Metabolomic study of the LDL receptor null mouse fed a high-fat diet reveals profound perturbations in choline metabolism that are shared with ApoE null mice

Failure to express or expression of dysfunctional low-density lipoprotein receptors (LDLR) causes familial hypercholesterolemia in humans, a disease characterized by elevated blood cholesterol concentrations, xanthomas, and coronary heart disease, providing compelling evidence that high blood cholesterol concentrations cause atherosclerosis. In this study, we used 1H nuclear magnetic resonance spectroscopy to examine the metabolic profiles of plasma and urine from the LDLR knockout mice. Consistent with previous studies, these mice developed hypercholesterolemia and atherosclerosis when fed a high-fat/cholesterol/cholate-containing diet. In addition, multivariate statistical analysis of the metabolomic data highlighted significant differences in tricarboxylic acid cycle and fatty acid metabolism, as a result of high-fat/cholesterol diet feeding. Our metabolomic study also demonstrates that the effect of high-fat/cholesterol/cholate diet, LDLR gene deficiency, and the diet-genotype interaction caused a significant perturbation in choline metabolism, notably the choline oxidation pathway. Specifically, the loss in the LDLR caused a marked reduction in the urinary excretion of betaine and dimethylglycine, especially when the mice are fed a high-fat/cholesterol/cholate diet. Furthermore, as we demonstrate that these metabolic changes are comparable with those detected in ApoE knockout mice fed the same high-fat/cholesterol/cholate diet they may be useful for monitoring the onset of atherosclerosis across animal models

Complete intersections and mod p cochains

We give homotopy invariant definitions corresponding to three well known properties of complete intersections, for the ring, the module theory and the endomorphisms of the residue field, and we investigate them for the mod p cochains on a space, showing that suitable versions of the second and third are equivalent and that the first is stronger. We are particularly interested in classifying spaces of groups, and we give a number of examples. This paper follows on from arXiv:0906.4025 which considered the classical case of a commutative ring and arXiv:0906.3247 which considered the case of rational homotopy theory.Comment: To appear in AG

The Role of Legal Services in the Antipoverty Program

Large-scale adaptive radiations might explain the runaway success of a minority of extant vertebrate clades. This hypothesis predicts, among other things, rapid rates of morphological evolution during the early history of major groups, as lineages invade disparate ecological niches. However, few studies of adaptive radiation have included deep time data, so the links between extant diversity and major extinct radiations are unclear. The intensively studied Mesozoic dinosaur record provides a model system for such investigation, representing an ecologically diverse group that dominated terrestrial ecosystems for 170 million years. Furthermore, with 10,000 species, extant dinosaurs (birds) are the most speciose living tetrapod clade. We assembled composite trees of 614-622 Mesozoic dinosaurs/birds, and a comprehensive body mass dataset using the scaling relationship of limb bone robustness. Maximum-likelihood modelling and the node height test reveal rapid evolutionary rates and a predominance of rapid shifts among size classes in early (Triassic) dinosaurs. This indicates an early burst niche-filling pattern and contrasts with previous studies that favoured gradualistic rates. Subsequently, rates declined in most lineages, which rarely exploited new ecological niches. However, feathered maniraptoran dinosaurs (including Mesozoic birds) sustained rapid evolution from at least the Middle Jurassic, suggesting that these taxa evaded the effects of niche saturation. This indicates that a long evolutionary history of continuing ecological innovation paved the way for a second great radiation of dinosaurs, in birds. We therefore demonstrate links between the predominantly extinct deep time adaptive radiation of non-avian dinosaurs and the phenomenal diversification of birds, via continuing rapid rates of evolution along the phylogenetic stem lineage. This raises the possibility that the uneven distribution of biodiversity results not just from large-scale extrapolation of the process of adaptive radiation in a few extant clades, but also from the maintenance of evolvability on vast time scales across the history of life, in key lineages

Cape Vulture Gyps coprotheres caught in gin trap

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Using Variable Interval Reinforcement Schedules to Support Students in the Classroom: An Introduction With Illustrative Examples

When behaviors are reinforced with a variable interval reinforcement schedule, reinforcement is available only after an unknown period of time. These types of reinforcement schedules are most useful for reinforcing slow and steady responding and for differentially reinforcing behaviors that are incompatible with some problematic behaviors. This review helps define variable interval reinforcement schedules, uses the example of a strategy to manage thumb-sucking behavior to illustrate the implementation of these schedules, and describes potential applications in school and clinical settings

Functional binding interaction identified between the axonal CAM L1 and members of the ERM family

Ayeast two-hybrid library was screened using the cytoplasmic domain of the axonal cell adhesion molecule L1 to identify binding partners that may be involved in the regulation of L1 function. The intracellular domain of L1 bound to ezrin, a member of the ezrin, radixin, and moesin (ERM) family of membrane–cytoskeleton linking proteins, at a site overlapping that for AP2, a clathrin adaptor. Binding of bacterial fusion proteins confirmed this interaction. To determine whether ERM proteins interact with L1 in vivo, extracellular antibodies to L1 were used to force cluster the protein on cultured hippocampal neurons and PC12 cells, which were then immunolabeled for ERM proteins. Confocal analysis revealed a precise pattern of codistribution between ERMs and L1 clusters in axons and PC12 neurites, whereas ERMs in dendrites and spectrin labeling remained evenly distributed. Transfection of hippocampal neurons grown on an L1 substrate with a dominant negative ERM construct resulted in extensive and abnormal elaboration of membrane protrusions and an increase in axon branching, highlighting the importance of the ERM–actin interaction in axon development. Together, our data indicate that L1 binds directly to members of the ERM family and suggest this association may coordinate aspects of axonal morphogenesis

Electronic Payment Systems: Payment Gateways and Data Security Standards

The use of smartphones, tablets, and laptops allow electronic transactions to be made anytime, anywhere, and by anyone. This version of commerce, known as e-commerce or digital commerce, has become a mainstay in the way consumers shop. Online payments have essentially made cash payment systems virtually obsolete. Also, the Internet has made it possible for businesses to expand their reach across the globe. More importantly, due to the proliferation of social media as a guiding agent for purchasing decisions, e-commerce has evolved into one of the most significant driving forces into how businesses generate revenue (Wong 2018). According to the U.S. Census Bureau (2019), the year’s retail e-commerce sales reached 154.7 billion, and the data indicated that sales would continue to grow. Coexisting with the steady rise of sales is the need for skilled and knowledgeable workers. Torpey (2018) shared a Bureau of Labor and Statistics report which revealed that e-commerce employment is expected to reach approximately 450,000 by 2026. Many of these jobs require advanced knowledge of credit card standards and acceptance procedures. Aligned to these expectations, the purpose of this project was to garner an understanding of payment gateways (PGs) and Payment Card Industry Data Security Standards (PCI-DSS) to develop material to enhance an undergraduate e-commerce curriculum. The outcome of this research will be three-fold. First, it will offer qualitative outcomes on how students and teachers collaborated on gathering appropriate learning material to be used in the classroom. Second, the results of a quantitative student survey, administered near the end of the semester, will provide supporting evidence of the need to add this material into the curriculum. Third, using a scholarly practitioner model, the outcomes will bridge the gap between academia and real-world applications to equip students with the necessary knowledge to enter the workforce

Climate change adaptation, flood risks and policy coherence in integrated water resources management in England

Integrated water resources management (IWRM) assumes coherence between cognate aspects of water governance at the river basin scale, for example water quality, energy production and agriculture objectives. But critics argue that IWRM is often less ‘integrated’ in practice, raising concerns over inter-sectoral coherence between implementing institutions. One increasingly significant aspect of IWRM is adaptation to climate change-related risks, including threats from flooding, which are particularly salient in England. Although multiple institutional mechanisms exist for flood risk management (FRM), their coherence remains a critical question for national adaptation. This paper therefore (1) maps the multi-level institutional frameworks determining both IWRM and FRM in England; (2) examines their interaction via various inter-institutional coordinating mechanisms; and (3) assesses the degree of coherence. The analysis suggests that cognate EU strategic objectives for flood risk assessment demonstrate relatively high vertical and horizontal coherence with river basin planning. However, there is less coherence with flood risk requirements for land-use planning and national flood protection objectives. Overall, this complex governance arrangement actually demonstrates de-coherence over time due to ongoing institutional fragmentation. Recommendations for increasing IWRM coherence in England or re-coherence based on greater spatial planning and coordination of water-use and land-use strategies are proposed