A computational approach to the polymerizabilities of diallylamines

Some selected diallylamine monomers have been studied with the semiempirical PM3 method as model compounds for N,N-dialkyl-N-2-(alkoxycarbonyl)allylammonium salts, in order to build up a quantitative and qualitative relationship between the experimental cyclopolymerizabilities of the monomers and calculated parameters such as charge, energy, geometrical features, bond orders, local softness values and HOMO-LUMO gaps. The charges on nitrogen, vinyl and allyl carbons, the activation barriers, the local softness values and the HOMO-LUMO gaps are found to represent the polymerizability trend of the monomers in general. Three-dimensional structures have been proposed for the reactants and their transition states by geometry optimizations with PM3.     

Mating in the box jellyfish Copula sivickisi—Novel function of cnidocytes

Within cubozoans, a few species have developed a sexual reproduction system including mating and internal fertilization. One species, Copula sivickisi, is found in a large area of the indo pacific. They have separate sexes and when mature males and females meet they entangle their tentacles and the males transfer a sperm package, a spermatozeugmata, which is ingested by the female fertilizing her eggs internally. After 2–3 days, the females lay an embryo strand that sticks to the substrate and after another 2–3 days, the fully developed larvae leave the strand. We have examined the ultrastructure of the gonads and spermatozeugmata to look for structural adaptations to this specialized way of reproduction and understand how the fertilization takes place. Surprisingly, we discovered that the male gonads were heavily packed with cnidocytes of the isorhiza type and that they are transferred to the spermatozeugmata. The spermatozeugmata does not dissolve in the female gastrovascular cavity but is attached to the female gonad probably using the isorhizas. Here, the sperm cells are partly digested and the nuclei are released. The actual fertilization seems to happen through phagocytosis of the released nuclei by the epithelial cells. The female gonads are likewise packed with cnidocytes but of the eurytele type. They do not mature inside the female and putatively serve to protect the developing larvae once the embryo strand is laid. This specialized way of fertilization is to our knowledge novel and so is this first account of cnidocytes being directly involved in cnidarian reproduction. J. Morphol. 276:1055–1064, 2015. © 2015 Wiley Periodicals, Inc.     

Time-dependent sorption behavior of lentiviral vectors during anion-exchange chromatography

Use of lentiviral vectors (LVs) in clinical Cell and Gene Therapy applications is growing. However, functional product loss during capture chromatography, typically anion-exchange (AIEX), remains a significant unresolved challenge for the design of economic processes. Despite AIEX's extensive use, variable performance and generally low recovery is reported. This poor understanding of product loss mechanisms highlights a significant gap in our knowledge of LV adsorption and other types of vector delivery systems. This work demonstrates HIV-1-LV recovery over quaternary-amine membrane adsorbents is a function of time in the adsorbed state. Kinetic data for product loss in the column bound state was generated. Fitting a second order-like rate model, we observed a rapid drop in functional recovery due to increased irreversible binding for vectors encoding two separate transgenes ($t_{Y_{1/2}}$ = 12.7 and 18.7 min). Upon gradient elution, a two-peak elution profile implicating the presence of two distinct binding subpopulations is observed. Characterizing the loss kinetics of these two subpopulations showed a higher rate of vector loss in the weaker binding peak. This work highlights time spent in the adsorbed state as a critical factor impacting LV product loss and the need for consideration in LV AIEX process development workflows.     

ACPA decreases non-small cell lung cancer line growth through Akt/PI3K and JNK pathways in vitro

Therapeutic agents used for non-small cell lung cancer (NSCLC) have limited curative efficacy and may trigger serious adverse effects. Cannabinoid ligands exert antiproliferative effect and induce apoptosis on numerous epithelial cancers. We confirmed that CB1 receptor (CB1R) is expressed in NSCLC cells in this study. Arachidonoylcyclopropylamide (ACPA) as a synthetic, CB1R-specific ligand decreased proliferation rate in NSCLC cells by WST-1 analysis and real-time proliferation assay (RTCA). The half-maximal inhibitory concentration (IC50) dose of ACPA was calculated as 1.39 × 10⁻¹² M. CB1 antagonist AM281 inhibited the antiproliferative effect of ACPA. Flow cytometry and ultrastructural analyzes revealed significant early and late apoptosis with diminished cell viability. Nano-immunoassay and metabolomics data on activation status of CB1R-mediated pro-apoptotic pathways found that ACPA inhibited Akt/PI3K pathway, glycolysis, TCA cycle, amino acid biosynthesis, and urea cycle and activated JNK pathway. ACPA lost its chemical stability after 24 hours tested by liquid chromatography-mass spectrometry (LC–MS/MS) assay. A novel ACPA-PCL nanoparticle system was developed by nanoprecipitation method and characterized. Sustained release of ACPA-PCL nanoparticles also reduced proliferation of NSCLC cells. Our results demonstrated that low dose ACPA and ACPA-PCL nanoparticle system harbor opportunities to be developed as a novel therapy in NSCLC patients that require further in vivo studies beforehand to validate its anticancer effect.Subject terms: Cancer metabolism, Non-small-cell lung cancer, Apoptosis     

Predicting complex phenotype–genotype interactions to enable yeast engineering: Saccharomyces cerevisiae as a model organism and a cell factory

There is an increasing use of systems biology approaches in both “red” and “white” biotechnology in order to enable medical, medicinal, and industrial applications. The intricate links between genotype and phenotype may be explained through the use of the tools developed in systems biology, synthetic biology, and evolutionary engineering. Biomedical and biotechnological research are among the fields that could benefit most from the elucidation of this complex relationship. Researchers have studied fitness extensively to explain the phenotypic impacts of genetic variations. This elaborate network of dependencies and relationships so revealed are further complicated by the influence of environmental effects that present major challenges to our achieving an understanding of the cellular mechanisms leading to healthy or diseased phenotypes or optimized production yields. An improved comprehension of complex genotype–phenotype interactions and their accurate prediction should enable us to more effectively engineer yeast as a cell factory and to use it as a living model of human or pathogen cells in intelligent screens for new drugs. This review presents different methods and approaches undertaken toward improving our understanding and prediction of the growth phenotype of the yeast Saccharomyces cerevisiae as both a model and a production organism.     

The effects of boron-supplemented diets on adipogenesis-related gene expressions,anti-inflammatory,and antioxidative response in high-fat fed rats

The fatty liver syndrome caused by nutritional factors is a common cause of hepatic dysfunction globally. This research was designed to study the shielding effect of boron in rats fed a diet having high fat. Overall, 40 Wistar albino male rats were placed into one control and four treatment groups, that is, each having eight rats. Group I was provided with a standard rat diet while group II was only provided a high-fat diet for 60 days. Groups III, IV, and V were provided with 5, 10, and 20 mg/kg/day boron, respectively, by gastric gavage besides a high-fat diet for 60 days. Malondialdehyde was increased significantly in rats' blood and tissue because of high-fat diets. Glutathione was decreased significantly in blood and tissues because of a high-fat diet. Moreover, the activities of superoxide dismutase (SOD) and catalase (CAT) were decreased in the blood and tissues of the high-fat-fed rats. The genes expression for C-reactive protein, interleukin-1β, leptin, and tumor necrosis factor-α were increased while gene expression for peroxisome proliferator-activated receptors was decreased in the liver of rats fed with a high-fat diet. Contrariwise, boron supplementation improves antioxidative response in terms of increased SOD and CAT activities, gene expression regulation, and improved anti-inflammatory activities. In a nutshell, boron has dose-dependent shielding antioxidative and tissue regenerative effects in rats.     

A spatio-temporal mining approach towards summarizing and analyzing protein folding trajectories

Understanding the protein folding mechanism remains a grand challenge in structural biology. In the past several years, computational theories in molecular dynamics have been employed to shed light on the folding process. Coupled with high computing power and large scale storage, researchers now can computationally simulate the protein folding process in atomistic details at femtosecond temporal resolution. Such simulation often produces a large number of folding trajectories, each consisting of a series of 3D conformations of the protein under study. As a result, effectively managing and analyzing such trajectories is becoming increasingly important.