Relation between molecular shape and the morphology of self-assembling aggregates: a simulation study

Proteins can aggregate in a wide variety of structures, both compact and extended. We present simulations of a coarse-grained anisotropic model that reproduce many of the experimentally observed aggregate structures. Conversely, all structures predicted by our model have experimental counterparts (ribbons, multistranded fibrils, and vesicles). The model we use is that of a rodlike particle with an attractive (hydrophobic) stripe on its side. Our Monte Carlo simulations show that aggregate morphologies crucially depend on two parameters. The first one is the width of the attractive stripe and the second one is a presence or absence of attractive interactions at the particle ends. These results provide us with a generic insight into the relation between the shape of protein-protein interaction potential and the morphology of protein aggregates.     

Interactive language learning by robots: the transition from babbling to word forms

The advent of humanoid robots has enabled a new approach to investigating the acquisition of language, and we report on the development of robots able to acquire rudimentary linguistic skills. Our work focuses on early stages analogous to some characteristics of a human child of about 6 to 14 months, the transition from babbling to first word forms. We investigate one mechanism among many that may contribute to this process, a key factor being the sensitivity of learners to the statistical distribution of linguistic elements. As well as being necessary for learning word meanings, the acquisition of anchor word forms facilitates the segmentation of an acoustic stream through other mechanisms. In our experiments some salient one-syllable word forms are learnt by a humanoid robot in real-time interactions with naive participants. Words emerge from random syllabic babble through a learning process based on a dialogue between the robot and the human participant, whose speech is perceived by the robot as a stream of phonemes. Numerous ways of representing the speech as syllabic segments are possible. Furthermore, the pronunciation of many words in spontaneous speech is variable. However, in line with research elsewhere, we observe that salient content words are more likely than function words to have consistent canonical representations; thus their relative frequency increases, as does their influence on the learner. Variable pronunciation may contribute to early word form acquisition. The importance of contingent interaction in real-time between teacher and learner is reflected by a reinforcement process, with variable success. The examination of individual cases may be more informative than group results. Nevertheless, word forms are usually produced by the robot after a few minutes of dialogue, employing a simple, real-time, frequency dependent mechanism. This work shows the potential of human-robot interaction systems in studies of the dynamics of early language acquisition.     

A method for generation of arbitrary peptide libraries using genomic DNA

Random peptide libraries can be constructed either by in vitro synthesis of random peptides, or through translation of DNA sequences from synthetic random oligonucleotides. Here we describe an alternative way of making arbitrary peptide libraries with high diversity that can be used in screening as random peptide libraries. Genomic DNA digested with a frequent-cutting restriction enzyme recognizing four nucleotides will theoretically consist of small DNA pieces with average length of 256 nucleotides, and on average around 10⁷ fragments can be generated from a genome of 3 × 10⁹ bases. A peptide library translated from these fragments will have sufficient diversity for some protein interaction screening experiments. Moreover, the same genome digested with a different four-cutter enzyme or ligated into different reading frames will result in different nonoverlapping libraries. A series of such libraries could be generated with genomic DNAs from different species. In this study, human genomic DNA was digested with four-cutter restriction enzymes DpnII and Tsp509I, respectively, and cloned into yeast expression vector pGADT7 to generate arbitrary peptide libraries. These libraries were used in yeast two-hybrid assays to screen for binding motifs of the PDZ domain containing protein synectin. Our results showed that in addition to various native carboxy-terminal tails, synectin could also bind to many artificial ones, some of which contained a consensus sequence—(S/T)XC-COOH.     

The hummingbird's tongue: a self-assembling capillary syphon

We present the results of a combined experimental and theoretical investigation of the dynamics of drinking in ruby-throated hummingbirds. In vivo observations reveal elastocapillary deformation of the hummingbird''s tongue and capillary suction along its length. By developing a theoretical model for the hummingbird''s drinking process, we investigate how the elastocapillarity affects the energy intake rate of the bird and how its open tongue geometry reduces resistance to nectar uptake. We note that the tongue flexibility is beneficial for accessing, transporting and unloading the nectar. We demonstrate that the hummingbird can attain the fastest nectar uptake when its tongue is roughly semicircular. Finally, we assess the relative importance of capillary suction and a recently proposed fluid trapping mechanism, and conclude that the former is important in many natural settings.     

The design of a biochip: a self-assembling molecular-scale memory device

A design for a biochip memory device based on known materials and existing principles is presented. The fabrication of this memory system relies on the self-assembly of the nucleic acid junction system, which acts as the scaffolding for a molecular wire consisting of polyacetylene-like units. A molecular switch to control current is described which is based on the formation of a charge-transfer complex. A molecular-scale bit is presented which is based on oxidation-reduction potentials of metal atoms or clusters. The readable 'bit' which can be made of these components has a volume of 3 x 10(7) A3, and should operate at electronic speeds over short distances.     

Triggeps and switches in a self-assembling pore-forming portein

Protein engineering is being used to produce a collection of pore-forming proteings with applications in biotechnology. Knowledge provided by investigations of the mechanism of self-assembly of staphylococcal α-hemolysin has allowed the desigl of genetically and chemically modified tariants of the protein with pore-forming activities that can be triggered or switched mn-and-off by chemical, biochemical and physical inputs. Examples include α-hemolysins that are activated by specific proteases and α-hemolysins whose activity is controlled by divalent metal ions. These proteins have potential value in drug delivery as components of immunotoxils that aan be activated at the surfaces of target aells. Further applications are likely in improved encapsulation techniques for drugs, enzymes and cells.     

Cranial morphology and development: new light on the evolution of language

A hypothesis is presented which may explain within a single framework both the large behavioural differences and the large differences in head morphology between the great apes and humans. All these differences can be parsimoniously explained by a shift of few regulatory genes controlling the onset of the division of late migrating neurons in the human cortex. This simple shift resulted in the following effects: 1) the neurocranium responded to brain enlargement by increasing mineral deposition on its external surface, increasing its overall size and mass. 2) This increase in the braincase was largely achieved by developmental reabsoption of the face bones. 3) The relative shift in growth between these two skull components also induced a rearrangement at the basicranium level. This brought about the facial orthognatism of modernHomo and, as a mechanical by-product, the descent of the larynx into the throat. Brain enlargement led to a large increase in cognitive capacity, and as a developmental byproduct, produced a mechanical organ preadapted for speech, as well as bringing about the reduction of canines and the origin of the chin. In this study, the phylogenetic basis, the selective pressures, and the behavioural consequences of this process during hominization are examined. Cognitiveversus communicative aspects of human language are distinguished and discussed. Cognitive capacities were the first to be selected due to the survival advantage of mapping huge territories during the expansion of the Plio-Pleistocene savanna ecotone. The present hypothesis is then compared with current theories leading to the conclusion that it is a more parsimonious explanation. It integrates data from a wide array of fields of human biology, pathology and clinical medicine, all assessed from evolutionary and ecological perspectives.     

Artificial gills for robots: MFC behaviour in water

This paper reports on the first stage in developing microbial fuel cells (MFCs) which can operate underwater by utilizing dissolved oxygen. In this context, the cathodic half-cell is likened to an artificial gill. Such an underwater power generator has obvious potential for autonomous underwater robots. The electrical power from these devices increased proportionately with water flow rate, temperature and salinity. The current output at ambient temperature (null condition) was 32 microA and this increased by 200% (approximately 100 microA) as a result of a corresponding temperature increase (DeltaT) of 52 degrees C. Similarly, the effect of increasing the water flow rate resulted in an increase in the MFC output ranging from 135% to 150%. Furthermore, the same positive effect was recorded when artificial seawater was used instead, in which case the increase in the MFC current output was >100% (from 32 to 65 microA). There was a distinct difference in the MFC performance when operated under low turbulent as opposed to high turbulent flow rates. These findings can be advantageous in the design of underwater autonomous robots.     

Interaction of a self-assembling peptide with oligonucleotides: complexation and aggregation

Molecular interaction of a self-assembling peptide, EAK16-II, to single- and double-stranded oligodeoxynucleotides (ODNs) was investigated under various solution conditions. The molecular events leading to EAK-ODN complexation and further aggregation were elucidated using a series of spectroscopic and microscopic methods. Despite the ability to self-assemble, EAK molecules bind to ODN molecules first upon mixing, resulting in EAK-ODN complexes. The complexes further associate to form EAK-ODN aggregates. A method based on UV-Vis absorption and centrifugation was developed to quantify the fraction of ODNs in the aggregates. The results were used to construct binding isotherms via a binding density function analysis. To compare the effects of different pH values and nucleotide types, the modified noncooperative McGhee and von Hippel model was used to extract binding parameters from the binding isotherms. The binding constant of EAK to ODNs was higher at pH 4 than at pH 7, and no binding was observed at pH 11, indicating that the interaction involved is primarily electrostatic in nature. EAK bound more strongly to single-stranded ODNs. The EAK-ODN aggregates were further visualized using atomic force microscopy; their size distribution as a function of EAK concentration was monitored by dynamic light scattering. The timescale for the EAK-ODN aggregation was on the order of minutes by fluorescence anisotropy and steady-state light scattering experiments. Fluorescence quenching experiments demonstrated that the ODNs in the aggregates were less accessible to the solvent, demonstrating a potential of oligonucleotide encapsulation by the self-assembling peptide.     

Tandem SAM domain structure of human Caskin1: a presynaptic, self-assembling scaffold for CASK

The synaptic scaffolding proteins CASK and Caskin1 are part of the fibrous mesh of proteins that organize the active zones of neural synapses. CASK binds to a region of Caskin1 called the CASK interaction domain (CID). Adjacent to the CID, Caskin1 contains two tandem sterile α motif (SAM) domains. Many SAM domains form polymers so they are good candidates for forming the fibrous structures seen in the active zone. We show here that the SAM domains of Caskin1 form a new type of SAM helical polymer. The Caskin1 polymer interface exhibits a remarkable segregation of charged residues, resulting in a high sensitivity to ionic strength in?vitro. The Caskin1 polymers can be decorated with CASK proteins, illustrating how these proteins may work together to organize the cytomatrix in active zones.     

Sequence shuffle controls morphological consequences in a self-assembling tetrapeptide.

Peptide and protein self-assembly is a well-studied phenomenon in chemistry and biology, where nanoscopic building blocks exhibit rapid self-association to reveal supramolecular aggregates of defined structural features. These superstructures are stabilized by hydrophobic interactions, hydrogen bonding and a host of other noncovalent interactions. Thus, amino acid side chains in the primary structure hold importance in dictating secondary structures and preference for particular conformational signatures in peptide aggregates. This report describes contrasting nanoscale morphologies in antamanide-derived synthetic tetrapeptide mutants, which are composed by shuffling only two amino acids: phenylalanine and proline. Remarkable differences in ultrastructures in primary sequence-shuffled tetrapeptides suggest dissimilar aggregational pathways due to context-dependent location of proline and phenylalanine residues with respect to one another.     

Periodic orbits: a new language for neuronal dynamics.

A new nonlinear dynamical analysis is applied to complex behavior from neuronal systems. The conceptual foundation of this analysis is the abstraction of observed neuronal activities into a dynamical landscape characterized by a hierarchy of "unstable periodic orbits" (UPOs). UPOs are rigorously identified in data sets representative of three different levels of organization in mammalian brain. An analysis based on UPOs affords a novel alternative method of decoding, predicting, and controlling these neuronal systems.     

linkcomm: an R package for the generation, visualization, and analysis of link communities in networks of arbitrary size and type

SUMMARY: An essential element when analysing the structure, function, and dynamics of biological networks is the identification of communities of related nodes. An algorithm proposed recently enhances this process by clustering the links between nodes, rather than the nodes themselves, thereby allowing each node to belong to multiple overlapping or nested communities. The R package 'linkcomm' implements this algorithm and extends it in several aspects: (i) the clustering algorithm handles networks that are weighted, directed, or both weighted and directed; (ii) several visualization methods are implemented that facilitate the representation of the link communities and their relationships; (iii) a suite of functions are included for the downstream analysis of the link communities including novel community-based measures of node centrality; (iv) the main algorithm is written in C++ and designed to handle networks of any size; and (v) several clustering methods are available for networks that can be handled in memory, and the number of communities can be adjusted by the user. AVAILABILITY: The program is freely available from the Comprehensive R Archive Network (http://cran.r-project.org/) under the terms of the GNU General Public License (version 2 or later).     

Discovery of FZU-03,010 as a self-assembling anticancer amphiphile for acute myeloid leukemia

Recently various drug candidates with excellent anticancer potency have been demonstrated, whereas their clinical application largely suffers from several limitations especially poor solubility. Ursolic acid (UA) as one of ubiquitous pentacyclic triterpenes in plant kingdom exhibited versatile antiproliferative effects in various cancer cell lines. However, the unfavorable pharmaceutical properties became the main obstacle for its clinical development. With the aim of development of novel derivatives with enhanced potency, a series of diversified UA amphiphiles have been designed, synthesized, and pharmacologically evaluated. Amphiphile 10 (FZU-03,010) with significant improved antiproliferative effect can self-assemble into stable nanoparticles in water, which may serve as a promising candidate for further development.     

Self-organised path formation in a swarm of robots

In this paper, we study the problem of exploration and navigation in an unknown environment from an evolutionary swarm robotics perspective. In other words, we search for an efficient exploration and navigation strategy for a swarm of robots, which exploits cooperation and self-organisation to cope with the limited abilities of the individual robots. The task faced by the robots consists in the exploration of an unknown environment in order to find a path between two distant target areas. The collective strategy is synthesised through evolutionary robotics techniques, and is based on the emergence of a dynamic structure formed by the robots moving back and forth between the two target areas. Due to this structure, each robot is able to maintain the right heading and to efficiently navigate between the two areas. The evolved behaviour proved to be effective in finding the shortest path, adaptable to new environmental conditions, scalable to larger groups and larger environment size, and robust to individual failures.