X-ray Reflectivity Study of Polylysine Adsorption on the Surface of DMPS Monolayers.

The results of a systematic study on the adsorption of polylysine molecules of different lengths on the surface of a 1,2-dimyristoyl-sn-glycero-3-phospho-L-serine (DMPS) monolayer in the liquid (LE) and condensed (LC) states are presented. A compressibility diagram and the Volta potential were recorded with the Langmuir monolayer technique and further analyzed with the empirical approach. The structure of the monolayer films with adsorbed polypeptides was studied with synchrotron X-ray reflectometry. Two- and three-layer slab models describe the reflectivity data fairly well and reveal both the significant structural changes and the dehydration of the polar groups induced by all polylysines used at the maximal coverage of the monolayer interface in both the LE and LC states. On the one hand, in the LE phase of the monolayer (area per molecule A ≅ 70 Ǻ2), the integrated electron density of the lipid headgroup region is approximately half the density contained in the clean monolayer. This indicates both significant compaction and dehydration in the polar groups of the lipids, caused by the adsorption of polypeptides. On the other hand, in the LC state (A ≅ 40 Ǻ2), the degree of the hydration of the polar region is similar to that for the initial DMPS monolayer. However, both the electron density and the thickness of the head group region differ significantly from the values of these parameters for the clean monolayer in the LC state.

Molecular identification of the trematode P. ichunensis stat. n. from lungs of siberian tigers justified reappraisal of Paragonimus westermani species complex.

Flukes from the genus Paragonimus Braun, 1899 are medically important foodborne trematodes predominantly occurring throughout Asian countries. Providing molecular genetic characteristics based on ITS2 and partial 28 S rDNA of the paragonimids from the Russian Far East, Northeast, South, and Southeast Asian countries, we performed a partial reappraisal of Paragonimus westermani species complex. Members of this complex are genetically distinct worms with different divergence times and explosive expansion during Miocene-Pliocene epochs. We confirm the taxonomic status as valid species for P. ichunensis stat. n. (from the Russian Far East and Northern China), and P. filipinus (from the Philippines), which were previously considered subspecies of P. westermani, and reinstated the species name P. pulmonalis (from Japan). We suggest considering the worms from South Korea the Korean variety of P. ichunensis, because Korean specimens are sister and genetically closest to P. ichunensis from Northeast China and Primorsky region of Russia. Worms from South (India (type 2), Sri Lanka), Southeast (Malaysia, Vietnam, Thailand (types 1 and 2)) and East Asia (Taiwan) were left in the paragonimid systematics as Paragonimus sp. We propose to consider Indian worms of type 1 as true P. westermani, but in further revisions, due to the lack of holotype and unknown exact type locality, new type specimens (neotype) should be established.

Deep learning enables rapid identification of potent DDR1 kinase inhibitors.

We have developed a deep generative model, generative tensorial reinforcement learning (GENTRL), for de novo small-molecule design. GENTRL optimizes synthetic feasibility, novelty, and biological activity. We used GENTRL to discover potent inhibitors of discoidin domain receptor 1 (DDR1), a kinase target implicated in fibrosis and other diseases, in 21 days. Four compounds were active in biochemical assays, and two were validated in cell-based assays. One lead candidate was tested and demonstrated favorable pharmacokinetics in mice.