The parent analogy: a reassessment

According to the parent analogy, as a caretaker’s goodness, ability and intelligence increase, the likelihood that the caretaker will make arrangements for the attainment of future goods that are unnoticed or underappreciated by their dependents also increases. Consequently, if this analogy accurately represents our relationship to God, then we should expect to find many instances of inscrutable evil in the world. This argument in support of skeptical theism has recently been criticized by Dougherty. I argue that Dougherty’s argument is incomplete, for there are two plausible ways of construing the parent analogy’s conclusion. I supplement Dougherty’s case by offering a new argument against the parent analogy based on failed expectations concerning the amount of inscrutable evils encountered in the world. Consequently, there remains a significant empirical hurdle for skeptical theism to overcome if it is to maintain its status as a defeater for our reliability when tracking gratuitous evils.Publisher PDFPeer reviewe

A transcriptome-driven analysis of epithelial brushings and bronchial biopsies to define asthma phenotypes in U-BIOPRED

RATIONALE AND OBJECTIVES: Asthma is a heterogeneous disease driven by diverse immunologic and inflammatory mechanisms. We used transcriptomic profiling of airway tissues to help define asthma phenotypes. METHODS: The transcriptome from bronchial biopsies and epithelial brushings of 107 moderate-to-severe asthmatics were annotated by gene-set variation analysis (GSVA) using 42 gene-signatures relevant to asthma, inflammation and immune function. Topological data analysis (TDA) of clinical and histological data was used to derive clusters and the nearest shrunken centroid algorithm used for signature refinement. RESULTS: 9 GSVA signatures expressed in bronchial biopsies and airway epithelial brushings distinguished two distinct asthma subtypes associated with high expression of T-helper type 2 (Th-2) cytokines and lack of corticosteroid response (Group 1 and Group 3). Group 1 had the highest submucosal eosinophils, high exhaled nitric oxide (FeNO) levels, exacerbation rates and oral corticosteroid (OCS) use whilst Group 3 patients showed the highest levels of sputum eosinophils and had a high BMI. In contrast, Group 2 and Group 4 patients had an 86% and 64% probability of having non-eosinophilic inflammation. Using machine-learning tools, we describe an inference scheme using the currently-available inflammatory biomarkers sputum eosinophilia and exhaled nitric oxide levels along with OCS use that could predict the subtypes of gene expression within bronchial biopsies and epithelial cells with good sensitivity and specificity. CONCLUSION: This analysis demonstrates the usefulness of a transcriptomic-driven approach to phenotyping that segments patients who may benefit the most from specific agents that target Th2-mediated inflammation and/or corticosteroid insensitivity

An experimental test of non-local realism

Most working scientists hold fast to the concept of 'realism' - a viewpoint according to which an external reality exists independent of observation. But quantum physics has shattered some of our cornerstone beliefs. According to Bell's theorem, any theory that is based on the joint assumption of realism and locality (meaning that local events cannot be affected by actions in space-like separated regions) is at variance with certain quantum predictions. Experiments with entangled pairs of particles have amply confirmed these quantum predictions, thus rendering local realistic theories untenable. Maintaining realism as a fundamental concept would therefore necessitate the introduction of 'spooky' actions that defy locality. Here we show by both theory and experiment that a broad and rather reasonable class of such non-local realistic theories is incompatible with experimentally observable quantum correlations. In the experiment, we measure previously untested correlations between two entangled photons, and show that these correlations violate an inequality proposed by Leggett for non-local realistic theories. Our result suggests that giving up the concept of locality is not sufficient to be consistent with quantum experiments, unless certain intuitive features of realism are abandoned.Comment: Minor corrections to the manuscript, the final inequality and all its conclusions do not change; description of corrections (Corrigendum) added as new Appendix III; Appendix II replaced by a shorter derivatio

Male water striders attract predators to intimidate females into copulation

Despite recent advances in our understanding of sexual conflict and antagonistic coevolution between sexes, the role of interspecific interactions, such as predation, in these evolutionary processes remains unclear. In this paper, we present a new male mating strategy whereby a male water strider Gerris gracilicornis intimidates a female by directly attracting predators as long as she does not accept the male's coercive copulation attempt. We argue that this male strategy is a counteradaptation to the evolution of the female morphological shield protecting her genitalia from coercive intromission by water strider males. The G. gracilicornis mating system clearly represents an effect expected from models of the coevolutionary arms race between sexes, whereby one sex causes a decrease in the fitness component of the other sex. Moreover, our study demonstrates a crucial role that interspecific interactions such as predation can have in the antagonistic coevolution between sexes

Presence and Persistence of Ebola or Marburg Virus in Patients and Survivors: A Rapid Systematic Review

Background: The 2013-15 Ebola outbreak was unprecedented due to sustainedtransmission within urban environments and thousands of survivors. In 2014 the World Health Organization stated that there was insufficient evidence to give definitive guidance about which body fluids are infectious and when they pose a risk to humans. We report a rapid systematic review of published evidence on the presence of filoviruses in body fluids of infected people and survivors. Methods: Scientific articles were screened for information about filovirus in human body fluids. The aim was to find primary data that suggested high likelihood of actively infectious filovirus in human body fluids (viral RNA). Eligible infections were from Marburg virus (MARV or RAVV) and Zaire, Sudan, Taï Forest and Bundibugyo species of Ebola. [1] Cause of infection had to be laboratory confirmed (in practice either tissue culture or RT-PCR tests), or evidenced by compatible clinical history with subsequent positivity for filovirus antibodies or inflammatory factors. Data were extracted and summarized narratively. Results: 6831 unique articles were found, and after screening, 33 studies were eligible. For most body fluid types there were insufficient patients to draw strong conclusions, and prevalence of positivity was highly variable. Body fluids taken >16 days after onset were usually negative. In the six studies that used both assay methods RT-PCR tests for filovirus RNA gave positive results about 4 times more often than tissue culture. Conclusions: Filovirus was reported in most types of body fluid, but not in every sample from every otherwise confirmed patient. Apart from semen, most non-blood, RT-PCR positive samples are likely to be culture negative and so possibly of low infectious risk. Nevertheless, it is not apparent how relatively infectious many body fluids are during or after illness, even when culture-positive, not least because most test results come from more severe cases. Contact with blood and blood-stained body fluids remains the major risk for disease transmission because of the known high viral loads in blood

Sustainability of bioenergy – Mapping the risks & benefits to inform future bioenergy systems

Bioenergy is widely included in energy strategies for its GHG mitigation potential. Bioenergy technologies will likely have to be deployed at scale to meet decarbonisation targets, and consequently biomass will have to be increasingly grown/mobilised. Sustainability risks associated with bioenergy may intensify with increasing deployment and where feedstocks are sourced through international trade. This research applies the Bioeconomy Sustainability Indicator Model (BSIM) to map and analyse the performance of bioenergy across 126 sustainability issues, evaluating 16 bioenergy case studies that reflect the breadth of biomass resources, technologies, energy vectors and bio-products. The research finds common trends in sustainability performance across projects that can inform bioenergy policy and decision making. Potential sustainability benefits are identified for People (jobs, skills, income, energy access); for Development (economy, energy, land utilisation); for Natural Systems (soil, heavy metals), and; for Climate Change (emissions, fuels). Also, consistent trends of sustainability risks where focus is required to ensure the viability of bioenergy projects, including for infrastructure, feedstock mobilisation, techno-economics and carbon stocks. Emission mitigation may be a primary objective for bioenergy, this research finds bioenergy projects can provide potential benefits far beyond emissions - there is an argument for supporting projects based on the ecosystem services and/or economic stimulation they may deliver. Also given the broad dynamics and characteristics of bioenergy projects, a rigid approach of assessing sustainability may be incompatible. Awarding ‘credit’ across a broader range of sustainability indicators in addition to requiring minimum performances in key areas, may be more effective at ensuring bioenergy sustainability

The Chromatin Remodeler SPLAYED Regulates Specific Stress Signaling Pathways

Organisms are continuously exposed to a myriad of environmental stresses. Central to an organism's survival is the ability to mount a robust transcriptional response to the imposed stress. An emerging mechanism of transcriptional control involves dynamic changes in chromatin structure. Alterations in chromatin structure are brought about by a number of different mechanisms, including chromatin modifications, which covalently modify histone proteins; incorporation of histone variants; and chromatin remodeling, which utilizes ATP hydrolysis to alter histone-DNA contacts. While considerable insight into the mechanisms of chromatin remodeling has been gained, the biological role of chromatin remodeling complexes beyond their function as regulators of cellular differentiation and development has remained poorly understood. Here, we provide genetic, biochemical, and biological evidence for the critical role of chromatin remodeling in mediating plant defense against specific biotic stresses. We found that the Arabidopsis SWI/SNF class chromatin remodeling ATPase SPLAYED (SYD) is required for the expression of selected genes downstream of the jasmonate (JA) and ethylene (ET) signaling pathways. SYD is also directly recruited to the promoters of several of these genes. Furthermore, we show that SYD is required for resistance against the necrotrophic pathogen Botrytis cinerea but not the biotrophic pathogen Pseudomonas syringae. These findings demonstrate not only that chromatin remodeling is required for selective pathogen resistance, but also that chromatin remodelers such as SYD can regulate specific pathways within biotic stress signaling networks

Epstein-Barr Virus Evades CD4+ T Cell Responses in Lytic Cycle through BZLF1-mediated Downregulation of CD74 and the Cooperation of vBcl-2

Evasion of immune T cell responses is crucial for viruses to establish persistence in the infected host. Immune evasion mechanisms of Epstein-Barr virus (EBV) in the context of MHC-I antigen presentation have been well studied. In contrast, viral interference with MHC-II antigen presentation is less well understood, not only for EBV but also for other persistent viruses. Here we show that the EBV encoded BZLF1 can interfere with recognition by immune CD4+ effector T cells. This impaired T cell recognition occurred in the absence of a reduction in the expression of surface MHC-II, but correlated with a marked downregulation of surface CD74 on the target cells. Furthermore, impaired CD4+ T cell recognition was also observed with target cells where CD74 expression was downregulated by shRNA-mediated inhibition. BZLF1 downregulated surface CD74 via a post-transcriptional mechanism distinct from its previously reported effect on the CIITA promoter. In addition to being a chaperone for MHC-II αβ dimers, CD74 also functions as a surface receptor for macrophage Migration Inhibitory Factor and enhances cell survival through transcriptional upregulation of Bcl-2 family members. The immune-evasion function of BZLF1 therefore comes at a cost of induced toxicity. However, during EBV lytic cycle induced by BZLF1 expression, this toxicity can be overcome by expression of the vBcl-2, BHRF1, at an early stage of lytic infection. We conclude that by inhibiting apoptosis, the vBcl-2 not only maintains cell viability to allow sufficient time for synthesis and accumulation of infectious virus progeny, but also enables BZLF1 to effect its immune evasion function

Method for Quantitative Study of Airway Functional Microanatomy Using Micro-Optical Coherence Tomography

We demonstrate the use of a high resolution form of optical coherence tomography, termed micro-OCT (μOCT), for investigating the functional microanatomy of airway epithelia. μOCT captures several key parameters governing the function of the airway surface (airway surface liquid depth, periciliary liquid depth, ciliary function including beat frequency, and mucociliary transport rate) from the same series of images and without exogenous particles or labels, enabling non-invasive study of dynamic phenomena. Additionally, the high resolution of μOCT reveals distinguishable phases of the ciliary stroke pattern and glandular extrusion. Images and functional measurements from primary human bronchial epithelial cell cultures and excised tissue are presented and compared with measurements using existing gold standard methods. Active secretion from mucus glands in tissue, a key parameter of epithelial function, was also observed and quantified