. Moreover, in order to achieve further speed up of the method, we propose two new step size rules which lead to fast convergence and make the algorithm very easy to handle. We improve the performance of the algorithm further by applying a data-driven splitting scheme leading to a significant speed-up during the first iterations.

PGC-1α in aging and lifelong exercise training-mediated regulation of UPR in mouse liver.

Aging is associated with changes in several metabolic pathways affecting liver function including the adaptive unfolded protein response (UPR). On the other hand, exercise training has been shown to exert beneficial effects on metabolism in the liver and exercise training has been reported to affect hepatic UPR. PGC-1α is a transcriptional coactivator involved in exercise training-induced adaptations in skeletal muscle and liver. Therefore, the aim of the present study was to examine the impact of PGC-1α in aging and lifelong exercise training-induced hepatic UPR in mice. Liver was obtained from young (3months old), aged (15months old) and lifelong exercise trained aged wild-type (WT) and whole-body PGC-1α knockout (KO) mice. Hepatic BiP, IRE1α and cleaved ATF6 protein content increased, whereas PERK protein content was reduced with aging indicating both increased and decreased capacity of specific UPR pathways and increased activity of the ATF6 pathway in the liver with aging. Lifelong exercise training prevented the age-associated change in BiP and IRE1α protein, but not cleaved ATF6 protein and resulted in further decreased PERK protein. Taken together, the present study provides evidence that the capacity and activity of the three UPR pathways are differentially regulated in the liver with aging and lifelong exercise training. In addition, PGC-1α does not seem to regulate the activity of hepatic UPR in response to exercise training, but to influence the capacity of the liver to induce UPR in a pathway specific manner.

Edge Preserving and Noise Reducing Reconstruction for Magnetic Particle Imaging.

Magnetic particle imaging (MPI) is an emerging medical imaging modality which is based on the non-linear response of magnetic nanoparticles to an applied magnetic field. It is an important feature of MPI that even fast dynamic processes can be captured for 3D volumes. The high temporal resolution in turn leads to large amounts of data which have to be handled efficiently. But as the system matrix of MPI is non-sparse, the image reconstruction gets computationally demanding. Therefore, currently only basic image reconstruction methods such as Tikhonov regularization are used. However, Tikhonov regularization is known to oversmooth edges in the reconstructed image and to have only a limited noise reducing effect. In this work, we develop an efficient edge preserving and noise reducing reconstruction method for MPI. As regularization model, we propose to use the nonnegative fused lasso model, and we devise a discretization that is adapted to the acquisition geometry of the preclinical MPI scanner considered in this work. We develop a customized solver based on a generalized forward-backward scheme which is particularly suitable for the dense and not well-structured system matrices in MPI. Already a non-optimized prototype implementation processes a 3D volume within a few seconds so that processing several frames per second seems amenable. We demonstrate the improvement in reconstruction quality over the state-of-the-art method in an experimental medical setup for an in-vitro angioplasty of a stenosis.

Modelling the spatial distribution of Fasciola hepatica in dairy cattle in Europe.

A harmonized sampling approach in combination with spatial modelling is required to update current knowledge of fasciolosis in dairy cattle in Europe. Within the scope of the EU project GLOWORM, samples from 3,359 randomly selected farms in 849 municipalities in Belgium, Germany, Ireland, Poland and Sweden were collected and their infection status assessed using an indirect bulk tank milk (BTM) enzyme-linked immunosorbent assay (ELISA). Dairy farms were considered exposed when the optical density ratio (ODR) exceeded the 0.3 cut-off. Two ensemble-modelling techniques, Random Forests (RF) and Boosted Regression Trees (BRT), were used to obtain the spatial distribution of the probability of exposure to Fasciola hepatica using remotely sensed environmental variables (1-km spatial resolution) and interpolated values from meteorological stations as predictors. The median ODRs amounted to 0.31, 0.12, 0.54, 0.25 and 0.44 for Belgium, Germany, Ireland, Poland and southern Sweden, respectively. Using the 0.3 threshold, 571 municipalities were categorized as positive and 429 as negative. RF was seen as capable of predicting the spatial distribution of exposure with an area under the receiver operation characteristic (ROC) curve (AUC) of 0.83 (0.96 for BRT). Both models identified rainfall and temperature as the most important factors for probability of exposure. Areas of high and low exposure were identified by both models, with BRT better at discriminating between low-probability and high-probability exposure; this model may therefore be more useful in practise. Given a harmonized sampling strategy, it should be possible to generate robust spatial models for fasciolosis in dairy cattle in Europe to be used as input for temporal models and for the detection of deviations in baseline probability. Further research is required for model output in areas outside the eco-climatic range investigated.

Effect of lifelong resveratrol supplementation and exercise training on skeletal muscle oxidative capacity in aging mice; impact of PGC-1α.

BACKGROUND: The present study tested the hypothesis that lifelong resveratrol (RSV) supplementation counteracts an age-associated decrease in skeletal muscle oxidative capacity through peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α and that RSV combined with lifelong exercise training (EX) exerts additive effects through PGC-1α in mice. METHODS: 3 month old PGC-1α whole body knockout (KO) and wild type (WT) littermate mice were placed in cages with or without running wheel and fed either standard chow or standard chow with RSV supplementation (4 g/kg food) for 12 months. Young (3 months of age), sedentary mice on standard chow served as young controls. A graded running performance test and a glucose tolerance test were performed 2 and 1 week, respectively, before euthanization where quadriceps and extensor digitorum longus (EDL) muscles were removed. RESULTS: In PGC-1α KO mice, quadriceps citrate synthase (CS) activity, mitochondrial (mt)DNA content as well as pyruvate dehydrogenase (PDH)-E1α, cytochrome (Cyt) c and vascular endothelial growth factor (VEGF) protein content were 20-75% lower and, EDL capillary-to-fiber (C:F) ratio was 15-30% lower than in WT mice. RSV and/or EX had no effect on the C:F ratio in EDL. CS activity (P=0.063) and mtDNA content (P=0.013) decreased with age in WT mice, and CS activity, mtDNA content, PDH-E1α protein and VEGF protein increased ~1.5-1.8-fold with lifelong EX in WT, but not in PGC-1α KO mice, while RSV alone had no significant effect on these proteins. CONCLUSION: Lifelong EX increased activity/content of oxidative proteins, mtDNA and angiogenic proteins in skeletal muscle through PGC-1α, while RSV supplementation alone had no effect. Combining lifelong EX and RSV supplementation had no additional effect on skeletal muscle oxidative and angiogenic proteins.

Role of PGC-1α in exercise training- and resveratrol-induced prevention of age-associated inflammation.

BACKGROUND/AIM: Age-related metabolic diseases are often associated with low-grade inflammation. The aim of the present study was to investigate the role of the transcriptional co-activator PGC-1α in the potential beneficial effects of exercise training and/or resveratrol in the prevention of age-associated low-grade inflammation. To address this, a long-term voluntary exercise training and resveratrol supplementation study was conducted. EXPERIMENTAL SETUP: Three month old whole body PGC-1α KO and WT mice were randomly assigned to four groups: untrained chow-fed, untrained chow-fed supplemented with resveratrol, chow-fed voluntarily exercise trained and chow-fed supplemented with resveratrol and voluntarily exercise trained. The intervention lasted 12 months and three month old untrained chow-fed mice served as young controls. RESULTS: Voluntary exercise training prevented an age-associated increase (p<0.05) in systemic IL-6 and adiposity in WT mice. PGC-1α expression was required for a training-induced prevention of an age-associated increase (p<0.05) in skeletal muscle TNFα protein. Independently of PGC-1α, both exercise training and resveratrol prevented an age-associated increase (p<0.05) in skeletal muscle protein carbonylation. CONCLUSION: The present findings highlight that exercise training is a more effective intervention than resveratrol supplementation in reducing age-associated inflammation and that PGC-1α in part is required for the exercise training-induced anti-inflammatory effects.

Hybrid times: theses on the temporalities of cloning.

In this paper, I focus on Hans-Jörg Rheinberger's notion of "historiality", which provides a specific epistemology of time that abandons ideas of 'origin', 'influence or of history as a continuous and cumulative development. It is used here to frame a brief historical analysis of the coexistence and interference of different concepts of cloning and related views on temporalities of the organisms as well as shifting temporal concepts in popular debates about the risks of life sciences in the 1970s.

[Temporal layers of the clone. Remarks on a conceptual history]. / Zeitschichten des Klons. Anmerkungen zu einer Begriffsgeschichte.

This paper aims at a history of the clone concept in 20th-century life science and culture. The first part of the paper is concerned with conceptual history approaches. Here, the idea of 'Zeitschichten' by Reinhart Koselleck is discussed and its implications for the history of science are explored. In the following parts of the paper, I trace the historical dynamics of the clone concept in various fields of 20th-century life sciences. I argue that the clone concept, which originated in plant breeding around 1900, soon developed into a technical tool in a variety of research areas. With this, specific meanings became attached: the idea of standardization, genetic identity, and mass reproduction. A further connotation of the clone was the idea of stagnancy with respect to processes in time: The clone was seen as something that was exempt from evolutionary changes. In the last section of the paper, I trace the shifting meanings of the clone concept in the 1960s and 1970s, when the clone became a widespread metaphor that pointed to future biotechnologically driven possibilities to reshape the nature of human beings. In this regard, the debates of the 1970s are analyzed as a turning point: Whereas utopian and eugenic visions predominated the debates in the 1960s (when the human clone was seen as something which will occur in a distant future), the 1970s discussion focused on the advent of a biotechnological era and the human clone had became a reality.

[The two (and more) cultures of the "clone". Utopia and fiction in post-war discourses of life sciences]. / Die zwei (und mehr) Kulturen des "Klons". Utopie und Fiktion im biowissenschaftlichen Diskurs der Nachkriegszeit.

Since the late 1950s, "two cultures" has become a catch phrase for describing a deep divide between science and literature. When Charles P. Snow, who initiated this discussion, introduced the notion of "two cultures" in a lecture at the University in Cambridge in 1959, he referred to an incompatibility of scientific and literary worldviews in Western Societies. His thesis of two contradicting cultures immediately received a huge variety of different responses from philosophers, scientists, novelists and literary scholars. However, this article argues that this widespread debate was part of a broader post-war discourse on the impact of modern science on society, in which especially the idea of "scientific progress" was at stake. Central to this debate was the question of how scientific and technological progress could affect the notion of the "human" itself. The paper analyses the emerging discourse on cloning against this background. The constitutive role of fiction and imagination in both fields, science and literature, is explored by tracing the scientific, utopian and literary cultures in which figures of human clones have taken different shapes since the 1960s. At that time, scientists developed utopian views in which the "clone" became a metaphor for future possibilities of transcending and reshaping the human nature. Science fiction writers reacted to this by portraying the human clone as an individual and by depicting human clone figures in a psychological way