Bayesian Analysis of Data on Nest Success for Marsh Birds

Bayesian methods are an increasingly popular form of statistical analysis which uses informative prior distributions to help calculate posterior distributions of models that represent different hypotheses. Frequentist methods are contrasting methods that are used more commonly and more well known, but have come under recent criticism. I examined data gathered by Ellen Robertson, who used information theoretic methods for a Masters’ Thesis in Ecology and Environmental Science at the University of Maine to analyze the daily survival probabilities of marsh birds with a Bayesian perspective in order to get a sense of the Bayesian analysis. Results were as expected; when using uninformative prior distributions, the Bayesian analysis had almost the same results as Robertson’s. With the use of Robertson’s calculated parameter estimates as informative prior distributions, the Bayesian analysis still ended with similar results. The conclusions in all three versions of statistical analysis were the same. Hence, Bayesian methods can construct models representing hypotheses effectively

A Fighting Chance: The Proposed Servicemembers Access to Justice Act & Its Potential Effects on Binding Arbitration Agreements

In August 2008 a bill was introduced in the United States Senate that clearly states Uniformed Services Employment and Reemployment Rights of 1994 (USERRA) claims supersede any preexisting arbitration clauses in employment agreements. This bill, known as the Servicemembers Access to Justice Act (SAJA), would restore full access to the federal court system for USERRA plaintiffs. This paper examines the SAJA and its potential effects on the USERRA. It begins with a survey of the history behind the passage of the USERRA, as well as the FAA. Next, it describes the two federal circuit court decisions that have led to the proposal of the SAJA. A further section explores the SAJA itself. A commentary section follows, expressing disagreement with the court decisions and support for the SAJA, as it restores the privileged status bestowed upon veterans by Congress in the USERRA and its predecessor statutes. Finally, the conclusion looks forward to the passage of this much needed law

Anthropometric and physiological factors affecting batted ball speed of adolescent baseball players

Fifty-seven junior baseball players performed eight swings off a tee to record ball exit speed, as well as tests of grip strength, standing broad jump, lateral-to-medial (LM) jumps, chin-ups and chest pass with a medicine ball. The height, weight and age of each participant was also recorded. All anthropometric and physiological tests were significantly positively correlated with ball speed (p \u3c 0.05). Collinearity between variables meant that only chest pass (R² = 0.70, p = 0.000), body mass (ΔR² = 0.03, Δp = 0.021) and LM jump (ΔR² = 0.04, Δp = 0.005) made independent contributions to a stepwise linear regression. These findings corroborate the expectation that upper body power is a major determinant of batting speed, with leg power adding an additional, independent contribution to performance

Small molecule STING inhibition improves myocardial infarction remodeling

Aims: Myocardial infarction (MI) is a major global cause of death. Massive cell death leads to inflammation, which is necessary for ensuing wound healing. Extensive inflammation, however, promotes infarct expansion and adverse remodeling. The DNA sensing receptor cyclic GMP-AMP synthase and its downstream signaling effector stimulator of interferon genes (cGAS-STING) is central in innate immune reactions in infections or autoimmunity. Cytosolic double-strand DNA activates the pathway and down-stream inflammatory responses. Recent papers demonstrated that this pathway is also active following MI and that its genetic targeting improves outcome. Thus, we investigated if pharmacologic pathway inhibition is protective after MI in order to test its translational potential. Main methods: We investigated novel and selective small-molecule STING inhibitors that inhibit STING palmitoylation and multimerization and thereby downstream pathway activation in a preclinical murine MI model. We assessed structural and functional cardiac remodeling, infarct expansion and fibrosis, as well as cardiomyocyte hypertrophy and the expression of inflammatory genes. Key findings: Pharmacologic STING inhibition did not reduce mortality due to myocardial rupture in non-reperfused MI. Infarct size at day one was comparable. However, three weeks of pharmacologic STING inhibition after reperfused MI decreased infarct expansion and scarring, increased left ventricular systolic function to levels approaching normal values, and reduced myocardial hypertrophy. Significance: Selective small-molecule STING inhibition after myocardial infarction has the potential to improve wound healing responses and pathological remodeling and thereby attenuate the development of ischemic heart failure

Increased Thymic B Cells but Maintenance of Thymic Structure, T Cell Differentiation and Negative Selection in Lymphotoxin-α and TNF Gene-Targeted Mice

TNF, lymphotoxin (LT) and their receptors are expressed constitutively in the thymus. It remains unclear whether these cytokines play a role in normal thymic structure or function. We have investigated thymocyte differentiation, selection and thymic organogenesis in gene targeted mice lacking LTα, TNF, or both (TNF/LTα-/-). The thymus was normal in TNF/LTα-/- mice with regard to cell yields and stromal architecture. Detailed analysis of αβ and γδ T cell-lineage thymocyte subsets revealed no abnormalities, implying that neither TNF nor LT play an essential role in T cell differentiation or positive selection. The number and distribution of thymic CD11c+ dendritic cells was also normal in the absence of both TNF and LTα. A three-fold increase in B cell numbers was observed consistently in the TNF/LTα-/- thymus. This phenotype was due entirely to the LTα deficiency and associated with changes in the hemopoietic compartment, rather than the thymic stromal compartment of LTα-/- mice. Finally, specific Vβ8+ T cell deletion within the thymus following intrathymic injection of staphylococcal enterotoxin B (SEB) was TNF/LT independent. Thus, despite the presence of these cytokines and their receptors in the normal thymus, there appears no essential role for either TNF or LT in development of organ structure or for those processes associated with T cell repertoire selection

Paracrine factors released by stem cells of mesenchymal origin and their effects in cardiovascular disease: a systematic review of pre-clinical studies

Mesenchymal stem cell (MSC) therapy has gained significant traction in the context of cardiovascular repair, and have been proposed to exert their regenerative effects via the secretion of paracrine factors. In this systematic review, we examined the literature and consolidated available evidence for the “paracrine hypothesis”. Two Ovid SP databases were searched using a strategy encompassing paracrine mediated MSC therapy in the context of ischemic heart disease. This yielded 86 articles which met the selection criteria for inclusion in this study. We found that the MSCs utilized in these articles were primarily derived from bone marrow, cardiac tissue, and adipose tissue. We identified 234 individual protective factors across these studies, including VEGF, HGF, and FGF2; which are proposed to exert their effects in a paracrine manner. The data collated in this systematic review identifies secreted paracrine factors that could decrease apoptosis, and increase angiogenesis, cell proliferation, and cell viability. These included studies have also demonstrated that the administration of MSCs and indirectly, their secreted factors can reduce infarct size, and improve left ventricular ejection fraction, contractility, compliance, and vessel density. Furthering our understanding of the way these factors mediate repair could lead to the identification of therapeutic targets for cardiac regeneration

Photochemically controlled drug dosing from a polymeric scaffold

Purpose To develop the first photoactive biomaterial coating capable of controlled drug dosing via inclusion of synthesised drug-3,5-dimethoxybenzoin (DMB) conjugates in a poly(2-methyoxyethyl acrylate) (pMEA) scaffold. Methods Flurbiprofen- and naproxen-DMB conjugates were prepared via esterification and characterised via NMR spectroscopy and mass spectrometry following chromatographic purification. Conjugate photolysis was investigated in acetonitrile solution and within the pMEA matrix following exposure to low-power 365 nm irradiation. Photo-liberation of drug from pMEA into phosphate buffered saline was monitored using UV-vis spectroscopy. Results The synthetic procedures yielded the desired drug conjugates with full supporting characterisation. Drug regeneration through photolysis of the synthesised conjugates was successful in both acetonitrile solution and within the pMEA scaffold upon UV irradiation. Conjugates were retained within the pMEA scaffold with exclusive drug liberation following irradiation and increased drug dose with increasing exposure. Multi-dosing capacity was demonstrated though the ability of successive irradiation periods to generate further bursts of drug. Conclusion This study demonstrates the first application of photochemically controlled drug release from a biomaterial coating and the feasibility of using pMEA as a scaffold for housing the photoactive drug-DMB conjugates

The Role of Pathological Aging in Cardiac and Pulmonary Fibrosis

Aging promotes a range of degenerative pathologies characterized by progressive losses of tissue and/or cellular function. Fibrosis is the hardening, overgrowth and scarring of various tissues characterized by the accumulation of extracellular matrix components. Aging is an important predisposing factor common for fibrotic heart and respiratory disease. Age-related processes such as senescence, inflammaging, autophagy and mitochondrial dysfunction are interconnected biological processes that diminish the regenerative capacity of the aged heart and lung and have been shown to play a crucial role in cardiac fibrosis and idiopathic pulmonary fibrosis. This review focuses on these four processes of aging in relation to their role in fibrosis. It has long been established that the heart and lung are linked both functionally and anatomically when it comes to health and disease, with an ever-expanding aging population, the incidence of fibrotic disease and therefore the number of fibrosis-related deaths will continue to rise. There are currently no feasible therapies to treat the effects of chronic fibrosis therefore highlighting the importance of exploring the processes of aging and its role in inducing and exacerbating fibrosis of each organ. The focus of this review may help to highlight potential avenues of therapeutic exploration</p

Cellular plasticity in response to suppression of storage proteins in the Brassica napus embryo

The tradeoff between protein and oil storage in oilseed crops has been tested here in oilseed rape (Brassica napus) by analyzing the effect of suppressing key genes encoding protein storage products (napin and cruciferin). The phenotypic outcomes were assessed using NMR and mass spectrometry imaging, microscopy, transcriptomics, proteomics, metabolomics, lipidomics, immunological assays, and flux balance analysis. Surprisingly, the profile of storage products was only moderately changed in RNA interference transgenics. However, embryonic cells had undergone remarkable architectural rearrangements. The suppression of storage proteins led to the elaboration of membrane stacks enriched with oleosin (sixfold higher protein abundance) and novel endoplasmic reticulum morphology. Protein rebalancing and amino acid metabolism were focal points of the metabolic adjustments to maintain embryonic carbon/nitrogen homeostasis. Flux balance analysis indicated a rather minor additional demand for cofactors (ATP and NADPH). Thus, cellular plasticity in seeds protects against perturbations to its storage capabilities and, hence, contributes materially to homeostasis. This study provides mechanistic insights into the intriguing link between lipid and protein storage, which have implications for biotechnological strategies directed at improving oilseed crops