Nonadaptive Amino Acid Convergence Rates Decrease over Time.

Convergence is a central concept in evolutionary studies because it provides strong evidence for adaptation. It also provides information about the nature of the fitness landscape and the repeatability of evolution, and can mislead phylogenetic inference. To understand the role of adaptive convergence, we need to understand the patterns of nonadaptive convergence. Here, we consider the relationship between nonadaptive convergence and divergence in mitochondrial and model proteins. Surprisingly, nonadaptive convergence is much more common than expected in closely related organisms, falling off as organisms diverge. The extent of the convergent drop-off in mitochondrial proteins is well predicted by epistatic or coevolutionary effects in our "evolutionary Stokes shift" models and poorly predicted by conventional evolutionary models. Convergence probabilities decrease dramatically if the ancestral amino acids of branches being compared have diverged, but also drop slowly over evolutionary time even if the ancestral amino acids have not substituted. Convergence probabilities drop-off rapidly for quickly evolving sites, but much more slowly for slowly evolving sites. Furthermore, once sites have diverged their convergence probabilities are extremely low and indistinguishable from convergence levels at randomized sites. These results indicate that we cannot assume that excessive convergence early on is necessarily adaptive. This new understanding should help us to better discriminate adaptive from nonadaptive convergence and develop more relevant evolutionary models with improved validity for phylogenetic inference

Now the wars are over: The past, present and future of Scottish battlefields

Battlefield archaeology has provided a new way of appreciating historic battlefields. This paper provides a summary of the long history of warfare and conflict in Scotland which has given rise to a large number of battlefield sites. Recent moves to highlight the archaeological importance of these sites, in the form of Historic Scotland’s Battlefields Inventory are discussed, along with some of the problems associated with the preservation and management of these important cultural sites

Evaluation of range of motion restriction within the hip joint

In Total Hip Arthroplasty, determining the impingement free range of motion requirement is a complex task. This is because in the native hip, motion is restricted by both impingement as well as soft tissue restraint. The aim of this study is to determine a range of motion benchmark which can identify motions which are at risk from impingement and those which are constrained due to soft tissue. Two experimental methodologies were used to determine motions which were limited by impingement and those motions which were limited by both impingement and soft tissue restraint. By comparing these two experimental results, motions which were limited by impingement were able to be separated from those motions which were limited by soft tissue restraint. The results show motions in extension as well as flexion combined with adduction are limited by soft tissue restraint. Motions in flexion, flexion combined with abduction and adduction are at risk from osseous impingement. Consequently, these motions represent where the maximum likely damage will occur in femoroacetabular impingement or at most risk of prosthetic impingement in Total Hip Arthroplasty

Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.

The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition

Nucleocytoplasmic transport: a thermodynamic mechanism

The nuclear pore supports molecular communication between cytoplasm and nucleus in eukaryotic cells. Selective transport of proteins is mediated by soluble receptors, whose regulation by the small GTPase Ran leads to cargo accumulation in, or depletion from the nucleus, i.e., nuclear import or nuclear export. We consider the operation of this transport system by a combined analytical and experimental approach. Provocative predictions of a simple model were tested using cell-free nuclei reconstituted in Xenopus egg extract, a system well suited to quantitative studies. We found that accumulation capacity is limited, so that introduction of one import cargo leads to egress of another. Clearly, the pore per se does not determine transport directionality. Moreover, different cargo reach a similar ratio of nuclear to cytoplasmic concentration in steady-state. The model shows that this ratio should in fact be independent of the receptor-cargo affinity, though kinetics may be strongly influenced. Numerical conservation of the system components highlights a conflict between the observations and the popular concept of transport cycles. We suggest that chemical partitioning provides a framework to understand the capacity to generate concentration gradients by equilibration of the receptor-cargo intermediary.Comment: in press at HFSP Journal, vol 3 16 text pages, 1 table, 4 figures, plus Supplementary Material include

Protein disulphide isomerase-assisted functionalization of proteinaceous substrates

Protein disulphide isomerase (PDI) is an enzyme that catalyzes thiol-disulphide exchange reactions among a broad spectrum of substrates, including proteins and low-molecular thiols and disulphides. As the first protein-folding catalyst reported, the study of PDI has mainly involved the correct folding of several cysteine-containing proteins. Its application on the functionalization of protein-based materials has not been extensively reported. Herein, we review the applications of PDI on the modification of proteinaceous substrates and discuss its future potential. The mechanism involved in PDI functionalization of fibrous protein substrates is discussed in detail. These approaches allow innovative applications in textile dyeing and finishing, medical textiles, controlled drug delivery systems and hair or skin care products.We thank to FCT 'Fundacao para a Ciencia e Tecnologia' (scholarship SFRH/BD/38363/2007) for providing Margarida Fernandes the grant for PhD studies

School Effects on the Wellbeing of Children and Adolescents

Well-being is a multidimensional construct, with psychological, physical and social components. As theoretical basis to help understand this concept and how it relates to school, we propose the Self-Determination Theory, which contends that self-determined motivation and personality integration, growth and well-being are dependent on a healthy balance of three innate psychological needs of autonomy, relatedness and competence. Thus, current indicators involve school effects on children’s well-being, in many diverse modalities which have been explored. Some are described in this chapter, mainly: the importance of peer relationships; the benefits of friendship; the effects of schools in conjunction with some forms of family influence; the school climate in terms of safety and physical ecology; the relevance of the teacher input; the school goal structure and the implementation of cooperative learning. All these parameters have an influence in promoting optimal functioning among children and increasing their well-being by meeting the above mentioned needs. The empirical support for the importance of schools indicates significant small effects, which often translate into important real-life effects as it is admitted at present. The conclusion is that schools do make a difference in children’s peer relationships and well-being

Measurement of quarkonium production in proton–lead and proton–proton collisions at 5.02 TeV with the ATLAS detector

The modification of the production of J/ψ, ψ(2S), and Υ(nS) (n=1,2,3) in p+Pb collisions with respect to their production in pp collisions has been studied. The p+Pb and pp datasets used in this paper correspond to integrated luminosities of 28 nb−1 and 25 pb−1 respectively, collected in 2013 and 2015 by the ATLAS detector at the LHC, both at a centre-of-mass energy per nucleon pair of 5.02 TeV. The quarkonium states are reconstructed in the dimuon decay channel. The yields of J/ψ and ψ(2S) are separated into prompt and non-prompt sources. The measured quarkonium differential cross sections are presented as a function of rapidity and transverse momentum, as is the nuclear modification factor, RpPb for J/ψ and Υ(nS). No significant modification of the J/ψ production is observed while Υ(nS) production is found to be suppressed at low transverse momentum in p+Pb collisions relative to pp collisions. The production of excited charmonium and bottomonium states is found to be suppressed relative to that of the ground states in central p+Pb collisions

University rankings:What do they really show?

University rankings as developed by the media are used by many stakeholders in higher education: students looking for university places; academics looking for university jobs; university managers who need to maintain standing in the competitive arena of student recruitment; and governments who want to know that public funds spent on universities are delivering a world class higher education system. Media rankings deliberately draw attention to the performance of each university relative to all others, and as such they are undeniably simple to use and interpret. But one danger is that they are potentially open to manipulation and gaming because many of the measures underlying the rankings are under the control of the institutions themselves. This paper examines media rankings (constructed from an amalgamation of variables representing performance across numerous dimensions) to reveal the problems with using a composite index to reflect overall performance. It ends with a proposal for an alternative methodology which leads to groupings rather than point estimates

Pharmaceutical electrochemistry: the electrochemical detection of aspirin utilising screen printed graphene electrodes as sensors platforms.

A sensitive electrochemical sensor was designed for acetyl salicylic acid detection using graphene modified Screen Printed Electrodes. The electrochemical response of the sensor with graphene was improved compared to Screen Printed Electrodes without graphene and displayed an excellent analytical performance for the detection of acetyl salicylic acid. The high acetyl salicylic acid loading capacity on the electrode surface and the outstanding electric conductivity of graphene were also discussed in this manuscript. When a range of different concentrations of acetyl salicylic acid from 0.1 to 100 μM into a pH 4 buffer solution (N defined as the sample size N = 9) were plotted against the oxidation peak a linear response was observed. The detection limit was found to be 0.09 μM based on (3-σ/slope). Screen Printed Graphene electrodes sensors methodology is shown to be useful for quantifying low levels of acetyl salicylic acid in a buffer solution as well as in biological matrixes such as human oral fluid. A linear response was obtained over a range of concentrations from 10 to 150 μM into a human oral fluid solution (N = 10) giving a detection limit of 8.7 μM