The instability of Alexander-McTague crystals and its implication for nucleation

We show that the argument of Alexander and McTague, that the bcc crystalline structure is favored in those crystallization processes where the first order character is not too pronounced, is not correct. We find that any solution that satisfies the Alexander-McTague condition is not stable. We investigate the implication of this result for nucleation near the pseudo- spinodal in near-meanfield systems.Comment: 20 pages, 0 figures, submitted to Physical Review

Self-guided trails – a route to more responsible tourism?

In recent years, the tourism industry has faced criticism by turning its attention to the development of more responsible tourism. This is a form of tourism that is mindful of the diverse needs of host communities, local business and the visitor. This paper investigates the development of more responsible tourism from the perspective of a popular tourist product – the self-guided trail or route. The trail or route provides a themed and interpreted journey through the urban or rural landscape, creating links between sites, attractions and other tourism businesses by providing information and storytelling along the way. These products have a global appeal and are becoming more prolific. Through a literature review on trails, the paper analyses their key characteristics and the rationales of developers and concludes that trails have the potential to contribute to more responsible tourism development. The paper proposes a series of planning principles which are derived from the literature and examples of good practice therein which may assist trail developers in creating more responsible tourism routes and trails. The discussion concludes with a case study of a project in Cornwall in the south-west of the UK, where responsible planning has underpinned recent trail development

Experience and Challenges from Clinical Trials with Malaria Vaccines in Africa.

Malaria vaccines are considered amongst the most important modalities for potential elimination of malaria disease and transmission. Research and development in this field has been an area of intense effort by many groups over the last few decades. Despite this, there is currently no licensed malaria vaccine. Researchers, clinical trialists and vaccine developers have been working on many approached to make malaria vaccine available.African research institutions have developed and demonstrated a great capacity to undertake clinical trials in accordance to the International Conference on Harmonization-Good Clinical Practice (ICH-GCP) standards in the last decade; particularly in the field of malaria vaccines and anti-malarial drugs. This capacity is a result of networking among African scientists in collaboration with other partners; this has traversed both clinical trials and malaria control programmes as part of the Global Malaria Action Plan (GMAP). GMAP outlined and support global strategies toward the elimination and eradication of malaria in many areas, translating in reduction in public health burden, especially for African children. In the sub-Saharan region the capacity to undertake more clinical trials remains small in comparison to the actual need.However, sustainability of the already developed capacity is essential and crucial for the evaluation of different interventions and diagnostic tools/strategies for other diseases like TB, HIV, neglected tropical diseases and non-communicable diseases. There is urgent need for innovative mechanisms for the sustainability and expansion of the capacity in clinical trials in sub-Saharan Africa as the catalyst for health improvement and maintained

Kinetic modelling of competition and depletion of shared miRNAs by competing endogenous RNAs

Non-conding RNAs play a key role in the post-transcriptional regulation of mRNA translation and turnover in eukaryotes. miRNAs, in particular, interact with their target RNAs through protein-mediated, sequence-specific binding, giving rise to extended and highly heterogeneous miRNA-RNA interaction networks. Within such networks, competition to bind miRNAs can generate an effective positive coupling between their targets. Competing endogenous RNAs (ceRNAs) can in turn regulate each other through miRNA-mediated crosstalk. Albeit potentially weak, ceRNA interactions can occur both dynamically, affecting e.g. the regulatory clock, and at stationarity, in which case ceRNA networks as a whole can be implicated in the composition of the cell's proteome. Many features of ceRNA interactions, including the conditions under which they become significant, can be unraveled by mathematical and in silico models. We review the understanding of the ceRNA effect obtained within such frameworks, focusing on the methods employed to quantify it, its role in the processing of gene expression noise, and how network topology can determine its reach.Comment: review article, 29 pages, 7 figure

The origin of large molecules in primordial autocatalytic reaction networks

Large molecules such as proteins and nucleic acids are crucial for life, yet their primordial origin remains a major puzzle. The production of large molecules, as we know it today, requires good catalysts, and the only good catalysts we know that can accomplish this task consist of large molecules. Thus the origin of large molecules is a chicken and egg problem in chemistry. Here we present a mechanism, based on autocatalytic sets (ACSs), that is a possible solution to this problem. We discuss a mathematical model describing the population dynamics of molecules in a stylized but prebiotically plausible chemistry. Large molecules can be produced in this chemistry by the coalescing of smaller ones, with the smallest molecules, the `food set', being buffered. Some of the reactions can be catalyzed by molecules within the chemistry with varying catalytic strengths. Normally the concentrations of large molecules in such a scenario are very small, diminishing exponentially with their size. ACSs, if present in the catalytic network, can focus the resources of the system into a sparse set of molecules. ACSs can produce a bistability in the population dynamics and, in particular, steady states wherein the ACS molecules dominate the population. However to reach these steady states from initial conditions that contain only the food set typically requires very large catalytic strengths, growing exponentially with the size of the catalyst molecule. We present a solution to this problem by studying `nested ACSs', a structure in which a small ACS is connected to a larger one and reinforces it. We show that when the network contains a cascade of nested ACSs with the catalytic strengths of molecules increasing gradually with their size (e.g., as a power law), a sparse subset of molecules including some very large molecules can come to dominate the system.Comment: 49 pages, 17 figures including supporting informatio

Protein Folding Activity of the Ribosome is involved in Yeast Prion Propagation.

6AP and GA are potent inhibitors of yeast and mammalian prions and also specific inhibitors of PFAR, the protein-folding activity borne by domain V of the large rRNA of the large subunit of the ribosome. We therefore explored the link between PFAR and yeast prion [PSI(+)] using both PFAR-enriched mutants and site-directed methylation. We demonstrate that PFAR is involved in propagation and de novo formation of [PSI(+)]. PFAR and the yeast heat-shock protein Hsp104 partially compensate each other for [PSI(+)] propagation. Our data also provide insight into new functions for the ribosome in basal thermotolerance and heat-shocked protein refolding. PFAR is thus an evolutionarily conserved cell component implicated in the prion life cycle, and we propose that it could be a potential therapeutic target for human protein misfolding diseases

Bootstrapping the energy flow in the beginning of life.

This paper suggests that the energy flow on which all living structures depend only started up slowly, the low-energy, initial phase starting up a second, slightly more energetic phase, and so on. In this way, the build up of the energy flow follows a bootstrapping process similar to that found in the development of computers, the first generation making possible the calculations necessary for constructing the second one, etc. In the biogenetic upstart of an energy flow, non-metals in the lower periods of the Periodic Table of Elements would have constituted the most primitive systems, their operation being enhanced and later supplanted by elements in the higher periods that demand more energy. This bootstrapping process would put the development of the metabolisms based on the second period elements carbon, nitrogen and oxygen at the end of the evolutionary process rather than at, or even before, the biogenetic even

Behavioural Salinity Preferences of Juvenile Green Sturgeon \u3ci\u3eAcipenser medirostris\u3c/i\u3e Acclimated to Fresh Water and Full-Strength Salt Water

To quantify the salinity preference of juvenile green sturgeon Acipenser medirostris, two groups of A. medirostris [140 days post hatch (dph); total length (LT) 38.0–52.5 cm] were acclimated to either near fresh water (mean ± S.E. salinity = 3.2 ± 0.6) or full-strength salt water (34.1 ± 1.2) over 8 weeks. Following acclimation, the two groups were divided into experimental and control groups, where experimental A. medirostris from both freshwater and saltwater acclimations were individually introduced (200–220 dph) into a rectangular salinity-preference flume (maximum salinity gradient: 5–33). Control A. medirostris were presented with only their acclimation water (fresh water or salt water) on both sides of the flume. It was demonstrated that A. medirostris acclimated to both salt water and fresh water spent a significantly greater amount of time on the side of the testing area with the highest salinity concentration (P \u3c 0.05 and P \u3c 0.001, respectively) while control A. medirostris spent an equal amount of time on each side of the flume. These findings indicate that juvenile A. medirostris are not only capable of detecting salt water within the first year of their lives but perhaps are actively seeking out saline environments as they move through a watershed. Establishing A. medirostris salinity preferences provides a better understanding of the early life history of this threatened species, shedding light on possible outmigration timing

Tetrahymena thermophila and Candida albicans Group I intron-derived ribozymes can catalyze the trans-excision-splicing reaction

Group I intron-derived ribozymes can catalyze a variety of non-native reactions. For the trans-excision-splicing (TES) reaction, an intron-derived ribozyme from the opportunistic pathogen Pneumocystis carinii catalyzes the excision of a predefined region from within an RNA substrate with subsequent ligation of the flanking regions. To establish TES as a general ribozyme-mediated reaction, intron-derived ribozymes from Tetrahymena thermophila and Candida albicans, which are similar to but not the same as that from Pneumocystis, were investigated for their propensity to catalyze the TES reaction. We now report that the Tetrahymena and Candida ribozymes can catalyze the excision of a single nucleotide from within their ribozyme-specific substrates. Under the conditions studied, the Tetrahymena and Candida ribozymes, however, catalyze the TES reaction with lower yields and rates [Tetrahymena (kobs) = 0.14/min and Candida (kobs) = 0.34/min] than the Pneumocystis ribozyme (kobs = 3.2/min). The lower yields are likely partially due to the fact that the Tetrahymena and Candida catalyze additional reactions, separate from TES. The differences in rates are likely partially due to the individual ribozymes ability to effectively bind their 3′ terminal guanosines as intramolecular nucleophiles. Nevertheless, our results demonstrate that group I intron-derived ribozymes are inherently able to catalyze the TES reaction

Functional impact and evolution of a novel human polymorphic inversion that disrupts a gene and creates a fusion transcript

Since the discovery of chromosomal inversions almost 100 years ago, how they are maintained in natural populations has been a highly debated issue. One of the hypotheses is that inversion breakpoints could affect genes and modify gene expression levels, although evidence of this came only from laboratory mutants. In humans, a few inversions have been shown to associate with expression differences, but in all cases the molecular causes have remained elusive. Here, we have carried out a complete characterization of a new human polymorphic inversion and determined that it is specific to East Asian populations. In addition, we demonstrate that it disrupts the ZNF257 gene and, through the translocation of the first exon and regulatory sequences, creates a previously nonexistent fusion transcript, which together are associated to expression changes in several other genes. Finally, we investigate the potential evolutionary and phenotypic consequences of the inversion, and suggest that it is probably deleterious. This is therefore the first example of a natural polymorphic inversion that has position effects and creates a new chimeric gene, contributing to answer an old question in evolutionary biology