New proposed mechanism of actin-polymerization-driven motility

We present the first numerical simulation of actin-driven propulsion by elastic filaments. Specifically, we use a Brownian dynamics formulation of the dendritic nucleation model of actin-driven propulsion. We show that the model leads to a self-assembled network that exerts forces on a disk and pushes it with an average speed. This simulation approach is the first to observe a speed that varies nonmonotonically with the concentration of branching proteins (Arp2/3), capping protein, and depolymerization rate, in accord with experimental observations. Our results suggest a new interpretation of the origin of motility. When we estimate the speed that this mechanism would produce in a system with realistic rate constants and concentrations as well as fluid flow, we obtain a value that is within an order-of-magnitude of the polymerization speed deduced from experiments.     

Alcohol-induced breast cancer: a proposed mechanism

Alcohol consumption increases the risk for breast cancer in women by still undefined means. Alcohol metabolism is known to produce reactive oxygen species (ROS), and breast cancer is associated with high levels of hydroxyl radical (^·OH) modified DNA, point mutations, single strand nicks, and chromosome rearrangement. Furthermore, ROS modification of DNA can produce the mutations and DNA damage found in breast cancer. Alcohol dehydrogenase (ADH) and xanthine oxidoreductase (XOR) are expressed and regulated in breast tissues and aldehyde oxidase (AOX) may be present as well. Mammary gland XOR is an efficient source of ROS. Recently, hepatic XOR and AOX were found to generate ROS in two ways from alcohol metabolism: by acetaldehyde consumption and by the intrinsic NADH oxidase activity of both XOR and AOX. The data obtained suggests that: (1) expression of ADH and XOR or AOX in breast tissue provides the enzymes that generate ROS; (2) metabolism of alcohol produces acetaldehyde and NADH that can both be substrates for XOR or AOX and thereby result in ROS formation; and (3) ROS generated by XOR or AOX can induce the carcinogenic mutations and DNA damage found in breast cancer. Accumulation of iron coupled with diminished antioxidant defenses in breast tissue with advancing age provide additional support for this hypothesis because both result in elevated ROS damage that may exacerbate the risk for ROS-induced breast cancer.     

A proposed mechanism for the sol-gel transformation

The transformation from gel to sol in cell cytoplasm is treated as the transition from a lattice of macromolecules linked by Ca⁺⁺ ions to a random distribution of the macromolecules. The transition is a cooperative process, whose probability is expressed in terms of the theory of runs. The process is related to cell metabolism by the assumption that available Ca⁺⁺ concentration is regulated by metabolically produced endogenous chelating agents. Contribution 681 from the Division of Basic Health Sciences, Emory University.     

A proposed mechanism of thermophily in facultative thermophiles

Glyceraldehyde-3-phosphate dehydrogenase in crude extracts of $\text{Bacillus coagulans}$ KU, a facultative thermophile, showed marked thermolability whether the cells were grown at mesophilic or thermophilic temperature. When extracts were brought to a given ionic strength by the addition of salt and then heat treated, it was possible to confer heat resistance well in excess of the thermophilic growth temperature. Disc electrophoresis is indicative that portions of the profiles are quite different between extracts of cells grown at 37° and 55°. Based on the data, a mechanism of thermophily is postulated that is different from any thus far proposed for thermophilic microorganisms.     

A proposed mechanism for multiplication of neural signals

The probability of the joint occurrence of two statistically independent events is the product of the probabilities of the individual events. This fact is used to show that a neuron which detects coincident arrivals of spikes from two input neurons can function as a multiplier, i.e. its average output spike frequency is proportional to the product of the average input spike frequencies. The theoretical analysis is checked in two ways: (a) Computer simulations confirm the derived expressions for the output frequency and show that increasing the jitter in the input spike trains improves the operation of the multiplier by making the output spike train more regular (b) Experimentally recorded spike trains are used to demonstrate that the type and amount of jitter present in real spike trains is adequate for satisfactory operation of the proposed scheme for multiplication. The operating characteristics of the proposed multiplier make it an attractive candidate for the multiplicative mechanism that is involved in the optomotor response of insects.     

DNA recombination protein-dependent mechanism of homoplasmy and its proposed functions

Homoplasmy is a basic genetic state of mitochondria, in which all of the hundreds to thousands of mitochondrial (mt)DNA copies within a cell or an individual have the same nucleotide-sequence. It was recently found that "vegetative segregation" to generate homoplasmic cells is an active process under genetic control. In the yeast Saccharomyces cerevisiae, the Mhr1 protein which catalyzes a key reaction in mtDNA homologous recombination, plays a pivotal role in vegetative segregation. Conversely, within the nuclear genome, homologous DNA recombination causes genetic diversity. Considering these contradictory roles of this key reaction in DNA recombination, possible functions of homoplasmy are discussed.     

Nitrosylmyoglobin as antioxidant--kinetics and proposed mechanism for reduction of hydroperoxides

Nitrosylmyoglobin (MbFe^IINO), which is believed to have a protective role during ischemia and reperfusion injury, was oxidized by tert-butyl hydroperoxide (t-BuOOH), and by hydrogen peroxide (H₂O₂) to the nitrite anion and metmyoglobin (MbFe^III). Further characterization of the reaction of MbFe^IINO with excess of t-BuOOH was investigated with respect to reaction stoichiometry, temperature and pH dependence. It was found that the reaction between MbFe^IINO with excess of t-BuOOH followed a simple stoichiometry and had moderate pH and temperature dependence with the activation parameters ΔH^‡ = 57.4 ± 1.4 kJ mol^- 1 and ΔS^‡ = - 112.0 ± 5.1 J mol^- 1 K^- 1, which is consistent with an associative reaction mechanism. Moreover, t-BuOOH-induced oxidation of MbFe^IINO did not result in any detectable formation of the hypervalent myoglobin (Mb) species, i.e. perferrylmyoglobin, (^√MbFe^IV = O) or ferrylmyoglobin (MbFe^IV = O), and hereby differed from H₂O₂-induced oxidation of MbFe^IINO, which results in the formation of MbFe^IV = O. Based on the obtained results and on published data, different mechanisms for the reaction of the MbFe^IINO with t-BuOOH and H₂O₂ are proposed.     

Hemolytic mechanism of dioscin proposed by molecular dynamics simulations

Saponins are a class of compounds containing a triterpenoid or steroid core with some attached carbohydrate modules. Many saponins cause hemolysis. However, the hemolytic mechanism of saponins at the molecular level is not yet fully understood. In an attempt to explore this issue, we have studied dioscin—a saponin with high hemolytic activity—through extensive molecular dynamics (MD) simulations. Firstly, all-atom MD simulations of 8 ns duration were conducted to study the stability of the dioscin–cholesterol complex and the cholesterol–cholesterol complex in water and in decane, respectively. MM-GB/SA computations indicate that the dioscin–cholesterol complex is energetically more favorable than the cholesterol–cholesterol complex in a non-polar environment. Next, several coarse-grained MD simulations of 400 ns duration were conducted to directly observe the distribution of multiple dioscin molecules on a DPPC-POPC-PSM-CHOL lipid bilayer. Our results indicate that dioscin can penetrate into the lipid bilayer, accumulate in the lipid raft micro-domain, and then bind cholesterol. This leads to the destabilization of lipid raft and consequent membrane curvature, which may eventually result in the hemolysis of red cells. This possible mechanism of hemolysis can well explain some experimental observations on hemolysis.     

Cadmium-induced forelimb ectrodactyly: a proposed mechanism of teratogenesis

We have attempted to elucidate the mechanism of cadmium teratogenesis utilizing inbred mouse strains sensitive (C57BL/6J) or resistant (SWV) to the embryotoxic effect of this common heavy metal contaminant. Carbonic anhydrase activity of whole-embryo homogenates was moderately depressed in C57BL/6J mice compared to a slight and transient decrease in the resistant SWV mice. Embryonic erythrocytes were similarly examined, and the cadmium did not have any effect on carbonic anhydrase activity in either strain. Likewise, histochemical examination of carbonic anhydrase activity did not reveal any effect of cadmium in the embryos of their strain. Generally, the zinc concentration of embryos was not affected by cadmium administration. However, increased levels of zinc were observed in cadmium-exposed yolk sacs of both strains suggesting that cadmium produces an adverse effect on yolk sac function. Untreated C57BL/6J units (embryo plus surrounding extraembryonic membranes), embryos, and yolk sacs had much lower hemoglobin concentrations than those observed in untreated SWV units, embryos, and yolk sacs. Additionally, cadmium exposure significantly decreased C57BL/6J embryonic hemoglobin levels on gestation day 10 (PM) and increased C57BL/6J yolk sac hemoglobin levels on gestation days 10 (AM) and 10 (PM). No difference in hemoglobin concentration was observed between untreated and cadmium-treated SWV embryos or yolk sacs. We propose that cadmium induces forelimb ectrodactyly by creating an acidotic embryonic environment and that the primary site at which cadmium exerts its teratogenic effect might be the yolk sac.     

A proposed mechanism for myosin magnesium adenosine triphosphatase activity

A formal mechanism for the myosin MgATPase is proposed. The basic characteristics of this mechanism require that the binding of substrate at either one of two equivalent nucleotide sites of uncomplexed myosin prevents binding of substrate at the other unoccupied site (i.e. negative cooperativity) and that the rapid formation of a myosin-product complex permits binding of substrate at the unoccupied site. Analogue computer kinetic simulations indicate that the proposed mechanism is compatible with the observed transient phase kinetics characterizing the interaction of the enzyme with MgATP. In addition, analysis of the derived rate equation show that the mechanism is also consistent with existing steady-state kinetic data for the myosin MgATPase. A simpler mechanism is proposed for the subfragment-1 MgATPase that is shown to be compatible with the existing kinetic data. Features of the proposed myosin MgATPase mechanism are incorporated into a model of contraction which utilizes the bipartite structure and nucleotide site interaction of the myosin crossbridge to provide an efficient utilization of ATP in the contraction cycle.     

Visfatin in pregnancy: proposed mechanism of peptide delivery

Visfatin is a newly identified 52 kD adipocytokine that appears to have insulinomimetic properties. We examined visfatin expression in visceral fat from lean and pregnant women. Visfatin gene expression was seven times higher in omental fat of pregnant women than in lean women. Both immunohistochemistry and immunoblot confirmed that visfatin protein was much higher in pregnant women than in nonpregnant women. However, serum visfatin was 20.8 ± 7.7 ng/ml (n = 7) in lean women as compared to only a slight increase to 40.3 ng/ml in pregnant women (n = 4). We measured visfatin mRNA content of human placenta and found that placenta expresses high levels of visfatin mRNA and protein. At a concentration of 2 nM, visfatin and insulin produced nearly identical increase in glucose transport. The discrepancy between the elevated visfatin expression and tissue visfatin compared to only a small increase in serum visfatin is a matter of controversy. The data on serum visfatin concentrations are replete with contradictory data. Taken together, we suggest that visfatin is not a hormone. Instead, we propose that visfatin acts in either a paracrine or autocrine mode. This hypothesis would explain what various laboratories have found widely discrepant values for serum visfatin. Since visfatin potently and efficaciously induced glucose transport in a cell culture model, any hypothetical role for visfatin in pregnancy should include the possibility that it may play a role in maternal/fetal glucose metabolism or distribution and that it may do so by acting locally.     

A proposed mechanism for the catalatic action of catalase

A detailed mechanism for catalatic action has been proposed which includes the formation of Chance's catalase compound I in the first step and hydride ion transfer in the second step. The first (oxidative) step involves direct reaction of hematin iron with an ionized H2O2 molecule, followed by an oxidation of the iron to Fe IV. The second step is assumed to depend upon the reductive action of a second H2O2 molecule on Chance's compound I through a catalyzed hybride ion transfer, resulting in the regeneration of uncomplexed catalase. Differences between the catalatic and peroxidative actions of catalase are discussed briefly in respect to the proposed mechanism for catalatic action. The rationale of the proposed mechanism is based to a considerable extent upon the type of ligand binding by the hematin iron of catalase, and this type of ligand bonding is contrasted with ligand binding in methemoglobin, which does not show catalatic activity. Finally, the dispositions of electrons in the outer electronic orbitals of the hematin iron of catalase and methemoglobin are discussed, as a means of justifying formulae presented for catalase and methemoglobin and their derivatives. One of the features of the proposed catalatic mechanism is the assumption, based on electron spin number, that the sixth coordination position around the hematin iron of uncomplexed catalase is unoccupied.     

Structure and proposed mechanism for the pH-sensing Helicobacter pylori chemoreceptor TlpB

pH sensing is crucial for survival of most organisms, yet the molecular basis of such sensing is poorly understood. Here, we present an atomic resolution structure of the periplasmic portion of the acid-sensing chemoreceptor, TlpB, from the gastric pathogen Helicobacter pylori. The structure reveals a universal signaling fold, a PAS domain, with a molecule of urea bound with high affinity. Through biophysical, biochemical, and in?vivo mutagenesis studies, we show that urea and the urea-binding site residues play critical roles in the ability of H.?pylori to sense acid. Our signaling model predicts that protonation events at Asp114, affected by changes in pH, dictate the stability of TlpB through urea binding.     

Immunological templates: a new model and proposed mechanism of immunogenicity

Immunogenicity of an antigen is dependent both on possession of antigenic determinants, including the haptenic portion(s) of the antigen, and binding groups. The binding groups are necessary for processing of the antigen to occur whereas the antigenic determinants specify the antibody structure. Some arrangements of these antigenic determinants in relation to the binding groups are proposed, as well as the relationships of these ligands during processing on a cellular processing template to form an antibody RNA. The antibody RNA is manufactured by a unique mode of inverse translation.     

Algal biofuels

The world is facing energy crisis and environmental issues due to the depletion of fossil fuels and increasing CO₂ concentration in the atmosphere. Growing microalgae can contribute to practical solutions for these global problems because they can harvest solar energy and capture CO₂ by converting it into biofuel using photosynthesis. Microalgae are robust organisms capable of rapid growth under a variety of conditions including in open ponds or closed photobioreactors. Their reduced biomass compounds can be used as the feedstock for mass production of a variety of biofuels. As another advantage, their ability to accumulate or secrete biofuels can be controlled by changing their growth conditions or metabolic engineering. This review is aimed to highlight different forms of biofuels produced by microalgae and the approaches taken to improve their biofuel productivity. The costs for industrial-scale production of algal biofuels in open ponds or closed photobioreactors are analyzed. Different strategies for photoproduction of hydrogen by the hydrogenase enzyme of green algae are discussed. Algae are also good sources of biodiesel since some species can make large quantities of lipids as their biomass. The lipid contents for some of the best oil-producing strains of algae in optimized growth conditions are reviewed. The potential of microalgae for producing petroleum related chemicals or ready-make fuels such as bioethanol, triterpenic hydrocarbons, isobutyraldehyde, isobutanol, and isoprene from their biomass are also presented.