Volcanism of the Late Silurian Eastport Formation of the Coastal Volcanic Belt, Passamaquoddy Bay, New Brunswick: GAC–MAC Halifax 2022 Pre-Meeting Field Trip

This field trip is an excursion through the exquisite, nearly pristine exposures of a Silurian, felsic-dominated bimodal volcanic and sedimentary sequence exposed in the Passamaquoddy Bay area of southwestern, New Brunswick (Eastport Formation). These rocks form the northwest extension of the Coastal Volcanic Belt that extends from southwestern New Brunswick to the southern coast of Maine. The sequence is significant because it is part of a large bimodal igneous province with evidence for supervolcano-scale eruptions that began to form during the close of the Salinic Orogeny (about 424 Ma), and continued into the Acadian Orogeny (421–400 Ma). The geochemical characteristic of the rocks can be explained by extension related volcanism but the specific drivers of the extension are uncertain. The Passamaquoddy Bay sequence is 4 km thick and comprises four cycles of basaltic-rhyolitic volcanism. Basaltic volcanism typically precedes rhyolitic volcanism in Cycles 1–3. Cycle 4 represents the waning stages of volcanism and is dominated by peritidal sediments and basaltic volcanics. A spectrum of eruptive and emplacement mechanisms is represented ranging from the Hawaiian and Strombolian-type volcanism of the basaltic flows and pyroclastic scoria deposits, to highly explosive sub-Plinian to Plinian rhyolitic pyroclastic eruptions forming pyroclastic density currents (PDC) and high grade rheomorphic ignimbrites. During this field trip we will examine key exposures illustrating this spectrum of eruptive and emplacement processes, and their diagnostic characteristics, along with evidence for the interaction between mafic and felsic magmas and a variety of peperitic breccias formed as a result of emplacement of flows on wet peritidal sediments. The constraints the depositional setting and voluminous bimodal volcanism places on tectonic models will also be considered.Cette sortie sur le terrain est une excursion à travers les magnifiques affleurements pratiquement non altérés d'une séquence volcanique et sédimentaire bimodale silurienne à dominance felsique exposée dans la région de la baie de Passamaquoddy, au sud-ouest du Nouveau-Brunswick (Formation d'Eastport). Ces roches forment le prolongement nord-ouest de la Ceinture volcanique côtière qui s'étend du sud-ouest du Nouveau-Brunswick à la côte sud du Maine. La séquence est importante car elle fait partie d'une grande province ignée bimodale comprenant des preuves de super éruptions volcaniques qui ont commencé à se former à la fin de l'orogenèse salinique (environ 424 Ma) et se sont poursuivies pendant l'orogenèse acadienne (421–400 Ma). La caractéristique géochimique des roches peut être expliquée par le volcanisme lié à l'extension, mais les facteurs spécifiques de l'extension sont incertains. La séquence de la baie de Passamaquoddy a une épaisseur de 4 km et comprend quatre cycles de volcanisme basaltique-rhyolitique. Le volcanisme basaltique précède généralement le volcanisme rhyolitique dans les cycles 1–3. Le cycle 4 représente les stades décroissants du volcanisme et est dominé par des sédiments péritidaux et des roches volcaniques basaltiques. Une variété de mécanismes éruptifs et de mises en place est représentée, allant du volcanisme de type hawaïen et strombolien des coulées basaltiques et des dépôts de scories pyroclastiques, aux éruptions pyroclastiques rhyolitiques hautement explosives sous-pliniennes à pliniennes formant des courants de densité pyroclastiques et des ignimbrites rhéomorphes à haute teneur. Au cours de cette visite sur le terrain, nous examinerons les affleurements clés illustrant cette gamme de processus éruptifs et de mises en place, et leurs caractéristiques diagnostiques, ainsi que les preuves de l'interaction entre les magmas mafiques et felsiques et une variété de brèches pépéritiques formées à la suite de la mise en place de coulées sur des sédiments péritidaux humides. Les contraintes que le contexte de dépôt et le vaste volcanisme bimodal imposent aux modèles tectoniques seront également examinées

Advance diaspora diplomacy in a networked world

The role of diaspora in cultural exchange, international affairs and in economic development is now well established. What is new is the increasing proliferation of national strategies to harness them actively for public diplomacy. This article addresses the rise of Australia’s only formal, global diaspora network: Advance – Australia’s Global Community which has acted self-consciously to become an instrument of public diplomacy. Emerging from a small base in New York, Advance sought to ‘open doors’ for Australians in the world’s biggest market. Cultivating a strong membership base of well-connected individuals in the arts, commerce and professions, Advance developed its network centrality by building partnerships with state governments, Australian universities and federal government agencies. As an elite organisation of high-profile Australians overseas, Advance has developed into a global organisation communicating Australian culture and economic achievements to both Australian national audiences and foreign constituencies

Identifying gaps and providing recommendations to address shortcomings in the investigation of acne sequelae by the Personalising Acne: Consensus of Experts panel

Background: The physical sequelae of acne include erythema, hyperpigmentation, and scarring, which are highly burdensome for patients. Early, effective treatment can potentially limit and prevent sequelae development, but there is a need for guidance for and evidence of prevention-oriented management to improve patient outcomes. Objective: To identify unmet needs of acne sequelae and generate expert recommendations to address gaps in clinical guidance. Methods: The Personalizing Acne: Consensus of Experts panel of 13 dermatologists used a modified Delphi approach to achieve a consensus on the clinical aspects of acne sequelae. A consensus was defined as ≥75% of the dermatologists voting agree or strongly agree. All voting was electronic and blinded. Results: The panel identified gaps in current guidance and made recommendations related to acne sequelae. These included identification and classification of sequelae, pertinent points to consider for patient consultations, and management aimed at reducing the development of sequelae. Limitations: The recommendations are based on expert opinion and made in the absence of high-quality evidence. Conclusions: The identified gaps should help inform future research and guideline development for acne sequelae. The consensus-based recommendations should also support the process of consultations throughout the patient journey, helping to reduce the development and burden of acne sequelae through improved risk factor recognition, early discussion, and appropriate management

The Personalised Acne Care Pathway-Recommendations to guide longitudinal management from the Personalising Acne: Consensus of Experts

Background: Acne is a chronic disease with a varying presentation that requires long-term management. Despite this, the clinical guidelines for acne offer limited guidance to facilitate personalized or longitudinal management of patients. Objectives: To generate recommendations to support comprehensive, personalized, long-term patient management that address all presentations of acne and its current and potential future burden. Methods: The Personalising Acne: Consensus of Experts panel consisted of 13 dermatologists who used a modified Delphi approach to reach consensus on statements related to longitudinal acne management. The consensus was defined as ≥75% voting agree or strongly agree. All voting was electronic and blinded. Results: Key management domains, consisting of distinct considerations, points to discuss with patients, and pivot points were identified and incorporated into the Personalised Acne Care Pathway. Long-term treatment goals and expectations and risk of (or fears about) sequelae are highlighted as particularly important to discuss frequently with patients. Limitations: Recommendations are based on expert opinion, which could potentially differ from patients\u27 perspectives. Regional variations in health care systems may not have been captured. Conclusions: The Personalised Acne Care Pathway provides practical recommendations to facilitate the longitudinal management of acne, which can be used by health care professionals to optimize and personalize care throughout the patient journey

Dendritic Cells from Lupus-Prone Mice Are Defective in Repressing Immunoglobulin Secretion

Autoimmunity results from a breakdown in tolerance mechanisms that regulate autoreactive lymphocytes. We recently showed that during innate immune responses, secretion of IL-6 by dendritic cells (DCs) maintained autoreactive B cells in an unresponsive state. In this study, we describe that TLR4-activated DCs from lupus-prone mice are defective in repressing autoantibody secretion, coincident with diminished IL-6 secretion. Reduced secretion of IL-6 by MRL/lpr DCs reflected diminished synthesis and failure to sustain IL-6 mRNA production. This occurred coincident with lack of NF-κB and AP-1 DNA binding and failure to sustain IκBα phosphorylation. Analysis of individual mice showed that some animals partially repressed Ig secretion despite reduced levels of IL-6. This suggests that in addition to IL-6, DCs secrete other soluble factor(s) that regulate autoreactive B cells. Collectively, the data show that MRL/lpr mice are defective in DC/IL-6-mediated tolerance, but that some individuals maintain the ability to repress autoantibody secretion by an alternative mechanism. The Journal of Immunology, 2007, 178: 4803–4810

Neurophysiology

Contains research objectives and reports on three research projects.National Aeronautics and Space Administration (Grant NsG-496)U.S. Air Force (Aeronautical Systems Division) under Contract AF33 (616)-7783The Teagle Foundation, Inc.National Institutes of Health (Grant MH-04737-03)National Institutes of Health (Grant NB-04897-01)National Science Foundation (Grant G-16526)Bell Telephone Laboratories, Inc

The spontaneous release of a high-molecular-weight aggregate containing immunoglobulin G from the surface of Ehrlich ascites tumor cells

The spontaneous release of tumor cell antigens from the cell surface into the circulation has been proposed as a mechanism whereby tumors may escape the immune response of the host. In this study we have found that Ehrlich ascites tumor cells after removal from the host (mouse) spontaneously release significant amounts of cell surface components during incubation for 1 h in cold isotonic buffer. Immunodiffusion studies revealed that immunoglobulin G (IgG) and a complement component (C3) are included in this spontaneously released material. These surface-bound humoral immune components are apparently released in the form of a high-molecular-weight aggregate (cell coat particle) as shown by ultracentrifugation and ultrafiltration experiments. Precipitation of IgG from the cell coat particle preparation with antibodies directed against mouse IgG followed by detergent gel electrophoresis of the immune precipitate revealed five major bands in addition to the heavy and light chains of IgG. These results suggest that host IgG is tightly bound to several other components at the cell surface, perhaps in the form of immune complexes. IgG is localized on the tumor cell surface in a highly heterogeneous pattern with the appearance of patches and caps in some cells as shown by immuno-fluorescence analysis. The possibility that humoral immune components bind to the tumor cell surface and result in the shedding of high-molecular-weight aggregates of cell surface antigens into extracellular fluids is discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/38207/1/400090311_ftp.pd

A practical drug discovery project at the undergraduate level

A practical drug discovery project for third-year undergraduates is described. No previous knowledge of medicinal chemistry is assumed. Initial lecture-workshops cover the basic principles; then students are asked to improve the profile of a weakly potent, poorly soluble PI3K inhibitor (1). Compound array design, molecular modelling and screening data analysis are followed by laboratory work in which each student, as part of a team, attempts to synthesise at least two target compounds. The project benefits from significant industrial support, including lectures, student mentoring and consumables. The aim is to make the learning experience as close as possible to real-life industrial situations. Forty-eight target compounds have been prepared, the best of which (5b, 5j, 6b and 6ap) improved the potency and aqueous solubility of the lead compound (1) by 100-1000 fold and 10-fold, respectively

\u3ci\u3eFundulus\u3c/i\u3e as the premier teleost model in environmental biology: Opportunities for new insights using genomics

A strong foundation of basic and applied research documents that the estuarine fish Fundulus heteroclitus and related species are unique laboratory and field models for understanding how individuals and populations interact with their environment. In this paper we summarize an extensive body of work examining the adaptive responses of Fundulus species to environmental conditions, and describe how this research has contributed importantly to our understanding of physiology, gene regulation, toxicology, and ecological and evolutionary genetics of teleosts and other vertebrates. These explorations have reached a critical juncture at which advancement is hindered by the lack of genomic resources for these species. We suggest that a more complete genomics toolbox for F. heteroclitus and related species will permit researchers to exploit the power of this model organism to rapidly advance our understanding of fundamental biological and pathological mechanisms among vertebrates, as well as ecological strategies and evolutionary processes common to all living organisms

Lovastatin Inhibits VEGFR and AKT Activation: Synergistic Cytotoxicity in Combination with VEGFR Inhibitors

BACKGROUND: In a recent study, we demonstrated the ability of lovastatin, a potent inhibitor of mevalonate synthesis, to inhibit the function of the epidermal growth factor receptor (EGFR). Lovastatin attenuated ligand-induced receptor activation and downstream signaling through the PI3K/AKT pathway. Combining lovastatin with gefitinib, a potent EGFR inhibitor, induced synergistic cytotoxicity in a variety of tumor derived cell lines. The vascular endothelial growth factor receptor (VEGFR) and EGFR share similar activation, internalization and downstream signaling characteristics. METHODOLOGY/PRINCIPAL FINDINGS: The VEGFRs, particularly VEGFR-2 (KDR, Flt-1), play important roles in regulating tumor angiogenesis by promoting endothelial cell proliferation, survival and migration. Certain tumors, such as malignant mesothelioma (MM), also express both the VEGF ligand and VEGFRs that act in an autocrine loop to directly stimulate tumor cell growth and survival. In this study, we have shown that lovastatin inhibits ligand-induced VEGFR-2 activation through inhibition of receptor internalization and also inhibits VEGF activation of AKT in human umbilical vein endothelial cells (HUVEC) and H28 MM cells employing immunofluorescence and Western blotting. Combinations of lovastatin and a VEGFR-2 inhibitor showed more robust AKT inhibition than either agent alone in the H28 MM cell line. Furthermore, combining 5 µM lovastatin treatment, a therapeutically relevant dose, with two different VEGFR-2 inhibitors in HUVEC and the H28 and H2052 mesothelioma derived cell lines demonstrated synergistic cytotoxicity as demonstrated by MTT cell viability and flow cytometric analyses. CONCLUSIONS/SIGNIFICANCE: These results highlight a novel mechanism by which lovastatin can regulate VEGFR-2 function and a potential therapeutic approach for MM through combining statins with VEGFR-2 inhibitors