Potential automata. Application to the genetic code III

In previous notes, we have described both mathematical properties of potential (n-switches) and potential-Hamiltonian (Liénard systems) continuous differential systems, and also biological applications, especially those concerning primitive cyclic RNAs related to the genetic code. In the present note, we give a general definition of a potential automaton, and we show that a discrete Hopfield-like system already introduced by Goles et al. is a good candidate for such a potential automaton: it has a Lyapunov functional that decreases on its trajectories and whose time derivative is just its discrete velocity. Then we apply this new notion of potential automaton to the genetic code. We show in particular that the consideration of only physicochemical properties of amino-acids, like their molecular weight, hydrophobicity and ability to create hydrogen bonds suffices to build a potential decreasing on trajectories corresponding to the synonymy classes of the genetic code. Such an 'a minima' construction reinforces the classical stereochemical hypothesis about the origin of the genetic code and authorizes new views about the optimality of its synonymy classes.     

Testing meter, rhythm, and tempo discriminations in pigeons

Rhythmic grouping and discrimination is fundamental to music. When compared to the perception of pitch, rhythmic abilities in animals have received scant attention until recently. In this experiment, four pigeons were tested with three types of auditory rhythmic discriminations to investigate their processing of this aspect of sound and music. Two experiments examined a meter discrimination in which successively presented idiophonic sounds were repeated in meters of different lengths in a go/no-go discrimination task. With difficulty, the birds eventually learned to discriminate between 8/4 and 3/4 meters constructed from cymbal and tom drum sounds at 180 beats per minute. This discrimination subsequently transferred to faster tempos, but not to different drum sounds or their combination. Experiment 3 tested rhythmic and arrhythmic patterns of sounds. After 40 sessions of training, these same pigeons showed no discrimination. Experiment 4 tested repetitions of a piano sound at fast and slow tempos. This discrimination was readily learned and showed transfer to novel tempos. The pattern of results suggests that pigeons can time periodic auditory events, but their capacity to understand generalized rhythmic groupings appears limited.     

Facilitation of Mitochondrial Outer and Inner Membrane Permeabilization and Cell Death in Oxidative Stress by a Novel Bcl-2 Homology 3 Domain Protein

We identified a sequence homologous to the Bcl-2 homology 3 (BH3) domain of Bcl-2 proteins in SOUL. Tissues expressed the protein to different extents. It was predominantly located in the cytoplasm, although a fraction of SOUL was associated with the mitochondria that increased upon oxidative stress. Recombinant SOUL protein facilitated mitochondrial permeability transition and collapse of mitochondrial membrane potential (MMP) and facilitated the release of proapoptotic mitochondrial intermembrane proteins (PMIP) at low calcium and phosphate concentrations in a cyclosporine A-dependent manner in vitro in isolated mitochondria. Suppression of endogenous SOUL by diced small interfering RNA in HeLa cells increased their viability in oxidative stress. Overexpression of SOUL in NIH3T3 cells promoted hydrogen peroxide-induced cell death and stimulated the release of PMIP but did not enhance caspase-3 activation. Despite the release of PMIP, SOUL facilitated predominantly necrotic cell death, as revealed by annexin V and propidium iodide staining. This necrotic death could be the result of SOUL-facilitated collapse of MMP demonstrated by JC-1 fluorescence. Deletion of the putative BH3 domain sequence prevented all of these effects of SOUL. Suppression of cyclophilin D prevented these effects too, indicating that SOUL facilitated mitochondrial permeability transition in vivo. Overexpression of Bcl-2 and Bcl-x_L, which can counteract the mitochondria-permeabilizing effect of BH3 domain proteins, also prevented SOUL-facilitated collapse of MMP and cell death. These data indicate that SOUL can be a novel member of the BH3 domain-only proteins that cannot induce cell death alone but can facilitate both outer and inner mitochondrial membrane permeabilization and predominantly necrotic cell death in oxidative stress.     

Excessive Na+/H+ Exchange in Disruption of Dendritic Na+ and Ca2+ Homeostasis and Mitochondrial Dysfunction following in Vitro Ischemia

Neuronal dendrites are vulnerable to injury under diverse pathological conditions. However, the underlying mechanisms for dendritic Na⁺ overload and the selective dendritic injury remain poorly understood. Our current study demonstrates that activation of NHE-1 (Na⁺/H⁺ exchanger isoform 1) in dendrites presents a major pathway for Na⁺ overload. Neuronal dendrites exhibited higher pH_i regulation rates than soma as a result of a larger surface area/volume ratio. Following a 2-h oxygen glucose deprivation and a 1-h reoxygenation, NHE-1 activity was increased by ∼70–200% in dendrites. This elevation depended on activation of p90 ribosomal S6 kinase. Moreover, stimulation of NHE-1 caused dendritic Na⁺_i accumulation, swelling, and a concurrent loss of Ca²⁺_i homeostasis. The Ca²⁺_i overload in dendrites preceded the changes in soma. Inhibition of NHE-1 or the reverse mode of Na⁺/Ca²⁺ exchange prevented these changes. Mitochondrial membrane potential in dendrites depolarized 40 min earlier than soma following oxygen glucose deprivation/reoxygenation. Blocking NHE-1 activity not only attenuated loss of dendritic mitochondrial membrane potential and mitochondrial Ca²⁺ homeostasis but also preserved dendritic membrane integrity. Taken together, our study demonstrates that NHE-1-mediated Na⁺ entry and subsequent Na⁺/Ca²⁺ exchange activation contribute to the selective dendritic vulnerability to in vitro ischemia.     

Potential respiration is a better respiratory predictor than biomass in young Artemia salina

These experiments test whether respiration can be predicted better from biomass or from potential respiration, a measurement of the mitochondrial and microsomal respiratory electron transport systems. For nearly a century Kleiber's law or a similar precursor have argued the importance of biomass in predicting respiration. In the last decade, a version of the Metabolic Theory of Ecology has elaborated on Kleiber's Law adding emphasis to the importance of biomass in predicting respiration. We argue that Kleiber's law works because biomass packages mitochondria and microsomal electron transport complexes. On a scale of five orders of magnitude we have shown previously that potential respiration predicts respiration as well as biomass in marine zooplankton. Here, using cultures of the branchiopod, Artemia salina and on a scale of less than 2 orders of magnitude, we investigated the power of biomass and potential respiration in predicting respiration. We measured biomass, respiration and potential respiration in Artemia grown in different ways and found that potential respiration (Ф) could predict respiration (R), both in µlO₂ h⁻¹ (R = 0.924Φ + 0.062, r² = 0.976), but biomass (as mg dry mass) could not (R = 27.02DM + 8.857, r² = 0.128). Furthermore the R/Ф ratio appeared independent of age and differences in the food source.     

Zinc-induced Neurotoxicity Mediated by Transient Receptor Potential Melastatin 7 Channels

Transient receptor potential melastatin 7 (TRPM7) channels are novel Ca²⁺-permeable non-selective cation channels ubiquitously expressed. Activation of TRPM7 channels has been shown to be involved in cellular Mg²⁺ homeostasis, diseases caused by abnormal magnesium absorption, and in Ca²⁺-mediated neuronal injury under ischemic conditions. Here we show strong evidence suggesting that TRPM7 channels also play an important role in cellular Zn²⁺ homeostasis and in Zn²⁺-mediated neuronal injury. Using a combination of fluorescent Zn²⁺ imaging, small interfering RNA, pharmacological analysis, and cell injury assays, we show that activation of TRPM7 channels augmented Zn²⁺-induced injury of cultured mouse cortical neurons. The Zn²⁺-mediated neurotoxicity was inhibited by nonspecific TRPM7 blockers Gd³⁺ or 2-aminoethoxydiphenyl borate, and by knockdown of TRPM7 channels with small interfering RNA. In addition, Zn²⁺-mediated neuronal injury under oxygen-glucose deprivation conditions was also diminished by silencing TRPM7. Furthermore, we show that overexpression of TRPM7 channels in HEK293 cells increased intracellular Zn²⁺ accumulation and Zn²⁺-induced cell injury, while silencing TRPM7 by small interfering RNA attenuated the Zn²⁺-mediated cell toxicity. Thus, TRPM7 channels may represent a novel target for neurological disorders where Zn²⁺ toxicity plays an important role.     

Beaked whale auditory evoked potential hearing measurements

Several mass strandings of beaked whales have recently been correlated with military exercises involving mid-frequency sonar highlighting unknowns regarding hearing sensitivity in these species. We report the hearing abilities of a stranded juvenile beaked whale (Mesoplodon europaeus) measured with auditory evoked potentials. The beaked whale’s modulation rate transfer function (MRTF) measured with a 40-kHz carrier showed responses up to an 1,800 Hz amplitude modulation (AM) rate. The MRTF was strongest at the 1,000 and 1,200 Hz AM rates. The envelope following response (EFR) input–output functions were non-linear. The beaked whale was most sensitive to high frequency signals between 40 and 80 kHz, but produced smaller evoked potentials to 5 kHz, the lowest frequency tested. The beaked whale hearing range and sensitivity are similar to other odontocetes that have been measured.     

Efflux permease CgAcr3-1 of Corynebacterium glutamicum is an arsenite-specific antiporter

Resistance to arsenite (As(III)) by cells is generally accomplished by arsenite efflux permeases from Acr3 or ArsB unrelated families. We analyzed the function of three Acr3 proteins from Corynebacterium glutamicum, CgAcr3-1, CgAcr3-2, and CgAcr3-3. CgAcr3-1 conferred the highest level of As(III) resistance and accumulation in vivo. CgAcr3-1 was also the most active when everted membranes vesicles from Escherichia coli or C. glutamicum mutants were assayed for efflux with different energy sources. As(III) and antimonite (Sb(III)) resistance and accumulation studies using E. coli or C. glutamicum arsenite permease mutants clearly show that CgAcr3-1 is specific for As(III). In everted membrane vesicles expressing CgAcr3-1, dissipation of either the membrane potential or the pH gradient of the proton motive force did not prevent As(III) uptake, whereas dissipation of both components eliminated uptake. Further, a mutagenesis study of CgAcr3-1 suggested that a conserved cysteine and glutamate are involved in active transport. Therefore, we propose that CgAcr3-1 is an antiporter that catalyzes arsenite-proton exchange with residues Cys129 and Glu305 involved in efflux.     

SORL1 and SIRT1 mRNA expression and promoter methylation levels in aging and Alzheimer’s Disease

Alzheimer’s Disease (AD) is a neurodegenerative disorder and the most common cause of dementia among the elderly. Efforts have been made to understand the genetic and epigenetic mechanisms involved in the development of this disease. As SORL1 (sortilin-related receptor) and SIRT1 (sirtuin 1) genes have been linked to AD pathogenesis, we aimed to investigate their mRNA expression and promoter DNA methylation in post mortem brain tissues (entorhinal and auditory cortices and hippocampus) from healthy elderly subjects and AD patients. We also evaluated these levels in peripheral blood leukocytes from young, healthy elderly and AD patients, investigating whether there was an effect of age on these profiles. The comparative CT method by Real Time PCR and MALDI-TOF mass spectrometry were used to analyze gene expression and DNA methylation, respectively. SORL1 gene was differently expressed in the peripheral blood leukocytes and might act as a marker of aging in this tissue. Furthermore, we found that SORL1 promoter DNA methylation might act as one of the mechanisms responsible for the differences in expression observed between blood and brain for both healthy elderly and AD patients groups. The impact of these studied genes on AD pathogenesis remains to be better clarified.     

Xylem tension affects growth-induced water potential and daily elongation of maize leaves

Diurnal rates of leaf elongation vary in maize (Zea mays L.) and are characterized by a decline each afternoon. The cause of the afternoon decline was investigated. When the atmospheric environment was held constant in a controlled environment, and water and nutrients were adequately supplied to the soil or the roots in solution, the decline persisted and indicated that the cause was internal. Inside the plants, xylem fluxes of water and solutes were essentially constant during the day. However, the forces moving these components changed. Tensions rose in the xylem, and gradients of growth-induced water potentials decreased in the surrounding growing tissues of the leaf. These potentials, measured with isopiestic thermocouple psychrometry, changed because the roots became less conductive to water as the day progressed. The increased tensions were reversed by applying pressure to the soil/root system, which rehydrated the leaf. Afternoon elongation immediately recovered to rapid morning rates. The rapid morning rates did not respond to soil/root pressurization. It was concluded that increased xylem tension in the afternoon diminished the gradients in growth-induced water potential and thus inhibited elongation. Because increased tensions cause a similar but larger inhibition of elongation if maize dehydrates, these hydraulics are crucial for shaping the growth-induced water potential and thus the rates of leaf elongation in maize over the entire spectrum of water availability.