α-Nemertides, a novel family of marine peptide neurotoxins from ribbon worms

Ribbon worms (nemerteans) are marine predators, which capture their prey using a proboscis containing a mixture of toxins which brings on rapid paralysis. We have discovered a novel family of peptides (a-nemertides), of which one causes death in green crabs and targets invertebrate voltage-gated sodium channels at low nanomolar concentrations, suggesting a role as drug lead for novel insecticidal and anti-parasitic agents

Higlights from Gastro Update Europe 2019

This narrative review summarizes a selection of recent, clinically-important novel gastrointestinal developments, presented and discussed at the European Gastro Update In Budapest. The selected topics reflect what the distinguished faculty considered of vital importance to be communicated to the astute busy gastro-hep clinician, who is eager to stay well informed of important novel developments in his discipline. Whenever appropriate a personal comment or addition was added to further raise the educational value of this review. Given its narrative character, statements and conclusions are largely expert opinion-based and referencing is limited to the selected images

LEP1 vs. Future Colliders: Effective Operators And Extended Gauge Group

In an effective Lagrangian approach to physics beyond the Standard Model, it has been argued that imposing $SU(2) \times U(1)$ invariance severely restricts the discovery potential of future colliders. We exhibit a possible way out in an extended gauge group context.Comment: 14 pages , CERN-TH.6573/92 ULB.TH.04/92 (phyzzx, 3 eps-figs incl.

Novel conopeptides of the I-superfamily occur in several clades of cone snails

The I-superfamily of conotoxins represents a new class of peptides in the venom of some Conus species. These toxins are characterized by four disulfide bridges and inhibit or modify ion channels of nerve cells. When testing venoms from 11 Conus species for a functional characterization, blocking activity on potassium channels (like Kv1.1 and Kv1.3 channels, but not Kv1.2 channels) was detected in the venom of Conus capitaneus, Conus miles, Conus vexillum and Conus virgo. Analysis at the cDNA level of these venoms using primers designed according to the amino acid sequence of a potassium channel blocking toxin (ViTx) from C. virgo confirmed the presence of structurally homologous peptides in these venoms. Moreover, peptides belonging to the I-superfamily, but with divergent amino acid sequences, were found in Conus striatus and Conus imperialis. In all cases, the sequences of the precursors' prepro-regions exhibited high conservation, whereas the sequences of the mature peptides ranged from almost identical to highly divergent between species. We then performed phylogenetic analyses of new and published mitochondrial 16S rDNA sequences representing 104 haplotypes from these and numerous other Conus species, using Bayesian, maximum-likelihood, maximum-parsimony and neighbor-joining methods of inference. Cone snails known to possess I-superfamily toxins were assigned to five different major clades in all of the resulting gene trees. Moreover, I-superfamily conopeptides were detected both in vermivorous and piscivorous species of Conus, thus demonstrating the widespread presence of such toxins in this speciose genus beyond evolutionary and ecological groups

Experimental conversion of a defensin into a neurotoxin: Implications for origin of toxic function

Scorpion K+ channel toxins and insect defensins share a conserved three-dimensional structure and related biological activities (defense against competitors or invasive microbes by disrupting their membrane functions), which provides an ideal system to study how functional evolution occurs in a conserved structural scaffold. Using an experimental approach, we show that the deletion of a small loop of a parasitoid venom defensin possessing the “scorpion toxin signature” (STS) can remove steric hindrance of peptide-channel interactions and result in a neurotoxin selectively inhibiting K+ channels with high affinities. This insect defensin-derived toxin adopts a hallmark scorpion toxin fold with a common cysteine-stabilized α-helical and β-sheet motif, as determined by nuclear magnetic resonance analysis. Mutations of two key residues located in STS completely diminish or significantly decrease the affinity of the toxin on the channels, demonstrating that this toxin binds to K+ channels in the same manner as scorpion toxins. Taken together, these results provide new structural and functional evidence supporting the predictability of toxin evolution. The experimental strategy is the first employed to establish an evolutionary relationship of two distantly related protein families

Generation of the Baryon Asymmetry of the Universe within the Left--Right Symmetric Model

Fermions scattering off first-order phase transition bubbles, in the framework of $SU(2)_L\otimes SU(2)_R\otimes U(1)$ models, may generate the Baryon Asymmetry of the Universe (BAU), either at the $LR$-symmetry-breaking scale, or at the weak scale. In the latter case, the baryon asymmetry of the Universe is related to CP violation in the $K_0$--$\bar K_0$ system.Comment: 17 pages, CERN--TH 6747/92, ULB--TH--07/92, UAB-FT-298/9