Chirality and life

The crucial role of homochirality and chiral homogeneity in the self-replication of contemporary biopolymers is emphasized, and the experimentally demonstrated advantages of these chirality attributes in simpler polymeric systems are summarized. The implausibility of life without chirality and hence of a biogenic scenario for the origin of chiral molecules is stressed, and chance and determinate abiotic mechanisms for the origin of chirality are reviewed briefly in the context of their potential viability on the primitive Earth. It is concluded that all such mechanisms would be non-viable, and that the turbulent prebiotic environment would require an ongoing extraterrestrial source for the accumulation of chiral molecules on the primitive Earth. A scenario is described wherein the circularly polarized ultraviolet synchrotron radiation from the neutron star remnants of supernovae engenders asymmetric photolysis of the racemic constituents in the organic mantles on interstellar dust grains, whereupon these chiral constituents are transported repetitively to the primative Earth by direct accretion of the interstellar dust or through impacts of comets and asteroids.     

Intracellular trafficking of polyamidoamine-poly(ethylene glycol) block copolymers in DNA delivery

The delivery of nucleic acids has the potential to revolutionize medicine by allowing previously untreatable diseases to be clinically addressed. Viral delivery systems have shown immunogenicity and toxicity dangers, but synthetic vectors have lagged in transfection efficiency. Previously, we developed a modular, linear-dendritic block copolymer architecture with high gene transfection efficiency compared to commercial standards. This rationally designed system makes use of a cationic dendritic block to condense the anionic DNA and forms complexes with favorable endosomal escape properties. The linear block provides biocompatibility and protection from serum proteins, and can be functionalized with a targeting ligand. In this work, we quantitate performance of this system with respect to intracellular barriers to gene delivery using both high-throughput and traditional approaches. An image-based, high-throughput assay for endosomal escape is described and applied to the block copolymer system. Nuclear entry is demonstrated to be the most significant barrier to more efficient delivery and will be addressed in future versions of the system.     

Supernovae, neutron stars and biomolecular chirality

Recent theoretical and experimental investigations of the origin of biomolecular chirality are reviewed briefly. Biotic and abiotic theories are evaluated critically with the conclusion that asymmetric photochemical processes with circulary polarized light (CPL), particularly asymmetric photolyses, constitute the most viable mechanisms. Solar CPL sources appear too weak and random to be effective. We suggest an alternative CPL source, namely, the synchrotron radiation from the neutron star remnants of supernova explosions. This could asymmetrically process racemic compounds in the organic mantles of the dust grains in interstellar clouds, and the resulting chiral molecules could be transferred to Earth by cold accretion as the solar system periodically traverses these interstellar clouds.     

Responses of serum chemokines to dramatic changes of air pollution levels,a panel study

Abstract

Background: Despite the in vitro and in vivo evidence, studies are limited in evaluating whether chemokines are potential inflammatory mediators in response to air pollution exposure in humans.

Methods: We conducted a panel study coinciding with the Beijing Olympics, when temporary air pollution controls were implemented. We measured a suite of serum chemokines among healthy adults before, during and after the Olympics, respectively. Linear mixed-effect models were used to evaluate changes in chemokine levels over the three time periods.

Results: In response to the 50% drop in air pollution levels during the games, levels of RANTES, MCP-2, and TARC decreased by 25.8%, 20.9% and 35.3%, respectively (p?<?0.001) from pre-Olympics, and then increased by 45.8%, 34.9% and 61.5%, respectively (p?<?0.001) after the games when air pollution levels went up again. Similar patterns were observed in subgroup analyses by sex, age, smoking and body mass index. GRO-α and IL-8 decreased significantly during the games (22.5% and 30.4%), and increased non-significantly after the games. Eotaxin-1 only increased significantly from during- to post-games.

Conclusions: The strongest associations with air pollution levels were observed among RANTES, TARC and MCP-2. Those chemokines may play important roles in the air pollution-induced inflammatory pathway.     

Asymmetric introgression between fishes in the Red River basin of Texas is associated with variation in water quality

When ecologically divergent taxa encounter one another, hybrid zones can form when reproductive isolation is incomplete. The location of such hybrid zones can be influenced by environmental variables, and an ecological context can provide unique insights into the mechanisms by which species diverge and are maintained. Two ecologically differentiated species of small benthic fishes, the endemic and imperiled prairie chub, Macrhybopsis australis, and the shoal chub, Macrhybopsis hyostoma, are locally sympatric within the upper Red River Basin of Texas. We integrated population genomic data and environmental data to investigate species divergence and the maintenance of species boundaries in these two species. We found evidence of advanced‐generation asymmetric hybridization and introgression, with shoal chub alleles introgressing more frequently into prairie chubs than the reciprocal. Using a Bayesian Genomic Cline framework, patterns of genomic introgression were revealed to be quite heterogeneous, yet shoal chub alleles were found to have likely selectively introgressed across species boundaries significantly more often than prairie chub alleles, potentially explaining some of the observed asymmetry in hybridization. These patterns were remarkably consistent across two sampled geographic regions of hybridization. Several environmental variables were found to significantly predict individual admixture, suggesting ecological isolation might maintain species boundaries.     

On-line capillary column immobilised metal affinity chromatography/electrospray ionisation mass spectrometry for the selective analysis of histidine-containing peptides

Capillary column immobilised metal affinity chromatography (IMAC) has been combined on-line with electrospray ionisation/quadrupole time-of-flight mass spectrometry for the fractionation of histidine-containing peptides. IMAC beads (Poros 20MC, 20 microm) containing imidodiacetate chelating groups on a cross-linked poly(styrene-divinylbenzene) support were packed into a fused silica column (250 microm i.d.), which was interfaced to the electrospray ion source of the spectrometer. A Cu(II) activated column was used to isolate histidine-containing peptides from tryptic and other peptide mixtures with an average breakthrough of 9.1%, to reduce the complexity of the mass spectral analysis. The analysis cycle time was reduced to less than 15 min, at an optimum flow rate of 7.5 microL/min, without sacrificing peptide selectivity. Direct coupling of capillary IMAC with MS allows on-line separation, using MS compatible loading and elution buffers, and detection in a high-throughput fashion when compared to off-line strategies.