Unseen Structures Research Articles

Protein kinase C and extracellular signal-regulated kinase regulate movement, attachment, pairing and egg release in Schistosoma mansoni.

Protein kinases C (PKCs) and extracellular signal-regulated kinases (ERKs) are evolutionary conserved cell signalling enzymes that coordinate cell function. Here we have employed biochemical approaches using ‘smart’ antibodies and functional screening to unravel the importance of these enzymes to Schistosoma mansoni physiology. Various PKC and ERK isotypes were detected, and were differentially phosphorylated (activated) throughout the various S. mansoni life stages, suggesting isotype-specific roles and differences in signalling complexity during parasite development. Functional kinase mapping in adult worms revealed that activated PKC and ERK were particularly associated with the adult male tegument, musculature and oesophagus and occasionally with the oesophageal gland; other structures possessing detectable activated PKC and/or ERK included the Mehlis' gland, ootype, lumen of the vitellaria, seminal receptacle and excretory ducts. Pharmacological modulation of PKC and ERK activity in adult worms using GF109203X, U0126, or PMA, resulted in significant physiological disturbance commensurate with these proteins occupying a central position in signalling pathways associated with schistosome muscular activity, neuromuscular coordination, reproductive function, attachment and pairing. Increased activation of ERK and PKC was also detected in worms following praziquantel treatment, with increased signalling associated with the tegument and excretory system and activated ERK localizing to previously unseen structures, including the cephalic ganglia. These findings support roles for PKC and ERK in S. mansoni homeostasis, and identify these kinase groups as potential targets for chemotherapeutic treatments against human schistosomiasis, a neglected tropical disease of enormous public health significance.

Designing Highly Tunable Semiflexible Filament Networks

Stiff or semi-flexible polymers have the potential to generate a diverse family of network-based materials. Such materials differ significantly in structure from those seen in polymeric systems formed from molecules approximated by the freely jointed chain. The solution behavior is well known for specific biological examples such as F-actin, microtubules, DNA etc. under the influence of cross-linking proteins or specific ionic conditions. However, a general picture of phase behavior and the range of accessible structures as a function of flexibility, length, attractive potential, and concentration has not yet emerged as these parameters are often difficult to tune experimentally. Here we show an approach to this problem by modeling filament assembly under the influence of a modified Lennard-Jones potential, and a rich variety of network structures, as seen in biological and synthetic examples, are generated. Our results reveal that previously observed networks of bundles seen in F-actin systems are not unique to certain cross-linkers but occupy a tunable position in the phase diagram. Further modification of filament parameters allows the generation of hierarchically structured networks not seen in flexible polymer systems. Our coarse-grained model, inspired by models of F-actin networks with explicit cross-linkers, greatly expands the accessible parameter space. Approximating the effect of crosslinkers by a Lennard-Jones like potential allows for a more tunable representation of filament attraction and binding. The network phases are observed and diagrammed, showing transitions between distinct structures. Morphological properties of the networks are quantitatively examined using connectivity analysis, radial pair distribution functions and a scaling analysis. Detailing the effects of semi-flexible filament parameters on structure and connectivity in this way provides a roadmap for the design of highly tunable hierarchical networks and aids in the discovery of previously unseen structures for novel bioinspired materials.

Self-Organization of a Mesoscale Bristle into Ordered, Hierarchical Helical Assemblies

Mesoscale hierarchical helical structures with diverse functions are abundant in nature. Here we show how spontaneous helicity can be induced in a synthetic polymeric nanobristle assembling in an evaporating liquid. We use a simple theoretical model to characterize the geometry, stiffness, and surface properties of the pillars that favor the adhesive self-organization of bundles with pillars wound around each other. The process can be controlled to yield highly ordered helical clusters with a unique structural hierarchy that arises from the sequential assembly of self-similar coiled building blocks over multiple length scales. We demonstrate their function in the context of self-assembly into previously unseen structures with uniform, periodic patterns and controlled handedness and as an efficient particle-trapping and adhesive system.

Local descriptors of protein structure: A systematic analysis of the sequence‐structure relationship in proteins using short‐ and long‐range interactions

Local protein structure representations that incorporate long-range contacts between residues are often considered in protein structure comparison but have found relatively little use in structure prediction where assembly from single backbone fragments dominates. Here, we introduce the concept of local descriptors of protein structure to characterize local neighborhoods of amino acids including short- and long-range interactions. We build a library of recurring local descriptors and show that this library is general enough to allow assembly of unseen protein structures. The library could on average re-assemble 83% of 119 unseen structures, and showed little or no performance decrease between homologous targets and targets with folds not represented among domains used to build it. We then systematically evaluate the descriptor library to establish the level of the sequence signal in sets of protein fragments of similar geometrical conformation. In particular, we test whether that signal is strong enough to facilitate correct assignment and alignment of these local geometries to new sequences. We use the signal to assign descriptors to a test set of 479 sequences with less than 40% sequence identity to any domain used to build the library, and show that on average more than 50% of the backbone fragments constituting descriptors can be correctly aligned. We also use the assigned descriptors to infer SCOP folds, and show that correct predictions can be made in many of the 151 cases where PSI-BLAST was unable to detect significant sequence similarity to proteins in the library. Although the combinatorial problem of simultaneously aligning several fragments to sequence is a major bottleneck compared with single fragment methods, the advantage of the current approach is that correct alignments imply correct long range distance constraints. The lack of these constraints is most likely the major reason why structure prediction methods fail to consistently produce adequate models when good templates are unavailable or undetectable. Thus, we believe that the current study offers new and valuable insight into the prediction of sequence-structure relationships in proteins.

High-resolution infrared imaging of young outflow-sources

We discuss recent results from near-infrared bispectrum speckle interferometry observations of the young outflow sources in the S140 and Mon R2 star forming regions. With spatial resolutions down to 0.075'', our data represent the highest resolution images obtained so far for these objects and exhibit previously unseen complex structures in the immediate vicinity of the young stellar objects. We discuss the relation of these structures to the jets and outflows.

High-resolution optical imaging of the Large Magellanic Cloud plerion 0540 - 69

view Abstract Citations (48) References (13) Co-Reads Similar Papers Volume Content Graphics Metrics Export Citation NASA/ADS High-Resolution Optical Imaging of the Large Magellanic Cloud Plerion 0540-69 Caraveo, P. A. ; Bignami, G. F. ; Mereghetti, S. ; Mombelli, M. Abstract The Crab-like SNR 0540-69 in the LMC has been investigated using the ESO NTT (New Technology Telescope) equipped with SUSI (SUperb Seeing Imager). B, V, O III, S II, and Hα images were collected under very good seeing conditions, yielding unprecedented detail on the picture of the expanding shell as well as of the synchrotron nebula, which is shown to harbor two maxima of emission. Both of these are seen to have magnitudes comparable to that of the optical pulsar reported by Middleditch et al. (1987), the northern one appearing more compact. The Hα image shows previously unseen structures, apparently unrelated to the expanding shell as well as to the synchrotron nebula. The Hα extent of the remnant is significantly smaller than that at other wavelengths and shows a symmetric pattern centered on the northern maximum of continuum emission which could very well be the optical counterpart of PSR 0540-69. Publication: The Astrophysical Journal Pub Date: August 1992 DOI: 10.1086/186498 Bibcode: 1992ApJ...395L.103C Keywords: Magellanic Clouds; Pulsars; Supernova Remnants; Astronomical Spectroscopy; Emission Spectra; H Alpha Line; Line Spectra; Synchrotron Radiation; Astronomy full text sources ADS | data products SIMBAD (4) NED (2)

An Electron Microscopic Study of Human Epidermis

Since the introduction of the electron microscope there have been a series of improvements in both the microscope and in the technics of preparing the tissue. These have resulted in its present accuracy and widespread use in the biomedical field. The electron microscope has increased resolving power attainable in sections from the previous limit of 2,000 Angstroms with the light microscope to the present limit of 20 Angstroms. In so doing, it has led to a description of many previously unseen structures, and thus to much new terminology in the field of anatomy. Many concepts on structure have had to be revised and many others have been upheld and extended by this new visual aid.