PubMed Health⌕ Search

Biomedical subjects

Thomas Pfeiffer

Publications and source records attributed to Thomas Pfeiffer.

17 recordsLinked to original sources

Optimizing time and resource allocation trade-offs for investment into morphological and behavioral defense.

Prey organisms are confronted with time and resource allocation trade-offs. Time allocation trade-offs partition time, for example, between foraging effort to acquire resources and behavioral defense. Resource allocation trade-offs partition the acquired resources between multiple traits, such as growth or morphological defense. We develop a mathematical model for prey organisms that comprise time and resource allocation trade-offs for multiple defense traits. Fitness is determined by growth and survival during ontogeny. We determine optimal defense strategies for environments that differ in their resource abundance, predation risk, and defense effectiveness. We compare the results with results of simplified models where single defense traits are optimized. Our results indicate that selection acts in favor of integrated traits. The selective advantage of expressing multiple defense traits is most pronounced at intermediate environmental conditions. Optimizing single traits generally leads to a more pronounced response of the defense traits, which implies that studying single traits leads to an overestimation of their response to predation. Behavioral defense and morphological defense compensate for and augment each other depending on predator densities and the effectiveness of the defense mechanisms. In the presence of time constraints, the model shows peak investment into morphological and behavioral defense at intermediate resource levels.

Animals↗

Digital cows grazing on digital grounds.

Picture a pasture open to all (...) As a rational being, each herdsman seeks to maximize his gain. Explicitly or implicitly, more or less consciously, he asks, "What is the utility to me of adding one more animal to the herd?" This utility has one negative and one positive component. 1) The positive component is a function of the increment of one animal. Since the herdsman receives all the proceeds from the sale of the additional animal, the positive utility is nearly +1. 2) The negative component is a function of the additional overgrazing created by one more animal. Since, however, the effects of overgrazing are shared by all the herdsmen, the negative utility for any particular decision-making herdsman is only a fraction of -1. Adding together the component partial utilities, the rational herdsman concludes that the only sensible course for him to pursue is to add another animal to the herd. And another; and another...

Altruism↗

Experimental tests for an evolutionary trade-off between growth rate and yield in E. coli.

Theoretical studies have predicted a trade-off between growth rate and yield in heterotrophic organisms. Here we test for the existence of this trade-off by analyzing the growth characteristics of 12 E. coli B populations that evolved for 20,000 generations under a constant selection regime. We performed three different tests. First, we analyzed changes in growth rate and yield over evolutionary time for each population. Second, we tested for a negative correlation between rate and yield across the 12 populations. Finally, we isolated clones from four selected populations and tested for a negative correlation between rate and yield within these populations. We did not find evidence for a trade-off based on the first two tests. However, we did observe a trade-off based on the within-population correlation of yield and rate. Our results indicate that, at least for the populations studied here, an analysis of the within-population diversity might be the most sensitive test for the existence of a trade-off. The observation of a trade-off within, but not between, populations suggests that the populations evolved different genetic solutions for growth in the selective environment, which in turn led to different physiological constraints.

Biological Evolution↗

Simulating the evolution of signal transduction pathways.

We use a generic model of a network of proteins that can activate or deactivate each other to explore the emergence and evolution of signal transduction networks and to gain a basic understanding of their general properties. Starting with a set of non-interacting proteins, we evolve a signal transduction network by random mutation and selection to fulfill a complex biological task. In order to validate this approach we base selection on a fitness function that captures the essential features of chemotactic behavior as seen in bacteria. We find that a system of as few as three proteins can evolve into a network mediating chemotaxis-like behavior by acting as a "derivative sensor". Furthermore, we find that the dynamics and topology of such networks show many similarities to the natural chemotaxis pathway, that the response magnitude can increase with increasing network size and that network behavior shows robustness towards variations in some of the internal parameters. We conclude that simulating the evolution of signal transduction networks to mediate a certain behavior may be a promising approach for understanding the general properties of the natural pathway for that behavior.

Animals↗

The evolution of connectivity in metabolic networks.

Processes in living cells are the result of interactions between biochemical compounds in highly complex biochemical networks. It is a major challenge in biology to understand causes and consequences of the specific design of these networks. A characteristic design feature of metabolic networks is the presence of hub metabolites such as ATP or NADH that are involved in a high number of reactions. To study the emergence of hub metabolites, we implemented computer simulations of a widely accepted scenario for the evolution of metabolic networks. Our simulations indicate that metabolic networks with a large number of highly specialized enzymes may evolve from a few multifunctional enzymes. During this process, enzymes duplicate and specialize, leading to a loss of biochemical reactions and intermediary metabolites. Complex features of metabolic networks such as the presence of hubs may result from selection of growth rate if essential biochemical mechanisms are considered. Specifically, our simulations indicate that group transfer reactions are essential for the emergence of hubs.

Biomass↗

Evolution of cooperation by generalized reciprocity.

The evolution of cooperation by direct reciprocity requires that individuals recognize their present partner and remember the outcome of their last encounter with that specific partner. Direct reciprocity thus requires advanced cognitive abilities. Here, we demonstrate that if individuals repeatedly interact within small groups with different partners in a two person Prisoner's Dilemma, cooperation can emerge and also be maintained in the absence of such cognitive capabilities. It is sufficient for an individual to base their decision of whether or not to cooperate on the outcome of their last encounter--even if it was with a different partner.

Altruism↗

Genetic association of cytokines polymorphisms with autoimmune hepatitis and primary biliary cirrhosis in the Chinese.

AIM: To characterize gene polymorphism of several cytokine gene in-patients with AIH and PBC and to analyze the difference of the polymorphism distribution between Chinese patients and healthy controls. METHODS: The study population consisted of 62 patients with AIH, and 77 patients with PBC. The genetic profile of four cytokines was analyzed by restriction fragment length polymorphism after specific PCR amplification (PCR-RFLP) or sequence-specific primers PCR (SSP-PCR). The analyzed gene polymorphism included interleukin-1 (IL-1) (at position +3 953 and IL-1RN intron 2), IL-6 (at position -174), IL-10 promoter (at position -1 082, -819, and -592). The control group consisted of 160 healthy blood donors. RESULTS: The majority of Chinese people including patients and healthy controls exhibited IL-1B 1,1 genotype, and there was no significant difference in AIH, PBC patients and controls. There were highly statistically significant differences in the distribution of the IL-1RN gene polymorphism between the patients with PBC compared with controls. The frequency of IL-1RN 1,1 was significantly higher (90.9% vs 79.4%, P = 0.03) and the frequency of IL-1RN 1,2 was significantly lower in PBC patients (6.5% vs 17.5%, P = 0.01). No statistical difference was observed between AIH patients and controls. All of the 160 healthy controls and 62 cases of AIH patients exhibited IL-6-174GG genotype, and there were four cases, which expressed IL-6-174GC genotype in 77 cases of PBC patients. The frequency of IL-6-174GC was markedly significantly higher in PBC patients compared with controls (5.2% vs 0%, P = 0.004). No statistically significant difference was found in the distribution of IL-10 promoter genotype in AIH and PBC patients compared with controls. CONCLUSION: The polymorphisms of IL-1RN and IL-6 -174G/C appear to be associated with PBC in Chinese patients.

Adolescent↗

Game-theoretical approaches to studying the evolution of biochemical systems.

Evolutionary optimization has been successfully used to increase our understanding of key properties of biochemical systems. Traditional optimization is, however, often insufficient for gaining deeper insights into the evolution of such systems because usually there is a mutual relationship between the properties optimized by evolution and the properties of the environment. Thus, by evolving towards optimal properties, organisms change their environment, which in turn alters the optimum. Evolutionary game theory provides an appropriate framework for analyzing evolution in such 'dynamic fitness landscapes'. We therefore argue that it is a promising approach to studying the evolution of biochemical systems. Indeed, recent studies have applied evolutionary game theory to key issues in the evolution of energy metabolism.

Evolution, Molecular↗

Genetic association of vitamin D receptor polymorphisms with autoimmune hepatitis and primary biliary cirrhosis in the Chinese.

BACKGROUND: Autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) are two autoimmune diseases of unknown etiology. Genetic factors appear to be involved in the pathogenesis of both diseases. Vitamin D has been shown to exert multiple immunomodulatory effects, which acts through its own receptor (VDR). Polymorphisms of VDR had been implicated in several autoimmune diseases. In the present study, the association between Chinese patients with AIH, PBC and the polymorphisms in exon 2, intron 8 and exon 9 of vitamin D receptor genes was studied. METHODS: Four candidate gene loci were investigated in 49 patients with AIH, 58 patients with PBC, and 160 healthy controls. The VDR polymorphisms were assessed by FokI, BsmI, ApaI, and TaqI endonuclease digestion after specific polymerase chain reaction (PCR) amplification. RESULTS: The result show a significant difference in FokI polymorphism between AIH patients and controls (chi(2) = 5.47, P = 0.019), and a significant association in BsmI polymorphisms between PBC patients and controls (chi(2) = 6.52, P = 0.01). Furthermore the distribution of FokI, BsmI, ApaI, and TaqI gene types differed between Chinese healthy controls and Caucasian healthy controls. CONCLUSION: It is suggested that there is a genetic link of VDR polymorphisms to autoimmune liver diseases such as AIH and PBC in Chinese patients. Further studies are needed to elucidate the mechanisms by which VDR polymorphisms contribute to the lose of immune tolerance in autoimmune diseases.

Adolescent↗

Cytotoxic T lymphocyte associated antigen-4 gene polymorphisms confer susceptibility to primary biliary cirrhosis and autoimmune hepatitis in Chinese population.

AIM: To investigate the association between Chinese patients with autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and the polymorphisms of cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) gene promoter (-318) and exon 1 (+49). METHODS: CTLA-4 promoter (-318 T/C) and exon1 (+49A/G) polymorphisms were genotyped via restriction fragment length polymorphism methods in 62 Chinese AIH patients, 77 Chinese PBC patients and 160 healthy controls. RESULTS: We found a significant association in CTLA-4 gene exon1 49 A/G polymorphism between PBC patients and controls (P = 0.006) and the frequency of G alleles was significantly increased in comparison with controls (P = 0.0046, OR = 1.8). We also found the frequency of C alleles in promoter -318 was significantly increased in AIH patients compared with controls (P = 0.02, OR = 0.41). Although the genotype distribution of the CTLA-4 exon 1-promoter gene was not significantly different between AIH and PBC patients and controls, the occurrence of GG-CC was increased in two groups of patients (AIH: 32.3%, PBC: 37.7%, control: 22.5%). CONCLUSION: Polymorphisms of CTLA-4 gene probably confer susceptibility to AIH and PBC in Chinese population.

Adolescent↗

Evolution of cross-feeding in microbial populations.

Although limited by a single resource, microbial populations that grow for long periods in continuous culture (chemostat) frequently evolve stable polymorphisms. These polymorphisms may be maintained by cross-feeding, where one strain partially degrades the primary energy resource and excretes an intermediate that is used as an energy resource by a second strain. It is unclear what selective advantage cross-feeding strains have over a single competitor that completely degrades the primary resource. Here we show that cross-feeding may evolve in microbial populations as a consequence of the following optimization principles: the rate of ATP production is maximized, the concentration of enzymes of the pathway is minimized, and the concentration of intermediates of the pathway is minimized.

Adaptation, Physiological↗

[Genetic association of tumor necrosis factor (TNF)-alpha polymorphisms with primary biliary cirrhosis and autoimmune liver diseases in a Chinese population].

OBJECTIVE: Autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) are two autoimmune diseases of unknown etiology. Genetic factors appear to be involved in the pathogenesis of both diseases. Tumor necrosis factor (TNF)-alpha is one of the proinflammatory cytokines and immunomodulators, and is implicated in the pathogenesis of AIH and PBC. In this study, we studied the association between Chinese patients with AIH, PBC and the polymorphisms in promoter-region polymorphisms of the TNF-alpha gene at position -308 and -238. METHODS: We have investigated four candidate gene loci in 49 patients with AIH, 58 patients with PBC, and 160 healthy controls. The polymorphisms were assessed by the PCR specifically for the single-nucleotide polymorphisms. RESULTS: We found the difference in the TNF-alpha gene at position -308 genotype distributions between Chinese health controls and Caucasian health controls. Although the percent of TNF-alpha*2 was decrease on PBC patient group (10.34% vs. 16.88%), there was no significant difference between PBC patients and health control in the Chinese. There were also no significant differences between AIH and health control on the TNF-alpha gene at position -308 and -238. CONCLUSION: Our findings suggest that the TNF-alpha promoter-region polymorphisms distribution is different between differe of ethnic groups; there are no genetic links of the TNF-alpha promoter-region polymorphisms to AIH and PBC in Chinese.

Adult↗

[Genetic association of vitamin D receptor polymorphisms with primary biliary cirrhosis and autoimmune liver diseases on Chinese].

OBJECTIVE: To study the association between the polymorphisms of vitamin D receptor (VDR) gene and autoimmune liver diseases and (AIH) and primary biliary cirrhosis (PBC) in Chinese. METHODS: PCR-RELP was used to investigate the polymorphisms in exon 2, and exon 7 to exon 9 of VDR among 49 AIH patients, 58 PBC patients, and 160 healthy controls, all Chinese. VDR polymorphisms were assessed by FokI, BsmI, ApaI, and TaqI endonucleases restriction fragment length polymorphism analysis after specific polymerase chain reaction (PCR) amplification. RESULTS: The distribution of VDR gene polymorphism in Chinese was similar to those in Koreans and Japanese, and different from those in the Germans and Spaniards. The percentage of ff phenotype carriers was significantly higher in the AIH patients than in the healthy controls (34.7% vs. 48.1%, chi(2) = 5.47, P = 0.019) and the percentage of Ff phenotype carriers was lower in the AIH patients than in the healthy controls (34.7% vs. 48.1%, P = 0.057). The percentage of Bb phenotype carriers was significantly lower in the PBC patients than in the healthy controls (5.2% vs. 17.5%, P = 0.021) and. the percentage of bb phenotype carriers was significantly higher in the PBC patients than in the healthy controls (94.8% vs. 80.6%, chi(2) = 6.52, P = 0.01). We also detected a significant association of the BsmI polymorphisms in PBC patients in comparison with controls (P = 0.01). Furthermore we found the difference in the FokI, BsmI, ApaI, and TaqI genotype distribution between Chinese health controls and Caucasian health controls. CONCLUSION: There is a significant association between FokI polymorphism and AIH and a significant association between the BsmI polymorphisms and PBC in Chinese.

Adult↗

An evolutionary scenario for the transition to undifferentiated multicellularity.

The evolutionary transition from single cells toward multicellular forms of life represents one of the major transitions in the evolution of complex organisms. In this transition, single autonomously reproducing cells became parts of larger reproducing entities that eventually constituted a new unit of selection. The first step in the evolutionary transition to multicellularity likely was the evolution of simple, undifferentiated cell clusters. However, what the selective advantage of such cell clusters may have been remains unclear. Here, we argue that in populations of unicellular organisms with cooperative behavior, clustering may be beneficial by reducing interactions with noncooperative individuals. In support of this hypothesis, we present a set of computer simulations showing that clustering can evolve as a biological, heritable trait for cells that cooperate in the use of external energy resources. Following the evolution of simple cell clusters, further benefits could have arisen from the exchange of resources between cells of a cluster.

Adenosine Triphosphate↗

Evaluation of a new device for noninvasive measurement of nonshunted pulmonary capillary blood flow in patients with acute lung injury.

OBJECTIVES: To evaluate the performance of a new device for noninvasive measurement of nonshunted pulmonary capillary blood flow (PCBF) by partial CO2 rebreathing. DESIGN AND SETTING: Prospective clinical trial in an intensive care unit of a university hospital. PATIENTS AND PARTICIPANTS: Twenty mechanically ventilated patients with acute lung injury. INTERVENTIONS: Variations in PEEP of +/-3 cmH2O. MEASUREMENTS AND RESULTS: Initially PCBF was measured invasively as cardiac output minus venous admixture (Q(VA)/Q(t)) flow, and by partial CO2 rebreathing at baseline PEEP (PEEP(b)). The PEEP was then reduced by 3 cmH2O (to PEEP(b-3)) and measurements were repeated after 30 min. PEEP was then increased by 6 cmH2O (to PEEP(b+3)), and measurements were repeated after 10, 20, and 30 min. The overall correlation coefficient between noninvasive and invasive PCBF measurements at PEEP(b) was high ( r=0.97), with close agreement between methods being observed (0.1+/-0.6 l/min, bias and precision, respectively). Accordingly, both the correlation coefficient and agreement between methods for changes in PCBF from PEEP(b-3) to PEEP(b+3) levels were satisfactory ( r=0.71; 0.2+/-0.5 l/min, bias and precision). The new device was able to detect the correct PCBF trend in 17 of 20 patients investigated and in all patients who showed invasive PCBF changes equal to or greater than 0.3 l/min ( n=12). Noninvasive PCBF changes were stable as early as 10 min after variation in PEEP, as compared to 30 min values. CONCLUSIONS: The new device appears to be clinically useful for the monitoring of PCBF in patients suffering from acute lung injury. Our results suggest that titration of PEEP aimed at improving PCBF can be performed with the new device.

Adolescent↗

Potential contact sites between the protein and RNA subunit in the Bacillus subtilis RNase P holoenzyme.

We have detected by nucleotide analog interference mapping (NAIM) AMPalphaS and IMPalphaS modifications in Bacillus subtilis RNase P RNA that interfere with binding of the homologous protein subunit. Interference as well as some enhancement effects were clustered in two main areas, in P10.1a/L10.1 and P12 of the specificity domain (cluster 1, domain I) and in P2, P3, P15.1, J18/2 and J19/4 of the catalytic domain (cluster 2a, domain II). Minor interferences in P1 and P19 and a strong and weak enhancement effect in P19 represent a third area located in domain II (cluster 2b). Our results suggest that P3, P2-J18/2 and J19/4 are key elements for anchoring of the protein to the catalytic domain close to the scissile phosphodiester in enzyme-substrate complexes. Sites of interference or enhancement in clusters 1 and 2a are located at distances between 65 and 130 A from each other in the current 3D model of a full-length RNase P RNA-substrate complex. Taking into account that the RNase P protein monomer can bridge a maximum distance of about 40 A, simultaneous direct contacts to the two aforementioned potential RNA-binding areas would be incompatible with our current understanding of bacterial RNase P RNA architecture. Our findings suggest that the current 3D model has to be rearranged in order to reduce the distance between clusters 1 and 2a. Alternatively, based on the recent finding that B. subtilis RNase P forms a tetramer consisting of two protein and two RNA subunits, cluster 1 may reflect one protein contact site in domain I, and cluster 2a a separate one in domain II.

Bacillus subtilis↗