Not on the edge: the syntax and pragmatics of clause-initial negation in Swedish

The possibility of topicalizing sentential negation is severely restricted in the Germanic V2-languages. In this paper, we show that negative preposing was more frequent and less restricted in earlier stages of Swedish: approx. 8 % of all occurrences of negation are clause initial in Old Swedish, compared to less than 0.5 % in present day Swedish. We propose that this change in frequency can be traced to the syntactic status of the negative element. More specifically, we argue that Old Swedish eigh 'not' may function as a syntactic head and cliticize to the finite verb in [C-0]. This possibility is not open to the XP inte 'not' in Modern Swedish. In Modern Swedish, we argue that the restrictions on negative preposing instead are related to more general pragmatic restrictions on the information expressed in [Spec,CP]: according to our hypothesis, negative preposing is licensed by contrast

Exploring the Interactions between two Ligands, UCB-J and UCB-F, and Synaptic Vesicle Glycoprotein 2 Isoforms

In silico modeling was applied to study the efficiency of two ligands, namely, UCB-J and UCB-F, to bind to isoforms of the synaptic vesicle glycoprotein 2 (SV2) that are involved in the regulation of synaptic function in the nerve terminals, with the ultimate goal to understand the selectivity of the interaction between UCB-J and UCB-F to different isoforms of SV2. Docking and large-scale molecular dynamics simulations were carried out to unravel various binding patterns, types of interactions, and binding free energies, covering hydrogen bonding and nonspecific hydrophobic interactions, water bridge, π–π, and cation−π interactions. The overall preference for bonding types of UCB-J and UCB-F with particular residues in the protein pockets can be disclosed in detail. A unique interaction fingerprint, namely, hydrogen bonding with additional cation−π interaction with the pyridine moiety of UCB-J, could be established as an explanation for its high selectivity over the SV2 isoform A (SV2A). Other molecular details, primarily referring to the presence of π–π interactions and hydrogen bonding, could also be analyzed as sources of selectivity of the UCB-F tracer for the three isoforms. The simulations provide atomic details to support future development of new selective tracers targeting synaptic vesicle glycoproteins and their associated diseases