On Disciplinary Fragmentation and Scientific Progress

Why are some scientific disciplines, such as sociology and psychology, more fragmented into conflicting schools of thought than other fields, such as physics and biology? Furthermore, why does high fragmentation tend to coincide with limited scientific progress? We analyzed a formal model where scientists seek to identify the correct answer to a research question. Each scientist is influenced by three forces: (i) signals received from the correct answer to the question; (ii) peer influence; and (iii) noise. We observed the emergence of different macroscopic patterns of collective exploration, and studied how the three forces affect the degree to which disciplines fall apart into divergent fragments, or so-called “schools of thought”. We conducted two simulation experiments where we tested (A) whether the three forces foster or hamper progress, and (B) whether disciplinary fragmentation causally affects scientific progress and vice versa. We found that fragmentation critically limits scientific progress. Strikingly, there is no effect in the opposite causal direction. What is more, our results shows that at the heart of the mechanisms driving scientific progress we find (i) social interactions, and (ii) peer disagreement. In fact, fragmentation is increased and progress limited if the simulated scientists are open to influence only by peers with very similar views, or when within-school diversity is lost. Finally, disciplines where the scientists received strong signals from the correct answer were less fragmented and experienced faster progress. We discuss model’s implications for the design of social institutions fostering interdisciplinarity and participation in science.     

Mechanism of cell death of rat cardiac fibroblasts induced by serum depletion

Serum starvation has recently been shown to cause cell death of cardiac fibroblasts and increased synthesis of extracellular matrix proteins in the surviving cells. In the present study, events occurring in the dying cells were investigated. Cultured adult rat cardiac fibroblasts were exposed to serum-free medium. Cell number was measured using a Coulter Counter Channelyzer. The activity of the extracellular signal-regulated or mitogen-activated protein kinases (ERK1/2, p42/p44^MAPK), the p38 kinase (p38^MAPK), the c-Jun N-terminal kinases (p46/p54^JNK), and Akt kinase was assessed by Western blotting and phospho-specific antibodies. Caspase 7-cleavage was investigated by Western blotting and specific antibodies. Caspase 3 activity was measured by detection of its cleaved substrate. The appearance of necrosis was studied by inclusion of trypan blue. Apoptosis was assessed by DNA ladder formation. The mRNA expression of Bax and Bcl-2 was investigated by quantitative real-time PCR. Serum withdrawal led to the death of 26% of cultured isolated cardiac fibroblasts during the first 5 h. The activity of the p42/p44^MAPK as well as of Akt kinase was partially reduced. For p46/p54^JNK and p38^MAPK, elevated phosphorylation was measured. Inhibition of p46/p54^JNK and p38^MAPK activity by SB202190 did not affect the decrease in cell number. Cleavage of caspase7 was detected after 90 min. However, no activation of caspase 3 was measured. DNA fragmentation was not found after serum depletion. Trypan blue staining, however, was observed in 16% of the cells after 5 h. The mRNA levels of both Bax and Bcl-2 were increased after 30 min. These results indicate the appearance of necrosis during serum starvation in cardiac fibroblasts. However, some processes typical of apoptosis were also detected.     

Implementation of Novel Design Features for qPCR-Based eDNA Assessment

Environmental stewardship requires timely, accurate information related to the status of a given ecosystem and the species that occupy it. Recent advances in the application of the highly sensitive real-time quantitative polymerase chain reaction (qPCR) towards identification of constituents within environmental DNA (eDNA) now allow targeted detection of the presence of species-specific biological material within a localized geographic region. However, as with all molecular techniques predicated on the specificity and sensitivity of the PCR assay, careful validation of each eDNA qPCR assay in development must be performed both under controlled laboratory conditions and when challenged with field-derived eDNA samples. Such a step-wise approach forms the basis for incorporation of innovative qPCR design features that strengthen the implementation and interpretation of the eDNA assay. This includes empirical determination that the qPCR assay is refractory to the presence of human DNA and the use of a tripartite assay approach comprised of 1) a primer set targeting plant chloroplast that evaluates the presence of amplifiable DNA from field samples to increase confidence in a negative result, 2) an animal group primer set to increase confidence in the assay result, and 3) a species-specific primer set to assess presence of DNA from the target species. To demonstrate this methodology, we generated eDNA assays specific for the North American bullfrog (Lithobates (Rana) catesbeiana) and the Rocky Mountain tailed frog (Ascaphus montanus) and characterized each with respect to detection sensitivity and specificity with demonstrated performance in a field survey scenario. The qPCR design features presented herein address specific challenges of eDNA assays thereby increasing their interpretative power.     

Understanding the evolutionary processes of fungal fruiting bodies: correlated evolution and divergence times in the Psathyrellaceae

Fruiting body evolution is one of the central topics in fungal evolutionary biology. A number of hypotheses have been developed to explain the contemporary diversity of fruiting body forms, but their evaluation has been hampered by the lack of well-sampled data sets and suitable statistical methods. Phylogenetic evidence of the physiological changes that accompany switches in fruiting body type is lacking, and very little is known about the age of major events of fruiting body evolution. Based on a new multigene phylogeny, by using Bayesian methods, we demonstrate the existence of correlation between a number of morphological features and switches from nondeliquescent to deliquescent (autodigesting) fruiting bodies in the mushroom family Psathyrellaceae. Our results show that switches in the anatomy of two types of spacer cells (cystidia and pseudoparaphyses) and basidia (bimorphic or monomorphic) as well as the structure of the mushroom cap follow the evolution of deliquescent fruiting bodies, which suggests strong functional linkage between these traits. We performed Bayes factor-based tests, referred hereafter to as evolutionary pathway test (EPT), to decide which of the correlated characters were gained first during evolution. The EPTs strongly suggest that deliquescence was gained first, followed after short waiting times by the other morphological features. Bayesian relaxed molecular clock analyses suggest that the various events of switching between fruiting body types occurred independently at various ages during the history of the family. The utility of two mushroom fossils (Archaemarasmius and Protomycena), the only ones with unambiguous taxonomic positions, for the calibration of agaric trees were also examined. Based on our results, we suggest that the evolutionary benefit of deliquescence may be prevention against desiccation via accelerated ontogeny of the fruiting body. Hypotheses regarding the functional significance of the correlated evolution are presented and discussed. Further, we argue that the changes in fruiting body types in mushrooms in general can be attributed to independent events (e.g., dispersal and adaptation) and not to particular geologic ages.     

Genome-wide prediction methods for detecting genetic effects of donor chromosome segments in introgression populations

Background

Introgression populations are used to make the genetic variation of unadapted germplasm or wild relatives of crops available for plant breeding. They consist of introgression lines that carry small chromosome segments from an exotic donor in the genetic background of an elite line. The goal of our study was to investigate the detection of favorable donor chromosome segments in introgression lines with statistical methods developed for genome-wide prediction.

Results

Computer simulations showed that genome-wide prediction employing heteroscedastic marker variances had a greater power and a lower false positive rate compared with homoscedastic marker variances when the phenotypic difference between the donor and recipient lines was controlled by few genes. The simulations helped to interpret the analyses of glycosinolate and linolenic acid content in a rapeseed introgression population and plant height in a rye introgression population. These analyses support the superiority of genome-wide prediction approaches that use heteroscedastic marker variances.

Conclusions

We conclude that genome-wide prediction methods in combination with permutation tests can be employed for analysis of introgression populations. They are particularly useful when introgression lines carry several donor segments or when the donor segments of different introgression lines are overlapping.     

Morpholine-induced formation of l-alanine dehydrogenase activity in Mycobacterium strain HE5

An NAD-dependent, morpholine-stimulated l-alanine dehydrogenase activity was detected in crude extracts from morpholine-, pyrrolidine-, and piperidine-grown cells of Mycobacterium strain HE5. Addition of morpholine to the assay mixture resulted in an up to 4.6-fold increase of l-alanine dehydrogenase activity when l-alanine was supplied at suboptimal concentration. l-Alanine dehydrogenase was purified to near homogeneity using a four-step purification procedure. The native enzyme had a molecular mass of 160 kDa and contained one type of subunit with a molecular mass of 41 kDa, indicating a tetrameric structure. The sequence of 30 N-terminal amino acids was determined and showed a similarity of up to 81% to that of various alanine dehydrogenases. The pH optimum for the oxidative deamination of l-alanine, the only amino acid converted by the enzyme, was determined to be pH 10.1, and apparent K _m values for l-alanine and NAD were 1.0 and 0.2 mM, respectively. K _m values of 0.6, 0.02, and 72 mM for pyruvate, NADH, and NH₄ ⁺, respectively, were estimated at pH 8.7 for the reductive amination reaction. Received: 25 September 1998 / Accepted: 11 March 1999     

Potent inhibition of local and disseminated tumor growth in immunocompetent mouse models by a bispecific antibody construct specific for Murine CD3

Bispecific single-chain antibody constructs specific for human CD3 have been extensively studied for antitumor activity in human xenograft models using severe combined immunodeficient mice supplemented with human T cells. High efficacy at low effector-to-target ratios, independence of T cell costimuli and a potent activation of previously unstimulated polyclonal T cells were identified as hallmarks of this class of bispecific antibodies. Here we studied a bispecific single-chain antibody construct (referred to as ‘bispecific T cell engager’, BiTE) in an immunocompetent mouse model. This was possible by the use of a murine CD3-specific BiTE, and a syngeneic melanoma cell line (B16F10) expressing the human Ep-CAM target. The murine CD3-specific BiTE, called 2C11x4-7 prevented in a dose-dependent fashion the outgrowth of subcutaneously growing B16/Ep-CAM tumors with daily i.v. injections of 5 or 50 μg BiTE which was most effective. Treatment with 2C11x4-7 was effective even when it was started 10 days after tumor cell inoculation but delayed treatments showed a reduction in the number of cured animals. 2C11x4-7 was also highly active in a lung tumor colony model. When treatment was started on the day of intravenous tumor cell injection, seven out of eight animals stayed free of lung tumors, and three out of eight animals when treatment was started on day 5. Our study shows that BiTEs also have a high antitumor activity in immunocompetent mice and that there is no obvious need for costimulation of T cells by secondary agents. Bernd Schlereth and Petra Kleindienst contributed equally to this work.     

Head proportion and shape of the head of children between 2 and 7 years--results of a longitudinal study

Based upon a longitudinal anthropometric study with integrated picture documentation, the head proportion and head shape of two to seven years old children will be analysed. The study was initiated in April 2002 in the administrative districts of Potsdam and Potsdam-Mittelmark (Germany). 351 boys and girls have been measured and photographed. The children shall be examined up to four years until September 2006 with a half year investigation distance. Twenty-three anthropometric dimensions have been measured including six dimensions of the head. These dimensions of the head are the head length, head breadth, auricular height, interpupillary distance, facial height and lower face height. Furthermore, digital pictures have been taken of each child. So the head of each child can be examined in a frontal view (Norma frontalis) and in a lateral view (Norma lateralis) and will be analysed relating to changing proportions of the head. The results demonstrated and discussed here are based on a longitudinal succession of photos and point out a method to make individual patterns of the changing head proportions and head shape visual on pictures.