The Response of a Biocompatible Liquid Crystal to Ions and Chemistry on Nanostructured Surfaces

Traditional lyotropic liquid crystals are composed of amphiphilic molecules forming assemblies in water. Disodium cromoglycate (cromolyn or DSCG) – an antiasthmatic drug – is a novel and unusual lyotropic liquid crystal because it is not amphiphilic, and yet, it exhibits large birefringence (shininess) when dissolved in water forming lyotropic liquid crystal. In the work, DSCG liquid crystal is doped with different types of salt such as sodium chloride and sodium perchlorate, and the response in the changes of birefringence and liquid crystal transition temperature is studied. We find that addition of certain type of salts enhance the propensity of formation of liquid crystal phase of DSCG, whereas other type inhibit the formation of liquid crystal. This discovery is pleasantly perplexing because it contradicts the general observation that addition of salt often disrupts the tendency of structure formation – for example, spreading salt in the winter time to help melt the ice on the roadway. In another effort to control the structural organization of the molecules within this liquid crystal phase – so-called liquid crystal orientation, I synthesized oligo-ethylene glycol (OEG)-terminated alkanethiols and overlay them to form self-assembled monolayers (SAM) on a nanostructured gold film. We use this unique combination of chemistry and surface nanotopography to control the liquid crystal orientation. The hypothesis, promising results and interpretation will be presented. Because of DSCG is an antiasthmatic drug and has been shown not to denature protein folding at the concentrations that give rise to liquid crystal phases, this work imparts both fundamental understanding of a novel liquid crystal and explore application of detecting presence of toxic ions and protein binding event

Learning to Count

Through this thesis, I describe my field placement at Health Protection NSW (HPNSW) in fulfilment of the requirements of the Master of Philosophy in Applied Epidemiology (MAE). After spending much of my first year in COVID-19 pandemic response activities, the second year of my MAE was mainly based in the Communicable Diseases Branch (CDB) of HPNSW, as a member of the team responding to other notifiable conditions in NSW. My epidemiological study project focuses on these other notifiable conditions. In this project, I reviewed the surveillance data for a range of notifiable conditions, for changes in the epidemiology that may be attributable to the events of 2020, particularly the restriction of international travel. The findings showed a decrease in the incidence of most travel-related notifiable conditions in NSW, with the notable exception of tuberculosis. In light of the lifting of travel restrictions in late 2021, these findings were presented to a range of HPNSW staff, to inform planning for future surveillance strategies in NSW. My data analysis project was driven by the Environmental Health Branch of HPNSW, but with extensive input from both CDB and the medical entomologists at the Institute of Clinical Pathology and Medical Research (ICPMR), the state arboviral reference laboratory. I reviewed the last decade of data from the NSW Arbovirus Surveillance and Mosquito Monitoring Program (ASMMP), and the corresponding human notification data for Ross River virus (RRV) and Barmah Forest virus (BFV) infections. I attended a laboratory visit to the ICPMR Medical Entomology Laboratory, and a field visit to a mosquito trapping site at Sydney Olympic Park. I also assisted with the weekly EHB reporting of ASMMP data. In CDB, I was the main contact person for vector-borne diseases for the latter half of 2021. All these activities enabled me to ground the design and analysis of these data in real world context. The findings of the project, and recommendations for the ASMMP derived from these findings, were presented to stakeholders. These finding supported the continued use of trapped mosquito counts to inform human RRV and BFV risk, and indicated that in future analyses, it could be useful to include a time lag between mosquito numbers and human notifications, which had not previously been attempted in the analysis of these data in NSW. (Please see attached under "Table of Contents" for the rest of the abstract - due to technological issues, only some of the text would load here

The Nairobi Summit and Reproductive Justice: Unmet Needs for People with Infertility.

The Nairobi Summit, held in November 2019 and convened by the United Nations Fund for Population Activities, claims to have represented "all nations and peoples, and all segments" of society during its high-level conference. The overall aim of the summit was to mobilize political will and financial commitments that are urgently needed to "finally and fully" implement the 1994 International Conference on Population and Development (ICPD) Program of Action. Despite the recommendation by ICPD to incorporate infertility care in reproductive health services, the new Nairobi Statement largely neglects the topic of infertility. This is particularly troublesome as infertility is a global health problem affecting between 52.6 and 72.4 million couples worldwide, with a high prevalence in low- and middle-income settings. For many people around the world, infertility constitutes an emotional, social, and financial burden, yet appropriate services directed toward preventing and addressing infertility are often inaccessible, unaffordable, or nonexistent. With the impetus of a wider reproductive justice community, we call for the integration of infertility into global reproductive health research and practice, urging policy makers, practitioners, researchers, activists, and funders worldwide to bring focused attention to addressing challenges posed by a lack of safe, effective, and dignified fertility management among those in need

Angiotensin II Facilitates Breast Cancer Cell Migration and Metastasis

Breast cancer metastasis is a leading cause of death by malignancy in women worldwide. Efforts are being made to further characterize the rate-limiting steps of cancer metastasis, i.e. extravasation of circulating tumor cells and colonization of secondary organs. In this study, we investigated whether angiotensin II, a major vasoactive peptide both produced locally and released in the bloodstream, may trigger activating signals that contribute to cancer cell extravasation and metastasis. We used an experimental in vivo model of cancer metastasis in which bioluminescent breast tumor cells (D3H2LN) were injected intra-cardiacally into nude mice in order to recapitulate the late and essential steps of metastatic dissemination. Real-time intravital imaging studies revealed that angiotensin II accelerates the formation of metastatic foci at secondary sites. Pre-treatment of cancer cells with the peptide increases the number of mice with metastases, as well as the number and size of metastases per mouse. In vitro, angiotensin II contributes to each sequential step of cancer metastasis by promoting cancer cell adhesion to endothelial cells, trans-endothelial migration and tumor cell migration across extracellular matrix. At the molecular level, a total of 102 genes differentially expressed following angiotensin II pre-treatment were identified by comparative DNA microarray. Angiotensin II regulates two groups of connected genes related to its precursor angiotensinogen. Among those, up-regulated MMP2/MMP9 and ICAM1 stand at the crossroad of a network of genes involved in cell adhesion, migration and invasion. Our data suggest that targeting angiotensin II production or action may represent a valuable therapeutic option to prevent metastatic progression of invasive breast tumors

Genetic Drivers of Heterogeneity in Type 2 Diabetes Pathophysiology

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P \u3c 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care

Genetic drivers of heterogeneity in type 2 diabetes pathophysiology

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P &lt; 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care.</p

The trans-ancestral genomic architecture of glycemic traits

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 x 10(-8)), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution. A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.Peer reviewe

Harnessing the NEON data revolution to advance open environmental science with a diverse and data-capable community

It is a critical time to reflect on the National Ecological Observatory Network (NEON) science to date as well as envision what research can be done right now with NEON (and other) data and what training is needed to enable a diverse user community. NEON became fully operational in May 2019 and has pivoted from planning and construction to operation and maintenance. In this overview, the history of and foundational thinking around NEON are discussed. A framework of open science is described with a discussion of how NEON can be situated as part of a larger data constellation—across existing networks and different suites of ecological measurements and sensors. Next, a synthesis of early NEON science, based on >100 existing publications, funded proposal efforts, and emergent science at the very first NEON Science Summit (hosted by Earth Lab at the University of Colorado Boulder in October 2019) is provided. Key questions that the ecology community will address with NEON data in the next 10 yr are outlined, from understanding drivers of biodiversity across spatial and temporal scales to defining complex feedback mechanisms in human–environmental systems. Last, the essential elements needed to engage and support a diverse and inclusive NEON user community are highlighted: training resources and tools that are openly available, funding for broad community engagement initiatives, and a mechanism to share and advertise those opportunities. NEON users require both the skills to work with NEON data and the ecological or environmental science domain knowledge to understand and interpret them. This paper synthesizes early directions in the community’s use of NEON data, and opportunities for the next 10 yr of NEON operations in emergent science themes, open science best practices, education and training, and community building

Gastrointestinal impactions in backyard poultry.

In contrast to conventional commercial poultry, which are raised primarily in controlled indoor environments, backyard poultry are typically raised in less restricted settings, potentially exposing them to a greater variety of ingestible substances, including multiple types of forage. Consequently, problems such as gastrointestinal impactions caused by ingesta have been noted in backyard poultry. To determine the prevalence of these impactions in backyard poultry, we performed a retrospective database search for autopsy submissions to the California Animal Health and Food Safety laboratory system and found that gastrointestinal impaction was associated with the death of 42 backyard poultry cases (40 chickens, 1 turkey, and 1 goose) from January 2013 to July 2018. In 32 of these 42 (76%) cases, the impaction was caused by fibrous plant material, 7 (17%) by compacted feed, and 3 (7%) by miscellaneous ingesta (tortilla, plastic, and wood shavings). The large proportion of grass impactions indicate that foraging is the predominant source of impaction material in backyard poultry, and that long grasses may be a significant health hazard for poultry. Backyard, pasture-raised, and free-range poultry producers are advised to maintain short pastures, avoid feeds that may expand in the gastrointestinal tract, and provide adequate grit to prevent impactions

Assessment of Prevalence and Diversity of Antimicrobial Resistant <i>Escherichia coli</i> from Retail Meats in Southern California

Retail meat products may serve as reservoirs and conduits for antimicrobial resistance, which is frequently monitored using Escherichia coli as indicator bacteria. In this study, E. coli isolation was conducted on 221 retail meat samples (56 chicken, 54 ground turkey, 55 ground beef, and 56 pork chops) collected over a one-year period from grocery stores in southern California. The overall prevalence of E. coli in retail meat samples was 47.51% (105/221), with E. coli contamination found to be significantly associated with meat type and season of sampling. From antimicrobial susceptibility testing, 51 isolates (48.57%) were susceptible to all antimicrobials tested, 54 (51.34%) were resistant to at least 1 drug, 39 (37.14%) to 2 or more drugs, and 21 (20.00%) to 3 or more drugs. Resistance to ampicillin, gentamicin, streptomycin, and tetracycline were significantly associated with meat type, with poultry counterparts (chicken or ground turkey) exhibiting higher odds for resistance to these drugs compared to non-poultry meats (beef and pork). From the 52 E. coli isolates selected to undergo whole-genome sequencing (WGS), 27 antimicrobial resistance genes (ARGs) were identified and predicted phenotypic AMR profiles with an overall sensitivity and specificity of 93.33% and 99.84%, respectively. Clustering assessment and co-occurrence networks revealed that the genomic AMR determinants of E. coli from retail meat were highly heterogeneous, with a sparsity of shared gene networks