Jazz, Kant and Zen: The Philosophy of Improvisation

Transgression and experimentation are at the heart of the musical composition with which this work begins. The compositional approaches employed developed from a consideration of Kant’s Critique of Judgement (1790) which offers a compelling explanation for the apparently bizarre “claim to objectivity” commonly made in judgements of taste. Kant’s final conclusion around the source of the claim is, for me, disappointing. This current work re-examines and extends his argument through an elision with Zen writing, and offers an alternate account. It is posited that the “claim to objectivity” operates as a linguistic marker, acknowledging the presence of experience that is trans-rational and supra-linguistic, and indicating a point/place at which language ceases to be viable. It relies on and incites an implicit shared understanding that aesthetic experience often exceeds language, and further indicates that one or more of the myriad unspeakable things are accessible nearby. This understanding is explored in relation to compositional practice, finding a powerful synergy with the writing of composers, improvisers, and avant-garde/jazz theorists. The work concludes with the suggestion that aesthetic experience and the “beautiful” may therefore signpost the ineffable, referring back to the score with which this work began.</jats:p

A Pilgrimage in Search of Robert Frank’s Americans

The extensive contemporary discussions around online platforms have revolutionised our understanding of photographic destinations. In its great variety—between semi professional showcase platforms such as Flickr, through social media sharing ostensibly for fun, to personally tailored and curtailed sharing sites such as Snapchat, photography has been radicalised by these technological developments. One of the predilections of the internet is the anonymising and occluding of authorship. Anonymous photography is in itself hugely interesting, but for now let’s restrict ourselves and assume that we still have an interest in the notion of authorship. Is there a place for the notion of the ‘artist’ in online sharing and photography? If the internet is a mass of neo-anonymous output, structured and re-structured constantly by algorithmic operations, as the gallery and archive retrench and become increasingly defensive and exclusive in increasingly desperate attempts at life-boating themselves, is there now a place for the power of the artist? It seems to me that such a place has existed since the early 20th century and is experiencing an enormous resurgence at the moment, exactly because of digital technology and the internet. It is not without problems of its own, certainly, but it offers the possibility of independence, of longevity, a curated statement and of being signally identified as the author of the works contained, with all the notions of ‘career’ that accompanies. It is the book

The genetic architecture of resistance to virus infection in Drosophila.

Variation in susceptibility to infection has a substantial genetic component in natural populations, and it has been argued that selection by pathogens may result in it having a simpler genetic architecture than many other quantitative traits. This is important as models of host-pathogen co-evolution typically assume resistance is controlled by a small number of genes. Using the Drosophila melanogaster multiparent advanced intercross, we investigated the genetic architecture of resistance to two naturally occurring viruses, the sigma virus and DCV (Drosophila C virus). We found extensive genetic variation in resistance to both viruses. For DCV resistance, this variation is largely caused by two major-effect loci. Sigma virus resistance involves more genes - we mapped five loci, and together these explained less than half the genetic variance. Nonetheless, several of these had a large effect on resistance. Models of co-evolution typically assume strong epistatic interactions between polymorphisms controlling resistance, but we were only able to detect one locus that altered the effect of the main effect loci we had mapped. Most of the loci we mapped were probably at an intermediate frequency in natural populations. Overall, our results are consistent with major-effect genes commonly affecting susceptibility to infectious diseases, with DCV resistance being a near-Mendelian trait.European Research Council (Grant ID: DrosophilaInfection 281668), NERC (Grant ID: NE/L004232/1), São Paulo Research Foundation (FAPESP) (Grant IDs: 2015/08307-3, 2013/ 25991-0), Cambridge Commonwealth, European & International Trust, China Scholarship CouncilThis is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1111/mec.1376

Screening Prevalence and Incidence of Colorectal Cancer Among American Indian/Alaskan Natives in the Indian Health Service

BackgroundStudies on colorectal cancer (CRC) screening and incidence among American Indian/Alaska Natives (AI/AN) are few.AimsOur aim was to determine CRC screening prevalence and to calculate CRC incidence among AI/AN receiving care within the Indian Health Service (IHS).MethodsA retrospective cohort study of AI/AN who utilized IHS from 1996 to 2004. AI/AN who were average-risk for CRC and received primary care within IHS were identified by searching the IHS Resource Patient Management System for selected ICD-9/CPT codes (n&nbsp;=&nbsp;142,051). CRC screening prevalence was calculated and predictors of screening were determined for this group. CRC incidence rates were ascertained for the entire AI/AN population ages 50-80 who received IHS medical care between 1996 and 2004 (n&nbsp;=&nbsp;283,717).ResultsCRC screening was performed in 4.0% of average-risk AI/AN. CRC screening was more common among women than men (RR&nbsp;=&nbsp;1.6, 95% CI 1.4-1.7) and among AI/AN living in the Alaska region compared to the Pacific Coast region (RR&nbsp;=&nbsp;2.5, 95% CI 2.2-2.8) while patients living in the Northern Plains (RR&nbsp;=&nbsp;0.4, 95% CI 0.3-0.4) were less likely to have been screened. CRC screening was less common among patients with a greater number of primary care visits. The age-adjusted CRC incidence among AI/AN ages 50-80 was 227 cancers per 100,000 person-years.ConclusionsCRC was common among AI/AN receiving medical care within IHS. However, CRC screening prevalence was far lower than has been reported for the U.S. population

A gene associated with social immunity in the burying beetle Nicrophorus vespilloides.

Some group-living species exhibit social immunity, where the immune response of one individual can protect others in the group from infection. In burying beetles, this is part of parental care. Larvae feed on vertebrate carcasses which their parents smear with exudates that inhibit microbial growth. We have sequenced the transcriptome of the burying beetle Nicrophorus vespilloides and identified six genes that encode lysozymes-a type of antimicrobial enzyme that has previously been implicated in social immunity in burying beetles. When females start breeding and producing antimicrobial anal exudates, we found that the expression of one of these genes was increased by approximately 1000 times to become one of the most abundant transcripts in the transcriptome. Females varied considerably in the antimicrobial properties of their anal exudates, and this was strongly correlated with the expression of this lysozyme. We conclude that we have likely identified a gene encoding a key effector molecule in social immunity and that it was recruited during evolution from a function in personal immunity.This work was funded by ERC grant DrosophilaInfection 281668 to F.M.J., NERC grant no. NE/H019731/1 to R.M.K., ERC grant BALDWINIAN_BEETLES 310785 to R.M.K. and a Wolfson Merit Award to R.M.K.This is the final version of the article. It first appeared from Royal Society Publishing via https://doi.org/10.1098/rspb.2015.273

Virus evolution in Wolbachia-infected Drosophila

Wolbachia, a common vertically transmitted symbiont, can protect insects against viral infection and prevent mosquitoes from transmitting viral pathogens. For this reason, Wolbachia-infected mosquitoes are being released to prevent the transmission of dengue and other arboviruses. An important question for the long-term success of these programmes is whether viruses can evolve to escape the antiviral effects of Wolbachia. We have found that Wolbachia altered the outcome of competition between strains of the DCV virus in Drosophila. However, Wolbachia still effectively blocked the virus genotypes that were favoured in the presence of the symbiont. We conclude that Wolbachia did cause an evolutionary response in viruses, but this has little or no impact on the effectiveness of virus blocking

Virus evolution in Wolbachia-infected Drosophila

Wolbachia, a common vertically transmitted symbiont, can protect insects against viral infection and prevent mosquitoes from transmitting viral pathogens. For this reason, Wolbachia-infected mosquitoes are being released to prevent the transmission of dengue and other arboviruses. An important question for the long-term success of these programmes is whether viruses can evolve to escape the antiviral effects of Wolbachia. We have found that Wolbachia altered the outcome of competition between strains of the DCV virus in Drosophila. However, Wolbachia still effectively blocked the virus genotypes that were favoured in the presence of the symbiont. We conclude that Wolbachia did cause an evolutionary response in viruses, but this has little or no impact on the effectiveness of virus blocking

Cyclic AMP-specific phosphodiesterase, PDE8A1, is activated by protein kinase A-mediated phosphorylation

The cyclic AMP-specific phosphodiesterase PDE8 has been shown to play a pivotal role in important processes such as steroidogenesis, T cell adhesion, regulation of heart beat and chemotaxis. However, no information exists on how the activity of this enzyme is regulated. We show that under elevated cAMP conditions, PKA acts to phosphorylate PDE8A on serine 359 and this action serves to enhance the activity of the enzyme. This is the first indication that PDE8 activity can be modulated by a kinase, and we propose that this mechanism forms a feedback loop that results in the restoration of basal cAMP levels. (C) 2012 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserve

Sleep deprivation causes memory deficits by negatively impacting neuronal connectivity in hippocampal area CA1

Brief periods of sleep loss have long-lasting consequences such as impaired memory consolidation. Structural changes in synaptic connectivity have been proposed as a substrate of memory storage. Here, we examine the impact of brief periods of sleep deprivation on dendritic structure. In mice, we find that five hours of sleep deprivation decreases dendritic spine numbers selectively in hippocampal area CA1 and increased activity of the filamentous actin severing protein cofilin. Recovery sleep normalizes these structural alterations. Suppression of cofilin function prevents spine loss, deficits in hippocampal synaptic plasticity, and impairments in long-term memory caused by sleep deprivation. The elevated cofilin activity is caused by cAMP-degrading phosphodiesterase-4A5 (PDE4A5), which hampers cAMP-PKA-LIMK signaling. Attenuating PDE4A5 function prevents changes in cAMP-PKA-LIMK-cofilin signaling and cognitive deficits associated with sleep deprivation. Our work demonstrates the necessity of an intact cAMP-PDE4-PKA-LIMK-cofilin activation-signaling pathway for sleep deprivation-induced memory disruption and reduction in hippocampal spine density

The causes and consequences of changes in virulence following pathogen host shifts.

Emerging infectious diseases are often the result of a host shift, where the pathogen originates from a different host species. Virulence--the harm a pathogen does to its host-can be extremely high following a host shift (for example Ebola, HIV, and SARs), while other host shifts may go undetected as they cause few symptoms in the new host. Here we examine how virulence varies across host species by carrying out a large cross infection experiment using 48 species of Drosophilidae and an RNA virus. Host shifts resulted in dramatic variation in virulence, with benign infections in some species and rapid death in others. The change in virulence was highly predictable from the host phylogeny, with hosts clustering together in distinct clades displaying high or low virulence. High levels of virulence are associated with high viral loads, and this may determine the transmission rate of the virus.BL and FMJ are supported by a NERC grant (NE/L004232/1), a European Research Council grant (281668, DrosophilaInfection), a Junior Research Fellowship from Christ’s College, Cambridge (BL) and a Royal Society University Research Fellowship (FMJ). JDH is supported by a Royal Society University Research Fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.This is the final published version. It first appeared at http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1004728