The absorption into the systemic circulation of compounds administered intraperitoneally in large volumes was investigated in the rat. The influence on absorption of molecular weight, lipid-water partition coefficient (K), and dissociation constant (pKa) was studied. Nine neutral compounds ranging in molecular weight from 18 to 2 million demonstrated absorptions that decreased with increasing molecular weight. Five compounds were tested with variable lipid partition (K) values (0.001–3.3) and the absorptions increased from 57 to 96% as the K values increased. A series of nine acids and bases covering a wide range of pKa values (0.9–9.9) were investigated. For the acids, absorption increased with increasing pKa value, while for the bases absorption decreased with increasing pKa. For both groups of compounds absorption was directly related to the extent of ionization at physiologic pH. As has been documented for other biological membranes, the peritoneal membrane in the rat was found to behave in a lipoid manner. Unionized or lipid-soluble compounds are absorbed to a greater extent than ionized or lipid-insoluble compounds, and neutral compounds are absorbed in relation to their molecular weights.

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Most DNA in-vivo is strongly bent, including in the nucleosome. Experimental evidence on cyclization of DNA fragments shorter than 100 base-pairs points to the fact that strongly bent DNA --most relevant from a biological perspective --is considerably moreflexible than expected. We propose a general quantitative framework of polymer deformation, Energy Convex Hull (ECH), which includes both the weak and strong bending regimes on the same footing, based on a single physical principle. As the bending deformation increases beyond a certain (polymer-specific) point, the change in the convexity properties of the effective deformation energy of the polymer makes the harmonic deformation energetically unfavorable: in this strong bending regime the energy of the polymer varies linearly with the average deformation, as the system follows the convex hull of the deformation energy function. As a result, the energy of strongly bent DNA is effectively lowered, the bending proceeds via two ''phases'': strongly bent(kinks) and weekly bent. Predictions of ECH are verified againstrecent experiments on DNA cyclization. Counter-intuitively, cyclization probability of very short DNA loops is predicted to increase with decreasing loop length. We use ECH to gain insights into the energetic and structural aspects of strongly bent DNA in the nucleosome.

The modulation of chromatin is orchestrated by Nucleosome Binding Proteins (NBPs). The nucleosome surface has been hypothesized as a therapeutic target due to its capacity to modulate chromatin architecture. Herein, we evaluated if Nucleosome Binding Peptides (NBPeps) would be able to occupy the nucleosome surface directly, thereby modulating chromatin status and influencing phenotypic outcomes. To understand how the nucleosome structure is affected by NBPeps, we performed biochemical assays indicating that distinct NBPeps present differential actions on the nucleosome structure despite binding to similar target regions on the nucleosome. Cellbased assays and animal models demonstrated that the NBPeps penetrate the cell and have specific effects on cell physiology and phenotypic outcome, suggesting that NBPeps might have important therapeutic implications. Support or Funding Information This work has been supported by CNPq for KT,VF and IT fellowships, Fap‐DF grant number 04/2017 for GS, iNEXT grant number 6756, funded by the Horizon 2020 programme of the European Union, for HI.