Author response

We recently reported that the C2AB portion of Synaptotagmin 1 (Syt1) could self-assemble into Ca(2+)-sensitive ring-like oligomers on membranes, which could potentially regulate neurotransmitter release. Here we report that analogous ring-like oligomers assemble from the C2AB domains of other Syt isoforms (Syt2, Syt7, Syt9) as well as related C2 domain containing protein, Doc2B and extended Synaptotagmins (E-Syts). Evidently, circular oligomerization is a general and conserved structural aspect of many C2 domain proteins, including Synaptotagmins. Further, using electron microscopy combined with targeted mutations, we show that under physiologically relevant conditions, both the Syt1 ring assembly and its rapid disruption by Ca(2+) involve the well-established functional surfaces on the C2B domain that are important for synaptic transmission. Our data suggests that ring formation may be triggered at an early step in synaptic vesicle docking and positions Syt1 to synchronize neurotransmitter release to Ca(2+) influx. DOI: http://dx.doi.org/10.7554/eLife.17262.00

Cognition, emotion, and arithmetic in primary school: A cross-cultural investigation

The study investigated cross‐cultural differences in variability and average performance in arithmetic, mathematical reasoning, symbolic and non‐symbolic magnitude processing, intelligence, spatial ability, and mathematical anxiety in 890 6‐ to 9‐year‐old children from the United Kingdom, Russia, and China. Cross‐cultural differences explained 28% of the variance in arithmetic and 17.3% of the variance in mathematical reasoning, with Chinese children outperforming the other two groups. No cross‐cultural differences were observed for spatial ability and mathematical anxiety. In all samples, symbolic magnitude processing and mathematical reasoning were independently related to early arithmetic. Other factors, such as non‐symbolic magnitude processing, mental rotation, intelligence, and mathematical anxiety, produced differential patterns across the populations. The results are discussed in relation to potential influences of parental practice, school readiness, and linguistic factors on individual differences in early mathematics

A Simple Tetraminocalix[4]arene as a Highly Efficient Catalyst under "On-Water" Conditions through Hydrophobic Amplification of Weak Hydrogen Bonds

8The simple tetraminocalix[4]arene 1, which contains weak H-bond-donor NH2 groups, is reported to be a highly efficient organocatalyst for the Vinylogous Mukaiyama Aldol Reaction (VMAR) of 2-(trimethylsilyloxy)furan 5 with α-ketoesters 6 a-l under "on-water" conditions owing to the hydrophobic amplification of weak H-bond interactions. The catalytic efficiency of calixarene catalyst 1 was shown to be closely related to its recognition abilities towards the reactants 5 and 6 through a multipoint recognition model. The proposed model provided good explanations for the differences on the reaction rate acceleration and on the stereoselectivity observed with different substrates.partially_openembargoed_20180509De Rosa, Margherita; La Manna, Pellegrino; Soriente, Annunziata; Gaeta, Carmine; Talotta, Carmen; Hickey, Neal; Geremia, Silvano; Neri, PlacidoDe Rosa, Margherita; La Manna, Pellegrino; Soriente, Annunziata; Gaeta, Carmine; Talotta, Carmen; Hickey, JAMES NEIL; Geremia, Silvano; Neri, Placid

The Immune Response: Romanticism and the Radical Literary History of Smallpox Inoculation

My dissertation untangles the oxymoron of Romantic medicine. The literary history of inoculation, I contend, reveals that smallpox eradication was as much a triumph of the literary imagination as it was an achievement of Enlightenment science. Underlying this argument is the larger disciplinary question: Who counts as a producer of scientific knowledge? My project uncovers a surprisingly literary history of medicine that includes poetry and imaginative fiction in the discovery, propagation, and implementation of Edward Jenner's controversial discovery of the smallpox vaccine in 1796. Our own anti-vaccination campaigns recapitulate many of these same controversies. Most famously, Dr. Andrew Wakefield's bogus 1998 study linking MMR to autism compelled thousands of parents to deny their children this important vaccine. These biopolitical issues have only intensified in the globalized twenty-first century, and the debates about the large-scale management of disease depend on our literary-historical memory of the first vaccine scares and our attention to the narratives of those who lived through the alternatives of disfigurement, disease, and death.My approach places metaphor and medical reality in the balance. I track the uses of inoculation from its botanical origins, to controversies about safety, to its potential to manage global plague, and finally to its nineteenth-century contraction into clinical propaganda. The first section handles inoculation's early history via John Milton's concept of virtuous trial in Comus, Areopagitica, and Paradise Lost. While John Dryden and Lady Mary Wortley Montagu's smallpox poems employ metaphor as mere euphemism and concealment, Erasmus Darwin and William Blake begin to imagine Milton's tested virtue more explicitly as a kind of salubrious inoculation against the corruptions of disease. In my second section on Romantic-era poetry and prose, I argue that, for Blake, John Keats, and Mary Shelley, the metaphor of inoculation models both a revolutionary politics and a cosmopolitan ethics, materializing abstract theories of reform into a medically reproducible practice. I close with a third section on the Victorian endpoint of this radical discourse of inoculation and the consolidation of medical authority into the figure of the all-seeing detective in Arthur Conan Doyle's Sherlock Holmes stories. Inoculation's long historical reach and unassailable record for saving lives demand that we continue to recover and to scrutinize these medical, literary, and political origins

Does number word inversion affect arithmetic processes in adults?

Neuropsychological and developmental findings suggest that number word inversion complicates numerical processing. The aim of this study was to look for adverse effects of number word inversion in neurologically healthy adults. Addition problems were presented verbally to native speakers from China and from Germany in two different ways: familiar vs. unfamiliar (i.e., inverted number words in Chinese and non-inverted number words in German). While Chinese participants had more difficulties when confronted with problems presented in unfamiliar Chinese number words, German participants did not show more difficulties solving addition problems presented in the unfamiliar structure. Moreover, for both groups, addition problems were more difficult when a carry operation was needed and this carry effect was more pronounced for German participants. Inverted number words thus seem to complicate arithmetic processing in populations where arithmetic processing is an accomplished skill, highlighting the relevance of finding ways to deal with inversion-related difficulties in mathematics education. (DIPF/Orig.