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Adequate stability, manufacturability, and safety are crucial to bringing an antibody-based biotherapeutic to the market. Following the concept of holistic in silico developability, we introduce a physicochemical description of 91 market-stage antibody-based biotherapeutics based on orthogonal molecular properties of variable regions (Fvs) embedded in different simulation environments, mimicking conditions experienced by antibodies during manufacturing, formulation, and in vivo. In this work, the evaluation of molecular properties includes conformational flexibility of the Fvs using molecular dynamics (MD) simulations. The comparison between static homology models and simulations shows that MD significantly affects certain molecular descriptors like surface molecular patches. Moreover, the structural stability of a subset of Fv regions is linked to changes in their specific molecular interactions with ions in different experimental conditions. This is supported by the observation of differences in protein melting temperatures upon addition of NaCl. A DEvelopability Navigator In Silico (DENIS) is proposed to compare mAb candidates for their similarity with market-stage biotherapeutics in terms of physicochemical properties and conformational stability. Expanding on our previous developability guidelines (Ahmed et al. Proc. Natl. Acad. Sci. 2021 , 118 (37), e2020577118), the hydrodynamic radius and the protein strand ratio are introduced as two additional descriptors that enable a more comprehensive in silico characterization of biotherapeutic drug candidates. Test cases show how this approach can facilitate identification and optimization of intrinsically developable lead candidates. DENIS represents an advanced computational tool to progress biotherapeutic drug candidates from discovery into early development by predicting drug properties in different aqueous environments.

Background: Salinity as a most significant environmental challenges affects the growth and productivity of plants worldwide. In this study, the ionic and iso-osmotic effects of salt stress were investigated in Aeluropus littoralis L., a halophyte grass species from Poaceae family, by cDNA-amplified fragment length polymorphism (cDNA-AFLP) technique. To dissect the two different effects (ionic and osmotic) exerted by salt stress, various ionic agents including 200 and 400 mM sodium chloride (NaCl), 200 and 400 mM potassium chloride (KCl) as well as 280 and 406 gl - 1 (- 0.9 and - 1.4 MPa) polyethylene glycol 6000 (PEG) as their iso-osmotic concentrations were applied., Results: Application of KCl and PEG significantly reduced the fresh weight (FW) of A. littoralis seedlings compared to control while NaCl treatment markedly enhanced the FW. At the transcriptome level, different observations of changes in gene expression have been made in response of A. littoralis to ionic and osmotic stresses. Out of 69 transcript derived fragments (TDFs), 42 TDFs belong to 9 different groups of genes involved in metabolism (11.6%), transcription (10.2%), ribosomal protein (8.7%), protein binding (8.7%) transporter (5.8%), translation (5.8%), signal transduction (4.3%), nucleosome assembly protein (2.9%) and catabolism (2.9%). The 44 and 28 percent of transcripts were expressed under ionic stress (NaCl-specific and KCl-specific) and osmotic stress (common with NaCl, KCl and PEG), respectively which indicating a greater response of plants to ionic stress than osmotic stress. Expression pattern of eight candidate TDFs including; SYP81 , CAND1 , KATN , ISB1 , SAMDC , GLY1 , HAK18 and ZF30 was evaluated by RT-qPCR at high salinity levels and recovery condition., Conclusion: Differential regulation of these TDFs was observed in root and shoot which confirm their role in salt stress tolerance and provide initial insights into the transcriptome of A. littoralis . Expression pattern of ionic and osmotic-related TDFs at A. littoralis can be taken as an indication of their functional relevance at different salt and drought stresses., Competing Interests: Competing InterestsThe authors declare that they have no competing interests.

Load transmission is an important function of the meniscus. In articular cartilage, proteoglycans help maintain hydration via negatively charged moieties. We aimed to investigate the influence of electrostatic effects on stiffness of meniscal tissue. Circular discs from bovine menisci of 8 mm diameter and 5 mm thickness were placed within a confined compression chamber. The apparatus was bathed in distilled water, 0.14 M PBS or 3 M PBS before being subjected to 5% ramp compressive strain and held for 300s. FEBio software was used to fit resultant relaxation curves to a non-linear poroviscoelastic model with strain dependent Holmes-Mow permeability. Analysis was conducted using one-way ANOVA with Tukey post-hoc analysis. 10 samples were tested in each solution. Significant differences (p < 0.05) were observed between the values for Young's modulus, zero strain dependent permeability and the viscoelastic coefficient for samples tested in 3 M PBS as compared to deionised water/0.14 M PBS. No significant differences were observed in the strain dependent/stiffening coefficients or the relaxation time. Approximately 79% of the stiffness of the meniscus appears attributable to ionic effects. Ionic effects play a significant role in the mechanical stiffness of the meniscus. It is important to include the influence of ionic effects when developing mathematical models of this tissue., (Copyright © 2018. Published by Elsevier Ltd.)