2,600 research outputs found
Genomic and phenotypic signatures of climate adaptation in an Anolis lizard
Get PDFIntegrated knowledge on phenotype, physiology and genomic adaptations is required to understand the effects of climate on evolution. The functional genomic basis of organismal adaptation to changes in the abiotic environment, its phenotypic consequences, and its possible convergence across vertebrates, are still understudied. In this study, we use a comparative approach to verify predicted gene functions for vertebrate thermal adaptation with observed functions underlying repeated genomic adaptations in response to elevation in the lizard Anolis cybotes. We establish a direct link between recurrently evolved phenotypes and functional genomics of altitude-related climate adaptation in three highland and lowland populations in the Dominican Republic. We show that across vertebrates, genes contained in this interactome are expressed within the brain and during development. These results are relevant to elucidate the effect of global climate change across vertebrates, and might aid in furthering insight into gene-environment relationships under disturbances to external homeostasis
A Reevaluation of Sexual Dimorphism in the Postcranium of the Chasmosaurine Ceratopsid Chasmosaurus belli (Dinosauria: Ornithischia)
Get PDFThe sexual dimorphism attributed to Chasmosaurus belli by Sternberg (1927) is revisited and reevaluated. A reexamination of the two specimens originally considered by Sternberg reveals that they are less complete than first suggested, with only a moderate amount of overlapping material between them. Only a few of the postcranial elements (humeri, sternal plates, and presacral vertebrae) show evidence of dimorphism, the significance of which is either doubtful or equivocal. Instead of representing sexual dimorphs, it is likely that the two specimens belong to separate species, C. belli and C. russelli, as evidenced by their distinct frill morphologies and by their stratigraphic segregation within the Dinosaur Park Formation of Alberta. These findings emphasize the need to remain sceptical about claims advocating sexual dimorphism in the fossil record in the absence of statistical significance or stratigraphic control
A Review of Salvage Treatment Options for Disease Progression After Radiation Therapy for Localized Prostate Cancer
Get PDFRecurrence of prostate cancer after initial treatment with radiation therapy (RT) is highly dependent on pretreatment risk group and unfortunately, a proportion of patients fail primary treatment. The treatment of recurrence after primary radiation is rapidly changing with advances in imaging and it is important to distinguish those with a local failure from those with distant failure. If disease remains locally confined, salvage treatment with a variety of techniques can still provide a potential cure. Patients with distant failure are often treated with androgen deprivation, or in those with a shorter life expectancy, conservative management. In patients with a higher burden of metastatic disease, there is emerging evidence that chemotherapy and advanced androgen therapy can improve survival. We review the relevant literature on available salvage treatment options and appropriate patient selection for patients with recurrent prostate cancer after RT. We report on the efficacy and adverse effects of the currently available local salvage modalities including salvage radical prostatectomy, high dose rate and low dose rate brachytherapy, cryotherapy, high intensity focused ultrasound, and stereotactic body RT. We additionally discuss diagnosis of oligometastatic disease on imaging and current approaches to treatment with either radiation or surgery. While a full review of chemotherapy and advanced androgen therapies is beyond the scope of this article we briefly discuss their use in the treatment of newly diagnosed recurrence after radiation
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Bars, Nightclubs, and Cancer Prevention: New Approaches to Reduce Young Adult Cigarette Smoking.
Get PDFIntroductionTobacco contributes to multiple cancers, and it is largely preventable. As overall smoking prevalence in California declines, smoking has become concentrated among high-risk groups. Targeting social/cultural groups (i.e., "peer crowds") that share common values, aspirations, and activities in social venues like bars and nightclubs may reach high-risk young adult smokers. Lack of population data on young adult peer crowds limits the ability to assess the potential reach of such interventions.MethodsThis multimodal population-based household survey included young adults residing in San Francisco and Alameda counties. Data were collected in 2014 and analyzed in 2016. Multivariable logistic regressions assessed smoking by sociodemographic factors, attitudes, self-rated health, peer crowd affiliation, and bar/nightclub attendance.ResultsSmoking prevalence was 15.1% overall; 35.3% of respondents sometimes or frequently attended bars. In controlled analyses, bar attendance (AOR=2.13, 95% CI=1.00, 4.53) and binge drinking (AOR=3.17, 95% CI=1.59, 6.32) were associated with greater odds of smoking, as was affiliation with "Hip Hop" (AOR=4.32, 95% CI=1.48, 12.67) and "Country" (AOR=3.13, 95% CI=1.21, 8.09) peer crowds. Multivariable models controlling for demographics estimated a high probability of smoking among bar patrons affiliating with Hip Hop (47%) and Country (52%) peer crowds.ConclusionsBar attendance and affiliation with certain peer crowds confers significantly higher smoking risk. Interventions targeting Hip Hop and Country peer crowds could efficiently reach smokers, and peer crowd-tailored interventions have been associated with decreased smoking and binge drinking. Targeted interventions in bars and nightclubs may be an efficient way to address these cancer risks
Preparation of Brand New Ligand Architectures Incorporating N-Heterocyclic Carbene Complexes with Carboranyl Substituents: Coordination Chemistry, Catalytic Evaluation and Anticancer Properties
Get PDFIn this thesis two very different types of ligand classes are brought together, namely N-heterocyclic carbenes (NHCs) and carboranes. Chapter one discusses the fundamental structure and bonding involved in these two types of compound. An account of the synthetic strategies employed in the literature for the synthesis of NHCs and carboranes, and the techniques employed to coordinate these ligands to various metal centres is discussed.
Chapter two discusses the synthetic strategies explored towards a new hybrid ligand scaffold that fuses N-heterocyclic carbenes (NHCs) and o-carborane. A focal point of this work was to demonstrate the tailorability of this novel ligand system. A detailed account of the techniques employed for the characterisation of these novel ligands is given.
Chapter three discusses the synthetic challenges associated with deprotonation of the zwitterionic ligand precursors reported in Chapter 2. A deprotonation study revealed that the ligand must possess an ethyl linker or longer between the imidazolium and the carborane for a free carbene to be isolated. Subsequent coordination to various metal centres, including titanium, iron and rhodium, is explored.
The synthesis and full characterisation of RhI-NHC complexes that exhibit closo-carboranyl substituents is described in Chapter four. These complexes display unprecedented chemistry with a rare example of a RhI-metallacycle coordinating through both the NHC and the carbon vertex of the carborane. The catalytic activity of these complexes was probed in the hydrosilylation of acetophenone.
Chapter five investigates the application of our NHC-carborane ligands to the higher oxidation states of RhIII and IrIII as well as RuII. We have discovered that the nature of the α-substituent of the NHC, as well as reaction conditions, can determine the vertex at which cyclometallation occurs. A series of IrIII complexes were successfully cyclometallated through the NHC and either a carbon atom or the B3/B6 vertex of the cage. Examination of the Ir complexes in the transfer hydrogenation of acetophenone revealed that cyclometallation through the carborane has a profound effect on the catalytic activity, indicating a bifunctional mechanism and involvement of the carborane moiety.
Chapter six describes the diverse coordination modes of NHC-carborane ligands at AgI. The steric nature of the ligand precursor plays a crucial role in the overall stability and the type of silver complex formed, with the first structurally elucidated example of AgI directly bound through the carborane reported. In addition, a series of carboranyl complexes derived from the natural product theobromine were synthesised. The antiproliferative properties of these complexes against the HCT116 (colon) cancer cell line was evaluated
Frontiers in Fast Voltammetry: Novel Analytes and Applications
Get PDFElectrochemical sensors are beneficial towards the development and advancement of monitoring devices. As this type of technology progresses, so does our ability to create state-of-the-art sensing strategies to probe environmental and biological systems at the source. In the environment, it is essential to monitor particularly harmful contaminants like trace metals in order to better mitigate risk. Additionally, biological molecules are often times challenging to measure because matrices are complex and difficult to probe; Recent advancements in chemical ex vivo and in vivo sensing platforms have offered insight into physiological processes. The brain in particular requires a sophisticated, implantable sensor as biomarkers from the periphery do not reflect brain concentrations. The overarching goal of this dissertation is to develop electrochemical sensing strategies to measure molecules that are chemically elusive in the environment and in the brain using a powerful electrochemical technique called fast-scan cyclic voltammetry (FSCV). FSCV offers selective and sensitive measurements in real-time on an electrode small enough to probe systems without perturbation or eliciting an immune response. While traditionally employed to measure dopamine neurotransmission in vivo, here we expand the scope of FSCV to explore novel analytes and model systems, including those beyond the brain. First, we discuss the significance of on-site, in situ and real-time analysis for trace metal monitoring in dynamic environmental systems. We introduce our approach using ionophore-grafted carbon fiber microelectrodes (CFM) to selectively detect Cu(II) metal ions and characterize the Cu(II)-ionophore grafted CFM interface.
Second, we explore the functionality of human induced pluripotent stem cells derived into serotonin neurons (5-HTNs) in a multifaceted voltammetric and biophysical study, finding that 5-HTNs possess in vivo chemical characteristics. We then investigate the electroactivity of glutamate, a neurotransmitter that is difficult to measure electrochemically, finding that glutamate electropolymerizes forming poly-glutamic acid (PGA) at high potentials and fast scan rates. We characterize the PGA coating and our results suggests that glutamate polymerizes in brain tissue, improving the sensitivity of sensors during in vivo analysis. Finally, we present a sensing strategy for direct, enzyme- free glutamate detection while avoiding polymerization and characterize the analytical performance of the glutamate voltammetric signature. Together, our data showcases the power of FSCV for rapid trace metal monitoring, serotonin detection in 5-HTNs, electropolymerization, and sensing of new and challenging analytes
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