Precursors of Cytochrome Oxidase in Cytochrome-Oxidase-Deficient Cells of Neurospora crassa

Three different cell types of Neurospora crassa deficient in cytochrome oxidase were studied: the nuclear mutant cni-1, the cytoplasmic mutant mi-1 and copper-depleted wild-type cells. * 1. The enzyme-deficient cells have retained a functioning mitochondrial protein synthesis. It accounted for 12–16% of the total protein synthesis of the cell. However, the analysis of mitochondrial translation products by gel electrophoresis revealed that different amounts of individual membrane proteins were synthesized. Especially mutant cni-1 produced large amounts of a small molecular weight translation product, which is barely detectable in wild-type. * 2. Mitochondrial preparations of cytochrome-oxidase-deficient cells were examined for precursors of cytochrome oxidase. The presence of polypeptide components of cytochrome oxidase in the mitochondria was established with specific antibodies. On the other hand, no significant amounts of heme a could be extracted. * 3. Radioactively labelled components of cytochrome oxidase were isolated by immunoprecipitation and analysed by gel electrophoresis. All three cell types contained the enzyme components 4–7, which are translated on cytoplasmic ribosomes. The mitochondrially synthesized components 1–3 were present in mi-1 mutant and in copper-depleted wild-type cells. In contrast, components 2 and 3 were not detectable in the nuclear mutant cni-1. Both relative and absolute amounts of these polypeptides in the enzyme-deficient cells were quite different from those in wild-type cells. * 4. The components of cytochrome oxidase found in the enzyme-deficient cells were tightly associated with the mitochondrial membranes. * 5. Processes, which affect and may control the production of enzyme precursors or their assembly to a functional cytochrome oxidase are discussed

Coupling of Glucose Deprivation with Impaired Histone H2B Monoubiquitination in Tumors

Metabolic reprogramming is associated with tumorigenesis. However, glucose metabolism in tumors is poorly understood. Here, we report that glucose levels are significantly lower in bulk tumor specimens than those in normal tissues of the same tissue origins. We show that mono-ubiquitinated histone H2B (uH2B) is a semi-quantitative histone marker for glucose. We further show that loss of uH2B occurs specifically in cancer cells from a wide array of tumor specimens of breast, colon, lung and additional 23 anatomic sites. In contrast, uH2B levels remain high in stromal tissues or non-cancerous cells in the tumor specimens. Taken together, our data suggest that glucose deficiency and loss of uH2B are novel properties of cancer cells in vivo, which may represent important regulatory mechanisms of tumorigenesis

Scorpion Biodiversity and Interslope Divergence at “Evolution Canyon”, Lower Nahal Oren Microsite, Mt. Carmel, Israel

BACKGROUND: Local natural laboratories, designated by us as the "Evolution Canyon" model, are excellent tools to study regional and global ecological dynamics across life. They present abiotic and biotic contrasts locally, permitting the pursuit of observations and experiments across diverse taxa sharing sharp microecological subdivisions. Higher solar radiation received by the "African savannah-like" south-facing slopes (AS) in canyons north of the equator than by the opposite "European maquis-like" north-facing slopes (ES) is associated with higher abiotic stress. Scorpions are a suitable taxon to study interslope biodiversity differences, associated with the differences in abiotic factors (climate, drought), due to their ability to adapt to dry environments. METHODOLOGY/PRINCIPAL FINDINGS: Scorpions were studied by the turning stone method and by UV light methods. The pattern observed in scorpions was contrasted with similar patterns in several other taxa at the same place. As expected, the AS proved to be significantly more speciose regarding scorpions, paralleling the interslope patterns in taxa such as lizards and snakes, butterflies (Rhopalocera), beetles (families Tenebrionidae, Dermestidae, Chrysomelidae), and grasshoppers (Orthoptera). CONCLUSIONS/SIGNIFICANCE: Our results support an earlier conclusion stating that the homogenizing effects of migration and stochasticity are not able to eliminate the interslope intra- and interspecific differences in biodiversity despite an interslope distance of only 100 m at the "EC" valley bottom. In our opinion, the interslope microclimate selection, driven mainly by differences in insolance, could be the primary factor responsible for the observed interslope pattern

Inhibition by calcium of adenine nucleotide translocation in mitochondria isolated from ehrlich ascites tumour cells

Digitalitzat per Artypla

Quiescience as a mechanism for cyclical hypoxia and acidosis

Tumour tissue characteristically experiences fluctuations in substrate supply. This unstable microenvironment drives constitutive metabolic changes within cellular populations and, ultimately, leads to a more aggressive phenotype. Previously, variations in substrate levels were assumed to occur through oscillations in the hæmodynamics of nearby and distant blood vessels. In this paper we examine an alternative hypothesis, that cycles of metabolite concentrations are also driven by cycles of cellular quiescence and proliferation. Using a mathematical modelling approach, we show that the interdependence between cell cycle and the microenvironment will induce typical cycles with the period of order hours in tumour acidity and oxygenation. As a corollary, this means that the standard assumption of metabolites entering diffusive equilibrium around the tumour is not valid; instead temporal dynamics must be considered

Thermodynamic Properties of the One-Dimensional Extended Quantum Compass Model in the Presence of a Transverse Field

The presence of a quantum critical point can significantly affect the thermodynamic properties of a material at finite temperatures. This is reflected, e.g., in the entropy landscape S(T; c) in the vicinity of a quantum critical point, yielding particularly strong variations for varying the tuning parameter c such as magnetic field. In this work we have studied the thermodynamic properties of the quantum compass model in the presence of a transverse field. The specific heat, entropy and cooling rate under an adiabatic demagnetization process have been calculated. During an adiabatic (de)magnetization process temperature drops in the vicinity of a field-induced zero-temperature quantum phase transitions. However close to field-induced quantum phase transitions we observe a large magnetocaloric effect

Diffuse-Charge Dynamics in Electrochemical Systems

The response of a model micro-electrochemical system to a time-dependent applied voltage is analyzed. The article begins with a fresh historical review including electrochemistry, colloidal science, and microfluidics. The model problem consists of a symmetric binary electrolyte between parallel-plate, blocking electrodes which suddenly apply a voltage. Compact Stern layers on the electrodes are also taken into account. The Nernst-Planck-Poisson equations are first linearized and solved by Laplace transforms for small voltages, and numerical solutions are obtained for large voltages. The ``weakly nonlinear'' limit of thin double layers is then analyzed by matched asymptotic expansions in the small parameter $\epsilon = \lambda_D/L$, where $\lambda_D$ is the screening length and $L$ the electrode separation. At leading order, the system initially behaves like an RC circuit with a response time of $\lambda_D L / D$ (not $\lambda_D^2/D$), where $D$ is the ionic diffusivity, but nonlinearity violates this common picture and introduce multiple time scales. The charging process slows down, and neutral-salt adsorption by the diffuse part of the double layer couples to bulk diffusion at the time scale, $L^2/D$. In the ``strongly nonlinear'' regime (controlled by a dimensionless parameter resembling the Dukhin number), this effect produces bulk concentration gradients, and, at very large voltages, transient space charge. The article concludes with an overview of more general situations involving surface conduction, multi-component electrolytes, and Faradaic processes.Comment: 10 figs, 26 pages (double-column), 141 reference

Cellular adaptations to hypoxia and acidosis during somatic evolution of breast cancer

Conceptual models of carcinogenesis typically consist of an evolutionary sequence of heritable changes in genes controlling proliferation, apoptosis, and senescence. We propose that these steps are necessary but not sufficient to produce invasive breast cancer because intraductal tumour growth is also constrained by hypoxia and acidosis that develop as cells proliferate into the lumen and away from the underlying vessels. This requires evolution of glycolytic and acid-resistant phenotypes that, we hypothesise, is critical for emergence of invasive cancer. Mathematical models demonstrate severe hypoxia and acidosis in regions of intraductal tumours more than 100 m from the basement membrane. Subsequent evolution of glycolytic and acid-resistant phenotypes leads to invasive proliferation. Multicellular spheroids recapitulating ductal carcinoma in situ (DCIS) microenvironmental conditions demonstrate upregulated glucose transporter 1 (GLUT1) as adaptation to hypoxia followed by growth into normoxic regions in qualitative agreement with model predictions. Clinical specimens of DCIS exhibit periluminal distribution of GLUT-1 and Na+/H+ exchanger (NHE) indicating transcriptional activation by hypoxia and clusters of the same phenotype in the peripheral, presumably normoxic regions similar to the pattern predicted by the models and observed in spheroids. Upregulated GLUT-1 and NHE-1 were observed in microinvasive foci and adjacent intraductal cells. Adaptation to hypoxia and acidosis may represent key events in transition from in situ to invasive cancer

Random walk with barriers: Diffusion restricted by permeable membranes

Restrictions to molecular motion by barriers (membranes) are ubiquitous in biological tissues, porous media and composite materials. A major challenge is to characterize the microstructure of a material or an organism nondestructively using a bulk transport measurement. Here we demonstrate how the long-range structural correlations introduced by permeable membranes give rise to distinct features of transport. We consider Brownian motion restricted by randomly placed and oriented permeable membranes and focus on the disorder-averaged diffusion propagator using a scattering approach. The renormalization group solution reveals a scaling behavior of the diffusion coefficient for large times, with a characteristically slow inverse square root time dependence. The predicted time dependence of the diffusion coefficient agrees well with Monte Carlo simulations in two dimensions. Our results can be used to identify permeable membranes as restrictions to transport in disordered materials and in biological tissues, and to quantify their permeability and surface area.Comment: 8 pages, 3 figures; origin of dispersion clarified, refs adde

A manganese photosensitive tricarbonyl molecule [Mn(CO)3(tpa-κ(3)N)]Br enhances antibiotic efficacy in a multi-drug-resistant Escherichia coli

Carbon monoxide-releasing molecules (CORMs) are a promising class of new antimicrobials, with multiple modes of action that are distinct from those of standard antibiotics. The relentless increase in antimicrobial resistance, exacerbated by a lack of new antibiotics, necessitates a better understanding of how such novel agents act and might be used synergistically with established antibiotics. This work aimed to understand the mechanism(s) underlying synergy between a manganese-based photoactivated carbon monoxide-releasing molecule (PhotoCORM), [Mn(CO)3(tpa-κ(3)N)]Br [tpa=tris(2-pyridylmethyl)amine], and various classes of antibiotics in their activities towards Escherichia coli EC958, a multi-drug-resistant uropathogen. The title compound acts synergistically with polymyxins [polymyxin B and colistin (polymyxin E)] by damaging the bacterial cytoplasmic membrane. [Mn(CO)3(tpa-κ(3)N)]Br also potentiates the action of doxycycline, resulting in reduced expression of tetA, which encodes a tetracycline efflux pump. We show that, like tetracyclines, the breakdown products of [Mn(CO)3(tpa-κ(3)N)]Br activation chelate iron and trigger an iron starvation response, which we propose to be a further basis for the synergies observed. Conversely, media supplemented with excess iron abrogated the inhibition of growth by doxycycline and the title compound. In conclusion, multiple factors contribute to the ability of this PhotoCORM to increase the efficacy of antibiotics in the polymyxin and tetracycline families. We propose that light-activated carbon monoxide release is not the sole basis of the antimicrobial activities of [Mn(CO)3(tpa-κ(3)N)]Br