Multilevel Selection in Models of Prebiotic Evolution: Compartments and Spatial Self-organization

In this paper we explore the impact of new levels ofselection in models of early evolution.We contrast two types of higher levels of selection. On the one hand we look at spatially explicitmodels of replicators in which, by a process of self-organization, new levels of selection ariseas large scale spatial patterns with a dynamics of their own. Alternatively externally imposedlevels of selection above the basic replicators are created by enclosing the replicators in vesicles.In this paper we first review some results on the impact of emerging higher levels of selection onthe evolutionary persistence of interacting co-evolvingreplicator systems. Moreover, we presenta vesicle model, which can potentially integrate emerging and imposed levels of selection. We use the models to examinethe classical problem information integration in early evolution.Supplementary material to this paper is available in electronic form at http://dx.doi.org/10.1023/A:1025754907141     

The Role of Complex Formation and Deleterious Mutations for the Stability of RNA-Like Replicator Systems

In the RNA world hypothesis, RNA(-like) self-replicators are suggested as the central player of prebiotic evolution. However, there is a serious problem in the evolution of complexity in such replicators, i.e., the problem of parasites. Parasites, which are replicated by catalytic replicators (catalysts), but do not replicate the others, can destroy a whole replicator system by exploitation. Recently, a theoretical study underlined complex formation between replicators--an often neglected but realistic process--as a stabilizing factor in a replicator system by demonstrating that complex formation can shift the viable range of diffusion intensity to higher values. In the current study, we extend the previous study of complex formation. Firstly, by investigating a well-mixed replicator system, we establish that complex formation gives parasites an implicit advantage over catalysts, which makes the system significantly more vulnerable to parasites. Secondly, by investigating a spatially extended replicator system, we show that the formation of traveling wave patterns plays a crucial role in the stability of the system against parasites, and that because of this the effect of complex formation is not straightforward; i.e., whether complex formation stabilizes or destabilizes the spatial system is a complex function of other parameters. We give a detailed analysis of the spatial system by considering the pattern dynamics of waves. Furthermore, we investigate the effect of deleterious mutations. Surprisingly, high mutation rates can weaken the exploitation of the catalyst by the parasite.     

Cloning and expression of vacuolar proton-pumping ATPase subunits in the follicular epithelium of the bullfrog endolymphatic sac

In an investigation aimed at clarifying the mechanism of crystal dissolution of the calcium carbonate lattice in otoconia (the mineral particles embedded in the otolithic membrane) of the endolymphatic sac (ELS) of the bullfrog, cDNAs encoding the A- and E-subunits of bullfrog vacuolar proton-pumping ATPase (V-ATPase) were cloned and sequenced. The cDNA of the A-subunit consisted of an 11-bp 5'-untranslated region (UTR), a 1,854-bp open reading frame (ORF) encoding a protein comprising 617 amino acids with a calculated molecular mass of 68,168 Da, and a 248-bp 3'-UTR followed by a poly(A) tail. The cDNA of the E-subunit consisted of a 72-bp 5'-UTR, a 681-bp ORF encoding a protein of 226 amino acids with a calculated molecular mass of 26,020 Da, and a 799-bp 3'-UTR followed by a poly(A) tail. Western blot and immunofluorescence analyses using specific anti-peptide antisera against the V-ATPase A- and E-subunits revealed that these subunits were present in the ELS, urinary bladder, skin, testes, and kidneys. In the ELS, positive cells were scattered in the follicular epithelium which, as revealed by electron microscopy, corresponds to the location of mitochondria-rich cells. These findings suggest that V-ATPase, including the A- and E-subunits, exists in mitochondria-rich cells of the ELS, which might be involved in dissolution of the calcium carbonate crystals in the lumen of the ELS.     

Anaerobic expression of the gyrA gene demonstrated by β-galactosidase activity in gyrA::Mu-lac fusion derivatives of Escherichia coli

Abstract E. coli C600Δ lac was infected with a Mu- lac defective phage. Lysogens resistant to ampicillin (25 μg/ml) and nalidixic acid (20 μg/ml) were unable to grow anaerobically and insensitive to nalidixic acid (150 μg/ml), indicating formation of gyrA ::Mu- lac fusions. Mapping of the Mu- lac by P1 phage cotransduction with two different gyrA linked Tn 10 transposon loci suggests that the insertion is located in the gyrA gene. These fusion derivatives form small uncolored colonies on lactose MacConkey agar plates aerobically. When these plates are placed in an anaerobic jar for about 4 h, the colonies turn red indicating that the inserted lac gene is expressed only under anaerobic environment. Thus the gyrA promoter is activated under the anaerobic environment and loss of gyrA activity prevents anaerobic cell growth.     

Tannic acid is a natural β-secretase inhibitor that prevents cognitive impairment and mitigates Alzheimer-like pathology in transgenic mice

Amyloid precursor protein (APP) proteolysis is essential for production of amyloid-β (Aβ) peptides that form β-amyloid plaques in brains of Alzheimer disease (AD) patients. Recent focus has been directed toward a group of naturally occurring anti-amyloidogenic polyphenols known as flavonoids. We orally administered the flavonoid tannic acid (TA) to the transgenic PSAPP mouse model of cerebral amyloidosis (bearing mutant human APP and presenilin-1 transgenes) and evaluated cognitive function and AD-like pathology. Consumption of TA for 6 months prevented transgene-associated behavioral impairment including hyperactivity, decreased object recognition, and defective spatial reference memory, but did not alter nontransgenic mouse behavior. Accordingly, brain parenchymal and cerebral vascular β-amyloid deposits and abundance of various Aβ species including oligomers were mitigated in TA-treated PSAPP mice. These effects occurred with decreased cleavage of the β-carboxyl-terminal APP fragment, lowered soluble APP-β production, reduced β-site APP cleaving enzyme 1 protein stability and activity, and attenuated neuroinflammation. As in vitro validation, we treated well characterized mutant human APP-overexpressing murine neuron-like cells with TA and found significantly reduced Aβ production associated with less amyloidogenic APP proteolysis. Taken together, these results raise the possibility that dietary supplementation with TA may be prophylactic for AD by inhibiting β-secretase activity and neuroinflammation and thereby mitigating AD pathology.     

Electrochemical mutagen screening using microbial chip

Electrochemical microbial chip for mutagen screening were microfabricated and characterized by scanning electrochemical microscopy (SECM). Salmonella typhimurium TA1535 with a plasmid pSK1002 carrying a umuC'-'lacZ fusion gene was used for the whole cell mutagen sensor. The TA1535/pSK1002 cells were exposed to mutagen solutions containing 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamido (AF-2), mitomycin C (MMC) or 2-aminoanthracene (2-AA) and embedded in a microcavity (5nl) on a glass substrate using collagen gel. The beta-galactosidase expression on the microbial chip was electrochemically monitored using p-aminophenyl-beta-d-galactopyranoside (PAPG) as the enzymatic substrate. This system has several advantages compared with the conventional umu test: drastic reduction of the sample volume, less time-consuming for beta-galactosidase detection (free from substrate reaction time) and lower detection limit for the three mutagens (AF-2, MMC, 2-AA). Finally, a multi-sample assay was carried out using the microbial array chip with four microcavities.     

Synthesis and antibacterial activity of novel neamine derivatives

Synthesis and activity of derivatives at the O5 or O6 positions of 1-N-((S)-4-amino-2-hydroxybutyryl)-3′,4′-dideoxyneamine, which is the neamine moiety of arbekacin, were reported. Among these results, the 5-O-aminoethylaminocarbonyl derivative showed effective activity against Staphylococcus aureus expressing a bifunctional aminoglycoside-modifying enzyme AAC(6′)-APH(2″).     

The covalent modification of spectrin in red cell membranes by the lipid peroxidation product 4-hydroxy-2-nonenal

Spectrin strengthens the red cell membrane through its direct association with membrane lipids and through protein-protein interactions. Spectrin loss reduces the membrane stability and results in various types of hereditary spherocytosis. However, less is known about acquired spectrin damage. Here, we showed that α- and β-spectrin in human red cells are the primary targets of the lipid peroxidation product 4-hydroxy-2-nonenal (HNE) by immunoblotting and mass spectrometry analyses. The level of HNE adducts in spectrin (particularly α-spectrin) and several other membrane proteins was increased following the HNE treatment of red cell membrane ghosts prepared in the absence of MgATP. In contrast, ghost preparation in the presence of MgATP reduced HNE adduct formation, with preferential β-spectrin modification and increased cross-linking of the HNE-modified spectrins. Exposure of intact red cells to HNE resulted in selective HNE-spectrin adduct formation with a similar preponderance of HNE-β-spectrin modifications. These findings indicate that HNE adduction occurs preferentially in spectrin at the interface between the skeletal proteins and lipid bilayer in red cells and suggest that HNE-spectrin adduct aggregation results in the extrusion of damaged spectrin and membrane lipids under physiological and disease conditions.