Philosophy of Hope

The philosophy of hope centers on two interlocking sets of questions. The first concerns the nature of hope. Specific questions here include how to analyze hope, how hope motivates us, and whether there is only one type of hope. The second set concerns the value of hope. Key questions here include whether and when it is good to hope and whether there is a virtue of hope. Philosophers of hope tend to proceed from the first set of questions to the second. This is a natural approach, for one might expect that you must develop a basic understanding of what hope is before you can determine its value. The structure of this chapter thus follows this approach. But readers should not be misled: there is in fact a good deal of feedback between the two sets of questions. A theory of hope is more plausible to the extent that it fits well with plausible ideas about the value of hope. So the movement from hope’s nature to its value is one of emphasis rather than a strict, step-wise process

Ret receptor tyrosine kinase sustains proliferation and tissue maturation in intestinal epithelia.

Expression of the Ret receptor tyrosine kinase is a defining feature of enteric neurons. Its importance is underscored by the effects of its mutation in Hirschsprung disease, leading to absence of gut innervation and severe gastrointestinal symptoms. We report a new and physiologically significant site of Ret expression in the intestine: the intestinal epithelium. Experiments in Drosophila indicate that Ret is expressed both by enteric neurons and adult intestinal epithelial progenitors, which require Ret to sustain their proliferation. Mechanistically, Ret is engaged in a positive feedback loop with Wnt/Wingless signalling, modulated by Src and Fak kinases. We find that Ret is also expressed by the developing intestinal epithelium of mice, where its expression is maintained into the adult stage in a subset of enteroendocrine/enterochromaffin cells. Mouse organoid experiments point to an intrinsic role for Ret in promoting epithelial maturation and regulating Wnt signalling. Our findings reveal evolutionary conservation of the positive Ret/Wnt signalling feedback in both developmental and homoeostatic contexts. They also suggest an epithelial contribution to Ret loss-of-function disorders such as Hirschsprung disease

In-hospital informal caregivers' needs as perceived by themselves and by the nursing staff in Northern Greece: A descriptive study

<p>Abstract</p> <p>Background</p> <p>Informal care is common in many countries, especially in Greece, where families provide care in hospitals. Health education and informational needs are important factors for family members which are often underestimated by nursing staff. The aim of this study was to compare the perceptions of the nurses and the in-hospital informal caregivers about the in-hospital informal caregivers' knowledge and informational needs, as well as the factors that influence these perceptions.</p> <p>Methods</p> <p>This was a non-experimental descriptive study conducted in three general hospitals in Greece. The sample consisted of 320 nurses and 370 in-hospital informal caregivers who completed questionnaires. Descriptive statistics were analyzed using t-tests; group comparisons were conducted using ANOVA.</p> <p>Results</p> <p>The score of the questionnaire for health education and informational needs was significantly greater for informal caregivers (57.1 ± 6.9 and 26.6 ± 2.8) than for nurses (53.4 ± 5.7 and 22.4 ± 3.1) (p < 0.001). For the nursing staff, the factors that influence the informational needs of patients' caregivers were <it>level of education </it>and <it>working experience</it>, while for the caregivers the <it>level of education </it>was independently associated with the score for the health education needs. Finally, <it>age, marital status</it>, and <it>level of education </it>of informal caregivers' were independently associated with informational needs.</p> <p>Conclusions</p> <p>The in-hospital informal caregivers perceived that they have more educational and informational needs than the nurses did. The findings of this study also show that the nursing staff has to identify the needs of in-hospital informal caregivers in order to be able to meet these needs.</p

Spleen transcriptome response to infection with avian pathogenic Escherichia coli in broiler chickens

<p>Abstract</p> <p>Background</p> <p>Avian pathogenic <it>Escherichia coli </it>(APEC) is detrimental to poultry health and its zoonotic potential is a food safety concern. Regulation of antimicrobials in food-production animals has put greater focus on enhancing host resistance to bacterial infections through genetics. To better define effective mechanism of host resistance, global gene expression in the spleen of chickens, harvested at two times post-infection (PI) with APEC, was measured using microarray technology, in a design that will enable investigation of effects of vaccination, challenge, and pathology level.</p> <p>Results</p> <p>There were 1,101 genes significantly differentially expressed between severely infected and non-infected groups on day 1 PI and 1,723 on day 5 PI. Very little difference was seen between mildly infected and non-infected groups on either time point. Between birds exhibiting mild and severe pathology, there were 2 significantly differentially expressed genes on day 1 PI and 799 on day 5 PI. Groups with greater pathology had more genes with increased expression than decreased expression levels. Several predominate immune pathways, Toll-like receptor, Jak-STAT, and cytokine signaling, were represented between challenged and non-challenged groups. Vaccination had, surprisingly, no detectible effect on gene expression, although it significantly protected the birds from observable gross lesions. Functional characterization of significantly expressed genes revealed unique gene ontology classifications during each time point, with many unique to a particular treatment or class contrast.</p> <p>Conclusions</p> <p>More severe pathology caused by APEC infection was associated with a high level of gene expression differences and increase in gene expression levels. Many of the significantly differentially expressed genes were unique to a particular treatment, pathology level or time point. The present study not only investigates the transcriptomic regulations of APEC infection, but also the degree of pathology associated with that infection. This study will allow for greater discovery into host mechanisms for disease resistance, providing targets for marker assisted selection and advanced drug development.</p

The authority of pleasure

The aim of the paper is to reassess the prospects of a widely neglected affective conception of the aesthetic evaluation and appreciation of art. On the proposed picture, the aesthetic evaluation and appreciation of art are non-contingently constituted by a particular kind of pleasure. Artworks that are valuable qua artworks merit, deserve, and call for a certain pleasure, the same pleasure that reveals (or at least purports to reveal) them to be valuable in the way that they are, and constitutes their aesthetic evaluation and appreciation. This is why and how art is non-contingently related to pleasure. Call this, the Affective View. While I don’t advance conclusive arguments for the Affective View in this paper, I aim to reassess its prospects by (1) undermining central objections against it, (2) dissociating it from hedonism about the value of artworks (the view that this value is grounded in, and explained by, its possessors’ power to please), and (3) introducing some observations on the practice of art in support of it. Given that the objections I discuss miss their target, and given the observations in support of it, I conclude that the Affective View is worth serious reconsideration

Evolution of the avian β-defensin and cathelicidin genes

Background: β-defensins and cathelicidins are two families of cationic antimicrobial peptides (AMPs) with a broad range of antimicrobial activities that are key components of the innate immune system. Due to their important roles in host defense against rapidly evolving pathogens, the two gene families provide an ideal system for studying adaptive gene evolution. In this study we performed phylogenetic and selection analyses on β-defensins and cathelicidins from 53 avian species representing 32 orders to examine the evolutionary dynamics of these peptides in birds. Results and conclusions: Avian β-defensins are found in a gene cluster consisting of 13 subfamiles. Nine of these are conserved as one to one orthologs in all birds, while the others (AvBD1, AvBD3, AvBD7 and AvBD14) are more subject to gene duplication or pseudogenisation events in specific avian lineages. Avian cathelicidins are found in a gene cluster consisting of three subfamilies with species-specific duplications and gene loss. Evidence suggested that the propiece and mature peptide domains of avian cathelicidins are possibly co-evolving in such a way that the cationicity of the mature peptide is partially neutralised by the negative charge of the propiece prior to peptide secretion (further evidence obtained by repeating the analyses on primate cathelicidins). Negative selection (overall mean d

Expression and functional analyses of liver expressed antimicrobial peptide-2 (LEAP-2) variant forms in human tissues

The antimicrobial peptide Liver Expressed Antimicrobial Peptide-2 (LEAP-2) is proposed to function as part of the vertebrate innate immune system. However, the highly conserved nature of the LEAP-2 peptide primary structure among vertebrates suggests more fundamental physiological roles. RT-PCR analyses confirmed expression of LEAP-2 mRNA variants in human gastro-intestinal (GI) epithelial tissues and THP-1 monocytes. Three cDNA products indicative of at least three different spliced transcripts were observed. Translation of the cDNA sequences supported synthesis of transcripts encoding the secreted LEAP-2 peptide and two variants lacking signal sequences suggesting intracellular localisation. The synthesis and cytoplasmic localisation of LEAP-2 peptides in epithelia was supported by immunohistochemical analyses. Functional data suggested that LEAP-2 is not involved in the physiological response of GI epithelia to iron, nor is it mitogenic for epithelial cells or chemotactic for THP-1 monocytes. However, changes in the LEAP-2 transcript patterns associated with the challenge of THP-1 monocytes with lipopolysaccharide (100 ng/ml) were supportive of the peptides having multiple roles in the innate immune response