Impact of the solvent capacity constraint on E. coli metabolism

<p>Abstract</p> <p>Background</p> <p>Obtaining quantitative predictions for cellular metabolic activities requires the identification and modeling of the physicochemical constraints that are relevant at physiological growth conditions. Molecular crowding in a cell's cytoplasm is one such potential constraint, as it limits the solvent capacity available to metabolic enzymes.</p> <p>Results</p> <p>Using a recently introduced flux balance modeling framework (FBAwMC) here we demonstrate that this constraint determines a metabolic switch in <it>E. coli </it>cells when they are shifted from low to high growth rates. The switch is characterized by a change in effective optimization strategy, the excretion of acetate at high growth rates, and a global reorganization of <it>E. coli </it>metabolic fluxes, the latter being partially confirmed by flux measurements of central metabolic reactions.</p> <p>Conclusion</p> <p>These results implicate the solvent capacity as an important physiological constraint acting on <it>E. coli </it>cells operating at high metabolic rates and for the activation of a metabolic switch when they are shifted from low to high growth rates. The relevance of this constraint in the context of both the aerobic ethanol excretion seen in fast growing yeast cells (Crabtree effect) and the aerobic glycolysis observed in rapidly dividing cancer cells (Warburg effect) should be addressed in the future.</p

Managing Incidental Genomic Findings in Clinical Trials: Fulfillment of the Principle of Justice

<p>Managing Incidental Genomic Findings in Clinical Trials: Fulfillment of the Principle of Justice</p

Sex-Differential Herbivory in Androdioecious Mercurialis annua

Males of plants with separate sexes are often more prone to attack by herbivores than females. A common explanation for this pattern is that individuals with a greater male function suffer more from herbivory because they grow more quickly, drawing more heavily on resources for growth that might otherwise be allocated to defence. Here, we test this ‘faster-sex’ hypothesis in a species in which males in fact grow more slowly than hermaphrodites, the wind-pollinated annual herb Mercurialis annua. We expected greater herbivory in the faster-growing hermaphrodites. In contrast, we found that males, the slower sex, were significantly more heavily eaten by snails than hermaphrodites. Our results thus reject the faster-sex hypothesis and point to the importance of a trade-off between defence and reproduction rather than growth

Body composition in older acute stroke patients after treatment with individualized, nutritional supplementation while in hospital

<p>Abstract</p> <p>Background</p> <p>Individualized, nutritional support reduced undernutrition among older stroke patients and improved quality of life in our recent randomized, controlled trial. Weight control thus seems to be important after stroke, and methods for monitoring nutritional status need to be simple and non-invasive. Here we aimed to assess if the nutritional intervention altered body composition in men and women in this study cohort, and also to examine the correlation between the methods for assessing body-, fat- and fat-free mass.</p> <p>Methods</p> <p>Acute stroke patients > 65 years at nutritional risk were randomized to either individualized, nutritional treatment with energy- and protein rich supplementation (intervention, n = 58) or routine, nutritional care (control, n = 66) while in hospital. Body composition was assessed with anthropometry and bioelectrical impedance. The follow-up period was three months.</p> <p>Results</p> <p>During the first week while in hospital, weight loss was smaller in the intervention group compared with the controls (P = 0.013). After three months weight- and fat loss were significant in both men and women. Whereas no significant differences were found in changes in body composition between the male study groups, in the women both weight loss (P = 0.022) and fat loss (P = 0.005) was smaller in the intervention group compared with the controls. A high correlation (r = 0.87) between mid upper arm circumference (MUAC) and body mass index (BMI) was found.</p> <p>Conclusions</p> <p>Individualized nutritional support to older stroke patients in hospital was beneficial for maintaining an adequate body mass and body composition the first week and seemed to have a preventive effect on fat loss among women, but not among men after three months. Measurement of MUAC may be used in the assessment of nutritional status when BMI cannot be obtained.</p> <p>Trial registration</p> <p>This trial is registered with ClinicalTrials.gov, number NCT00163007.</p

Accelerated Profile HMM Searches

Profile hidden Markov models (profile HMMs) and probabilistic inference methods have made important contributions to the theory of sequence database homology search. However, practical use of profile HMM methods has been hindered by the computational expense of existing software implementations. Here I describe an acceleration heuristic for profile HMMs, the “multiple segment Viterbi” (MSV) algorithm. The MSV algorithm computes an optimal sum of multiple ungapped local alignment segments using a striped vector-parallel approach previously described for fast Smith/Waterman alignment. MSV scores follow the same statistical distribution as gapped optimal local alignment scores, allowing rapid evaluation of significance of an MSV score and thus facilitating its use as a heuristic filter. I also describe a 20-fold acceleration of the standard profile HMM Forward/Backward algorithms using a method I call “sparse rescaling”. These methods are assembled in a pipeline in which high-scoring MSV hits are passed on for reanalysis with the full HMM Forward/Backward algorithm. This accelerated pipeline is implemented in the freely available HMMER3 software package. Performance benchmarks show that the use of the heuristic MSV filter sacrifices negligible sensitivity compared to unaccelerated profile HMM searches. HMMER3 is substantially more sensitive and 100- to 1000-fold faster than HMMER2. HMMER3 is now about as fast as BLAST for protein searches

The Changing Life Science Patent Landscape

What have we learned from 20 tumultuous years of patent law in the life sciences? Is patenting likely to be as important for the industry in the future?Ope

Of Bits and Bugs — On the Use of Bioinformatics and a Bacterial Crystal Structure to Solve a Eukaryotic Repeat-Protein Structure

Pur-α is a nucleic acid-binding protein involved in cell cycle control, transcription, and neuronal function. Initially no prediction of the three-dimensional structure of Pur-α was possible. However, recently we solved the X-ray structure of Pur-α from the fruitfly Drosophila melanogaster and showed that it contains a so-called PUR domain. Here we explain how we exploited bioinformatics tools in combination with X-ray structure determination of a bacterial homolog to obtain diffracting crystals and the high-resolution structure of Drosophila Pur-α. First, we used sensitive methods for remote-homology detection to find three repetitive regions in Pur-α. We realized that our lack of understanding how these repeats interact to form a globular domain was a major problem for crystallization and structure determination. With our information on the repeat motifs we then identified a distant bacterial homolog that contains only one repeat. We determined the bacterial crystal structure and found that two of the repeats interact to form a globular domain. Based on this bacterial structure, we calculated a computational model of the eukaryotic protein. The model allowed us to design a crystallizable fragment and to determine the structure of Drosophila Pur-α. Key for success was the fact that single repeats of the bacterial protein self-assembled into a globular domain, instructing us on the number and boundaries of repeats to be included for crystallization trials with the eukaryotic protein. This study demonstrates that the simpler structural domain arrangement of a distant prokaryotic protein can guide the design of eukaryotic crystallization constructs. Since many eukaryotic proteins contain multiple repeats or repeating domains, this approach might be instructive for structural studies of a range of proteins

Multifaceted value profiles of forest owner categories in South Sweden: The river helge å catchment as a case study

Forest landscapes provide benefits from a wide range of goods, function and intangible values. But what are different forest owner categories\u27 profiles of economic use and non-use values? This study focuses on the complex forest ownership pattern of the River Helge å catchment including the Kristianstad Vattenrike Biosphere Reserve in southern Sweden. We made 89 telephone interviews with informants representing the four main forest owner categories. Our mapping included consumptive and non-consumptive direct use values, indirect use values, and non-use values such as natural and cultural heritage. While the value profiles of non-industrial forest land owners and municipalities included all value categories, the forest companies focused on wood production, and the Swedish Environmental Protection Agency on nature protection. We discuss the challenges of communicating different forest owners\u27 economic value profiles among stakeholders, the need for a broader suite of forest management systems, and fora for collaborative planning. © 2013 The Author(s)

Low Frequency Groans Indicate Larger and More Dominant Fallow Deer (Dama dama) Males

Background: Models of honest advertisement predict that sexually selected calls should signal male quality. In most vertebrates, high quality males have larger body sizes that determine higher social status and in turn higher reproductive success. Previous research has emphasised the importance of vocal tract resonances or formant frequencies of calls as cues to body size in mammals. However, the role of the acoustic features of vocalisations as cues to other quality-related phenotypic characteristics of callers has rarely been investigated. Methodology/Principal Findings: We examined whether the acoustic structure of fallow deer groans provides reliable information on the quality of the caller, by exploring the relationships between male quality (body size, dominance rank, and mating success) and the frequency components of calls (fundamental frequency, formant frequencies, and formant dispersion). We found that body size was not related to the fundamental frequency of groans, whereas larger males produced groans with lower formant frequencies and lower formant dispersion. Groans of high-ranking males were characterised by lower minimum fundamental frequencies and to a lesser extent, by lower formant dispersions. Dominance rank was the factor most strongly related to mating success, with higher-ranking males having higher mating success. The minimum fundamental frequency and the minimum formant dispersion were indirectly related to male mating success (through dominance rank). Conclusion/Significance: Our study is the first to show that sexually selected vocalisations can signal social dominance in mammals other than primates, and reveals that independent acoustic components encode accurate information on different phenotypic aspects of male quality