Can a consecutive double turn conformation be considered as a peptide based molecular scaffold for supramolecular helix in the solid state?

Helices and sheets are ubiquitous in nature. However, there are also some examples of self-assembling molecules forming supramolecular helices and sheets in unnatural systems. Unlike supramolecular sheets there are a very few examples of peptide sub-units that can be used to construct supramolecular helical architectures using the backbone hydrogen bonding functionalities of peptides. In this report we describe the design and synthesis of two single turn/bend forming peptides (Boc-Phe-Aib-Ile-OMe 1 and Boc-Ala-Leu-Aib-OMe 2) (Aib: alpha-aminoisobutyric acid) and a series of double-turn forming peptides (Boc-Phe-Aib-IIe-Aib-OMe 3, Boc-Leu-Aib-Gly-Aib-OMe 4 and Boc-gamma-Abu-Aib-Leu-Aib-OMe 5) (gamma-Abu: gamma-aminobutyric acid). It has been found that, in crystals, on self-assembly, single turn/bend forming peptides form either a supramolecular sheet (peptide 1) or a supramolecular helix (peptide 2). unlike self-associating double turn forming peptides, which have only the option of forming supramolecular helical assemblages. (c) 2005 Elsevier Ltd. All rights reserved.

Where should the nuclei be located?

The positions of nuclei in orbital representations are discussed. Some misleading representations in the scientific literature are highlighted and more realistic diagrams are presented.

Truth in complex adaptive systems models should be based on truth by constructive verification

It is argued that the truth status of emergent properties of complex adaptive systems models should be based on an epistemology of proof by constructive verification and therefore on the ontological axioms of a non-realist logical system such as constructivism or intuitionism. ‘Emergent’ properties of complex adaptive systems (CAS) models create particular epistemological and ontological challenges. These challenges bear directly on current debates in the philosophy of mathematics and in theoretical computer science. CAS research, with its emphasis on computer simulation, is heavily reliant on models which explore the entailments of Formal Axiomatic Systems (FAS). The incompleteness results of Gödel, the incomputability results of Turing, and the Algorithmic Information Theory results of Chaitin, undermine a realist (platonic) truth model of emergent properties. These same findings support the hegemony of epistemology over ontology and point to alternative truth models such as intuitionism, constructivism and quasi-empiricism.

Fecal microbiota in patients receiving enteral feeding are highly variable and may be altered in those who develop diarrhea

Background: The pathogenesis of diarrhea in patients receiving enteral feeding includes colonic water secretion, antibiotic prescription, and enteropathogenic colonization, each of which involves an interaction with the gastrointestinal microbiota. Objective: The objective was to investigate temporal changes in the concentrations of fecal microbiota and short-chain fatty acids (SCFAs) in patients starting 14-d of enteral feeding and to compare these changes between patients who do and do not develop diarrhea. Design: Twenty patients starting exclusive nasogastric enteral feeding were monitored for 14 d. Fecal samples were collected at the start, middle, and end of this period and were analyzed for major bacterial groups by using culture independent fluorescence in situ hybridization and for SCFAs by using gas-liquid chromatography. Results: Although no significant changes in fecal microbiota or SCFAs were observed during enteral feeding, stark alterations occurred within individual patients. Ten patients (50%) developed diarrhea, and these patients had significantly higher concentrations of clostridia (P = 0.026) and lower concentrations (P = 0.069) and proportions (P = 0.029) of bifidobacteria. Patients with and without diarrhea had differences in the proportion of bifidobacteria (median: 0.4% and 3.7%; interquartile range: 0.8 compared with 4.3; P = 0.035) and clostridia (median: 10.4% and 3.7%; interquartile range: 14.7 compared with 7.0; P = 0.063), respectively, even at the start of enteral feeding. Patients who developed diarrhea had higher concentrations of total fecal SCFAs (P = 0.044), acetate (P = 0.029), and butyrate (P = 0.055). Conclusion: Intestinal dysbiosis occurs in patients who develop diarrhea during enteral feeding and may be involved in its pathogenesis. Am J Clin Nutr 2009; 89: 240-7.

Ribosome modulation factor protects Escherichia coli during heat stress, but this may not be dependent on ribosome dimerisation

The role of ribosome modulation factor (RMF) in protecting heat-stressed Escherichia coli cells was identified by the observation that cultures of a mutant strain lacking functional RMF (HMY15) were highly heat sensitive in stationary phase compared to those of the parent strain (W3110). No difference in heat sensitivity was observed between these strains in exponential phase, during which RMF is not synthesised. Studies by differential scanning calorimetry demonstrated that the ribosomes of stationary-phase cultures of the mutant strain had lower thermal stability than those of the parent strain in stationary phase, or exponential-phase ribosomes. More rapid breakdown of ribosomes in the mutant strain during heating was confirmed by rRNA analysis and sucrose density gradient centrifugation. Analyses of ribosome composition showed that the 100S dimers dissociated more rapidly during heating than 70S particles. While ribosome dimerisation is a consequence of the conformational changes caused by RMF binding, it may not therefore be essential for RMF-mediated ribosome stabilisation.

When we eat, which bacteria should we be feeding?

Diet therapy utilizing probiotics and prebiotics may help treat many common gastrointestinal complaints. From birth to about 2 years of age the human digestive tract changes from sterile to a complex ecosystem with at least 500 bacterial species, most of these are benign and even necessary, however, pathogenic species also colonize the digestive tract. The idea is that prebiotics and probiotics can be used to displace and neutralise these pathogens.

Can the cardiomyocyte cell cycle be reprogrammed?

Cardiac repair following myocardial injury is restricted due to the limited proliferative potential of adult cardiomyocytes. The ability of mammalian cardiomyocytes to proliferate is lost shortly after birth as cardiomyocytes withdraw from the cell cycle and differentiate. We do not fully understand the molecular and cellular mechanisms that regulate this cell cycle withdrawal, although if we could it might lead to the discovery of novel therapeutic targets for improving cardiac repair following myocardial injury. For the last decade, researchers have investigated cardiomyocyte cell cycle control, commonly using transgenic mouse models or recombinant adenoviruses to manipulate cell cycle regulators in vivo or in vitro. This review discusses cardiomyocyte cell cycle regulation and summarises recent data from studies manipulating the expressions and activities of cell cycle regulators in cardiomyocytes. The validity of therapeutic strategies that aim to reinstate the proliferative potential of cardiomyocytes to improve myocardial repair following injury will be discussed. (c) 2007 Elsevier Inc. All rights reserved.

Childhood obesity: should primary school children be routinely screened? A systematic review and discussion of the evidence

Background: Population monitoring has been introduced in UK primary schools in an effort to track the growing obesity epidemic. It has been argued that parents should be informed of their child's results, but is there evidence that moving from monitoring to screening would be effective? We describe what is known about the effectiveness of monitoring and screening for overweight and obesity in primary school children and highlight areas where evidence is lacking and research should be prioritised. Design: Systematic review with discussion of evidence gaps and future research. Data sources: Published and unpublished studies ( any language) from electronic databases ( inception to July 2005), clinical experts, Primary Care Trusts and Strategic Health Authorities, and reference lists of retrieved studies. Review methods: We included any study that evaluated measures of overweight and obesity as part of a population-level assessment and excluded studies whose primary outcome measure was prevalence. Results: There were no trials assessing the effectiveness of monitoring or screening for overweight and obesity. Studies focussed on the diagnostic accuracy of measurements. Information on the attitudes of children, parents and health professionals to monitoring was extremely sparse. Conclusions: Our review found a lack of data on the potential impact of population monitoring or screening for obesity and more research is indicated. Identification of effective weight reduction strategies for children and clarification of the role of preventative measures are priorities. It is difficult to see how screening to identify individual children can be justified without effective interventions.

Can misalignments in typical infants be used as a model for infantile esotropia?

PURPOSE. To investigate the nature of early ocular misalignments in human infants to determine whether they can provide insight into the etiology of esotropia and, in particular, to examine the correlates of misalignments. METHODS. A remote haploscopic photorefraction system was used to measure accommodation and vergence in 146 infants between 0 and 12 months of age. Infants underwent photorefraction immediately after watching a target moving between two of five viewing distances (25, 33, 50, 100, and 200 cm). In some instances, infants were tested in two conditions: both eyes open and one eye occluded. The resultant data were screened for instances of large misalignments. Data were assessed to determine whether accommodative, retinal disparity, or other cues were associated with the occurrence of misalignments. RESULTS. The results showed that there was no correlation between accommodative behavior and misalignments. Infants were more likely to show misalignments when retinal disparity cues were removed through occlusion. They were also more likely to show misalignments immediately after the target moved from a near to a far position in comparison to far-to-near target movement. DISCUSSION. The data suggest that the prevalence of misalignments in infants of 2 to 3 months of age is decreased by the addition of retinal disparity cues to the stimulus. In addition, target movement away from the infant increases the prevalence of misalignments. These data are compatible with the notion that misalignment are caused by poor sensitivity to targets moving away from the infant and support the theory that some forms of strabismus could be related to failure in a system that is sensitive to the direction of motion.

Motorcycle accident risk could be inflated by a time to arrival illusion

Purpose. Drivers adopt smaller safety margins when pulling out in front of motorcycles compared with cars. This could partly account for why the most common motorcycle/car accident involves a car violating a motorcyclist's right of way. One possible explanation is the size-arrival effect in which smaller objects are perceived to arrive later than larger objects. That is, drivers may estimate the time to arrival of motorcycles to be later than cars because motorcycles are smaller. Methods. We investigated arrival time judgments using a temporal occlusion paradigm. Drivers recruited from the student population (n = 28 and n = 33) saw video footage of oncoming vehicles and had to press a response button when they judged that vehicles would reach them. Results. In experiment 1, the time to arrival of motorcycles was estimated to be significantly later than larger vehicles (a car and a van) for different approach speeds and viewing times. In experiment 2, we investigated an alternative explanation to the size-arrival effect: that the smaller size of motorcycles places them below the threshold needed for observers to make an accurate time to arrival judgment using tau. We found that the motorcycle/car difference in arrival time estimates was maintained for very short occlusion durations when tau could be estimated for both motorcycles and cars. Conclusions. Results are consistent with the size-arrival effect and are inconsistent with the tau threshold explanation. Drivers estimate motorcycles will reach them later than cars across a range of conditions. This could have safety implications.