The evolution of RNAs with multiple functions

Increasing numbers of transcripts have been reported to transmit both protein-coding and regulatory information. Apart from challenging our conception of the gene, this observation raises the question as to what extent this phenomenon occurs across the genome and how and why such dual encoding of function has evolved in the eukaryotic genome. To address this question, we consider the evolutionary path of genes in the earliest forms of life on Earth, where it is generally regarded that proteins evolved from a cellular machinery based entirely within RNA. This led to the domination of protein-coding genes in the genomes of microorganisms, although it is likely that RNA never lost its other capacities and functionalities, as evidenced by cis-acting riboswitches and UTRs. On the basis that the subsequent evolution of a more sophisticated regulatory architecture to provide higher levels of epigenetic control and accurate spatiotemporal expression in developmentally complex organisms is a complicated task, we hypothesize: (i) that mRNAs have been and remain subject to secondary selection to provide trans-acting regulatory capability in parallel with protein-coding functions; (ii) that some and perhaps many protein-coding loci, possibly as a consequence of gene duplication, have lost protein-coding functions en route to acquiring more sophisticated trans-regulatory functions; (iii) that many transcripts have become subject to secondary processing to release different products; and (iv) that novel proteins have emerged within loci that previously evolved functionality as regulatory RNAs. In support of the idea that there is a dynamic flux between different types of informational RNAs in both evolutionary and real time, we review recent observations that have arisen from transcriptomic surveys of complex eukaryotes and reconsider how these observations impact on the notion that apparently discrete loci may express transcripts with more than one function. In conclusion, we posit that many eukaryotic loci have evolved the capacity to transact a multitude of overlapping and potentially independent functions as both regulatory and protein-coding RNAs

Testing potential new sites for optical telescopes in Australia

In coming years, Australia may find the need to build new optical telescopes to continue local programmes, contribute to global survey projects, and form a local multi-wavelength connection for the new radio telescopes being built. In this study, we refine possible locations for a new optical telescope by studying remotely sensed meteorological infrared data to ascertain expected cloud coverage rates across Australia, and combine these data with a digital elevation model using a geographic information system. We find that the best sites within Australia for building optical telescopes are likely to be on the highest mountains in the Hamersley Range in northwest Western Australia, while the MacDonnell Ranges in the Northern Territory may also be appropriate. We believe that similar seeing values to Siding Spring should be obtainable and with significantly more observing time at the identified sites. We expect to find twice as many clear nights as at current telescope sites. These sites are thus prime locations for future on-site testing

Teleology and Realism in Leibniz's Philosophy of Science

This paper argues for an interpretation of Leibniz’s claim that physics requires both mechanical and teleological principles as a view regarding the interpretation of physical theories. Granting that Leibniz’s fundamental ontology remains non-physical, or mentalistic, it argues that teleological principles nevertheless ground a realist commitment about mechanical descriptions of phenomena. The empirical results of the new sciences, according to Leibniz, have genuine truth conditions: there is a fact of the matter about the regularities observed in experience. Taking this stance, however, requires bringing non-empirical reasons to bear upon mechanical causal claims. This paper first evaluates extant interpretations of Leibniz’s thesis that there are two realms in physics as describing parallel, self-sufficient sets of laws. It then examines Leibniz’s use of teleological principles to interpret scientific results in the context of his interventions in debates in seventeenth-century kinematic theory, and in the teaching of Copernicanism. Leibniz’s use of the principle of continuity and the principle of simplicity, for instance, reveal an underlying commitment to the truth-aptness, or approximate truth-aptness, of the new natural sciences. The paper concludes with a brief remark on the relation between metaphysics, theology, and physics in Leibniz

Risk factors for delayed presentation and referral of symptomatic cancer: Evidence for common cancers

Background:It has been suggested that the known poorer survival from cancer in the United Kingdom, compared with other European countries, can be attributed to more advanced cancer stage at presentation. There is, therefore, a need to understand the diagnostic process, and to ascertain the risk factors for increased time to presentation.Methods:We report the results from two worldwide systematic reviews of the literature on patient-mediated and practitioner-mediated delays, identifying the factors that may influence these.Results:Across cancer sites, non-recognition of symptom seriousness is the main patient-mediated factor resulting in increased time to presentation. There is strong evidence of an association between older age and patient delay for breast cancer, between lower socio-economic status and delay for upper gastrointestinal and urological cancers and between lower education level and delay for breast and colorectal cancers. Fear of cancer is a contributor to delayed presentation, while sanctioning of help seeking by others can be a powerful mediator of reduced time to presentation. For practitioner delay, ‘misdiagnosis’ occurring either through treating patients symptomatically or relating symptoms to a health problem other than cancer, was an important theme across cancer sites. For some cancers, this could also be linked to inadequate patient examination, use of inappropriate tests or failing to follow-up negative or inconclusive test results.Conclusion:Having sought help for potential cancer symptoms, it is therefore important that practitioners recognise these symptoms, and examine, investigate and refer appropriately. © 2009 Cancer Research UK All rights reserved

The Palomar Testbed Interferometer Calibrator Catalog

The Palomar Testbed Interferometer (PTI) archive of observations between 1998 and 2005 is examined for objects appropriate for calibration of optical long-baseline interferometer observations - stars that are predictably point-like and single. Approximately 1,400 nights of data on 1,800 objects were examined for this investigation. We compare those observations to an intensively studied object that is a suitable calibrator, HD217014, and statistically compare each candidate calibrator to that object by computing both a Mahalanobis distance and a Principal Component Analysis. Our hypothesis is that the frequency distribution of visibility data associated with calibrator stars differs from non-calibrator stars such as binary stars. Spectroscopic binaries resolved by PTI, objects known to be unsuitable for calibrator use, are similarly tested to establish detection limits of this approach. From this investigation, we find more than 350 observed stars suitable for use as calibrators (with an additional $\approx 140$ being rejected), corresponding to $\gtrsim 95$ sky coverage for PTI. This approach is noteworthy in that it rigorously establishes calibration sources through a traceable, empirical methodology, leveraging the predictions of spectral energy distribution modeling but also verifying it with the rich body of PTI's on-sky observations.Comment: 100 pages, 7 figures, 7 tables; to appear in the May 2008ApJS, v176n

Education, knowledge, and symbolic form

This article aims to introduce Ernst Cassirer, and his philosophy of symbolic form, to education studies, and, in doing so, to challenge the widespread but deeply flawed views of knowledge and so-called knowledge-based education that have shaped recent education policy in England. After sketching the current educational landscape, and then some of the main lines of flight in Cassirer’s work, time is given to a comparison with Heidegger—a more familiar figure by far in Anglophone philosophy than Cassirer, and who contributed to the displacement of Cassirer—in order to illustrate more clearly Cassirer’s original contribution, in particular to the relationship between knowledge and time. Cassirer’s view of knowledge stands in marked and critical contrast to that which has shaped recent educational reform in England, as he sees knowledge as a productive and expressive matter, and repudiates what I call the ‘building-blocks’ picture of knowledge and the hierarchisation of subject areas

Prime movers : mechanochemistry of mitotic kinesins

Mitotic spindles are self-organizing protein machines that harness teams of multiple force generators to drive chromosome segregation. Kinesins are key members of these force-generating teams. Different kinesins walk directionally along dynamic microtubules, anchor, crosslink, align and sort microtubules into polarized bundles, and influence microtubule dynamics by interacting with microtubule tips. The mechanochemical mechanisms of these kinesins are specialized to enable each type to make a specific contribution to spindle self-organization and chromosome segregation

Eliminating Malaria Vectors.

Malaria vectors which predominantly feed indoors upon humans have been locally eliminated from several settings with insecticide treated nets (ITNs), indoor residual spraying or larval source management. Recent dramatic declines of An. gambiae in east Africa with imperfect ITN coverage suggest mosquito populations can rapidly collapse when forced below realistically achievable, non-zero thresholds of density and supporting resource availability. Here we explain why insecticide-based mosquito elimination strategies are feasible, desirable and can be extended to a wider variety of species by expanding the vector control arsenal to cover a broader spectrum of the resources they need to survive. The greatest advantage of eliminating mosquitoes, rather than merely controlling them, is that this precludes local selection for behavioural or physiological resistance traits. The greatest challenges are therefore to achieve high biological coverage of targeted resources rapidly enough to prevent local emergence of resistance and to then continually exclude, monitor for and respond to re-invasion from external populations

A Dynamical N-body Model for the Central Region of ω\omega Centauri

Supermassive black holes (SMBHs) are fundamental keys to understand the formation and evolution of their host galaxies. However, the formation and growth of SMBHs are not yet well understood. One of the proposed formation scenarios is the growth of SMBHs from seed intermediate-mass black holes (IMBHs, 10^2 to 10^5 M_{\odot}) formed in star clusters. In this context, and also with respect to the low mass end of the M-sigma relation for galaxies, globular clusters are in a mass range that make them ideal systems to look for IMBHs. Among Galactic star clusters, the massive cluster $\omega$ Centauri is a special target due to its central high velocity dispersion and also its multiple stellar populations. We study the central structure and dynamics of the star cluster $\omega$ Centauri to examine whether an IMBH is necessary to explain the observed velocity dispersion and surface brightness profiles. We perform direct N-body simulations to follow the dynamical evolution of $\omega$ Centauri. The simulations are compared to the most recent data-sets in order to explain the present-day conditions of the cluster and to constrain the initial conditions leading to the observed profiles. We find that starting from isotropic spherical multi-mass King models and within our canonical assumptions, a model with a central IMBH mass of 2% of the cluster stellar mass, i.e. a 5x10^4 M_{\odot} IMBH, provides a satisfactory fit to both the observed shallow cusp in surface brightness and the continuous rise towards the center of the radial velocity dispersion profile. In our isotropic spherical models, the predicted proper motion dispersion for the best-fit model is the same as the radial velocity dispersion one. (abridged)Comment: Accepted for publication in A&