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We report the use of wet‐spinning to 3D‐print gels from low‐molecular‐weight gelators (LMWGs) based on the 1,3 : 2,4‐dibenzylidenesorbitol (DBS) scaffold. Gel stripes assembled from DBS‐CONHNH2 and DBS‐COOH are printed, and their conductivities assessed. Printed gels based on DBS‐CONHNH2 can be loaded with Au(III), which is reduced in situ to form embedded gold nanoparticles (AuNPs). The conductivity of these gels increases because of electron transport mediated by the AuNPs, whereas the conductivity of DBS‐COOH, which does not promote AuNP formation, remains lower. We then fabricate multi‐component gel patterns comprised of spatially well‐defined domains of printed DBS‐CONHNH2/AuNP (higher conductivity) and DBS‐COOH (lower conductivity) resulting in soft multi‐domain materials with differential conductivity. Such materials have future prospects in applications such as soft nanoelectronics or tissue engineering. [ABSTRACT FROM AUTHOR]

This paper reports hybrid gels combining a low‐molecular‐weight gelator (LMWG) and a photoinitiated crosslinked polymer gel (PG). The presence of the PG enhanced the stiffness and strength of the gel. The gels were loaded with heparin, and in the hybrid gel, the interpenetrated LMWG and PG networks somewhat restricted its release. In terms of stem cell growth, the hybrid gel significantly improved the performance of the PG because of the presence of the LMWG, which is an excellent substrate for stem cells in its own right. Furthermore, the presence of heparin in the hybrid gels also enhanced stem cell proliferation over longer timescales. Finally, these gels were photopatterned within the well‐plates used for tissue culture, with patterning helping control stem cell proliferation. In summary, these hybrid gels combine the advantageous features of both LMWG and PG: rheological performance is endowed by the PG with stem cell compatibility provided by the LMWG. The hybrid gels also control the release of the bioactive agent heparin and have capacity to be shaped and patterned. Patterned gels such as these, capable of directing stem cell growth, have potential in regenerative medicine. [ABSTRACT FROM AUTHOR]

Hybrid gel beads based on combining a low‐molecular‐weight gelator (LMWG) with a polymer gelator (PG) demonstrate an enhanced ability to self‐propel in water, with the LMWG playing an active role. Hybrid gel beads were loaded with ethanol and shown to move in water owing to the Marangoni effect changes in surface tension caused by the expulsion of ethanol – smaller beads move farther and faster than larger beads. Flat shapes of the hybrid gel were cut using a "stamp" – circles moved the furthest, whereas stars showed more rotation on their own axes. Comparing hybrid LMWG/PG gel beads with PG‐only beads demonstrated that the LMWG speeds up the beads, enhancing the rate of self‐propulsion. Self‐assembly of the LMWG into a "solid‐like" network prevents its leaching from the gel. The LMWG also retains its own unique function – specifically, remediating methylene blue pollutant dye from basic water as a result of noncovalent interactions. The mobile hybrid beads accumulate this dye more effectively than PG‐only beads. Self‐propelling gel beads have potential applications in removal/delivery of active agents in environmental or biological settings. The ability of self‐assembling LMWGs to enhance mobility and control removal/delivery suggests that adding them to self‐propelling systems can add significant value. [ABSTRACT FROM AUTHOR]

This article describes the fabrication of new pH‐responsive hybrid gel beads combining the polymer gelator calcium alginate with two different low‐molecular‐weight gelators (LMWGs) based on 1,3 : 2,4‐dibenzylidene‐d‐sorbitol: pH‐responsive DBS‐COOH and thermally responsive DBS‐CONHNH2, thus clearly demonstrating that different classes of LMWG can be fabricated into gel beads by using this approach. We also demonstrate that self‐assembled multicomponent gel beads can be formed by using different combinations of these gelators. The different gel bead formulations exhibit different responsiveness – the DBS‐COOH network can disassemble within those beads in which it is present upon raising the pH. To exemplify preliminary data for a potential application for these hybrid gel beads, we explored aspects of the delivery of the lipid‐lowering active pharmaceutical ingredient (API) rosuvastatin. The release profile of this statin from the hybrid gel beads is pH‐dependent, with greater release at pH 7.4 than at pH 4.0 – primary control of this process results from the pKa of the API. The extent of pH‐mediated API release is also significantly further modified according to gel bead composition. The DBS‐COOH/alginate beads show rapid, highly effective drug release at pH 7.4, whereas the three‐component DBS‐COOH/DBS‐CONHNH2/alginate system shows controlled slow release of the API under the same conditions. These initial results indicate that such gel beads constitute a promising, versatile and easily tuned platform suitable for further development for controlled drug‐delivery applications. [ABSTRACT FROM AUTHOR]

Therizinosaurs are unusual theropods from the Upper Cretaceous of Asia and North America. North American representatives include Falcarius utahensis from central Utah, Nothronychus mckinleyi from west central New Mexico, and N. graffami from southern Utah. Nothronychus was quite large, with well‐developed forelimbs and pectoral girdle. In many respects, however, these structures were typical for conventional carnivorous theropods, although therizinosaurs have been hypothesized to be herbivorous using anatomical and functional inferences. There is no indication of increased range of motion within the forelimbs, as might be predicted for derived non‐avian theropods. The muscular anatomy of the pectoral girdle and forelimb of Nothronychus is reconstructed using visible muscle scars, data from extant birds and crocodilians, and models for other theropods. The osteology and inferred musculature is a mosaic of primitive and derived characters for theropods. A fossa pneumotricipitales may have been present in the proximal humerus. There was a well‐developed fossa brachialis in the distal humerus. The epicleidium of the furcula is deflected, reflecting either taphonomic deformation or possibly accommodation of M. supracoracoideus in a triosseal canal, but such a development has yet to be described in any non‐avian theropod. In many respects, the other muscular results were quite similar to those inferred for dromaeosaurs. [ABSTRACT FROM AUTHOR]

This paper reports the use of a self‐assembling hydrogel as a delivery vehicle for the Parkinson's disease drug l‐DOPA. Based on a two‐component combination of an l‐glutamine amide derivative and benzaldehyde, this gel has very soft rheological properties and self‐healing characteristics. It is demonstrated that the gel can be formulated to encapsulate l‐DOPA. These drug‐loaded gels are characterized, and rapid release of the drug is obtained from the gel network. This drug‐loaded hydrogel has appropriate rheological characteristics to be amenable for injection. This system is therefore tested as a vehicle for nasal delivery of neurologically‐active drugs—a drug delivery strategy that can potentially avoid first pass liver metabolism and bypass the blood–brain barrier, hence enhancing brain uptake. In vitro tests indicate that the gel has biocompatibility with respect to nasal epithelial cells. Furthermore, animal studies demonstrate that the nasal delivery of a gel loaded with 3H‐labeled l‐DOPA out‐performed a simple intranasal l‐DOPA solution. This is attributed to longer residence times of the gel in the nasal cavity resulting in increased blood and brain concentrations. It is demonstrated that the likely routes of brain penetration of intranasally‐delivered l‐DOPA gel involve the trigeminal and olfactory nerves connecting to other brain regions. [ABSTRACT FROM AUTHOR]

Therizinosaurs are highly modified, probably herbivorous, theropods from the Upper Cretaceous of Asia and North America. They are characterized by an extensively pneumatized axial skeleton, and in the derived forms, an incipiently opisthopubic pelvis. The evolution of such a pelvis is expected to be associated with extensive modification of the muscular system. The muscular system is reconstructed using observed muscle scars, reconstructions of the theropods Staurikosaurus and Tyrannosaurus, the ornithischian Maiasaura, and extant crocodilians and birds. The results indicate convergence with birds and ornithischian dinosaurs, such that the retroverted pubis in some maniraptorans can be regarded as analogous with the postacetabular bar in ornithischians. Functional implications also make derived therizinosaurs, such as Nothronychus, in some respects convergent with birds as the pubis is retroverted, becoming fused with the ischium, a laterally flaring synsacrum, and an avian‐like pes. [ABSTRACT FROM AUTHOR]

Nothronychus was a large, derived therizinosaur from the Upper Cretaceous of Utah and New Mexico. The genus is known from elements that have been referred to single individuals. Therizinosaurs were unusual maniraptoran theropods close to the origin of birds. The axial skeleton is extensively pneumatized, but CT scans reveal an apneumatic synsacrum. Inferred air sacs invade the basicranium, the presacral vertebrae, and the proximal caudal vertebrae, but bypassed the sacrum resulting in a caudosacral hiatus similar to some sauropods and reflecting the development of multiple diverticula from the abdominal air sac. The vertebral pneumatic chambers are described here and compared with those observed in the theropod Allosaurus and the recent avian Dinornis. The vertebrae of Nothronychus are intermediate between those two theropods. It is inferred to have possessed avian‐like abdominal air sacs. This theropod would have had unidirectional lungs, as in birds, but this character cannot be related to endothermy. CT‐scans of the vertebra of Nothronychus graffami reveal an intermediate structure between more basal theropods and birds. Uni‐directional airflow as in birds is supported, but this trait does not necessarily imply endothermy. [ABSTRACT FROM AUTHOR]

This Full Paper reports the formation of silver (Ag) NPs within spatially resolved two‐component hydrogel beads, which combine a low‐molecular‐weight gelator (LMWG) DBS‐CONHNH2 and a polymer gelator (PG) calcium alginate. The AgNPs are formed through in situ reduction of AgI, with the resulting nanoparticle‐loaded gels being characterised in detail. The antibacterial activity of the nanocomposite gel beads was tested against two drug‐resistant bacterial strains, often associated with hospital‐acquired infections: vancomycin‐resistant Enterococcus faecium (VRE) and Pseudomonas aeruginosa (PA14), and the AgNP‐loaded gels showed good antimicrobial properties against both types of bacteria. It is suggested that the gel bead format of these AgNP‐loaded hybrid hydrogels makes them promising versatile materials for potential applications in orthopaedics or wound healing. [ABSTRACT FROM AUTHOR]

With the goal of imposing shape and structure on supramolecular gels, we combine a low‐molecular‐weight gelator (LMWG) with the polymer gelator (PG) calcium alginate in a hybrid hydrogel. By imposing thermal and temporal control of the orthogonal gelation methods, the system either forms an extended interpenetrating network or core–shell‐structured gel beads—a rare example of a supramolecular gel formulated inside discrete gel spheres. The self‐assembled LMWG retains its unique properties within the beads, such as remediating PdII and reducing it in situ to yield catalytically active Pd0 nanoparticles. A single PdNP‐loaded gel bead can catalyse the Suzuki–Miyaura reaction, constituting a simple and easy‐to‐use reaction‐dosing form. These uniquely shaped and structured LMWG‐filled gel beads are a versatile platform technology with great potential in a range of applications. [ABSTRACT FROM AUTHOR]

Shewanella oneidensis is an electrogenic microbe which could be more widely applied in biosensing and fuel cell applications if better methods existed to promote electrode‐biofilm formation. This paper reports a simple procedure that converts agarose, a cheap and readily available polymer, into a modified "MAgarose" material which will form biocompatible hydrogels that embed gold nanoparticles (AuNPs) along the fibers to yield a composite material with a conductivity ca. 80 times higher than an unmodified agarose‐AuNP gel. Proof‐of‐concept bioelectrochemical experiments using Shewanella oneidensis show that when these MAgarose‐AuNP gels are used to coat carbon veil there is a 10‐fold increase in oxidative microbial current production when tested in a 3‐electrode cell set‐up. Microscopy results show that this can be attributed to the ability of the composite hydrogel to support MR‐1 growth throughout the 3D matrix. [ABSTRACT FROM AUTHOR]

A two‐component self‐sorting hydrogel based on acylhydrazide and carboxylic acid derivatives of 1,3:2,4‐dibenzylidene‐d‐sorbitol (DBS‐CONHNH2 and DBS‐COOH) is reported. A heating–cooling cycle induces the self‐assembly of DBS‐CONHNH2, followed by the self‐assembly of DBS‐COOH induced by decreasing pH. Although the networks are formed sequentially, there is spectroscopic evidence of interactions between them, which impact on the mechanical properties and significantly enhance the ability of these low‐molecular‐weight gelators (LMWGs) to form gels when mixed. The DBS‐COOH network can be switched "off" and "on" within the two‐component gel through a pH change. By using a photo‐acid generator, the two‐component gel can be prepared combining the thermal trigger with photo‐irradiation. Photo‐patterned self‐assembly of DBS‐COOH within a pre‐formed DBS‐CONHNH2 gel under a mask yields spatially controlled multi‐domain gels. Different gel domains can have different functions, for example, controlling the rate of release of heparin incorporated into the gel, or directing gold nanoparticle assembly. Such photo‐patterned multi‐component hydrogels have potential applications in regenerative medicine or bio‐nano‐electronics. [ABSTRACT FROM AUTHOR]

1,3:2,4‐Dibenzylidene‐d‐sorbitol (DBS), a simple, commercially relevant compound, was found to self‐assemble as a result of intermolecular noncovalent interactions into supramolecular gels in deep eutectic solvents (DESs) based on choline chloride combined with alcohols/ureas. DBS formed gels at a loading of 5 % w/v. Rheology confirmed the gel‐like nature of the materials, electron microscopy and X‐ray diffraction indicated underpinning nanofibrillar DBS networks, and differential scanning calorimetry showed the DES nature of the liquid‐like phase was retained. The ionic conductivities of the gels were similar to those of the unmodified DESs, thus proving the deep eutectic nature of the ionic liquid‐like phase. Gelation was tolerant of ionic additives Li+, Mg2+, and Ca2+; the resulting gels had similar conductivities to electrolyte dissolved in the native DES. The low‐molecular‐weight gelator DBS is thus a low‐cost additive that forms gels in DESs from readily available constituents, with conductivity levels suitable for practical applications. Inexpensive, but valuable: The low‐molecular‐weight gelator 1,3:2,4‐dibenzylidene‐d‐sorbitol (DBS) self‐assembled into nanofibers in deep eutectic solvents (DESs) formed between choline chloride and various hydrogen‐bond donors (see picture) without significantly altering the ionic conductivity of the DES. The gels formed in this way from readily available constituents showed conductivity levels suitable for practical applications. [ABSTRACT FROM AUTHOR]

This study reports the ability of synthetically simple, commercially viable sugar‐derived 1,3:2,4‐dibenzylidenesorbitol‐4′,4"‐diacylhydrazide (DBS‐CONHNH2) to support cell growth. Simple mixing and orthogonal self‐sorting can formulate heparin, agarose, and heparin‐binding micelles into these gels—easily incorporating additional function. Interestingly, the components used in the gel formulation, direct the ability of cells to grow, meaning the chemical programming of these multi‐component gels is directly translated to the biological systems in contact with them. This simple approach has potential for future development in regenerative medicine. Chemistry directs biology: The orthogonal components used in a commercially relevant self‐assembled gel program the biological outcomes. [ABSTRACT FROM AUTHOR]

Abstract: A family of four self‐assembling lipopeptides containing Ala‐Lys peptides attached to a C16 aliphatic chain were synthesised. These compounds form two enantiomeric pairs that bear a diastereomeric relationship to one another (C16‐ l‐Ala‐ l‐Lys/C16‐ d‐Ala‐ d‐Lys) and (C16‐ d‐Ala‐ l‐Lys/C16‐ l‐Ala‐ d‐Lys). These diastereomeric pairs have very different critical micelle concentrations (CMCs). The self‐assembled multivalent (SAMul) systems bind biological polyanions as a result of the cationic lysine groups on their surfaces. For heparin binding, there was no significant enantioselectivity, but there was a binding preference for the diastereomeric assemblies with lower CMCs. Conversely, for DNA binding, there was significant enantioselectivity for systems displaying d‐lysine ligands, with a further slight preference for attachment to l‐alanine, with the CMC being irrelevant. [ABSTRACT FROM AUTHOR]

This paper reports a small family of cationic surfactants designed to bind polyanions such as DNA and heparin. Each molecule has the same hydrophilic cationic ligand and a hydrophobic aliphatic group with eighteen carbon atoms with one, two, or three alkene groups within the hydrophobic chain (C18-1, C18-2 and C18-3). Dynamic light scattering indicates that more alkenes lead to geometric distortion, giving rise to larger self-assembled multivalent (SAMul) nanostructures. Mallard Blue and Ethidium Bromide dye displacement assays demonstrate that heparin and DNA have markedly different binding preferences, with heparin binding most effectively to C18-1, and DNA to C18-3, even though the molecular structural differences of these SAMul systems are buried in the hydrophobic core. Multiscale modelling suggests that adaptive heparin maximises enthalpically favourable interactions with C18-1, while shape-persistent DNA forms a similar number of interactions with each ligand display, but with slightly less entropic cost for binding to C18-3-fundamental thermodynamic differences in SAMul binding of heparin or DNA. This study therefore provides unique insight into electrostatic molecular recognition between highly charged nanoscale surfaces in biologically relevant systems. [ABSTRACT FROM AUTHOR]

We present an r package, ggtree, which provides programmable visualization and annotation of phylogenetic trees., ggtree can read more tree file formats than other softwares, including newick, nexus, NHX, phylip and jplace formats, and support visualization of phylo, multiphylo, phylo4, phylo4d, obkdata and phyloseq tree objects defined in other r packages. It can also extract the tree/branch/node-specific and other data from the analysis outputs of beast, epa, hyphy, paml, phylodog, pplacer, r8s, raxml and revbayes software, and allows using these data to annotate the tree., The package allows colouring and annotation of a tree by numerical/categorical node attributes, manipulating a tree by rotating, collapsing and zooming out clades, highlighting user selected clades or operational taxonomic units and exploration of a large tree by zooming into a selected portion., A two-dimensional tree can be drawn by scaling the tree width based on an attribute of the nodes. A tree can be annotated with an associated numerical matrix (as a heat map), multiple sequence alignment, subplots or silhouette images., The package ggtree is released under the artistic-2.0 license. The source code and documents are freely available through bioconductor (). [ABSTRACT FROM AUTHOR]

A hydrogel based on 1,3:2,4-dibenzylidenesorbitol (DBS), modified with acyl hydrazides which extracts gold/silver salts from model waste is reported, with preferential uptake of precious heavy metals over other common metals. Reduction of gold/silver salts occurs spontaneously in the gel to yield metal nanoparticles located on the gel nanofibers. High nanoparticle loadings can be achieved, endowing the gel with electrochemical activity. These hybrid gels exhibit higher conductances than gels doped with carbon nanotubes, and can be used to modify electrode surfaces, enhancing electrocatalysis. We reason this simple, industrially and environmentally relevant approach to conducting materials is of considerable significance. [ABSTRACT FROM AUTHOR]

A hydrogel based on 1,3:2,4-dibenzylidenesorbitol (DBS), modified with acyl hydrazides which extracts gold/ silver salts from model waste is reported, with preferential uptake of precious heavy metals over other common metals. Reduction of gold/silver salts occurs spontaneously in the gel to yield metal nanoparticles located on the gel nanofibers. High nanoparticle loadings can be achieved, endowing the gel with electrochemical activity. These hybrid gels exhibit higher conductances than gels doped with carbon nanotubes, and can be used to modify electrode surfaces, enhancing electrocatalysis. We reason this simple, industrially and environmentally relevant approach to conducting materials is of considerable significance. [ABSTRACT FROM AUTHOR]

A simple approach to a patterned multidomain gel is reported, combining a pH-responsive low-molecular-weight gelator (LMWG) and a photoinducible polymer gelator (PG). Using SEM (scanning electron microscopy), NMR spectroscopy, and CD, we demonstrate that self-assembly of the LMWG network occurs in the presence of the PG network, but that the PG has an influence on LMWG assembly kinetics and morphology. The application of a mask during photoirradiation allows patterning of the PG network; we define the resulting system as a "multidomain gel"-one domain consists of a LMWG, whereas the patterned region contains both LMWG and PG networks. The different domains have different properties with regard to diffusion of small molecules, and both gelator networks can control diffusion rates to give systems capable of controlled release. Such materials may have future applications in multikinetic control of drug release, or as patterned scaffolds for directed tissue engineering. [ABSTRACT FROM AUTHOR]

This study investigates transgeden (TGD) dendrimers (polyamidoamine (PAMAM)-type dendrimers modified with rigid polyphenylenevinylene (PPV) cores) and compares their heparin-binding ability with commercially available PAMAM dendrimers. Although the peripheral ligands are near-identical between the two dendrimer families, their heparin binding is very different. At low generation (G1), TGD outperforms PAMAM, but at higher generation (G2 and G3), the PAMAMs are better. Heparin binding also depends strongly on the dendrimer/heparin ratio. We explain these effects using multiscale modelling. TGD dendrimers exhibit 'shape-persistent multivalency'; the rigidity means that small clusters of surface amines are locally well optimised for target binding, but it prevents the overall nanoscale structure from rearranging to maximise its contacts with a single heparin chain. Conversely, PAMAM dendrimers exhibit 'adaptive multivalency'; the flexibility means individual surface ligands are not so well optimised locally to bind heparin chains, but the nanostructure can adapt more easily and maximise its binding contacts. As such, this study exemplifies important new paradigms in multivalent biomolecular recognition. [ABSTRACT FROM AUTHOR]

Die Anwendung multivalenter Wechselwirkungen ist eine leistungsfähige Strategie biologischer Systeme, um eine hochaffine molekulare Erkennung zu erzielen. Seit kurzem richtet die Aufmerksamkeit der Synthesechemie vermehrt auf die selbstorganisierte anstelle einer kovalenten Synthese zur Anordnung von Liganden. Dieser Ansatz bietet mehrere Vorteile, z. B. eine einfache Synthese/Assemblierung, gezielt einstellbare Morphologien und Liganden, die Möglichkeit zum Einbau mehrerer aktiver Einheiten und die responsive Natur der Selbstorganisation. Wir zeigen, dass selbstorganisierte Multivalenz eine Strategie mit fundamentaler Bedeutung für den Entwurf synthetischer Nanosysteme ist, die in biologische Reaktionswege eingreifen können und potenzielle Anwendungen in der Nanomedizin finden. [ABSTRACT FROM AUTHOR]

Multivalency is a powerful strategy for achieving high-affinity molecular recognition in biological systems. Recently, attention has begun to focus on using self-assembly rather than covalent scaffold synthesis to organize multiple ligands. This approach has a number of advantages, including ease of synthesis/assembly, tunability of nanostructure morphology and ligands, potential to incorporate multiple active units, and the responsive nature of self-assembly. We suggest that self-assembled multivalency is a strategy of fundamental importance in the design of synthetic nanosystems to intervene in biological pathways and has potential applications in nanomedicine. [ABSTRACT FROM AUTHOR]

There continues to be considerable interest in the potential for applying Operational Research (OR) in less-developed countries. A recent paper provided a bibliography of published research from West Africa. This paper extends that bibliography to the other sub-Saharan nations, with the omission of South Africa. In some parts of this region, there have been numerous applications described in the literature, while in others there is very little on record. As in the earlier paper, the material has been collected from a wide range of journals, extending from the regular OR literature to many application journals. In addition to the references, the paper describes the manner of collection of this information, and discusses the resulting picture of OR in sub-Saharan Africa. [ABSTRACT FROM AUTHOR]

Protein crystallization has been revolutionized by the introduction of high-throughput technologies, which have led to a speeding up of the process while simultaneously reducing the amount of protein sample necessary. Nonetheless, the chemistry dimension of protein crystallization has remained relatively undeveloped. Most crystallization screens are based on the same set of precipitants. To address this shortcoming, the development of new protein precipitants based on poly-γ-glutamic acid (PGA) polymers with different molecular-weight ranges is reported here: PGA-LM (low molecular weight) of ~400 kDa and PGA-HM (high molecular weight) of >1.000 kDa. It is also demonstrated that protein precipitants can be expanded further to polymers with much higher molecular weight than those that are currently in use. Furthermore, the modification of PGA-like polymers by covalent attachments of glucosamine substantially improved their solubility without affecting their crystallization properties. Some preliminary PGA-based screens are presented here. [ABSTRACT FROM AUTHOR]

There is considerable interest in the potential for using operational research (O.R.) in developing countries. One sign of this is the formation of new societies for O.R. scientists in countries and regions where no such society had existed. Since 2003, such societies have been formed in several parts of Africa. This paper focuses on West Africa, and presents a bibliography of papers relating to applications of O.R. in the nations of this part of the continent. The paper describes the way in which the bibliography was collated and discusses the overall picture that the list of papers presents of the state of O.R. in the 18 countries that are considered. [ABSTRACT FROM AUTHOR]

The development of new crystallization platforms via the application of high-throughput technologies has delivered a plethora of crystallization plates suitable for robot-driven and manual setups. However, practically all these plates (except for microfluidic channel chips) are based on a very similar design and well (precipitant):drop (protein) volume ratios. A new type of crystallization plate (µplate) has therefore been developed and tested that still employs the classical vapour-diffusion technique but minimizes the precipitant well volume to 1.2 µl for a 150 nl protein drop setup. This enables a very significant saving on the total bulk of the crystallization screen, hence allowing the application of new, rare and expensive solutions in automated crystallization-screening procedures. Additionally, owing to the very low drop:well volume ratio, the new µplate can significantly accelerate the equilibrium time necessary for crystal nucleation and growth, in many cases shortening the high-throughput crystallization screening process to a few hours. [ABSTRACT FROM AUTHOR]

Abstract: Ciliary neurotrophic factor (CNTF) forms a functional receptor complex containing the CNTF receptor, gp130, and the leukemia inhibitory factor receptor (LIFR). However, the nature and stoichiometry of the receptor-mediated interactions in this complex have not yet been fully resolved. We show here that signaling by CNTF, but not by LIF or oncostatin M (OSM), was abolished in cells overexpressing a LIFR mutant with the N-terminal cytokine binding domain deleted. Our results illustrate molecular differences between the CNTF active receptor complex and those of LIF and OSM and provide further support for the hexameric model of the CNTF receptor complex. [Copyright &y& Elsevier]

Comparisons were made among four categories of protein flexibility: (1) low-B-factor ordered regions, (2) high-B-factor ordered regions, (3) short disordered regions, and (4) long disordered regions. Amino acid compositions of the four categories were found to be significantly different from each other, with high-B-factor ordered and short disordered regions being the most similar pair. The high-B-factor (flexible) ordered regions are characterized by a higher average flexibility index, higher average hydrophilicity, higher average absolute net charge, and higher total charge than disordered regions. The low-B-factor regions are significantly enriched in hydrophobic residues and depleted in the total number of charged residues compared to the other three categories. We examined the predictability of the high-B-factor regions and developed a predictor that discriminates between regions of low and high B-factors. This predictor achieved an accuracy of 70% and a correlation of 0.43 with experimental data, outperforming the 64% accuracy and 0.32 correlation of predictors based solely on flexibility indices. To further clarify the differences between short disordered regions and ordered regions, a predictor of short disordered regions was developed. Its relatively high accuracy of 81% indicates considerable differences between ordered and disordered regions. The distinctive amino acid biases of high-B-factor ordered regions, short disordered regions, and long disordered regions indicate that the sequence determinants for these flexibility categories differ from one another, whereas the significantly-greater-than-chance predictability of these categories from sequence suggest that flexible ordered regions, short disorder, and long disorder are, to a significant degree, encoded at the primary structure level. [ABSTRACT FROM AUTHOR]

Protein molecules exhibit varying degrees of flexibility throughout their three-dimensional structures, with some segments showing little mobility while others may be so disordered as to be unresolvable by techniques such as X-ray crystallography. Atomic displacement parameters, or B-factors, from X-ray crystallographic studies give an experimentally determined indication of the degree of mobility in a protein structure. To provide better estimators of amino acid flexibility, we have examined B-factors from a large set of high-resolution crystal structures. Because of the differences among structures, it is necessary to normalize the B-factors. However, many proteins have segments of unusually high mobility, which must be accounted for before normalization can be performed. Accordingly, a median-based method from quality control studies was used to identify outliers. After removal of outliers from, and normalization of, each protein chain, the B-factors were collected for each amino acid in the set. It was found that the distribution of normalized B-factors followed a Gumbel, or extreme value distribution, and the location parameter, or mode, of this distribution was used as an estimator of flexibility for the amino acid. These new parameters have a higher correlation with experimentally determined B-factors than parameters from earlier methods. [ABSTRACT FROM AUTHOR]

Ciliary neurotrophic factor (CNTF) is a member of the gp130 family of cytokines. The functional receptor complex of CNTF is composed of the CNTF receptor α (CNTFR), gp130 and the leukemia inhibitory factor receptor (LIFR). Three regions on CNTF have been identified as binding sites for its receptors. The ligand–receptor interactions are mediated through the cytokine binding domains (CBDs) and/or the immunoglobulin-like domains of the receptors. However, in the case of CNTF, the precise nature of the protein–protein contacts in the signaling complex has not yet been resolved. In this study, we provide the first demonstration that the membrane distal CBD (CBD1) of LIFR associates in vitro with soluble CNTFR in the absence of CNTF. Moreover, purified CBD1 partially blocks CNTF signaling, but not that of interleukin-6 or LIF, in human embryonal carcinoma cell line Ntera/D1 cells. These data raise the possibility that LIFR has the capability to form a ligand-free complex with CNTFR. [Copyright &y& Elsevier]

A two‐component low‐molecular‐weight gelator (LMWG) formed from a modified amino acid and an aldehyde was formulated with active pharmaceutical ingredients (APIs). Basic APIs (propranolol, atropine) can be mixed with the LMWG prior to gel assembly while acidic APIs (naproxen, rosuvastatin) inhibit assembly by disrupting the LMWG imine bond and were loaded by diffusion after gel assembly. For diffusion‐loaded gels, the API in the liquid‐like phase was rapidly released, with the remainder, interacting with gel fibres, retained in the gel. Rosuvastatin release was particularly low with Saturation Transfer Difference (STD) NMR indicating interactions between the aromatic ring and the self‐assembled gel network. Propranolol also interacted with the gel via its aromatic unit, and its release led to gel erosion. Using agarose as a polymer gelator additive reinforced the gel, restricting erosion. In contrast, atropine was readily released over a period of hours ‐ it is primarily in the liquid‐like phase with STD NMR indicating no interactions with the gel network. The atropine‐loaded gel retained its thixotropic properties. Overall, APIs must be carefully chosen to optimise formulation/release. Of the APIs investigated, atropine has most potential for further development. Atropine has applications in treating myopia, and our results suggest potential ophthalmic applications of supramolecular gels. [ABSTRACT FROM AUTHOR]

Leukemia inhibitory factor (LIF), a member of the gpl30 family of helical cytokines, is involved in the hemopoietic and neural systems. The LIF signal transducing complex contains two receptor molecules, the LIF receptor (LIFR) and gp130. The extracellular region of the LIFR is unique in that it includes three membrane-proximal fibronectin type III domains and two cytokine binding domains (CBDs) separated by an immunoglobulin-like domain. Although some mutagenesis data on LIF are available, it is not yet known which regions of LIFR or gp130 bind LIF. Nor is it known whether LIFR contacts gp130 in a manner similar to the growth hormone receptor dimer and, if so, through which of its CBDs. To attempt to elucidate these matters and to investigate the receptor complex, models of the CBDs of LIFR and the CBD of gp130 were constructed. Analyses of the electrostatic isopotential surfaces of the CBD models suggest that gp130 and the membrane-proximal CBD of LIFR hetero-dimerize and bind LIF through contacts similar to those seen in the growth hormone receptor dimer. This work further demonstrates the utility of electrostatic analyses of homology models and suggests a strategy for biochemical investigations of the LIF-receptor complex. [ABSTRACT FROM AUTHOR]