4,653 research outputs found
Information processing and signal integration in bacterial quorum sensing
Bacteria communicate using secreted chemical signaling molecules called
autoinducers in a process known as quorum sensing. The quorum-sensing network
of the marine bacterium {\it Vibrio harveyi} employs three autoinducers, each
known to encode distinct ecological information. Yet how cells integrate and
interpret the information contained within the three autoinducer signals
remains a mystery. Here, we develop a new framework for analyzing signal
integration based on Information Theory and use it to analyze quorum sensing in
{\it V. harveyi}. We quantify how much the cells can learn about individual
autoinducers and explain the experimentally observed input-output relation of
the {\it V. harveyi} quorum-sensing circuit. Our results suggest that the need
to limit interference between input signals places strong constraints on the
architecture of bacterial signal-integration networks, and that bacteria likely
have evolved active strategies for minimizing this interference. Here we
analyze two such strategies: manipulation of autoinducer production and
feedback on receptor number ratios.Comment: Supporting information is in appendi
Programmable interactions with biomimetic DNA linkers at fluid membranes and interfaces
At the heart of the structured architecture and complex dynamics of
biological systems are specific and timely interactions operated by
biomolecules. In many instances, biomolecular agents are spatially confined to
flexible lipid membranes where, among other functions, they control cell
adhesion, motility and tissue formation. Besides being central to several
biological processes, \emph{multivalent interactions} mediated by reactive
linkers confined to deformable substrates underpin the design of
synthetic-biological platforms and advanced biomimetic materials. Here we
review recent advances on the experimental study and theoretical modelling of a
heterogeneous class of biomimetic systems in which synthetic linkers mediate
multivalent interactions between fluid and deformable colloidal units,
including lipid vesicles and emulsion droplets. Linkers are often prepared from
synthetic DNA nanostructures, enabling full programmability of the
thermodynamic and kinetic properties of their mutual interactions. The coupling
of the statistical effects of multivalent interactions with substrate fluidity
and deformability gives rise to a rich emerging phenomenology that, in the
context of self-assembled soft materials, has been shown to produce exotic
phase behaviour, stimuli-responsiveness, and kinetic programmability of the
self-assembly process. Applications to (synthetic) biology will also be
reviewed.Comment: 63 pages, revie
Representability of algebraic topology for biomolecules in machine learning based scoring and virtual screening
This work introduces a number of algebraic topology approaches, such as
multicomponent persistent homology, multi-level persistent homology and
electrostatic persistence for the representation, characterization, and
description of small molecules and biomolecular complexes. Multicomponent
persistent homology retains critical chemical and biological information during
the topological simplification of biomolecular geometric complexity.
Multi-level persistent homology enables a tailored topological description of
inter- and/or intra-molecular interactions of interest. Electrostatic
persistence incorporates partial charge information into topological
invariants. These topological methods are paired with Wasserstein distance to
characterize similarities between molecules and are further integrated with a
variety of machine learning algorithms, including k-nearest neighbors, ensemble
of trees, and deep convolutional neural networks, to manifest their descriptive
and predictive powers for chemical and biological problems. Extensive numerical
experiments involving more than 4,000 protein-ligand complexes from the PDBBind
database and near 100,000 ligands and decoys in the DUD database are performed
to test respectively the scoring power and the virtual screening power of the
proposed topological approaches. It is demonstrated that the present approaches
outperform the modern machine learning based methods in protein-ligand binding
affinity predictions and ligand-decoy discrimination
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An algal enzyme required for biosynthesis of the most abundant marine carotenoids.
Fucoxanthin and its derivatives are the main light-harvesting pigments in the photosynthetic apparatus of many chromalveolate algae and represent the most abundant carotenoids in the world's oceans, thus being major facilitators of marine primary production. A central step in fucoxanthin biosynthesis that has been elusive so far is the conversion of violaxanthin to neoxanthin. Here, we show that in chromalveolates, this reaction is catalyzed by violaxanthin de-epoxidase-like (VDL) proteins and that VDL is also involved in the formation of other light-harvesting carotenoids such as peridinin or vaucheriaxanthin. VDL is closely related to the photoprotective enzyme violaxanthin de-epoxidase that operates in plants and most algae, revealing that in major phyla of marine algae, an ancient gene duplication triggered the evolution of carotenoid functions beyond photoprotection toward light harvesting
Participation Versus Procedures in Non-Union Dispute Resolution
This study examines the resolution of conflict in non-union workplaces. Employee participation in workplace decision making and organizational dispute resolution procedures are two factors hypothesized to influence the outcomes of conflicts in the non-union workplace. The adoption of high involvement work systems is found to produce an organizational context in which both triggering events for conflict, such as disciplinary and dismissal decisions, and dispute resolution activities, such as grievance filing and appeals, are reduced in frequency. Dispute resolution procedures have mixed impacts. Greater due process protections in dispute resolution procedures in non-union workplaces are associated with increased grievance filing and higher appeal rates but do not have significant impacts on the precursors to conflict. This study provides evidence of substantial organizational level variation in non-union conflict resolution, suggesting the importance of expanding the predominant individual and group-level focus of current conflict management research to include more organizational-level factors. It also supports the importance to non-union employee representation of direct participation strategies involving employee involvement in the workplace, in addition to procedures that provide for off-line representation
Loss-of-function analysis of EphA receptors in retinotectal mapping
Peer reviewedPublisher PD
Naxitamab Activity in Neuroblastoma Cells Is Enhanced by Nanofenretinide and Nanospermidine
Neuroblastoma cells highly express the disialoganglioside GD2, a tumor-associated carbohydrate antigen, which is also expressed in neurons, skin melanocytes, and peripheral nerve fibers. Immunotherapy with monoclonal anti-GD2 antibodies has a proven efficacy in clinical trials and is included in the standard treatment for children with high-risk neuroblastoma. However, the strong neuro-toxicity associated with anti-GD2 antibodies administration has hindered, until now, the possibility for dose-escalation and protracted use, thus restraining their therapeutic potential. Strategies to increase the efficacy of anti-GD2 antibodies are actively sought, with the aim to enable chronic treatments that could eradicate minimal residual disease and subsequent relapses, often occurring after treatment. Here, we report that Nanofenretinide and Nanospermidine improved the expression of GD2 in neuroblastoma cells (CHP-134) and provided different effects in combination with the anti-GD2 antibody naxitamab. In particular, Nanofenretinide significantly increased the cytotoxic effect of naxitamab while Nanospermidine inhibited cell motility at extents proportional to naxitamab concentration. In neuroblastoma cells characterized by a low and heterogeneous basal expression of GD2, such as SH-SY5Y, which may represent the cell heterogeneity in tumors after chemotherapy, both Nanofenretinide and Nanospermidine increased GD2 expression in approximately 50% of cells, thus shifting the tumor population towards improved sensitivity to anti-GD2 antibodies
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