A Late Pleistocene channelized subglacial meltwater system on the Atlantic continental shelf south of Ireland

The study of palaeo-glacial landforms and sediments can give insights into the nature and dynamics of ice sheets. This is particularly the case with regards to the subglacial record, which is challenging to observe in contemporary glaciated settings and hence remains only partially understood. The subglacial hydrological system is an essential component of ice dynamics, where increased water pressure enhances ice motion and sediment deformation, thus reducing ice-bed contact. Tunnel valleys are large, sinuous, steep-sided incisions that, together with smaller scale meltwater channels, indicate subglacial meltwater discharge beneath large ice sheets. Through the use of high-resolution marine geophysical data, a system of buried and exposed tunnel valleys, possible subglacial or proglacial meltwater channels and palaeo-fluvial valleys have been identified across the shelf of the Celtic Sea between Ireland and Britain. The presence of steep-sided and overdeepened tunnel valleys is indicative of a large channelized meltwater drainage system beneath the former Irish Sea Ice Stream, the most extensive ice stream to drain the last British–Irish Ice Sheet. After the rapid ice expansion across the Celtic Sea shelf around 28–26 ka, the tunnel valleys were carved into both bedrock and glacigenic sediments and are associated with rapid ice stream retreat northwards into the Irish Sea Basin between 25.6 and 24.3 ka. The presence of a major subglacial meltwater system on the relatively shallow shelf suggests that significant erosive meltwater discharge occurred during the last deglaciation and highlights the important contribution of meltwater to the retreat of the British–Irish Ice Sheet on the continental shelf

Autoantibodies to synapsin I sequestrate synapsin I and alter synaptic function

Synapsin I is a phosphoprotein that coats the cytoplasmic side of synaptic vesicles and regulates their trafficking within nerve terminals. Autoantibodies against Syn I have been described in sera and cerebrospinal fluids of patients with numerous neurological diseases, including limbic encephalitis and clinically isolated syndrome; however, the effects and fate of autoantibodies in neurons are still unexplored. We found that in vitro exposure of primary hippocampal neurons to patient\u2019s autoantibodies to SynI decreased the density of excitatory and inhibitory synapses and impaired both glutamatergic and GABAergic synaptic transmission. These effects were reproduced with a purified SynI antibody and completely absent in SynI knockout neurons. Autoantibodies to SynI are internalized by Fc\u3b3II/III-mediated endocytosis, interact with endogenous SynI, and promote its sequestration and intracellular aggregation. Neurons exposed to human autoantibodies to SynI display a reduced density of SVs, mimicking the SynI loss-of-function phenotype. Our data indicate that autoantibodies to intracellular antigens such as SynI can reach and inactivate their targets and suggest that an antibody-mediated synaptic dysfunction may contribute to the evolution and progression of autoimmune-mediated neurological diseases positive for SynI autoantibodies

Reply to Comment on Conopeptide-Functionalized Nanoparticles Selectively Antagonize Extrasynaptic N-Methyl-d-aspartate Receptors and Protect Hippocampal Neurons from Excitotoxicity In Vitro

In this manuscript, we provide precise answers to the concerns expressed by Molokanova et al. in their comment. In our reply, we highlight that there is indeed substantial agreement between our study and the one reported in Nano Letters by the Molokanova’s group.1 We believe this is a very important aspect because it proves the validity of the chosen approach, i.e. PEGylated AuNPs carrying NMDAR antagonists and with an overall dimension large enough to prevent their diffusion into the synapse can exclusively antagonize extrasynaptic NMDAR-mediated currents and are thereby neuroprotective