Conservation and co-option in developmental programmes: the importance of homology relationships

One of the surprising insights gained from research in evolutionary developmental biology (evo-devo) is that increasing diversity in body plans and morphology in organisms across animal phyla are not reflected in similarly dramatic changes at the level of gene composition of their genomes. For instance, simplicity at the tissue level of organization often contrasts with a high degree of genetic complexity. Also intriguing is the observation that the coding regions of several genes of invertebrates show high sequence similarity to those in humans. This lack of change (conservation) indicates that evolutionary novelties may arise more frequently through combinatorial processes, such as changes in gene regulation and the recruitment of novel genes into existing regulatory gene networks (co-option), and less often through adaptive evolutionary processes in the coding portions of a gene. As a consequence, it is of great interest to examine whether the widespread conservation of the genetic machinery implies the same developmental function in a last common ancestor, or whether homologous genes acquired new developmental roles in structures of independent phylogenetic origin. To distinguish between these two possibilities one must refer to current concepts of phylogeny reconstruction and carefully investigate homology relationships. Particularly problematic in terms of homology decisions is the use of gene expression patterns of a given structure. In the future, research on more organisms other than the typical model systems will be required since these can provide insights that are not easily obtained from comparisons among only a few distantly related model species

Exploring possible links between Quaternary aggradation in the Upper Rhine Graben and the glaciation history of northern Switzerland

The Quaternary filling of the Upper Rhine Graben is an excellent archive to reconstruct sediment dynamics in response to climate change, in particular related to past glaciations of the Swiss Alpine Foreland. Here, a sediment sequence recovered by drilling for exploration purposes near Kronau is investigated, using a combination of sedimentological logging, provenance studies (heavy minerals and clast petrography), and luminescence dating. Several phases of coarse sediment aggradation are identified that possibly correlate to Marine Isotope Stages (MIS) 12 (478-424 ka), 10 (374-337 ka), 8 (300-243 ka), 6 (191-130 ka) and/or 4 (71-57 ka), and 2 (29-14 ka). Several of these phases have previously also been reported from cores recovered in the major Quaternary depo-centre near Heidelberg. This suggests that the observed coarse aggradation in the Upper Rhine Graben can be assigned to various glaciations in northern Switzerland: Mohlin (MIS 12), Habsburg (MIS 10 or 8), Beringen (MIS 6), an unnamed glacial advance during MIS 4, and Birrfeld (MIS 2). However, due to the limited data available, this hypothesis and the suggested correlations require further confirmation by applying the approach presented here to further cores from the Upper Rhine Graben.</p

Impact of Processing Conditions on Inter-tablet Coating Thickness Variations Measured by Terahertz In-Line Sensing.

A novel in-line technique utilising pulsed terahertz radiation for direct measurement of the film coating thickness of individual tablets during the coating process was previously developed and demonstrated on a production-scale coater. Here, we use this technique to monitor the evolution of tablet film coating thickness and its inter-tablet variability during the coating process under a number of different process conditions that have been purposefully induced in the production-scale coating process. The changes that were introduced to the coating process include removing the baffles from the coater, adding uncoated tablets to the running process, halting the drum, blockage of spray guns and changes to the spray rate. The terahertz sensor was able to pick up the resulting changes in average coating thickness in the coating drum and we report the impact of these process changes on the resulting coating quality.This work was conducted with financial support from the UK Technology Strategy Board (AB293H). H.L. And J.A.Z. would like to acknowledge the Engineering and Physical Sciences Research Council (EP/L019922/1) and the Newton Trust Cambridge for research funding. J.A.Z. would like to thank Gonville & Caius College, Cambridge for a research fellowship. The authors acknowledge Colorcon Ltd. and Meggle AG for providing the excipients used in this study, Provel Ltd. (Bolton, UK) for the kind loan of the mixing equipment to disperse the coating polymer and Staffan Folestad (AstraZeneca) for useful discussions. Additional data related to this publication is available as a supplementary data to this publication as well as at the University of Cambridge data repository (https://www.repository.cam.ac.uk).This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1002/jps.2450

Large-scale discovery of enhancers from human heart tissue.

Development and function of the human heart depend on the dynamic control of tissue-specific gene expression by distant-acting transcriptional enhancers. To generate an accurate genome-wide map of human heart enhancers, we used an epigenomic enhancer discovery approach and identified ∼6,200 candidate enhancer sequences directly from fetal and adult human heart tissue. Consistent with their predicted function, these elements were markedly enriched near genes implicated in heart development, function and disease. To further validate their in vivo enhancer activity, we tested 65 of these human sequences in a transgenic mouse enhancer assay and observed that 43 (66%) drove reproducible reporter gene expression in the heart. These results support the discovery of a genome-wide set of noncoding sequences highly enriched in human heart enhancers that is likely to facilitate downstream studies of the role of enhancers in development and pathological conditions of the heart

Conservation of shh cis-regulatory architecture of the coelacanth is consistent with its ancestral phylogenetic position

<p>Abstract</p> <p>Background</p> <p>The modern coelacanth (<it>Latimeria</it>) is the extant taxon of a basal sarcopterygian lineage and sister group to tetrapods. Apart from certain apomorphic traits, its morphology is characterized by a high degree of retention of ancestral vertebrate structures and little morphological change. An insight into the molecular evolution that may explain the unchanged character of <it>Latimeria </it>morphology requires the analysis of the expression patterns of developmental regulator genes and their <it>cis</it>-regulatory modules (CRMs).</p> <p>Results</p> <p>We describe the comparative and functional analysis of the <it>sonic hedgehog </it>(<it>shh</it>) genomic region of <it>Latimeria menadoensis</it>. Several putative enhancers in the <it>Latimeria shh </it>locus have been identified by comparisons to sarcopterygian and actinopterygian extant species. Specific sequence conservation with all known actinopterygian enhancer elements has been detected. However, these elements are selectively missing in more recently diverged actinopterygian and sarcopterygian species. The functionality of the putative <it>Latimeria </it>enhancers was confirmed by reporter gene expression analysis in transient transgenic zebrafish and chick embryos.</p> <p>Conclusions</p> <p><it>Latimeria shh </it>CRMs represent the ancestral set of enhancers that have emerged before the split of lobe-finned and ray-finned fishes. In contrast to lineage-specific losses and differentiations in more derived lineages, <it>Latimeria shh </it>enhancers reveal low levels of sequence diversification. High overall sequence conservation of <it>shh </it>conserved noncoding elements (CNE) is consistent with the general trend of high levels of conservation of noncoding DNA in the slowly evolving <it>Latimeria </it>genome.</p

Feasibility of Electronic Health Information and Surveillance System (eHISS) for disease symptom monitoring: A case of rural Ghana.

The current surge of mobile phone use in many African countries creates the opportunity to provide caregivers with limited access to the health care system with vital health recommendations. At the same time such communication system can be utilised to collect tempero-spatial data on disease symptoms

Trapped ions in optical lattices for probing oscillator chain models

We show that a chain of trapped ions embedded in microtraps generated by an optical lattice can be used to study oscillator models related to dry friction and energy transport. Numerical calculations with realistic experimental parameters demonstrate that both static and dynamic properties of the ion chain change significantly as the optical lattice power is varied. Finally, we lay out an experimental scheme to use the spin degree of freedom to probe the phase space structure and quantum critical behavior of the ion chain

Does the Identification of a Minimum Number of Cases Correlate With Better Adherence to International Guidelines Regarding the Treatment of Penile Cancer? Survey Results of the European PROspective Penile Cancer Study (E-PROPS)

Background: Penile cancer represents a rare malignant disease, whereby a small caseload is associated with the risk of inadequate treatment expertise. Thus, we hypothesized that strict guideline adherence might be considered a potential surrogate for treatment quality. This study investigated the influence of the annual hospital caseload on guideline adherence regarding treatment recommendations for penile cancer. Methods: In a 2018 survey study, 681 urologists from 45 hospitals in four European countries were queried about six hypothetical case scenarios (CS): local treatment of the primary tumor pTis (CS1) and pT1b (CS2); lymph node surgery inguinal (CS3) and pelvic (CS4); and chemotherapy neoadjuvant (CS5) and adjuvant (CS6). Only the responses from 206 head and senior physicians, as decision makers, were evaluated. The answers were assessed based on the applicable European Association of Urology (EAU) guidelines regarding their correctness. The real hospital caseload was analyzed based on multivariate logistic regression models regarding its effect on guideline adherence. Results: The median annual hospital caseload was 6 (interquartile range (IQR) 3–9). Recommendations for CS1–6 were correct in 79%, 66%, 39%, 27%, 28%, and 28%, respectively. The probability of a guideline-adherent recommendation increased with each patient treated per year in a clinic for CS1, CS2, CS3, and CS6 by 16%, 7.8%, 7.2%, and 9.5%, respectively (each p < 0.05); CS4 and CS5 were not influenced by caseload. A caseload threshold with a higher guideline adherence for all endpoints could not be perceived. The type of hospital care (academic vs. non-academic) did not affect guideline adherence in any scenario. Conclusions: Guideline adherence for most treatment recommendations increases with growing annual penile cancer caseload. Thus, the results of our study call for a stronger centralization of diagnosis and treatment strategies regarding penile cancer

Perovskite-perovskite tandem photovoltaics with optimized bandgaps

We demonstrate four and two-terminal perovskite-perovskite tandem solar cells with ideally matched bandgaps. We develop an infrared absorbing 1.2eV bandgap perovskite, $FA_{0.75}Cs_{0.25}Sn_{0.5}Pb_{0.5}I_3$, that can deliver 14.8 % efficiency. By combining this material with a wider bandgap $FA_{0.83}Cs_{0.17}Pb(I_{0.5}Br_{0.5})_3$ material, we reach monolithic two terminal tandem efficiencies of 17.0 % with over 1.65 volts open-circuit voltage. We also make mechanically stacked four terminal tandem cells and obtain 20.3 % efficiency. Crucially, we find that our infrared absorbing perovskite cells exhibit excellent thermal and atmospheric stability, unprecedented for Sn based perovskites. This device architecture and materials set will enable 'all perovskite' thin film solar cells to reach the highest efficiencies in the long term at the lowest costs

Evaluating the use of prostate-specific antigen as an instrument for early detection of prostate cancer beyond urologists: Results of a representative cross-sectional questionnaire study of general practitioners and internal specialists

OBJECTIVES The aim of this cross-sectional study was to evaluate the value of prostate-specific antigen (PSA) testing as a tool for early detection of prostate cancer (PCa) applied by general practitioners (GPs) and internal specialists (ISs) as well as to assess criteria leading to the application of PSA-based early PCa detection. METHODS Between May and December 2012, a questionnaire containing 16 items was sent to 600 GPs and ISs in the federal state Brandenburg and in Berlin (Germany). The independent influence of several criteria on the decision of GPs and ISs to apply PSA-based early PCa detection was assessed by multivariate logistic regression analysis (MLRA). RESULTS 392 evaluable questionnaires were collected (return rate 65%). 81% of the physicians declared that they apply PSA testing for early PCa detection; of these, 58 and 15% would screen patients until the age of 80 and 90 years, respectively. In case of a pathological PSA level, 77% would immediately refer the patient to a urologist, while 13% would re-assess elevated PSA levels after 3-12 months. Based on MLRA, the following criteria were independently associated with a positive attitude towards PSA-based early PCa detection: specialisation (application of early detection more frequent for GPs and hospital-based ISs) (OR 3.12; p < 0.001), physicians who use exclusively GP or IS education (OR 3.95; p = 0.002), and physicians who recommend yearly PSA assessment after the age of 50 (OR 6.85; p < 0.001). CONCLUSIONS GPs and ISs frequently apply PSA-based early PCa detection. In doing so, 13% would initiate specific referral to a urologist in case of pathological PSA values too late. Improvement of this situation could possibly result from specific educational activities for non-urological physicians active in fields of urological core capabilities, which should be guided by joint boards of the national associations of urology and general medicine