Investigating the Evolutionary Dynamics of Traits in Metazoa

Over the last 800 million years, animals have evolved an incredible array of diverse forms, life histories, ecologies, and traits. In the age of genome-scale resources for many animal taxa, researchers have a unique opportunity to investigate animal diversity and evolution through comparative genomic methods. These methods allow for studies not only of current diversity and evolutionary relationships, but also of ancient evolutionary dynamics and genomic repertoire. In order to study the evolution of diverse animal traits in a rigorous way however, researchers must not neglect the fundamental components of a robust comparative genomics study: well-supported phylogenies, high-quality genomic resources, and ways of applying comparative genomic methods to a phylogenetic tree. Here, I present three studies of animal trait evolution that address each of the three components above. First, I have leveraged current bioinformatic technologies to identify biases in phylogenomic studies stemming from transcriptome assembly errors, and determined the best practices for processing transcriptomic data for these studies (Chapter 1). I found that high-quality transcriptome assemblies yield richer datasets that are less prone to bias and ambiguity when used to create phylogenetic trees. Second, I have sequenced and assembled a new genomic dataset from a unique marine organism which occupies a crucial position for Cnidarian phylogeny (Chapter 2). This new genomic resource is an important contribution to studies of the evolution of novel cell types and mitochondrial structure. Third, I have investigated the patterns of gene gain and loss that characterize the evolution of one of the earliest-branching metazoan lineages in a well-supported phylogenomic context (Chapter 3). I established that animals in the phylum Porifera have lost traits associated with most other animal lineages, resulting in a derived form in extant sponges. The findings I lay out in this dissertation add to the growing body of knowledge concerning the evolution of non-bilaterian and early-branching metazoan lineages while also providing the scientific community with best practices for the accurate study of diverse traits in Metazoa

Demonstration of ultra-high-Q small mode volume toroid microcavities on a chip

Optical microcavities confine light spatially and temporally and find application in a wide range of fundamental and applied studies. In many areas, the microcavity figure of merit is not only determined by photon lifetime (or the equivalent quality-factor, Q), but also by simultaneous achievement of small mode volume V . Here we demonstrate ultra-high Q-factor small mode volume toroid microcavities on-a-chip, which exhibit a Q/V factor of more than $10^{6}(\lambda/n)^{-3}$. These values are the highest reported to date for any chip-based microcavity. A corresponding Purcell factor in excess of 200 000 and a cavity finesse of $2.8\times10^{6}$ is achieved, demonstrating that toroid microcavities are promising candidates for studies of the Purcell effect, cavity QED or biochemical sensingComment: 4 pages, 3 figures, Submitted to Applied Physics Letter

Ribbon reign: 20 years of postmodern influence on a cultural phenomenon

Diverse sociology theoretical constructs serve as the lens to examine the evolution of two popular symbols of US culture in the last 20 years: yellow ribbons displayed as decoration and awareness ribbons worn as personal accoutrement. This research was motivated by society's weakened state of "collective consciousness," whereby shared beliefs and values have declined and some have completely disappeared, and sought to determine whether symbols will survive in a culture without commitment to the social. Invoking Christopher Lasch's Culture of Narcissism, Jean Baudrillard's Simulacra and Simulation, David Riesman's theory of other-directedness from The Lonely Crowd, and Stjepan Mestrovic's Postemotional Society, this work examined the significance of public displays of ribbons (whether on animate or inanimate objects), theorized why certain diseases and social causes "earned" their awareness ribbons and others did not, and demonstrated that these ribbons have served as multivalent symbols to accommodate our culture in a postmodern world. These symbols have not maintained their unifying function and now serve at the whim of the individual participant or observer. Ultimately, the act of wearing or displaying awareness ribbons and yellow ribbons, like so many other symbols, has been severed from the idea and is a freefloating, simulacrum to be used in whatever mode our postmodern, postemotional society requires

Study of the 12C+12C fusion reactions near the Gamow energy

The fusion reactions 12C(12C,a)20Ne and 12C(12C,p)23Na have been studied from E = 2.10 to 4.75 MeV by gamma-ray spectroscopy using a C target with ultra-low hydrogen contamination. The deduced astrophysical S(E)* factor exhibits new resonances at E <= 3.0 MeV, in particular a strong resonance at E = 2.14 MeV, which lies at the high-energy tail of the Gamow peak. The resonance increases the present non-resonant reaction rate of the alpha channel by a factor of 5 near T = 8x10^8 K. Due to the resonance structure, extrapolation to the Gamow energy E_G = 1.5 MeV is quite uncertain. An experimental approach based on an underground accelerator placed in a salt mine in combination with a high efficiency detection setup could provide data over the full E_G energy range.Comment: 4 Pages, 4 figures, accepted for publication in Phys. Rev. Let

Identifying novel hypoxia-associated markers of chemoresistance in ovarian cancer

BACKGROUND Ovarian cancer is associated with poor long-term survival due to late diagnosis and development of chemoresistance. Tumour hypoxia is associated with many features of tumour aggressiveness including increased cellular proliferation, inhibition of apoptosis, increased invasion and metastasis, and chemoresistance, mostly mediated through hypoxia-inducible factor (HIF)-1α. While HIF-1α has been associated with platinum resistance in a variety of cancers, including ovarian, relatively little is known about the importance of the duration of hypoxia. Similarly, the gene pathways activated in ovarian cancer which cause chemoresistance as a result of hypoxia are poorly understood. This study aimed to firstly investigate the effect of hypoxia duration on resistance to cisplatin in an ovarian cancer chemoresistance cell line model and to identify genes whose expression was associated with hypoxia-induced chemoresistance. METHODS Cisplatin-sensitive (A2780) and cisplatin-resistant (A2780cis) ovarian cancer cell lines were exposed to various combinations of hypoxia and/or chemotherapeutic drugs as part of a 'hypoxia matrix' designed to cover clinically relevant scenarios in terms of tumour hypoxia. Response to cisplatin was measured by the MTT assay. RNA was extracted from cells treated as part of the hypoxia matrix and interrogated on Affymetrix Human Gene ST 1.0 arrays. Differential gene expression analysis was performed for cells exposed to hypoxia and/or cisplatin. From this, four potential markers of chemoresistance were selected for evaluation in a cohort of ovarian tumour samples by RT-PCR. RESULTS Hypoxia increased resistance to cisplatin in A2780 and A2780cis cells. A plethora of genes were differentially expressed in cells exposed to hypoxia and cisplatin which could be associated with chemoresistance. In ovarian tumour samples, we found trends for upregulation of ANGPTL4 in partial responders and down-regulation in non-responders compared with responders to chemotherapy; down-regulation of HER3 in partial and non-responders compared to responders; and down-regulation of HIF-1α in non-responders compared with responders. CONCLUSION This study has further characterized the relationship between hypoxia and chemoresistance in an ovarian cancer model. We have also identified many potential biomarkers of hypoxia and platinum resistance and provided an initial validation of a subset of these markers in ovarian cancer tissues

Alternative Splicing Variation: Accessing and Exploiting in Crop Improvement Programs

Alternative splicing (AS) is a gene regulatory mechanism modulating gene expression in multiple ways. AS is prevalent in all eukaryotes including plants. AS generates two or more mRNAs from the precursor mRNA (pre-mRNA) to regulate transcriptome complexity and proteome diversity. Advances in next-generation sequencing, omics technology, bioinformatics tools, and computational methods provide new opportunities to quantify and visualize AS-based quantitative trait variation associated with plant growth, development, reproduction, and stress tolerance. Domestication, polyploidization, and environmental perturbation may evolve novel splicing variants associated with agronomically beneficial traits. To date, pre-mRNAs from many genes are spliced into multiple transcripts that cause phenotypic variation for complex traits, both in model plant Arabidopsis and field crops. Cataloguing and exploiting such variation may provide new paths to enhance climate resilience, resource-use efficiency, productivity, and nutritional quality of staple food crops. This review provides insights into AS variation alongside a gene expression analysis to select for novel phenotypic diversity for use in breeding programs. AS contributes to heterosis, enhances plant symbiosis (mycorrhiza and rhizobium), and provides a mechanistic link between the core clock genes and diverse environmental clues

Generic medicines and generic substitution: contrasting perspectives of stakeholders in Ireland.

BACKGROUND: The Health (Pricing and Supply of Medical Goods) Act 2013 passed into law in July 2013 and legislated for generic substitution in Ireland. The aim of the study was to ascertain the knowledge and perceptions of stakeholders i.e. patients, pharmacists and prescribers, of generic medicines and to generic substitution with the passing of legislation. METHODS: Three stakeholder specific questionnaires were developed to assess knowledge of and perceptions to generic medicines and generic substitution. Purposive samples of patients, prescribers and pharmacists were analysed. Descriptive quantitative and qualitative analyses were undertaken. RESULTS AND DISCUSSION: A total of 762 healthcare professionals and 353 patients were recruited. The study highlighted that over 84 % of patients were familiar with generic medicines and are supportive of the concept of generic substitution. Approximately 74 % of prescribers and 84 % of pharmacists were supportive of generic substitution in most cases. The main areas of concern highlighted by the healthcare professionals that might impact on the successful implementation of the policy, were the issue of bioequivalence with generic medicines, the computer software systems used at present in general practitioner (GP) surgeries and the availability of branded generics. The findings from this study identify a high baseline rate of acceptance to generic medicines and generic substitution among patients, prescribers and pharmacists in the Irish setting. The concerns of the main stakeholders provide a valuable insight into the potential difficulties that may arise in its implementation, and the need for on-going reassurance and proactive dissemination of the impact of the generic substitution policy. CONCLUSION: The existing positive attitude to generic medicines and generic substitution among key stakeholders in Ireland to generic substitution, combined with appropriate support and collaboration should result in the desired increase in rates of prescribing, dispensing and use of generic medicines

The Queen Square Encephalitis Multidisciplinary Team Meeting - experience over three years, pre and post the COVID-19 pandemic

Background: Patients with suspected encephalitis continue to represent a diagnostic and therapeutic challenge, even in highly resourced centres. In February 2018, we set up a monthly in-person multidisciplinary team meeting (MDT). We describe the experience and outcomes of the MDT over three years. Methods: A retrospective analysis was performed to summarise patient demographics, MDT outcomes and final diagnoses. Results: Over the three-year period, 324 discussions of 238 patients took place. Cases were diverse; approximately 40% related to COVID-19 or brain infection, 40% autoimmune or other inflammatory disorders and 20% encephalitis mimics or uncertain aetiologies. Feedback from an online survey sent to referring teams and attendees highlighted the value of the MDT; 94% reported the discussion was useful and 69% reported resulting change in patient management. Conclusions: Multidisciplinary input is crucial in this challenging area, ensuring that all diagnostic avenues are explored and opening doors to novel diagnostics and therapeutics. It also supports clinicians dealing with unwell patients, including in centres where less specialist input is available, and when decisions have to be made where there is little or no evidence base

Uncertainties and robustness of the ignition process in type Ia supernovae

It is widely accepted that the onset of the explosive carbon burning in the core of a CO WD triggers the ignition of a SN Ia. The features of the ignition are among the few free parameters of the SN Ia explosion theory. We explore the role for the ignition process of two different issues: firstly, the ignition is studied in WD models coming from different accretion histories. Secondly, we estimate how a different reaction rate for C-burning can affect the ignition. Two-dimensional hydrodynamical simulations of temperature perturbations in the WD core ("bubbles") are performed with the FLASH code. In order to evaluate the impact of the C-burning reaction rate on the WD model, the evolution code FLASH_THE_TORTOISE from Lesaffre et al. (2006) is used. In different WD models a key role is played by the different gravitational acceleration in the progenitor's core. As a consequence, the ignition is disfavored at a large distance from the WD center in models with a larger central density, resulting from the evolution of initially more massive progenitors. Changes in the C reaction rate at T < 5e8 K slightly influence the ignition density in the WD core, while the ignition temperature is almost unaffected. Recent measurements of new resonances in the C-burning reaction rate (Spillane et al. 2007) do not affect the core conditions of the WD significantly. This simple analysis, performed on the features of the temperature perturbations in the WD core, should be extended in the framework of the state-of-the-art numerical tools for studying the turbulent convection and ignition in the WD core. Future measurements of the C-burning reactions cross section at low energy, though certainly useful, are not expected to affect dramatically our current understanding of the ignition process.Comment: 7 pages, 5 figures, A&A accepte

The influence of distributed leadership on teachers' organizational commitment: a multilevel approach

In the present study the effects of a cooperative leadership team, distributed leadership, participative decision-making, and context variables on teachers' organizational commitment are investigated. Multilevel analyses on data from 1522 teachers indicated that 9% of the variance in teachers' organizational commitment is attributable to differences between schools. The analyses revealed that especially the presence of a cooperative leadership team and the amount of leadership support played a significantly positive key role in predicting teachers' organizational commitment. Also, participative decision-making and distribution of the supportive leadership function had a significant positive impact on teachers' organizational commitment. In contrast, distribution of the supervisory leadership function and teachers' job experience had a significant negative impact