The American Philosophical Society and the rise of astronomy in the United States in the middle of the nineteenth century

Early geological investigations in the St David's area (Pembrokeshire) are described, particularly the work of Murchison. In a reconnaissance survey in 1835, he regarded a ridge of rocks at St David's as intrusive in unfossiliferous Cambrian; and the early Survey mapping (chiefly the work of Aveline and Ramsay) was conducted on that assumption, leading to the publication of maps in 1845 and 1857. The latter represented the margins of the St David's ridge as ‘Altered Cambrian’. So the supposedly intrusive ‘syenite’ was regarded as younger, and there was no Precambrian. These views were challenged by a local doctor, Henry Hicks, who developed an idea of the ex-Survey palaeontologist John Salter that the rocks of the ridge were stratified and had formed a Precambrian island, round which Cambrian sediments (now confirmed by fossil discoveries) had been deposited. Hicks subsequently proposed subdivision of his Precambrian into ‘Dimetian’, ‘Pebidian’, and (later) ‘Arvonian’, and he attempted correlations with rocks in Shropshire, North Wales, and even North America, seeking to develop the neo-Neptunist ideas of Sterry Hunt. The challenge to the Survey's work was countered in the 1880s by the Director General, Geikie, who showed that Hicks's idea of stratification in the Dimetian was mistaken. A heated controversy developed, several amateur geologists, supported by a group of Cambridge Sedgwickians, forming a coalition of ‘Archaeans’ against the Survey. Geikie was supported by Lloyd Morgan. Attention focused particularly on Ogof Lle-sugn Cave and St Non's Arch, with theory/controversy-ladenness of observations evident on both sides. Evidence from an eyewitness student record of a Geological Society meeting reveals the ‘sanit`ized’ nature of the official summary of the debate in QJGS. Field mapping early in the twentieth century by J. F. N. Green allowed a compromise consensus to be achieved, but Green's evidence for unconformity between the Cambrian and the Dimetian, obtained by excavation, can no longer be verified, and his consensual history of the area may need revision. Unconformity between the Cambrian and the Pebidian tuffs is not in doubt, however, and Precambrian at St David's is accepted. The study exhibits features of geological controversy and the British geological community in the nineteenth century. It also furnishes a further instance of the great influence of Murchison in nineteenth-century British geology and the side-effects of his controversy with Sedgwick.     

Jean Méry (1645–1722) and his ideas on the foetal blood flow

We present an analysis, and first full English translation, of a paper by Kant entitled ‘Über die Vulcane im Monde’ (1785). Kant became interested in the question of whether the mountains of the Moon were extinct volcanoes. Stimulated by the work of Herschel, Aepinus, and others, he considered the appearance of the Moon's surface and the possibility of lunar vulcanism. From this, he was led to consider the structures of mountain ranges on the Earth, which he decided were non-volcanic in origin, being produced by eruptions of vapours from the interior of the Earth soon after it formed from an original ‘chaos’. Kant developed his ideas in such a way as to yield a characteristic eighteenth-century ‘theory of the Earth’. We argue that the empirical base of his theory was provided by knowledge of the mountain ranges of Bohemia and Moravia. Analogies based on observations of the Moon further assisted in the construction of the theory. But the reasoning ran in two directions: what was seen on the Moon was construed in terms of what Kant knew of the Earth's topography; and the Earth's topography was presumed to be analogous to that of the Moon, for both the Earth and the Moon (and indeed all heavenly bodies) supposedly had essentially similar origins. Kant's ideas of 1785 are related to his earlier writings of 1754, 1755, and 1756, and also to the lectures on physical geography that he presented at Königsberg.     

Instruments of Music,Instruments of Science: Hermann von Helmholtz's Musical Practices,his Classicism,and his Beethoven Sonata

The young Hermann Helmholtz, in an 1838 letter home, declared that he always appreciated music much more when he played it for himself. Though a frequent concert-goer, and celebrated for his highly influential 1863 work on the physiological basis of music theory, Die Lehre von den Tonempfindungen, it is likely that Helmholtz's enduring engagement with music began with his initial, personal experience of playing music for himself. I develop this idea, shifting the discussion of Helmholtz's work on sound sensation back to its origins, and examine the role of his material interaction with musical instruments and music itself. In his sound sensation studies, Helmholtz understood sound as an external, physical object. But Helmholtz also conceived of sound in musical terms. Further, Helmholtz's particular musical tastes as well as his deeply personal interaction with musical instruments allowed him to reconcile his conception of sound as physical object with his conception of sound as music. Helmholtz's physiological theory of sound sensation was both the product of and constitutive of how he heard and created sound. I argue that Helmholtz himself was the embodied reconciliation of his physiological theory of sound sensation and his belief that musical aesthetics were historically and culturally contingent.     

The unconventional secretion of stress-inducible protein 1 by a heterogeneous population of extracellular vesicles

The co-chaperone stress-inducible protein 1 (STI1) is released by astrocytes, and has important neurotrophic properties upon binding to prion protein (PrP^C). However, STI1 lacks a signal peptide and pharmacological approaches pointed that it does not follow a classical secretion mechanism. Ultracentrifugation, size exclusion chromatography, electron microscopy, vesicle labeling, and particle tracking analysis were used to identify three major types of extracellular vesicles (EVs) released from astrocytes with sizes ranging from 20–50, 100–200, and 300–400 nm. These EVs carry STI1 and present many exosomal markers, even though only a subpopulation had the typical exosomal morphology. The only protein, from those evaluated here, present exclusively in vesicles that have exosomal morphology was PrP^C. STI1 partially co-localized with Rab5 and Rab7 in endosomal compartments, and a dominant-negative for vacuolar protein sorting 4A (VPS4A), required for formation of multivesicular bodies (MVBs), impaired EV and STI1 release. Flow cytometry and PK digestion demonstrated that STI1 localized to the outer leaflet of EVs, and its association with EVs greatly increased STI1 activity upon PrP^C-dependent neuronal signaling. These results indicate that astrocytes secrete a diverse population of EVs derived from MVBs that contain STI1 and suggest that the interaction between EVs and neuronal surface components enhances STI1–PrP^C signaling.     

Strong association of de novo copy number mutations with sporadic schizophrenia

Schizophrenia is an etiologically heterogeneous psychiatric disease, which exists in familial and nonfamilial (sporadic) forms. Here, we examine the possibility that rare de novo copy number (CN) mutations with relatively high penetrance contribute to the genetic component of schizophrenia. We carried out a whole-genome scan and implemented a number of steps for finding and confirming CN mutations. Confirmed de novo mutations were significantly associated with schizophrenia (P = 0.00078) and were collectively approximately 8 times more frequent in sporadic (but not familial) cases with schizophrenia than in unaffected controls. In comparison, rare inherited CN mutations were only modestly enriched in sporadic cases. Our results suggest that rare de novo germline mutations contribute to schizophrenia vulnerability in sporadic cases and that rare genetic lesions at many different loci can account, at least in part, for the genetic heterogeneity of this disease.     

MicroRNA Mirn140 modulates Pdgf signaling during palatogenesis

Disruption of signaling pathways such as those mediated by sonic hedgehog (Shh) or platelet-derived growth factor (Pdgf) causes craniofacial abnormalities, including cleft palate. The role that microRNAs play in modulating palatogenesis, however, is completely unknown. We show that, in zebrafish, the microRNA Mirn140 negatively regulates Pdgf signaling during palatal development, and we provide a mechanism for how disruption of Pdgf signaling causes palatal clefting. The pdgf receptor alpha (pdgfra) 3' UTR contained a Mirn140 binding site functioning in the negative regulation of Pdgfra protein levels in vivo. pdgfra mutants and Mirn140-injected embryos shared a range of facial defects, including clefting of the crest-derived cartilages that develop in the roof of the larval mouth. Concomitantly, the oral ectoderm beneath where these cartilages develop lost pitx2 and shha expression. Mirn140 modulated Pdgf-mediated attraction of cranial neural crest cells to the oral ectoderm, where crest-derived signals were necessary for oral ectodermal gene expression. Mirn140 loss of function elevated Pdgfra protein levels, altered palatal shape and caused neural crest cells to accumulate around the optic stalk, a source of the ligand Pdgfaa. These results suggest that the conserved regulatory interactions of mirn140 and pdgfra define an ancient mechanism of palatogenesis, and they provide candidate genes for cleft palate.