Calculation of the Three-Dimensional Structures of Two Antigenic Sequences, Pro–Pro–Pro–Pro–Asn–Pro–Asn–Asp–Pro and Pro–Pro–Pro–Pro–Asn–Pro–Asn–Asp–Pro–Pro–Pro, of the Circumsporozoite Protein From a Malaria-Causing Plasmodium

Using the chain build-up procedure based on the program ECEPP, we have computed the lowest energy structures for two terminally blocked subsequences from the antigenic circumsporozoite protein of Plasmodium berghei, that is known to cause malaria in animals. The full antigenic sequence is an octapeptide proline-rich tandem repeat, (Pro–Pro–Pro–Pro–Asn–Pro–Asn–Asp)₂. We computed the structures for the first octapeptide plus one Pro from the second octapeptide, terminally blocked CH₃CO–Pro–Pro–Pro–Pro–Asn–Pro–Asn–Asp–Pro–NHCH₃ as well as the first octpeptide with an additional three Pro residues from the adjoining unit, i.e., CH₃CO–Pro–Pro–Pro–Pro–Asn–Pro–Asn–Asp–Pro–Pro–Pro–NHCH₃. We find that the first sequence adopts a number of different low energy structures, the most probable of which has a probability of occurrence of 56 %. Addition of two more Pro residues results in the adoption a single, unique lowest energy structure that has a probability of occurrence of over 95 % without solvation effects and 86 % when solvation effects are included in the calculations. We predict that this structure may be the one recognized as a major antigenic determinant.     

Nonorthogonal tight-binding model with H–C–N–O parameterisation

A parametric nonorthogonal tight-binding model (NTBM1) with the set of parameters for H–C–N–O systems is presented. This model compares well with widely used semi-empirical AM1 and PM3/PM7 models but contains less fitting parameters per atom. All NTBM1 parameters are derived based on a criterion of the best agreement between the calculated and experimental values of bond lengths, valence angles and binding energies for various H–C–N–O molecules. Results for more than 200 chemical compounds are reported. Parameters are currently available for hydrogen, carbon, nitrogen, oxygen atoms and corresponding interatomic interactions. The model has a good transferability and can be used for both relaxation of large molecular systems (e.g., high-molecular compounds or covalent cluster complexes) and long-timescale molecular dynamics simulation (e.g., modelling of thermal decomposition processes). The program package based on this model is available for download at no cost from http://ntbm.info.     

The centromeric nucleosome-like CENP–T–W–S–X complex induces positive supercoils into DNA

The centromere is a specific genomic region upon which the kinetochore is formed to attach to spindle microtubules for faithful chromosome segregation. To distinguish this chromosomal region from other genomic loci, the centromere contains a specific chromatin structure including specialized nucleosomes containing the histone H3 variant CENP–A. In addition to CENP–A nucleosomes, we have found that centromeres contain a nucleosome-like structure comprised of the histone-fold CENP–T–W–S–X complex. However, it is unclear how the CENP–T–W–S–X complex associates with centromere chromatin. Here, we demonstrate that the CENP–T–W–S–X complex binds preferentially to ∼100 bp of linker DNA rather than nucleosome-bound DNA. In addition, we find that the CENP–T–W–S–X complex primarily binds to DNA as a (CENP–T–W–S–X)₂ structure. Interestingly, in contrast to canonical nucleosomes that negatively supercoil DNA, the CENP–T–W–S–X complex induces positive DNA supercoils. We found that the DNA-binding regions in CENP–T or CENP–W, but not CENP–S or CENP–X, are required for this positive supercoiling activity and the kinetochore targeting of the CENP–T–W–S–X complex. In summary, our work reveals the structural features and properties of the CENP–T–W–S–X complex for its localization to centromeres.     

The DNA–DNA spacing in gemini surfactants–DOPE–DNA complexes

Gemini surfactants from the homologous series of alkane-α,ω-diyl-bis(dodecyldimethylammonium bromide) (CnCS12, number of spacer carbons n = 2 – 12) and dioleoylphosphatidylethanolamine (DOPE) were used for cationic liposome (CL) preparation. CLs condense highly polymerized DNA creating complexes. Small-angle X-ray diffraction identified them as condensed lamellar phase L_α^C in the studied range of molar ratios CnGS12/DOPE in the temperature range 20 – 60 °C. The DNA–DNA distance (d_DNA) is studied in dependence to CnGS12 spacer length and membrane surface charge density. The high membrane surface charge densities (CnGS12/DOPE = 0.35 and 0.4 mol/mol) lead to the linear dependence of d_DNA vs. n correlating with the interfacial area of the CnGS12 molecule.     

News & Notes: Nucleotide Sequence of a DNA Fragment from Buchnera aphidicola (Aphid Endosymbiont) Containing the Genes aspS–trxB–serS–serC–aroA–rpsA–himD–tpiA

Buchnera aphidicola is an endosymbiont of aphids. The nucleotide sequence of an 11.5-kilobase DNA fragment from this prokaryotic organism was determined. Eight open reading frames were found coding for putative proteins involved in protein synthesis, serine and aromatic amino acid biosynthesis, as well as thioredoxin and carbohydrate metabolism. These results indicate that B. aphidicola has many genetic properties of free-living bacteria. Received: 31 December 1996 / Accepted: 6 January 1997     

Halogen–water–hydrogen bridges in biomolecules

The importance of water in biological systems has long been recognized in chemistry and biology communities. In this article we describe a new manner by which water affects biomolecular behaviors, called halogen–water–hydrogen bridge (XWH bridge), that is, one hydrogen bonding (H-bonding) in water-mediated H-bond bridge is replaced by halogen bonding (X-bonding). Although behaving similarly to water-mediated H-bond motif, the XWH bridge usually stands in multifurcated forms and possesses stronger directionality. Quantum mechanical analysis on several model and real systems reveals that the XWH bridges are more thermodynamically stable than other water-involved interactions, and this stability is further enhanced by the cooperation of X-bonding and H-bonding. Crystal structure survey clearly demonstrates the significance of XWH bridges in stabilization of biomolecular conformations and in mediation of protein–protein, protein–nucleic acid, and receptor–ligand recognition and binding. These findings shed light into the potential value of XWH bridges in drug design and biological engineering.     

Oligonucleotide-Mediated Au–Ag Core–Shell Nanoparticles

The bimetallic core–shell nanoparticles show unique plasmonic properties and their preparations and characterizations are currently under investigation. A new type of Au core–Ag shell (Au@Ag) nanoparticles is prepared by sandwiching the chemically attached Raman reporter molecules (RRMs) and a 12-base-long oligonucleotide between the 13 nm average size core-gold nanoparticles (AuNPs) and 9 nm and 21 nm average size of Ag shell. The synthesized Au@Ag nanoparticles are tested for their surface-enhanced Raman scattering (SERS) performance. It is found that the chemical attachment of the oligonucleotides along with the RRM improved the enhancement in Raman scattering more than one order of the magnitude with the Au@Ag nanoparticles with an average 9-nm shell thickness while the Au@Ag nanoparticles with 21 nm average shell thickness have poor SERS activity. A minimum enhancement factor of 1.0 × 10⁷ is estimated for the SERS active oligonucleotide-mediated Au@Ag nanoparticles. The approach may provide new routes for preparation of highly sensitive new generation of bimetallic core–shell nanoparticles.     

Dynamics of plant–pollinator–robber systems

Plant–pollinator–robber systems are considered, where the plants and pollinators are mutualists, the plants and nectar robbers are in a parasitic relation, and the pollinators and nectar robbers consume a common limiting resource without interfering competition. My aim is to show a mechanism by which pollination–mutualism could persist when there exist nectar robbers. Through the dynamics of a plant–pollinator–robber model, it is shown that (i) when the plants alone (i.e., without pollination–mutualism) cannot provide sufficient resources for the robbers’ survival but pollination–mutualism can persist in the plant–pollinator system, the pollination–mutualism may lead to invasion of the robbers, while the pollinators will not be driven into extinction by the robbers’ invasion. (ii) When the plants alone cannot support the robbers’ survival but persistence of pollination–mutualism in the plant–pollinator system is density-dependent, the pollinators and robbers could coexist if the robbers’ efficiency in translating the plant–robber interactions into fitness is intermediate and the initial densities of the three species are in an appropriate region. (iii) When the plants alone can support the robbers’ survival, the pollinators will not be driven into extinction by the robbers if their efficiency in translating the plant–pollinator interactions into fitness is relatively larger than that of the robbers. The analysis leads to an explanation for the persistence of pollination–mutualism in the presence of nectar robbers in real situations.     

Characterization of immunoreactive acetyl–Ser–Asp–Lys–Pro in human plasma and urine by liquid chromatography–electrospray mass spectrometry

The tetrapeptide AcSDKP, a natural and specific substrate of angiotensin I-converting enzyme (ACE), is a negative regulator of hematopoiesis. AcSDKP has been measured in various biological media using an enzyme immunoassay (EIA), but its presence in human plasma and urine has not been formally established. By using immunoaffinity extraction and liquid chromatography–electrospray mass spectrometry, we demonstrate that AcSDKP-like immunoreactivity measured with EIA in plasma and urine samples from untreated, captopril- (an ACE inhibitor) and AcSDKP-treated subjects corresponds to AcSDKP. The present study confirms that AcSDKP is naturally present in human plasma and urine and that EIA is reliable for its measurement in such media.     

Metabolomic changes in Caenorhabditis elegans lifespan mutants as evident from GC–EI–MS and GC–APCI–TOF–MS profiling

Lifespan mutants of the nematode Caenorhabditis elegans are a much studied aging model, however, aging-related changes at the metabolome level remain largely unexplored. To identify metabolic features connected to mitochondrial dysfunction, a hallmark of aging and age-related disease, we analyzed a short-lived mitochondrial mutant (mev-1(kn1)), a long-lived mutant with enhanced cellular maintenance (ife-2(ok306)) and the novel double mutant ife-2(ok306);mev-1(kn1) which is normal-lived, possibly through attenuation of the metabolic mev-1 phenotype. Metabolomic analysis involved coupled gas chromatography–mass spectrometry with electron ionization (GC–EI–MS) and, in addition, recently introduced GC with soft atmospheric pressure chemical ionization coupled to time-of-flight mass spectrometry (GC–APCI–TOF–MS) to yield complementary mass spectrometric information for enhanced metabolite annotation. Multivariate analysis allowed distinction of mev-1 and ife-2 mutants from the wild type, while suggesting still another, distinct metabolic phenotype for the ife-2;mev-1 double mutant. In mev-1(kn1), disturbed energy metabolism was indicated by upset TCA cycle homeostasis, elevated glycolytic substrate and lactic acid levels as well as depletion of free amino acids pools. Surprisingly, these mitochondrially related changes were retained in the ife-2;mev-1 mutant, as were highly elevated levels of the dipeptide glycylproline indicative of increased collagen catabolism. However, the double mutant reverted mev-1(kn1) changes in uric acid and long-chain fatty alcohol metabolism, two pathways connected to the peroxisomal compartment. Our results are in line with recent evidence for a critical role of this organelle in aging and demonstrate the usefulness of non-targeted metabolomics approaches for detecting complex metabolic changes in the study of mitochondrial dysfunction.     

Cylindrical Magnetosonic Solitary Waves by Modified Korteweg–de Vries–Burgers Equation in Electron–Positron–Ion Plasma

Plasma Physics Reports - Theoretical investigations are carried out for the cylindrical magnetosonic solitary waves in dissipative, hot electron–positron–ion plasma. By the reductive...     

Mobility unevenness in rock–paper–scissors models

We investigate a tritrophic system whose cyclic dominance is modelled by the rock–paper–scissors game. We consider that organisms of one or two species are affected by movement limitations, which unbalances the cyclic spatial game. Performing stochastic simulations, we show that mobility unevenness controls the population dynamics. In the case of one slow species, the predominant species depends on the level of mobility restriction, with the slow species being preponderant if the mobility limitations are substantial. If two species face mobility limitations, our outcomes show that being higher dispersive does not constitute an advantage in terms of population growth. On the contrary, if organisms move with higher mobility, they expose themselves to enemies more frequently, being more vulnerable to being eliminated. Finally, our findings show that biodiversity benefits in regions where species are slowed. Biodiversity loss for high mobility organisms, common to cyclic systems, may be avoided with coexistence probability being higher for robust mobility limitations. Our results may help biologists understand the dynamics of unbalanced spatial systems where organisms’ dispersal is fundamental to biodiversity conservation.     

Fluid–structure interaction in a fully coupled three-dimensional mitral–atrium–pulmonary model

This paper aims to investigate detailed mechanical interactions between the pulmonary haemodynamics and left heart function in pathophysiological situations (e.g. atrial fibrillation and acute mitral regurgitation). This is achieved by developing a complex computational framework for a coupled pulmonary circulation, left atrium and mitral valve model. The left atrium and mitral valve are modelled with physiologically realistic three-dimensional geometries, fibre-reinforced hyperelastic materials and fluid–structure interaction, and the pulmonary vessels are modelled as one-dimensional network ended with structured trees, with specified vessel geometries and wall material properties. This new coupled model reveals some interesting results which could be of diagnostic values. For example, the wave propagation through the pulmonary vasculature can lead to different arrival times for the second systolic flow wave (S2 wave) among the pulmonary veins, forming vortex rings inside the left atrium. In the case of acute mitral regurgitation, the left atrium experiences an increased energy dissipation and pressure elevation. The pulmonary veins can experience increased wave intensities, reversal flow during systole and increased early-diastolic flow wave (D wave), which in turn causes an additional flow wave across the mitral valve (L wave), as well as a reversal flow at the left atrial appendage orifice. In the case of atrial fibrillation, we show that the loss of active contraction is associated with a slower flow inside the left atrial appendage and disappearances of the late-diastole atrial reversal wave (AR wave) and the first systolic wave (S1 wave) in pulmonary veins. The haemodynamic changes along the pulmonary vessel trees on different scales from microscopic vessels to the main pulmonary artery can all be captured in this model. The work promises a potential in quantifying disease progression and medical treatments of various pulmonary diseases such as the pulmonary hypertension due to a left heart dysfunction.