MuSCA: A multi-scale source-sink carbon allocation model to explore carbon allocation in plants. An application to static apple tree structures

Background and aims: Carbon allocation in plants is usually represented at a topological scale, specific to each model. This makes the results obtained with different models, and the impact of their scales of representation, difficult to compare. In this study, we developed a multi-scale carbon allocation model (MuSCA) that allows the use of different, user-defined, topological scales of a plant, and assessment of the impact of each spatial scale on simulated results and computation time. Methods: Model multi-scale consistency and behaviour were tested on three realistic apple tree structures. Carbon allocation was computed at five scales, spanning from the metamer (the finest scale, used as a reference) up to first-order branches, and for different values of a sap friction coefficient. Fruit dry mass increments were compared across spatial scales and with field data. Key Results: The model was able to represent effects of competition for carbon assimilates on fruit growth. Intermediate friction parameter values provided results that best fitted field data. Fruit growth simulated at the metamer scale differed of ~1 % in respect to results obtained at growth unit scale and up to 60 % in respect to first order branch and fruiting unit scales. Generally, the coarser the spatial scale the more predicted fruit growth diverged from the reference. Coherence in fruit growth across scales was also differentially impacted, depending on the tree structure considered. Decreasing the topological resolution reduced computation time by up to four orders of magnitude. Conclusions: MuSCA revealed that the topological scale has a major influence on the simulation of carbon allocation. This suggests that the scale should be a factor that is carefully evaluated when using a carbon allocation model, or when comparing results produced by different models. Finally, with MuSCA, trade-off between computation time and prediction accuracy can be evaluated by changing topological scales

A Multi-Scale Model to explore Carbon Allocation in Plants

International audienceUnderstanding and simulating carbon allocation in plants is necessary to distribute carbohydrates among growing and competing organs and to predict plant growth and structure development in relation to climatic conditions. In this context several carbon allocation models have been developed but no clear consensus exists on (i) the most appropriate topological scale (organ, metamer, compartment...) to represent this process on complex plant structures, (ii) the importance of distances between organs in carbon transport, (iii) the priorities in carbon allocation among plant parts, that can depend on growth stages. Multi-scale tree graph (MTG) is a formalism allowing the representation of geometry and topology of a tree structure at different scales. In this study, several models were implemented to compute carbon allocation at user-defined spatial scales by using the MTG formalism. This allows multiple scales (e.g. metamer, growing unit, branch) to be combined during the computation of carbon allocation (e.g. allocation first within leafy shoots at metamer scale and then between growing units). The model describes carbon transport, taking into account the distances between sources and sinks, the strength of the sinks and the available carbohydrates, following the equations of the SIMWAL and QualiTree models. Simulations on simplified branching structures, represented at different scales, showed how the scales chosen to represent the system influence the results of predicted carbon allocation. This modelling approach will be first applied to apple tree to analyze the impact of the scale of representation (branch, growth unit, metamer, and inflorescence) on the predicted fruit growth variability which, in turn, will be compared with field observations. The present work is available through the OpenAlea platform and provides existing Functional Structural Plant Models with a new generic model to simulate carbon allocation in plants depending on user-defined biological hypotheses, such as the choice of the scale of representation or the effect of distance

A Digital Atlas to Characterize the Mouse Brain Transcriptome

Massive amounts of data are being generated in an effort to represent for the brain the expression of all genes at cellular resolution. Critical to exploiting this effort is the ability to place these data into a common frame of reference. Here we have developed a computational method for annotating gene expression patterns in the context of a digital atlas to facilitate custom user queries and comparisons of this type of data. This procedure has been applied to 200 genes in the postnatal mouse brain. As an illustration of utility, we identify candidate genes that may be related to Parkinson disease by using the expression of a dopamine transporter in the substantia nigra as a search query pattern. In addition, we discover that transcription factor Rorb is down-regulated in the barrelless mutant relative to control mice by quantitative comparison of expression patterns in layer IV somatosensory cortex. The semi-automated annotation method developed here is applicable to a broad spectrum of complex tissues and data modalities

Elevated expression of the chemokine-scavenging receptor D6 is associated with impaired lesion development in psoriasis

D6 is a scavenging-receptor for inflammatory CC chemokines that are essential for resolution of inflammatory responses in mice. Here, we demonstrate that D6 plays a central role in controlling cutaneous inflammation, and that D6 deficiency is associated with development of a psoriasis-like pathology in response to varied inflammatory stimuli in mice. Examination of D6 expression in human psoriatic skin revealed markedly elevated expression in both the epidermis and lymphatic endothelium in "uninvolved" psoriatic skin (ie, skin that was more than 8 cm distant from psoriatic plaques). Notably, this increased D6 expression is associated with elevated inflammatory chemokine expression, but an absence of plaque development, in uninvolved skin. Along with our previous observations of the ability of epidermally expressed transgenic D6 to impair cutaneous inflammatory responses, our data support a role for elevated D6 levels in suppressing inflammatory chemokine action and lesion development in uninvolved psoriatic skin. D6 expression consistently dropped in perilesional and lesional skin, coincident with development of psoriatic plaques. D6 expression in uninvolved skin also was reduced after trauma, indicative of a role for trauma-mediated reduction in D6 expression in triggering lesion development. Importantly, D6 is also elevated in peripheral blood leukocytes in psoriatic patients, indicating that upregulation may be a general protective response to inflammation. Together our data demonstrate a novel role for D6 as a regulator of the transition from uninvolved to lesional skin in psoriasis

Last Men Standing: Chlamydatus Portraits and Public Life in Late Antique Corinth

Notable among the marble sculptures excavated at Corinth are seven portraits of men wearing the long chlamys of Late Antique imperial office. This unusual costume, contemporary portrait heads, and inscribed statue bases all help confirm that new public statuary was created and erected at Corinth during the 4th and 5th centuries. These chlamydatus portraits, published together here for the first time, are likely to represent the Governor of Achaia in his capital city, in the company of local benefactors. Among the last works of the ancient sculptural tradition, they form a valuable source of information on public life in Late Antique Corinth

Framing the Issues: Moral Distress in Health Care

Moral distress in health care has been identified as a growing concern and a focus of research in nursing and health care for almost three decades. Researchers and theorists have argued that moral distress has both short and long-term consequences. Moral distress has implications for satisfaction, recruitment and retention of health care providers and implications for the delivery of safe and competent quality patient care. In over a decade of research on ethical practice, registered nurses and other health care practitioners have repeatedly identified moral distress as a concern and called for action. However, research and action on moral distress has been constrained by lack of conceptual clarity and theoretical confusion as to the meaning and underpinnings of moral distress. To further examine these issues and foster action on moral distress, three members of the University of Victoria/University of British Columbia (UVIC/UVIC) nursing ethics research team initiated the development and delivery of a multi-faceted and interdisciplinary symposium on Moral Distress with international experts, researchers, and practitioners. The goal of the symposium was to develop an agenda for action on moral distress in health care. We sought to develop a plan of action that would encompass recommendations for education, practice, research and policy. The papers in this special issue of HEC Forum arose from that symposium. In this first paper, we provide an introduction to moral distress; make explicit some of the challenges associated with theoretical and conceptual constructions of moral distress; and discuss the barriers to the development of research, education, and policy that could, if addressed, foster action on moral distress in health care practice. The following three papers were written by key international experts on moral distress, who explore in-depth the issues in three arenas: education, practice, research. In the fifth and last paper in the series, we highlight key insights from the symposium and the papers in the series, propose to redefine moral distress, and outline directions for an agenda for action on moral distress in health care

Protein phosphatase beta, a putative type-2A protein phosphatase from the human malaria parasite Plasmodium falciparum.

Protein phosphatases play a critical role in the regulation of the eukaryotic cell cycle and signal transduction. A putative protein serine/threonine phosphatase gene has been isolated from the human malaria parasite Plasmodium falciparum. The gene has an unusual intron that contains four repeats of 32 nucleotides and displays a high degree of size polymorphism among different strains of P. falciparum. The open reading frame reconstituted by removal of the intron encodes a protein of 466 amino acids with a predicted molecular mass of approximately 53.7 kDa. The encoded protein, termed protein phosphatase beta (PP-beta), is composed of two distinct domains. The C-terminal domain comprises 315 amino acids and exhibits a striking similarity to the catalytic subunits of the type-2A protein phosphatases. Database searches revealed that the catalytic domain has the highest similarity to Schizosaccharomyces pombe Ppa1 (58% identity and 73% similarity). However, it contains a hydrophilic insert consisting of five amino acids. The N-terminal domain comprises 151 amino acid residues and exhibits several striking features, including high levels of charged amino acids and asparagine, and multiple consensus phosphorylation sites for a number of protein kinases. An overall structural comparison of PP-beta with other members of the protein phosphatase 2A group revealed that PP-beta is more closely related to Saccharomyces cerevisiae PPH22. Southern blots of genomic DNA digests and chromosomal separations showed that PP-beta is a single-copy gene and is located on chromosome 9. A 2800-nucleotide transcript of this gene is expressed specifically in the sexual erythrocytic stage (gametocytes). The results indicate that PP-beta may be involved in sexual stage development

Evidence and Policy in Aid-Dependent Settings

This chapter examines how the political dynamics of aid relationships can affect the use of evidence within health policymaking. Empirical examples from Cambodia, Ethiopia and Ghana illustrate how relationships between national governments and donor agencies influence the ways in which evidence is generated, selected, or utilised to inform policymaking. We particularly consider how relationships with donors influence the underlying systems and processes of evidence use. We find a number of issues affecting which bodies or forms of evidence are taken to be policy relevant, including: levels of local technical capacity to utilise or synthesise evidence; differing stakeholder framing of issues; and the influence of non-state actors on sector-wide systems of agenda setting. The chapter also reflects on some of the key governance implications of these arrangements in which global actors promote forms of evidence use – often under a banner of technical efficiency – with limited consideration for local representation or accountability

Diammonium Glycyrrhizinate Upregulates PGC-1α and Protects against Aβ1–42-Induced Neurotoxicity

Mitochondrial dysfunction is a hallmark of beta-amyloid (Aβ)-induced neurotoxicity in Alzheimer's disease (AD), and is considered an early event in AD pathology. Diammonium glycyrrhizinate (DG), the salt form of Glycyrrhizin, is known for its anti-inflammatory effects, resistance to biologic oxidation and membranous protection. In the present study, the neuroprotective effects of DG on Aβ1–42-induced toxicity and its potential mechanisms in primary cortical neurons were investigated. Exposure of neurons to 2 µM Aβ1–42 resulted in significant viability loss and cell apoptosis. Accumulation of reactive oxygen species (ROS), decreased mitochondrial membrane potential, and activation of caspase-9 and caspase-3 were also observed after Aβ1–42 exposure. All these effects induced by Aβ1–42 were markedly reversed by DG treatment. In addition, DG could alleviate lipid peroxidation and partially restore the mitochondrial function in Aβ1–42-induced AD mice. DG also significantly increased the PGC-1α expression in vivo and in vitro, while knocking down PGC-1α partially blocked the protective effects, which indicated that PGC-1α contributed to the neuroprotective effects of DG. Furthermore, DG significantly decreased the escape latency and search distance and increased the target crossing times of Aβ1–42-induced AD mice in the Morris water maze test. Therefore, these results demonstrated that DG could attenuate Aβ1–42-induced neuronal injury by preventing mitochondrial dysfunction and oxidative stress and improved cognitive impairment in Aβ1–42-induced AD mice, indicating that DG exerted potential beneficial effects on AD

General practitioner workforce planning: assessment of four policy directions

<p>Abstract</p> <p>Background</p> <p>Estimating the supply of GPs into the future is important in forecasting shortages. The lengthy training process for medicine means that adjusting supply to meet demand in a timely fashion is problematic. This study uses Ireland as a case study to determine the future demand and supply of GPs and to assess the potential impact of several possible interventions to address future shortages.</p> <p>Methods</p> <p>Demand was estimated by applying GP visit rates by age and sex to national population projections. Supply was modelled using a range of parameters derived from two national surveys of GPs. A stochastic modelling approach was adopted to determine the probable future supply of GPs. Four policy interventions were tested: increasing vocational training places; recruiting GPs from abroad; incentivising later retirement; increasing nurse substitution to enable practice nurses to deliver more services.</p> <p>Results</p> <p>Relative to most other European countries, Ireland has few GPs per capita. Ireland has an ageing population and demand is estimated to increase by 19% by 2021. Without intervention, the supply of GPs will be 5.7% less than required in 2021. Increasing training places will enable supply to meet demand but only after 2019. Recruiting GPs from overseas will enable supply to meet demand continuously if the number recruited is approximately 0.8 per cent of the current workforce per annum. Later retirement has only a short-term impact. Nurse substitution can enable supply to meet demand but only if large numbers of practice nurses are recruited and allowed to deliver a wide range of GP services.</p> <p>Conclusions</p> <p>A significant shortfall in GP supply is predicted for Ireland unless recruitment is increased. The shortfall will have numerous knock-on effects including price increases, longer waiting lists and an increased burden on hospitals. Increasing training places will not provide an adequate response to future shortages. Foreign recruitment has ethical considerations but may provide a rapid and effective response. Increased nurse substitution appears to offer the best long-term prospects of addressing GP shortages and presents the opportunity to reshape general practice to meet the demands of the future.</p