4,065 research outputs found

    The inverse eigenvalue problem for a Hermitian reflexive matrix and the optimization problem

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    The inverse eigenvalue problem and the associated optimal approximation problem for Hermitian reflexive matrices with respect to a normal {k+1}-potent matrix are considered. First, we study the existence of the solutions of the associated inverse eigenvalue problem and present an explicit form for them. Then, when such a solution exists, an expression for the solution to the corresponding optimal approximation problem is obtained

    Dysregulation of glucose metabolism is an early event in sporadic Parkinson's disease

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    AbstractUnlike most other cell types, neurons preferentially metabolize glucose via the pentose phosphate pathway (PPP) to maintain their antioxidant status. Inhibiting the PPP in neuronal cell models causes cell death. In rodents, inhibition of this pathway causes selective dopaminergic cell death leading to motor deficits resembling parkinsonism. Using postmortem human brain tissue, we characterized glucose metabolism via the PPP in sporadic Parkinson's disease (PD), Alzheimer's disease (AD), and controls. AD brains showed increased nicotinamide adenine dinucleotide phosphate (NADPH) production in areas affected by disease. In PD however, increased NADPH production was only seen in the affected areas of late-stage cases. Quantifying PPP NADPH-producing enzymes glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase by enzyme-linked immunosorbent assay, showed a reduction in the putamen of early-stage PD and interestingly in the cerebellum of early and late-stage PD. Importantly, there was no decrease in enzyme levels in the cortex, putamen, or cerebellum of AD. Our results suggest that down-regulation of PPP enzymes and a failure to increase antioxidant reserve is an early event in the pathogenesis of sporadic PD

    Proteomic Analysis of GLUT4 Storage Vesicles Reveals Tumor Suppressor Candidate 5 (TUSC5) as a Novel Regulator of Insulin Action in Adipocytes.

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    Insulin signaling augments glucose transport by regulating glucose transporter 4 (GLUT4) trafficking from specialized intracellular compartments, termed GLUT4 storage vesicles (GSVs), to the plasma membrane. Proteomic analysis of GSVs by mass spectrometry revealed enrichment of 59 proteins in these vesicles. We measured reduced abundance of 23 of these proteins following insulin stimulation and assigned these as high confidence GSV proteins. These included established GSV proteins such as GLUT4 and insulin-responsive aminopeptidase, as well as six proteins not previously reported to be localized to GSVs. Tumor suppressor candidate 5 (TUSC5) was shown to be a novel GSV protein that underwent a 3.7-fold increase in abundance at the plasma membrane in response to insulin. siRNA-mediated knockdown of TUSC5 decreased insulin-stimulated glucose uptake, although overexpression of TUSC5 had the opposite effect, implicating TUSC5 as a positive regulator of insulin-stimulated glucose transport in adipocytes. Incubation of adipocytes with TNFα caused insulin resistance and a concomitant reduction in TUSC5. Consistent with previous studies, peroxisome proliferator-activated receptor (PPAR) γ agonism reversed TNFα-induced insulin resistance. TUSC5 expression was necessary but insufficient for PPARγ-mediated reversal of insulin resistance. These findings functionally link TUSC5 to GLUT4 trafficking, insulin action, insulin resistance, and PPARγ action in the adipocyte. Further studies are required to establish the exact role of TUSC5 in adipocytes

    Addressing the welfare needs of farmed lumpfish: knowledge gaps, challenges and solutions

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    Lumpfish (Cyclopterus lumpus L.) are increasingly being used as cleaner fish to control parasitic sea lice, one of the most important threats to salmon farming. However, lumpfish cannot survive feeding solely on sea lice, and their mortality in salmon net pens can be high, which has welfare, ethical and economic implications. The industry is under increasing pressure to improve the welfare of lumpfish, but little guidance exists on how this can be achieved. We undertook a knowledge gap and prioritisa tion exercise using a Delphi approach with participants from the fish farming sector, animal welfare, academia and regulators to assess consensus on the main challenges and potential solutions for improving lumpfish welfare. Consensus among participants on the utility of 5 behavioural and 12 physical welfare indicators was high (87–89%), reliable (Cronbach's alpha = 0.79, 95CI = 0.69–0.92) and independent of participant background. Participants highlighted fin erosion and body damage as the most use ful and practical operational welfare indicators, and blood parameters and behav ioural indicators as the least practical. Species profiling revealed profound differences between Atlantic salmon and lumpfish in relation to behaviour, habitat preferences, nutritional needs and response to stress, suggesting that applying a common set of welfare standards to both species cohabiting in salmon net-pens may not work well for lumpfish. Our study offers 16 practical solutions for improving the welfare of lumpfish and illustrates the merits of the Delphi approach for achieving consensus among stakeholders on welfare needs, targeting research where is most needed and generating workable solutions.info:eu-repo/semantics/publishedVersio

    Upregulation of the cell-cycle regulator RGC-32 in Epstein-Barr virus-immortalized cells

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    Epstein-Barr virus (EBV) is implicated in the pathogenesis of multiple human tumours of lymphoid and epithelial origin. The virus infects and immortalizes B cells establishing a persistent latent infection characterized by varying patterns of EBV latent gene expression (latency 0, I, II and III). The CDK1 activator, Response Gene to Complement-32 (RGC-32, C13ORF15), is overexpressed in colon, breast and ovarian cancer tissues and we have detected selective high-level RGC-32 protein expression in EBV-immortalized latency III cells. Significantly, we show that overexpression of RGC-32 in B cells is sufficient to disrupt G2 cell-cycle arrest consistent with activation of CDK1, implicating RGC-32 in the EBV transformation process. Surprisingly, RGC-32 mRNA is expressed at high levels in latency I Burkitt's lymphoma (BL) cells and in some EBV-negative BL cell-lines, although RGC-32 protein expression is not detectable. We show that RGC-32 mRNA expression is elevated in latency I cells due to transcriptional activation by high levels of the differentially expressed RUNX1c transcription factor. We found that proteosomal degradation or blocked cytoplasmic export of the RGC-32 message were not responsible for the lack of RGC-32 protein expression in latency I cells. Significantly, analysis of the ribosomal association of the RGC-32 mRNA in latency I and latency III cells revealed that RGC-32 transcripts were associated with multiple ribosomes in both cell-types implicating post-initiation translational repression mechanisms in the block to RGC-32 protein production in latency I cells. In summary, our results are the first to demonstrate RGC-32 protein upregulation in cells transformed by a human tumour virus and to identify post-initiation translational mechanisms as an expression control point for this key cell-cycle regulator

    Ecological Invasion, Roughened Fronts, and a Competitor's Extreme Advance: Integrating Stochastic Spatial-Growth Models

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    Both community ecology and conservation biology seek further understanding of factors governing the advance of an invasive species. We model biological invasion as an individual-based, stochastic process on a two-dimensional landscape. An ecologically superior invader and a resident species compete for space preemptively. Our general model includes the basic contact process and a variant of the Eden model as special cases. We employ the concept of a "roughened" front to quantify effects of discreteness and stochasticity on invasion; we emphasize the probability distribution of the front-runner's relative position. That is, we analyze the location of the most advanced invader as the extreme deviation about the front's mean position. We find that a class of models with different assumptions about neighborhood interactions exhibit universal characteristics. That is, key features of the invasion dynamics span a class of models, independently of locally detailed demographic rules. Our results integrate theories of invasive spatial growth and generate novel hypotheses linking habitat or landscape size (length of the invading front) to invasion velocity, and to the relative position of the most advanced invader.Comment: The original publication is available at www.springerlink.com/content/8528v8563r7u2742

    Characterisation of microvessel blood velocity and segment length in the brain using multi-diffusion-time diffusion-weighted MRI

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    From SAGE Publishing via Jisc Publications RouterHistory: received 2020-05-13, rev-recd 2020-10-24, accepted 2020-10-27, epub 2020-12-16Publication status: PublishedMulti-diffusion-time diffusion-weighted MRI can probe tissue microstructure, but the method has not been widely applied to the microvasculature. At long diffusion-times, blood flow in capillaries is in the diffusive regime, and signal attenuation is dependent on blood velocity (v) and capillary segment length (l). It is described by the pseudo-diffusion coefficient (D*=vl/6) of intravoxel incoherent motion (IVIM). At shorter diffusion-times, blood flow is in the ballistic regime, and signal attenuation depends on v, and not l. In theory, l could be estimated using D* and v. In this study, we compare the accuracy and repeatability of three approaches to estimating v, and therefore l: the IVIM ballistic model, the velocity autocorrelation model, and the ballistic approximation to the velocity autocorrelation model. Twenty-nine rat datasets from two strains were acquired at 7 T, with b-values between 0 and 1000 smm−2 and diffusion times between 11.6 and 50 ms. Five rats were scanned twice to assess scan-rescan repeatability. Measurements of l were validated using corrosion casting and micro-CT imaging. The ballistic approximation of the velocity autocorrelation model had lowest bias relative to corrosion cast estimates of l, and had highest repeatability

    Managed Aquifer Recharge as a Tool to Enhance Sustainable Groundwater Management in California

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    A growing population and an increased demand for water resources have resulted in a global trend of groundwater depletion. Arid and semi-arid climates are particularly susceptible, often relying on groundwater to support large population centers or irrigated agriculture in the absence of sufficient surface water resources. In an effort to increase the security of groundwater resources, managed aquifer recharge (MAR) programs have been developed and implemented globally. MAR is the approach of intentionally harvesting and infiltrating water to recharge depleted aquifer storage. California is a prime example of this growing problem, with three cities that have over a million residents and an agricultural industry that was valued at 47 billion dollars in 2015. The present-day groundwater overdraft of over 100 km3 (since 1962) indicates a clear disparity between surface water supply and water demand within the state. In the face of groundwater overdraft and the anticipated effects of climate change, many new MAR projects are being constructed or investigated throughout California, adding to those that have existed for decades. Some common MAR types utilized in California include injection wells, infiltration basins (also known as spreading basins, percolation basins, or recharge basins), and low-impact development. An emerging MAR type that is actively being investigated is the winter flooding of agricultural fields using existing irrigation infrastructure and excess surface water resources, known as agricultural MAR. California therefore provides an excellent case study to look at the historical use and performance of MAR, ongoing and emerging challenges, novel MAR applications, and the potential for expansion of MAR. Effective MAR projects are an essential tool for increasing groundwater security, both in California and on a global scale. This chapter aims to provide an overview of the most common MAR types and applications within the State of California and neighboring semi-arid regions

    Molecular excitation in the Interstellar Medium: recent advances in collisional, radiative and chemical processes

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    We review the different excitation processes in the interstellar mediumComment: Accepted in Chem. Re
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