Something from Nothing: Why Some Negative Existentials are Fundamental

It strikes many as obvious that negative facts—such as that Justin Trudeau is not the prime minister of Australia—are not fundamental: negative facts must ultimately be explained in terms of positive facts (for instance, that Justin Trudeau is the prime minister of Canada). I focus on a particular class of negative facts: contingent negative existentials (such as that there are no 10ft tall humans). If contingent negative existentials are not fundamental, then they must be explained. But the claim that contingent negative existentials are explained is in tension with the widely held view that any universal generalization can be explained by its instances together with a totality fact (i.e. a fact to the effect that the instances exhaust the relevant domain). This is because a totality fact is itself a negative existential, and equivalent to a universal generalization. If the explanation for any contingent negative existential must appeal to another contingent negative existential, then—unless there are no fundamental facts—not all contingent negative existentials can be non-fundamental. I argue that we should give up the age-old mantra that only positive facts can be fundamental. I show that at least some contingent negative existentials are fundamental. I first make the case for including a totality fact in the explanans for a contingent negative existential and show that alternative accounts for explaining such facts are inadequate. I then undermine the standard arguments for subscribing to the view that there are no negative facts—including negative existentials—at the fundamental level

Principle of Sufficient Reason

According to the Principle of Sufficient Reason (henceforth ‘PSR’), everything has an explanation or sufficient reason. This paper addresses three questions. First, how continuous is the contemporary notion of grounding with the notion of sufficient reason endorsed by Spinoza, Leibniz, and other rationalists? In particular, does a PSR formulated in terms of ground retain the intuitive pull and power of the PSR endorsed by the rationalists? Second, to what extent can the PSR avoid the formidable traditional objections levelled against it if it is formulated in terms of ground? And finally, how might historical discussion of the PSR shed light on the contemporary notion of grounding

Alzheimer’s disease-associated peptide Aβ₄₂ mobilizes ER Ca²⁺ via InsP₃R-dependent and -independent mechanisms

Dysregulation of Ca2+ homeostasis is considered to contribute to the toxic action of the Alzheimer’s Disease (AD) associated Amyloid β-peptide (Aβ). Ca2+ fluxes across the plasma membrane and release from intracellular stores have both been reported to underlie the Ca2+ fluxes induced by Aβ42. Here, we investigated the contribution of Ca2+ release from the endoplasmic reticulum (ER) to the effects of Aβ42 upon Ca2+ homeostasis and the mechanism by which Aβ42 elicited these effects. Consistent with previous reports, application of soluble oligomeric forms of Aβ42 exhibited Ca2+ mobilizing properties. The Aβ42-stimulated Ca2+ signals persisted in the absence of extracellular Ca2+ indicating a significant contribution of Ca2+ release from the ER Ca2+ store to the generation of these signals. Moreover, inositol 1,4,5-trisphosphate (InsP3) signaling contributed to Aβ42-stimulated Ca2+ release. The Ca2+ mobilizing effect of Aβ42 was also observed when applied to permeabilized cells deficient in InsP3 receptors revealing an additional direct effect of internalized Aβ42 upon the ER, and a mechanism for induction of toxicity by intracellular Aβ42

The susceptibility of roots to infection by an arbuscular mycorrhizal fungus in relation to age and phosphorus supply

An apparatus in which plant roots may be challenged uniformly with inoculum of arbuscular mycorrhizal fungi is described. Seedlings of leek (Allium porrum L.) or clover (Trifolium repens L.) were first grown non-symbiotically in the apparatus for 21 d at three rates of phosphorus (P) addition to soil (1 50 (PI), 450 (P3) and 750 (P5) mg P kg-1 soil). The positions of individual root tips were recorded, and the root systems then challenged with inoculum of Glomus mosseae (Nicol & Gerd.) Gerdemann & Trappe. Roots were excised 14 d later, and the probability of occurrence of internal infection in successive 3 mm (clover) or 5 mm (leek) sections of root was estimated in first-order laterals (clover) or main axes (leek) from the proportion of sections at each location of replicate roots that bore internal fungal structures. Only in the region of a root proximal to the position of the root tips at inoculation could data be used to investigate change of probability of infection with cell age. Here, there were sharp declines in probability of infection with proximal distance, in both hosts and in all P treatments. The decline of probability was greater in clover: when expressed in terms of cell age at the time of challenge, there was no infection at Pl in cells > 10 d old in leek and none in cells > 7 d old in clover. Models of the form log(e) [p(i)/(1-p(i))] = alpha + beta x distance, where p(i) is the estimated probability of infection and alpha and beta are constants, were fitted to these data. The odds on infection are [p(i)/(1-p(i))]. For leek, 8 was unaltered by P addition (P3 and P5 curves were parallel to P1) but from alpha it could be calculated that on average the odds on successful infection at any particular distance were reduced by 3 7 % and 70 % by P3 and P5 rates of P addition respectively. In clover the curves for the three P treatments were not parallel. Addition of P appeared to reduce the odds on infection of clover much more than those of leek. We conclude that the simplest explanation for the patterns of infection in leek is that P addition increased the time taken for soil inoculum of G. mosseae to infect roots: the mechanism in clover might be more complex

Towards Epistemic Justice in Islam

Epistemic injustice consists in a wrong done to someone in their capacity as a knower. I focus on epistemic injustice—more specifically, testimonial injustice—as it arises in the Qur’an. Verse 2:282 implies that the worth of a man’s testimony is twice that of a woman’s testimony. The divine norm suggested by the verse is in direct conflict with the norms that govern testimonial justice. These norms require that women should not be judged less reliable simply because they are women. But a divine norm that says that a woman’s testimony is worth less than a man’s also generates a puzzle for the norms that govern testimonial justice: when the divine norm that says that a woman’s testimony is worth half that of a man’s testimony is endorsed and internalised by Muslim women who then assert it, testimonial justice seems to require that we should take these women’s testimony to be less reliable than men’s testimony. I will argue that the solution to the puzzle lies in recognizing that the application of Quranic norms to a given situation requires getting some relevant facts right, and is not purely a matter of one’s values. As such, asserted Quranic norms are not subject to the deference characteristically demanded by testimonial justice

The Contingency of Creation and Divine Choice

According to the Principle of Sufficient Reason (‘PSR’), every fact has an explanation for why it obtains. If the PSR is true, there must be a sufficient reason for why God chose to create our world. But a sufficient reason for God’s choice plausibly necessitates that choice. It thus seems that God could not have done otherwise, and that our world exists necessarily. We therefore appear forced to pick between the PSR, and the contingency of creation and divine choice. I show that a third option remains open, and thus that it is possible to preserve the contingency of creation and divine choice even while endorsing the PSR. My solution depends on the coherence of a restricted modal realism. On this modal realism, there is more than one possible morally optimal created world, and for each such world there is an existing possibility in which God creates that world

Russell on Propositions

Bertrand Russell was neither the first nor the last philosopher to engage in serious theorizing about propositions. But his work between 1903, when he published The Principles of Mathematics, and 1919, when his final lectures on logical atomism were published, remains among the most important on the subject. And its importance is not merely historical. Russell’s rapidly evolving treatment of propositions during this period was driven by his engagement with – and discovery of – puzzles that either continue to shape contemporary theorizing about propositions, or ought to do so. Russell’s creative responses to these puzzles also laid the foundation for many later accounts (most obviously, contemporary ‘Russellian’ accounts of propositions). In this entry we provide an opinionated overview of Russell’s influential treatment of propositions, with a focus on the evolution of his views from 1903 to 1919. A growing secondary literature is dedicated to Russell’s changing views during this period, and their often complex or opaque motivations. We do not intervene overmuch in this ongoing scholarly discussion. Instead, our aim is to trace some of the central motivations for Russell’s evolving views, and highlight the extent to which these motivations remain relevant to contemporary theorizing about propositions

Major transcriptome re-organisation and abrupt changes in signalling, cell cycle and chromatin regulation at neural differentiation <em>in vivo</em>

Here, we exploit the spatial separation of temporal events of neural differentiation in the elongating chick body axis to provide the first analysis of transcriptome change in progressively more differentiated neural cell populations in vivo. Microarray data, validated against direct RNA sequencing, identified: (1) a gene cohort characteristic of the multi-potent stem zone epiblast, which contains neuro-mesodermal progenitors that progressively generate the spinal cord; (2) a major transcriptome reorganisation as cells then adopt a neural fate; and (3) increasing diversity as neural patterning and neuron production begin. Focussing on the transition from multi-potent to neural state cells, we capture changes in major signalling pathways, uncover novel Wnt and Notch signalling dynamics, and implicate new pathways (mevalonate pathway/steroid biogenesis and TGF beta). This analysis further predicts changes in cellular processes, cell cycle, RNA-processing and protein turnover as cells acquire neural fate. We show that these changes are conserved across species and provide biological evidence for reduced proteasome efficiency and a novel lengthening of S phase. This latter step may provide time for epigenetic events to mediate large-scale transcriptome re-organisation; consistent with this, we uncover simultaneous downregulation of major chromatin modifiers as the neural programme is established. We further demonstrate that transcription of one such gene, HDAC1, is dependent on FGF signalling, making a novel link between signals that control neural differentiation and transcription of a core regulator of chromatin organisation. Our work implicates new signalling pathways and dynamics, cellular processes and epigenetic modifiers in neural differentiation in vivo, identifying multiple new potential cellular and molecular mechanisms that direct differentiation

The development of endomycorrhizal root systems VIII. Effects of soil phosphorus and fungal colonization on the concentration of soluble carbohydrates in roots

Concentrations of phosphorus in shoot and soluble carbohydrates (fructose, glucose, sucrose and fructans) in root were measured in non-mycorrhizal and vesicular-arbuscular (VA) mycorrhizal (Glomus mosseae) leek plants (Allium porrum) raised at six concentrations of soil phosphate. In conditions when an increased concentration of soil phosphate reduced VA mycorrhizal infection, the concentrations of soluble carbohydrates in the root were at a maximum. Therefore the hypothesis that greater concentrations of soluble carbohydrates in roots favour VA mycorrhizal infection is discounted. There was a specific effect of VA mycorrhizas, in that infected roots contained a larger concentration of sucrose than did uninfected roots, in plants with similar phosphorus concentrations in dry matter of shoots. We conclude, first, that increased phosphorus supply from either phosphate addition to soil or VA mycorrhizal infection increases concentration of soluble carbohydrates in leek roots and, secondly, that the VA mycorrhizal root behaves as a particularly strong physiological sink when there is an excess concentration of sucrose in the host