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Recent advances in single‐cell transcriptomic data have greatly expanded our understanding of both spermatogenesis and the molecular mechanisms of male infertility. However, this growing wealth of data could also shed light on a seemingly unrelated biological problem: the genetic basis of mammalian brain size expansion throughout evolution. It is now increasingly recognized that the testis and brain share many cellular and molecular similarities including pivotal roles for the RAS/MAPK and PI3K/AKT/mTOR pathways, mutations in which are known to have a pronounced impact on cell proliferation. Most notably, in the stem cell lineages of both organs, new mutations have been shown to increase cellular output over time. These include ‘selfish’ mutations in spermatogonial stem cells, which disproportionately increase the proportion of mutant sperm, and—to draw a parallel—human‐specific mutations in neural stem cells which, by increasing the number of neurons, have been implicated in neocortical expansion. Here we speculate that the origin for many ‘expansion’‐associated mutations is the male germline and that as such, a deeper understanding of the mechanisms controlling testicular turnover may yield fresh insight into the biology and evolution of the brain. [ABSTRACT FROM AUTHOR]

Spermatogenesis involves a complex process of cellular differentiation maintained by spermatogonial stem cells (SSCs). Being critical to male reproduction, it is generally assumed that spermatogenesis starts and ends in equivalent transcriptional states in related species. Based on single-cell gene expression profiling, it has been proposed that undifferentiated human spermatogonia can be subclassified into four heterogenous subtypes, termed states 0, 0A, 0B, and 1. To increase the resolution of the undifferentiated compartment and trace the origin of the spermatogenic trajectory, we re-analysed the single-cell (sc) RNA-sequencing libraries of 34 post-pubescent human testes to generate an integrated atlas of germ cell differentiation. We then used this atlas to perform comparative analyses of the putative SSC transcriptome both across human development (using 28 foetal and pre-pubertal scRNA-seq libraries) and across species (including data from sheep, pig, buffalo, rhesus and cynomolgus macaque, rat, and mouse). Alongside its detailed characterisation, we show that the transcriptional heterogeneity of the undifferentiated spermatogonial cell compartment varies not only between species but across development. Our findings associate 'state 0B' with a suppressive transcriptomic programme that, in adult humans, acts to functionally oppose proliferation and maintain cells in a ready-to-react state. Consistent with this conclusion, we show that human foetal germ cells—which are mitotically arrested—can be characterised solely as state 0B. While germ cells with a state 0B signature are also present in foetal mice (and are likely conserved at this stage throughout mammals), they are not maintained into adulthood. We conjecture that in rodents, the foetal-like state 0B differentiates at birth into the renewing SSC population, whereas in humans it is maintained as a reserve population, supporting testicular homeostasis over a longer reproductive lifespan while reducing mutagenic load. Together, these results suggest that SSCs adopt differing evolutionary strategies across species to ensure fertility and genome integrity over vastly differing life histories and reproductive timeframes. [ABSTRACT FROM AUTHOR]

SUMMARY: Whole‐genome duplication (WGD) leads to the duplication of both coding and non‐coding sequences within an organism's genome, providing an abundant supply of genetic material that can drive evolution, ultimately contributing to plant adaptation and speciation. Although non‐coding sequences contain numerous regulatory elements, they have been understudied compared to coding sequences. In order to address this gap, we explored the evolutionary patterns of regulatory sequences, coding sequences and transcriptomes using conserved non‐coding elements (CNEs) as regulatory element proxies following the recent WGD event in opium poppy (Papaver somniferum). Our results showed similar evolutionary patterns in subgenomes of regulatory and coding sequences. Specifically, the biased or unbiased retention of coding sequences reflected the same pattern as retention levels in regulatory sequences. Further, the divergence of gene expression patterns mediated by regulatory element variations occurred at a more rapid pace than that of gene coding sequences. However, gene losses were purportedly dependent on relaxed selection pressure in coding sequences. Specifically, the rapid evolution of tissue‐specific benzylisoquinoline alkaloid production in P. somniferum was associated with regulatory element changes. The origin of a novel stem‐specific ACR, which utilized ancestral cis‐elements as templates, is likely to be linked to the evolutionary trajectory behind the transition of the PSMT1‐CYP719A21 cluster from high levels of expression solely in P. rhoeas root tissue to its elevated expression in P. somniferum stem tissue. Our findings demonstrate that rapid regulatory element evolution can contribute to the emergence of new phenotypes and provide valuable insights into the high evolvability of regulatory elements. Significance Statement: This study demonstrates that the rapid evolution of regulatory elements can drive the emergence of novel phenotypes in plants. Our investigation, in particular, revealed that the evolution of stem‐specific high‐expression patterns of BIAs genes in P. somniferum was linked to rapid changes in regulatory elements. [ABSTRACT FROM AUTHOR]

In an age in which anthropocentrism is increasingly under fire, the investment of the artistic tradition in that paradigm deserves particular attention. Portraiture is especially significant, as it seems to be the anthropocentric art form par excellence. It seems to reinforce key features of anthropocentrism: the distinction of the human from the nonhuman and the superiority of the former over the latter. We can pursue these questions most effectively if we distinguish descriptive ("weak") anthropocentrism from normative ("strong") anthropocentrism. The former involves some sort of focus on humans, the latter combines this with claims about their superiority over the nonhuman. Certain works by influential portraitists, such as Pablo Picasso, Frida Kahlo, and Ana Mendieta, contest both weak and strong anthropocentrism. Other portraits seem to be involved in weak anthropocentrism, but not necessarily strong anthropocentrism. Considering the artwork of Alice Neel and the philosophy of Judith Butler, I argue that such works have an important ethical role to play in orienting us in our relationships with humans, precisely in resisting strong anthropocentrism even in expressing weak anthropocentrism. [ABSTRACT FROM AUTHOR]

Microbes unculturable in vitro remain diagnostically challenging, dependent historically on clinical findings, histology, or targeted molecular detection. We applied whole-genome sequencing directly from tissue to diagnose infections with mycobacteria (leprosy) and parasites (coenurosis). Direct pathogen DNA sequencing provides flexible solutions to diagnosis of difficult pathogens in diverse contexts. [ABSTRACT FROM AUTHOR]

Selection leaves signatures in the DNA sequence of genes, with many test statistics devised to detect its action. While these statistics are frequently used to support hypotheses about the adaptive significance of particular genes, the effect these genes have on reproductive fitness is rarely quantified experimentally. Consequently, it is unclear how gene‐level signatures of selection are associated with empirical estimates of gene effect on fitness. Eukaryotic data sets that permit this comparison are very limited. Using the model plant Arabidopsis thaliana, for which these resources are available, we calculated seven gene‐level substitution and polymorphism‐based statistics commonly used to infer selection (dN/dS, NI, DOS, Tajima's D, Fu and Li's D*, Fay and Wu's H, and Zeng's E) and, using knockout lines, compared these to gene‐level estimates of effect on fitness. We found that consistent with expectations, essential genes were more likely to be classified as negatively selected. By contrast, using 379 Arabidopsis genes for which data was available, we found no evidence that genes predicted to be positively selected had a significantly different effect on fitness than genes evolving more neutrally. We discuss these results in the context of the analytic challenges posed by Arabidopsis, one of the only systems in which this study could be conducted, and advocate for examination in additional systems. These results are relevant to the evaluation of genome‐wide studies across species where experimental fitness data is unavailable, as well as highlighting an increasing need for the latter. [ABSTRACT FROM AUTHOR]

Mosaic loss of the Y chromosome (LOY) is the most frequent chromosomal aberration in aging men and is strongly correlated with mortality and disease. To date, studies of LOY have only been performed in humans, and so it is unclear whether LOY is a natural consequence of our relatively long lifespan or due to exposure to human-specific external stressors. Here, we explored whether LOY could be detected in rats. We applied a locus-specific PCR and target sequencing approach that we used as a proxy to estimate LOY in 339 samples covering eleven tissues from young and old individuals. We detected LOY in four tissues of older rats. To confirm the results from the PCR screening, we re-sequenced 60 full genomes from old rats, which revealed that the Y chromosome is the sole chromosome with low copy numbers. Finally, our results suggest that LOY is associated with other structural aberrations on the Y chromosome and possibly linked to the mosaic loss of the X chromosome. This is the first report, to our knowledge, demonstrating that the patterns of LOY observed in aging men are also present in a rodent, and conclude that LOY may be a natural process in placental mammals. Alberto Orta et al. demonstrate that frequent mosaic loss of chromosome Y (LOY) observed in aging men might also be present in rats. They show that, like in humans, LOY in rats is associated with aging, but is not dependent on environmental stressors, and may be a natural process in placental mammals. [ABSTRACT FROM AUTHOR]

William James is famous for his investigations of the "Varieties of Religious Experience" in which people encounter (what they take to be) the divine. But in his essay, "On a Certain Blindness in Human Beings," his interest is in our experiences, not of anything purportedly supernatural, but of one another. He thinks we need to cultivate the capacity to apprehend the intrinsic value of others, even and especially of strangers. We do so in experiences of the wonder and beauty of our fellow citizens, and of our harmony with them. Democratic societies require a sense of attraction to one another's form of life if they are to inspire shared commitments to public goods. Whereas we shouldn't reject the political significance of aversion, contestation, and dissonance, these negative attitudes do not suffice. Sustaining democratic engagement requires attractive attitudes, and among these are the wonder, beauty, and harmony that James promotes. [ABSTRACT FROM AUTHOR]

The mononuclear phagocyte system (MPS) is a family of cells including progenitors, circulating blood monocytes, resident tissue macrophages, and dendritic cells (DCs) present in every tissue in the body. To test the relationships between markers and transcriptomic diversity in the MPS, we collected from National Center for Biotechnology Information Gene Expression Omnibus (NCBI-GEO) a total of 466 quality RNA sequencing (RNA-seq) data sets generated from mouse MPS cells isolated from bone marrow, blood, and multiple tissues. The primary data were randomly downsized to a depth of 10 million reads and requantified. The resulting data set was clustered using the network analysis tool BioLayout. A sample-to-sample matrix revealed that MPS populations could be separated based upon tissue of origin. Cells identified as classical DC subsets, cDC1s and cDC2s, and lacking Fcgr1 (encoding the protein CD64) were contained within the MPS cluster, no more distinct than other MPS cells. A gene-to-gene correlation matrix identified large generic coexpression clusters associated with MPS maturation and innate immune function. Smaller coexpression gene clusters, including the transcription factors that drive them, showed higher expression within defined isolated cells, including monocytes, macrophages, and DCs isolated from specific tissues. They include a cluster containing Lyve1 that implies a function in endothelial cell (EC) homeostasis, a cluster of transcripts enriched in intestinal macrophages, and a generic lymphoid tissue cDC cluster associated with Ccr7. However, transcripts encoding Adgre1, Itgax, Itgam, Clec9a, Cd163, Mertk, Mrc1, Retnla, and H2-a/e (encoding class II major histocompatibility complex [MHC] proteins) and many other proposed macrophage subset and DC lineage markers each had idiosyncratic expression profiles. Coexpression of immediate early genes (for example, Egr1, Fos, Dusp1) and inflammatory cytokines and chemokines (tumour necrosis factor [Tnf], Il1b, Ccl3/4) indicated that all tissue disaggregation and separation protocols activate MPS cells. Tissue-specific expression clusters indicated that all cell isolation procedures also co-purify other unrelated cell types that may interact with MPS cells in vivo. Comparative analysis of RNA-seq and single-cell RNA-seq (scRNA-seq) data from the same lung cell populations indicated that MPS heterogeneity implied by global cluster analysis may be even greater at a single-cell level. This analysis highlights the power of large data sets to identify the diversity of MPS cellular phenotypes and the limited predictive value of surface markers to define lineages, functions, or subpopulations. The mononuclear phagocyte system is a family of cells present in every tissue in the body. A comprehensive network analysis of public transcriptomic data reveals the close relationships between tissue-resident cells of the mononuclear phagocyte system (macrophages and dendritic cells) and questions the utility of surface markers to define lineages, functions, or subpopulations. [ABSTRACT FROM AUTHOR]

The germline mutation rate (GMR) sets the pace at which mutations, the raw material of evolution, are introduced into the genome. By sequencing a dataset of unprecedently broad phylogenetic scope, Bergeron et al. estimated species-specific GMR, offering numerous insights into how this parameter shapes and is shaped by life-history traits. [ABSTRACT FROM AUTHOR]

One of the most significant physiological challenges to neonatal and juvenile ruminants is the development and establishment of the rumen. Using a subset of RNA-Seq data from our high-resolution atlas of gene expression in sheep (Ovis aries) we have provided the first comprehensive characterization of transcription of the entire gastrointestinal (GI) tract during the transition from pre-ruminant to ruminant. The dataset comprises 164 tissue samples from sheep at four different time points (birth, one week, 8 weeks and adult). Using network cluster analysis we illustrate how the complexity of the GI tract is reflected in tissueand developmental stage-specific differences in gene expression. The most significant transcriptional differences between neonatal and adult sheep were observed in the rumen complex. Comparative analysis of gene expression in three GI tract tissues from age-matched sheep and goats revealed species-specific differences in genes involved in immunity and metabolism. This study improves our understanding of the transcriptomic mechanisms involved in the transition from pre-ruminant to ruminant by identifying key genes involved in immunity, microbe recognition and metabolism. The results form a basis for future studies linking gene expression with microbial colonization of the developing GI tract and provide a foundation to improve ruminant efficiency and productivity through identifying potential targets for novel therapeutics and gene editing. [ABSTRACT FROM AUTHOR]

Chosen names reflect changes in societal values, personal tastes and cultural diversity. Vogues in name usage can be easily shown on a case by case basis, by plotting the rise and fall in their popularity over time. However, individual name choices are not made in isolation and trends in naming are better understood as group-level phenomena. Here we use network analysis to examine onomastic (name) datasets in order to explore the influences on name choices within the UK over the last 170 years. Using a large representative sample of approximately 22 million forenames from England and Wales given between 1838 and 2014, along with a complete population sample of births registered between 1996 and 2016, we demonstrate how trends in name usage can be visualised as network graphs. By exploring the structure of these graphs various patterns of name use become apparent, a consequence of external social forces, such as migration, operating in concert with internal mechanisms of change. In general, we show that the topology of network graphs can reveal naming vogues, and that naming vogues in part reflect social and demographic changes. Many name choices are consistent with a self-correcting feedback loop, whereby rarer names become common because there are virtues perceived in their rarity, yet with these perceived virtues lost upon increasing commonality. Towards the present day, we can speculate that the comparatively greater range of media, freedom of movement, and ability to maintain globally-distributed social networks increases the number of possible names, but also ensures they may more quickly be perceived as commonplace. Consequently, contemporary naming vogues are relatively short-lived with many name choices appearing a balance struck between recognisability and rarity. The data are available in multiple forms including via an easy-to-use web interface at . [ABSTRACT FROM AUTHOR]

Background: The domestic chicken ( Gallus gallus ) is widely used as a model in developmental biology and is also an important livestock species. We describe a novel approach to data integration to generate an mRNA expression atlas for the chicken spanning major tissue types and developmental stages, using a diverse range of publicly-archived RNA-seq datasets and new data derived from immune cells and tissues. Results: Randomly down-sampling RNA-seq datasets to a common depth and quantifying expression against a reference transcriptome using the mRNA quantitation tool Kallisto ensured that disparate datasets explored comparable transcriptomic space. The network analysis tool Graphia was used to extract clusters of co-expressed genes from the resulting expression atlas, many of which were tissue or cell-type restricted, contained transcription factors that have previously been implicated in their regulation, or were otherwise associated with biological processes, such as the cell cycle. The atlas provides a resource for the functional annotation of genes that currently have only a locus ID. We cross-referenced the RNA-seq atlas to a publicly available embryonic Cap Analysis of Gene Expression (CAGE) dataset to infer the developmental time course of organ systems, and to identify a signature of the expansion of tissue macrophage populations during development. Conclusion: Expression profiles obtained from public RNA-seq datasets – despite being generated by different laboratories using different methodologies – can be made comparable to each other. This meta-analytic approach to RNA-seq can be extended with new datasets from novel tissues, and is applicable to any species. [ABSTRACT FROM AUTHOR]

Sheep are a key source of meat, milk and fibre for the global livestock sector, and an important biomedical model. Global analysis of gene expression across multiple tissues has aided genome annotation and supported functional annotation of mammalian genes. We present a large-scale RNA-Seq dataset representing all the major organ systems from adult sheep and from several juvenile, neonatal and prenatal developmental time points. The Ovis aries reference genome (Oar v3.1) includes 27,504 genes (20,921 protein coding), of which 25,350 (19,921 protein coding) had detectable expression in at least one tissue in the sheep gene expression atlas dataset. Network-based cluster analysis of this dataset grouped genes according to their expression pattern. The principle of ‘guilt by association’ was used to infer the function of uncharacterised genes from their co-expression with genes of known function. We describe the overall transcriptional signatures present in the sheep gene expression atlas and assign those signatures, where possible, to specific cell populations or pathways. The findings are related to innate immunity by focusing on clusters with an immune signature, and to the advantages of cross-breeding by examining the patterns of genes exhibiting the greatest expression differences between purebred and crossbred animals. This high-resolution gene expression atlas for sheep is, to our knowledge, the largest transcriptomic dataset from any livestock species to date. It provides a resource to improve the annotation of the current reference genome for sheep, presenting a model transcriptome for ruminants and insight into gene, cell and tissue function at multiple developmental stages. [ABSTRACT FROM AUTHOR]

William James and Ralph Waldo Emerson are both committed individualists. However, in what do their individualisms consist and to what degree do they resemble each other? This essay demonstrates that James's individualism is strikingly similar to Emerson's. By taking James's own understanding of Emerson's philosophy as a touchstone, I argue that both see individualism to consist principally in self-reliance, receptivity, and vocation. Putting these two figures' understandings of individualism in comparison illuminates under-appreciated aspects of each figure, for example, the political implications of their individualism, the way that their religious individuality is politically engaged, and the importance of exemplarity to the politics and ethics of both of them. [ABSTRACT FROM AUTHOR]

The introduction of power as a key analytical concept was a watershed moment in the history of religious studies. But what exactly does it mean to embrace the turn to power? Does it mean giving up on the study of experiences, meanings, and beliefs? Or does it just mean changing how we approach them? In my book, Visions of Religion, I argue that we can retain experience and meaning as meaningful analytical concepts even after the turn to power. We can do so without embracing any of the key assumptions of perennialism or what Craig Martin calls neo-perennialism. In this response to Martin, I show that his categorization of my approach as neo-perennialist is based upon a series of misattributions. [ABSTRACT FROM AUTHOR]

Background: The availability of fast alignment-free algorithms has greatly reduced the computational burden of RNAseq processing, especially for relatively poorly assembled genomes. Using these approaches, previous RNA-seq datasets could potentially be processed and integrated with newly sequenced libraries. Confounding factors in such integration include sequencing depth and methods of RNA extraction and selection. Different selection methods (typically, either polyA-selection or rRNA-depletion) omit different RNAs, resulting in different fractions of the transcriptome being sequenced. In particular, rRNA-depleted libraries sample a broader fraction of the transcriptome than polyA-selected libraries. This study aimed to develop a systematic means of accounting for library type that allows data from these two methods to be compared. Results: The method was developed by comparing two RNA-seq datasets from ovine macrophages, identical except for RNA selection method. Gene-level expression estimates were obtained using a two-part process centred on the high-speed transcript quantification tool Kallisto. Firstly, a set of reference transcripts was defined that constitute a standardised RNA space, with expression from both datasets quantified against it. Secondly, a simple ratio-based correction was applied to the rRNA-depleted estimates. The outcome is an almost perfect correlation between gene expression estimates, independent of library type and across the full range of levels of expression. Conclusion: A combination of reference transcriptome filtering and a ratio-based correction can create equivalent expression profiles from both polyA-selected and rRNA-depleted libraries. This approach will allow meta-analysis and integration of existing RNA-seq data into transcriptional atlas projects. [ABSTRACT FROM AUTHOR]

The article presents the author's insights on the arguments related to intellectual virtue and civility. Topics discussed include the political concept of civility, the essays on civil discourse and intellectual virtue, and the interrelationships between intellectual virtue and civility and its relationship to the literature in political theology.

Alternative splicing, a mechanism of post-transcriptional RNA processing whereby a single gene can encode multiple distinct transcripts, has been proposed to underlie morphological innovations in multicellular organisms. Genes with developmental functions are enriched for alternative splicing events, suggestive of a contribution of alternative splicing to developmental programmes. The role of alternative splicing as a source of transcript diversification has previously been compared to that of gene duplication, with the relationship between the two extensively explored. Alternative splicing is reduced following gene duplication with the retention of duplicate copies higher for genes whichwere alternatively spliced prior to duplication. Furthermore, and unlike the case for overall gene number, the proportion of alternatively spliced genes has also increased in line with the evolutionary diversification of cell types, suggesting alternative splicing may contribute to the complexity of developmental programmes. Together these observations suggest a prominent role for alternative splicing as a source of functional innovation. However, it is unknown whether the proliferation of alternative splicing events indeed reflects a functional expansion of the transcriptome or instead results from weaker selection acting on larger species, which tend to have a higher number of cell types and lower population sizes. This article is part of the themed issue 'Evo-devo in the genomics era, and the origins of morphological diversity'. [ABSTRACT FROM AUTHOR]

Fibrillin-1 is a major component of the extracellular microfibrils, where it interacts with other extracellular matrix proteins to provide elasticity to connective tissues, and regulates the bioavailability of TGFβ family members. A peptide consisting of the C-terminal 140 amino acids of fibrillin-1 has recently been identified as a glucogenic hormone, secreted from adipose tissue during fasting and targeting the liver to release glucose. This fragment, called asprosin, also signals in the hypothalamus to stimulate appetite. Asprosin levels are correlated with many of the pathologies indicative of metabolic syndrome, including insulin resistance and obesity. Previous studies and reviews have addressed the therapeutic potential of asprosin as a target in obesity, diabetes and related conditions without considering mechanisms underlying the relationship between generation of asprosin and expression of the much larger fibrillin-1 protein. Profibrillin-1 undergoes obligatory cleavage at the cell surface as part of its assembly into microfibrils, producing the asprosin peptide as well as mature fibrillin-1. Patterns of FBN1 mRNA expression are inconsistent with the necessity for regulated release of asprosin. The asprosin peptide may be protected from degradation in adipose tissue. We present evidence for an alternative possibility, that asprosin mRNA is generated independently from an internal promoter within the 3′ end of the FBN1 gene, which would allow for regulation independent of fibrillin-synthesis and is more economical of cellular resources. The discovery of asprosin opened exciting possibilities for treatment of metabolic syndrome related conditions, but there is much to be understood before such therapies could be introduced into the clinic. • Asprosin is a glucogenic hormone coded by the 3' sequence of the fibrillin-1 gene. • It is not clear if asprosin is cleaved from fibrillin-1 or made independently. • Fibrillin-1 mRNA expression patterns are inconsistent with asprosin production. • Is asprosin transcribed from its own promoter or sequestered for later secretion? • It is important to have this information before asprosin can be used clinically. [ABSTRACT FROM AUTHOR]

Experimental and epidemiological data support the potential activity of acetaminophen against ovarian cancer (OVCA). In the present study, we sought to confirm the activity of acetaminophen in OVCA cell lines and to investigate the molecular basis of response. A total of 16 OVCA cell lines underwent pretreatment (baseline) genome-wide expression measurements and were then treated with and analyzed for acetaminophen sensitivity. Pearson's correlation analysis was performed to identify genes that were associated with OVCA acetaminophen response. The identified genes were subjected to pathway analysis, and the expression of each represented pathway was summarized using principal component analysis. OVCA acetaminophen response pathways were analyzed in 4 external clinico-genomic datasets from 820 women for associations with overall survival from OVCA. Acetaminophen exhibited antiproliferative activity against all tested OVCA cell lines, with half maximal inhibitory concentration values ranging from 63.2 to 403 µM. Pearson's correlation followed by biological pathway analysis identified 13 pathways to be associated with acetaminophen sensitivity (P<0.01). Associations were observed between patient survival from OVCA and expression of the following pathways: Development/angiotensin signaling via β-arrestin (P=0.04), protein folding and maturation/angiotensin system maturation (P=0.02), signal transduction/c-Jun N-terminal kinase (JNK) pathway (P=0.03) and androstenedione and testosterone biosynthesis and metabolism (P=0.02). We confirmed that acetaminophen was active against OVCA cells in vitro. Furthermore, we identified 4 molecular signaling pathways associated with acetaminophen response that may also affect overall survival in women with OVCA, including the JNK pathway, which has been previously implicated in the mechanism of action of acetaminophen and is predictive of decreased survival in women with OVCA. [ABSTRACT FROM AUTHOR]

After a long period of neglect, William James's political philosophy has been receiving significant attention in the past two decades. For the most part, however, those interested in his political thought do not attend to his philosophy of religion and vice versa. In this article, I argue that we can understand the individualism that James famously promotes in Varieties of Religious Experience as very much a political ideal. The sort of religious individuality that James endorses does not abjure social responsibility but rather involves an activist commitment to improve religious and societal institutions. [ABSTRACT FROM AUTHOR]

Rapidly evolving proteins can aid the identification of genes underlying phenotypic adaptation across taxa, but functional and structural elements of genes can also affect evolutionary rates. In plants, the 'edges' of exons, flanking intron junctions, are known to contain splice enhancers and to have a higher degree of conservation compared to the remainder of the coding region. However, the extent to which these regions may be masking indicators of positive selection or account for the relationship between dN/ dS and other genomic parameters is unclear. We investigate the effects of exon edge conservation on the relationship of dN/ dS to various sequence characteristics and gene expression parameters in the model plant Arabidopsis thaliana. We also obtain lineage-specific dN/ dS estimates, making use of the recently sequenced genome of Thellungiella parvula, the second closest sequenced relative after the sister species Arabidopsis lyrata. Overall, we find that the effect of exon edge conservation, as well as the use of lineage-specific substitution estimates, upon dN/ dS ratios partly explains the relationship between the rates of protein evolution and expression level. Furthermore, the removal of exon edges shifts dN/ dS estimates upwards, increasing the proportion of genes potentially under adaptive selection. We conclude that lineage-specific substitutions and exon edge conservation have an important effect on dN/ dS ratios and should be considered when assessing their relationship with other genomic parameters. [ABSTRACT FROM AUTHOR]

This article considers the different methods for determining sample sizes for Wald, likelihood ratio, and score tests for logistic regression. We review some recent methods, report the results of a simulation study comparing each of the methods for each of the three types of test, and provide Mathematica code for calculating sample size. We consider a variety of covariate distributions, and find that a calculation method based on a first order expansion of the likelihood ratio test statistic performs consistently well in achieving a target level of power for each of the three types of test. [ABSTRACT FROM AUTHOR]

Moral horror is an extreme emotional response to that which violates things we regard as sacred. In Robert Merrihew Adams's view, horror is a response to badness and not to wrongness, and so one could properly regard some actions as horrible but not wrong. In contrast, I argue that horror, when directed toward actions, is only appropriate for wrong actions. The reason is that horror involves moral disgust, and agents who committed a horrible action would have self-disgust, that is, they would be repulsive to themselves. I argue, with reference to killing in combat and in self-defense, that those who have done no wrong should not be in such a state. [ABSTRACT FROM AUTHOR]

'Searching for symbolic meanings,' Talal Asad says, 'is not the name of my game.' In putting things like this, Asad leads us to believe that the approach to the study of religion he favors, which focuses on social power, is at odds with the approach Clifford Geertz advances, which focuses on the interpretation of symbolic meaning. However, for a particular action or pattern of behavior to affect social power structures, it must possess symbolic meaning. So the social power approach and the interpretive approach are not as different as some of their respective advocates indicate. [ABSTRACT FROM AUTHOR]

In this reply to Kent Brintnall's response to my essay on Georges Bataille and the ethics of ecstasy, I explore two primary questions: whether instrumentalization is inherently violent and non-instrumentalization is inherently non-violent, and whether there is a way to intervene in the world that avoids both 'apathetic disengagement' and domination. I endorse the view that instrumentalization can be good as well as bad, and I suggest that it is possible to strive to intervene in the world without striving to master it. I make reference to Sarah Coakley as a Christian theologian who advances particular practices that aim for non-dominating intervention in theworld. [ABSTRACT FROM AUTHOR]

Davidson and Beaver (1977) extended the Bradley–Terry model to incorporate the possible effect of position within a choice set on the choices made in paired comparisons experiments. We further extend the Davidson–Beaver result to choice sets of any size and show, under a mild restriction, that designs optimal for the multinomial logit model are still optimal. Designs balanced for carry-over effects of all orders can be used to construct designs with a diagonal information matrix for attribute effects. The theoretical results are derived assuming equal merits and we discuss the possible consequences of assuming unequal merits in an example. [ABSTRACT FROM AUTHOR]

An essay is presented that discusses the rhetoric of experience, which is a conception of religious experience as private and immediate, in the context of scholarly study of religious experience. The author argues against scholar Robert H. Sharf's dismissal of the rhetoric of experience, which Sharf sees as mainly legitimating imperialist sociopolitical interests. Topics include Buddhist mystical experiences, mind-body dualism, and Pentecostal conversion experiences.