Malondialdehyde Acetaldehyde Adducts (MAA-Adducts) Direct Distinctive Pro-Inflammatory Responses in Endothelial and Macrophage Cell Lines

Chronic inflammation plays a critical role in the pathogenesis of atherosclerosis. At present, the mechanism(s) by which inflammation contributes to this disease isnot entirely understood. Inflammation is known to induce oxidative stress, of which one consequence is lipid peroxidation. This process leads to the production of malondialdehyde (MDA), which can subsequently break down to form acetaldehyde (AA). These two aldehyde by-products can covalently interact with the ε-amino group of lysineswithin proteins and lipoproteins leading to the formation of highly immunogenic malondialdehyde-acetaldehyde adducts (MAA-adducts). The aim of this study was to determine the in-vitro cytokine response of endothelial cells and macrophages treated with MAA-modified human serum albumin (HSA-MAA) and low-density lipoprotein (LDL-MAA). In addition, cells isolated from mice with exposure to MAA and high fat diets were stained and imaged for uptake of the modified macromolecules of interest. We found that exposure of endothelial cells resulted in increased expression of IL-6, TNF-α, ICAM-1, VCAM-1, and MCP-1 in response to incubation with HSA-MAA; whereas, the same treatment of macrophages resulted in increased expression of IL-6, TNF-α, and IL-1b. LDL-MAA incubationresulted in increased TNF-α expression in macrophages, but MCP-1 was elevated in endothelial cells. Interestingly, the quantitative and qualitative uptake of triglycerides was increased in both endothelial and macrophage cells when exposed to LDL-MAA compared to LDL alone. The results of these studies demonstrate that different MAA-adducts elicit unique responses in different cell types. Additionally, the presence of MAA appears to modulate the cells leading to increased uptake of triglycerides and further progression of the inflammatory response.https://digitalcommons.unmc.edu/emet_posters/1003/thumbnail.jp

Medical Student Engagement in a Virtual Learning Environment Positively Correlates with Course Performance and Satisfaction in Psychiatry

This article is made available for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.Introduction There has been a move to a “flipped classroom” (FC) in medical education. The FC promotes active learning and utilizes independent preparation prior to in-class sessions. Few studies have evaluated the effectiveness of the FC approach in medical education, specifically via virtual learning. The purpose of this study evaluates student and faculty perceptions of the FC approach and relationships between student engagement and performance. Method The first-year medical student psychiatry curriculum was redesigned with an FC approach and subsequently altered by COVID-19 to a virtual learning environment. A mixed-method approach was used to examine both qualitative assessment and quantitative performance data. Students and facilitators were invited to participate in surveys regarding the curriculum changes. Student performance data was collected via quizzes and examinations. Engagement was evaluated by student participation in National Board of Medical Examiners–style multiple-choice questions delivered via Top Hat®. Correlational analyses were used to evaluate associations between engagement and performance. T-tests were used to compare student satisfaction across 2019 and 2020. Results Performance on in-class questions was positively associated with class rank and performance (p < 0.005). More students were either satisfied or strongly satisfied (91.5%) in 2020 compared to 85.7% in 2019 (two-tailed t-test, p = 0.04). Most students (81.3%) preferred in-class questions to lectures. In 2020, 62.6% of student comments were positive regarding the psychiatry curriculum vs 33.3% in 2019. Over 61.5% of facilitators felt positive towards the changes. Conclusion Our results demonstrate a positive relationship between engagement and class performance. Students and facilitators positively perceived the approach, with students preferring in-class questions compared to lectures. Future research should evaluate overall performance on standardized tests, third-year clerkships, and number of students matching into psychiatry

Bending the curve of global freshwater biodiversity loss: an emergency recovery plan

Despite their limited spatial extent, freshwater ecosystems host remarkable biodiversity, including one-third of all vertebrate species. This biodiversity is declining dramatically: Globally, wetlands are vanishing three times faster than forests, and freshwater vertebrate populations have fallen more than twice as steeply as terrestrial or marine populations. Threats to freshwater biodiversity are well documented but coordinated action to reverse the decline is lacking. We present an Emergency Recovery Plan to bend the curve of freshwater biodiversity loss. Priority actions include accelerating implementation of environmental flows; improving water quality; protecting and restoring critical habitats; managing the exploitation of freshwater ecosystem resources, especially species and riverine aggregates; preventing and controlling nonnative species invasions; and safeguarding and restoring river connectivity. We recommend adjustments to targets and indicators for the Convention on Biological Diversity and the Sustainable Development Goals and roles for national and international state and nonstate actors

Identification of Synaptic Targets of Drosophila Pumilio

Drosophila Pumilio (Pum) protein is a translational regulator involved in embryonic patterning and germline development. Recent findings demonstrate that Pum also plays an important role in the nervous system, both at the neuromuscular junction (NMJ) and in long-term memory formation. In neurons, Pum appears to play a role in homeostatic control of excitability via down regulation of para, a voltage gated sodium channel, and may more generally modulate local protein synthesis in neurons via translational repression of eIF-4E. Aside from these, the biologically relevant targets of Pum in the nervous system remain largely unknown. We hypothesized that Pum might play a role in regulating the local translation underlying synapse-specific modifications during memory formation. To identify relevant translational targets, we used an informatics approach to predict Pum targets among mRNAs whose products have synaptic localization. We then used both in vitro binding and two in vivo assays to functionally confirm the fidelity of this informatics screening method. We find that Pum strongly and specifically binds to RNA sequences in the 3′UTR of four of the predicted target genes, demonstrating the validity of our method. We then demonstrate that one of these predicted target sequences, in the 3′UTR of discs large (dlg1), the Drosophila PSD95 ortholog, can functionally substitute for a canonical NRE (Nanos response element) in vivo in a heterologous functional assay. Finally, we show that the endogenous dlg1 mRNA can be regulated by Pumilio in a neuronal context, the adult mushroom bodies (MB), which is an anatomical site of memory storage

A global agenda for advancing freshwater biodiversity research

Global freshwater biodiversity is declining dramatically, and meeting the challenges of this crisis requires bold goals and the mobilisation of substantial resources. While the reasons are varied, investments in both research and conservation of freshwater biodiversity lag far behind those in the terrestrial and marine realms. Inspired by a global consultation, we identify 15 pressing priority needs, grouped into five research areas, in an effort to support informed stewardship of freshwater biodiversity. The proposed agenda aims to advance freshwater biodiversity research globally as a critical step in improving coordinated actions towards its sustainable management and conservation

A global agenda for advancing freshwater biodiversity research

Global freshwater biodiversity is declining dramatically, and meeting the challenges of this crisis requires bold goals and the mobilisation of substantial resources. While the reasons are varied, investments in both research and conservation of freshwater biodiversity lag far behind those in the terrestrial and marine realms. Inspired by a global consultation, we identify 15 pressing priority needs, grouped into five research areas, in an effort to support informed stewardship of freshwater biodiversity. The proposed agenda aims to advance freshwater biodiversity research globally as a critical step in improving coordinated actions towards its sustainable management and conservation.Peer reviewe

Accelerating environmental flow implementation to bend the curve of global freshwater biodiversity loss

Environmental flows (e-flows) aim to mitigate the threat of altered hydrological regimes in river systems and connected waterbodies and are an important component of integrated strategies to address multiple threats to freshwater biodiversity. Expanding and accelerating implementation of e-flows can support river conservation and help to restore the biodiversity and resilience of hydrologically altered and water-stressed rivers and connected freshwater ecosystems. While there have been significant developments in e-flow science, assessment, and societal acceptance, implementation of e-flows within water resource management has been slower than required and geographically uneven. This review explores critical factors that enable successful e-flow implementation and biodiversity outcomes in particular, drawing on 13 case studies and the literature. It presents e-flow implementation as an adaptive management cycle enabled by 10 factors: legislation and governance, financial and human resourcing, stakeholder engagement and co-production of knowledge, collaborative monitoring of ecological and social-economic outcomes, capacity training and research, exploration of trade-offs among water users, removing or retrofitting water infrastructure to facilitate e-flows and connectivity, and adaptation to climate change. Recognising that there may be barriers and limitations to the full and effective enablement of each factor, the authors have identified corresponding options and generalizable recommendations for actions to overcome prominent constraints, drawing on the case studies and wider literature. The urgency of addressing flow-related freshwater biodiversity loss demands collaborative networks to train and empower a new generation of e-flow practitioners equipped with the latest tools and insights to lead adaptive environmental water management globally. Mainstreaming e-flows within conservation planning, integrated water resource management, river restoration strategies, and adaptations to climate change is imperative. The policy drivers and associated funding commitments of the Kunming–Montreal Global Biodiversity Framework offer crucial opportunities to achieve the human benefits contributed by e-flows as nature-based solutions, such as flood risk management, floodplain fisheries restoration, and increased river resilience to climate change

The Double-stranded RNA–dependent Protein Kinase Differentially Regulates Insulin Receptor Substrates 1 and 2 in HepG2 Cells

The RNA-dependent protein kinase (PKR), initially known as a virus infection response protein, is found to differentially regulate two major players in the insulin signaling pathway, IRS1 and IRS2. PKR up-regulates the inhibitory phosphorylation of IRS1 and the expression of IRS2 at the transcriptional level

Estrogen/Estrogen Receptor Alpha Signaling in Mouse Posterofrontal Cranial Suture Fusion

BACKGROUND: While premature suture fusion, or craniosynostosis, is a relatively common condition, the cause is often unknown. Estrogens are associated with growth plate fusion of endochondral bones. In the following study, we explore the previously unknown significance of estrogen/estrogen receptor signaling in cranial suture biology. METHODOLOGY/PRINCIPAL FINDINGS: Firstly, estrogen receptor (ER) expression was examined in physiologically fusing (posterofrontal) and patent (sagittal) mouse cranial sutures by quantitative RT-PCR. Next, the cranial suture phenotype of ER alpha and ER beta knockout (alphaERKO, betaERKO) mice was studied. Subsequently, mouse suture-derived mesenchymal cells (SMCs) were isolated; the effects of 17-beta estradiol or the estrogen antagonist Fulvestrant on gene expression, osteogenic and chondrogenic differentiation were examined in vitro. Finally, in vivo experiments were performed in which Fulvestrant was administered subcutaneously to the mouse calvaria. Results showed that increased ERalpha but not ERbeta transcript abundance temporally coincided with posterofrontal suture fusion. The alphaERKO but not betaERKO mouse exhibited delayed posterofrontal suture fusion. In vitro, addition of 17-beta estradiol enhanced both osteogenic and chondrogenic differentiation in suture-derived mesenchymal cells, effects reversible by Fulvestrant. Finally, in vivo application of Fulvestrant significantly diminished calvarial osteogenesis, inhibiting suture fusion. CONCLUSIONS/SIGNIFICANCE: Estrogen signaling through ERalpha but not ERbeta is associated with and necessary for normal mouse posterofrontal suture fusion. In vitro studies suggest that estrogens may play a role in osteoblast and/or chondrocyte differentiation within the cranial suture complex

Community harvesting of trees used as dens and for food by the tree hyrax (Dendrohyrax arboreus) in the Pirie forest, South Africa

CITATION: Opperman, E. J., Cherry, M. I. & Makunga, N. P. 2018. Community harvesting of trees used as dens and for food by the tree hyrax (Dendrohyrax arboreus) in the Pirie forest, South Africa. Koedoe, 60(1):a1481, doi:10.4102/koedoe.v60i1.1481.The original publication is available at https://koedoe.co.zaPublication of this article was funded by the Stellenbosch University Open Access Fund.Forests in South Africa are harvested by local communities for multiple purposes and this affects the animals that inhabit them. The tree hyrax (Dendrohyrax arboreus) has a restricted distribution and utilises various tree species as dens and a source of food. In this article, we determined, through a series of interviews in the communities surrounding the Pirie forest, which plant species are harvested by local people and whether these overlap with those used by the tree hyrax. In addition, we determined the extent to which tree hyraxes are hunted by these communities. Of the trees used by the hyrax as dens in the Pirie forest, Afrocarpus falcatus, Schotia latifolia, Andrachne ovalis, Teclea natalensis and Apodytes dimidiata are important resources for local communities. But as these are harvested at relatively low levels, it is unlikely that current harvesting has a large impact on the tree hyrax. Opportunistic hunting occurs, but the hyrax is not targeted by hunters. Very limited commercial harvesting of A. falcatus has been taking place in the Pirie forest since 1975, but its impact on the hyrax population, although undetermined, is also unlikely to be high. We recommend that the Pirie forest tree hyrax population should be monitored by forest management in order to ascertain the impact of both commercial and community harvesting over the past quarter-century.https://koedoe.co.za/index.php/koedoe/article/view/1481Publisher's versio