Complete Genome Sequence of Vibrio parahaemolyticus Bacteriophage vB_VpaM_MAR

Vibrio parahaemolyticus is a major pathogen that is mainly associated with seafood and is a global food safety issue. Our objective was to isolate and completely sequence a specific phage against this bacterium. Phage vB_VpaM_MAR is able to lyse 76% of the V. parahaemolyticus strains tested. MAR belongs to the Myoviridae family and has a genome comprised of double-stranded DNA with a size of 41,351 bp, a G+C content of 51.3%, and 62 open reading frames (ORFs). Bioinformatic analysis showed that phage MAR is closely related to Vibrio phages VHML, VP58.5, and VP882 and Halomonas aquamarina phage ΦHAP-1.     

On a formal definition of organization

A mathematic definition is proposed to account for the intuitive features of what is usually meant by organization. To account for both functional and structural aspects of organization the rate at which information content of a system changes in time is examined. It can be shown that Shannon's expression for ambiguity in a channel has two different meanings according to whether one is interested in the information transmitted in the channel or in the information transmitted to the observer from a whole system in which the channel is a part of a redundant communication network. This was applied in a previous work to show that the effects of noise on the information content H of a system result in two kinds of ambiguities, “autonomy-producing” and “destructive” leading to increase and decrease in H, respectively. By making use of this observation and Shannon's definition of redundancy R, a single equation for $\text{d}\text{H}\text{dt}$ is proposed to define organization on the basis of a kinetics of change of information content of a system under the effects of environmental noise-producing factors accumulated in time. It is shown how these factors, obviously responsible for a decrease in H, i.e. a “disorganizing” effect, can be responsible also—under certain conditions and up to a certain time or “dose” of noise—for an initial increase in H interpreted as a process of “self”-organization. The autonomy-producing ambiguity is expressed by a term of decrease in redundancy, while a second term in the equation, of decrease in maximum-non-redundant-information content expresses the destructive ambiguity. A given organization is defined at least by three parameters, which determine the main features of its characteristic function H(t). One of them is the initial information content H₀ and has a structural meaning. A second parameter, with a dimension of time, has the meaning of a functional reliability, related to the overall resistance of the system to noise-producing factors. The third parameter, namely the initial redundancy R₀, is both structural and functional in character, since structural redundancy is known to help insure reliability. Various conditions on these parameters lead to various kinds of organizations, with and without self-organizing properties.     

The Q-cycle reviewed: How well does a monomeric mechanism of the bc1 complex account for the function of a dimeric complex?

Recent progress in understanding the Q-cycle mechanism of the bc₁ complex is reviewed. The data strongly support a mechanism in which the Q_o-site operates through a reaction in which the first electron transfer from ubiquinol to the oxidized iron–sulfur protein is the rate-determining step for the overall process. The reaction involves a proton-coupled electron transfer down a hydrogen bond between the ubiquinol and a histidine ligand of the [2Fe–2S] cluster, in which the unfavorable protonic configuration contributes a substantial part of the activation barrier. The reaction is endergonic, and the products are an unstable ubisemiquinone at the Q_o-site, and the reduced iron–sulfur protein, the extrinsic mobile domain of which is now free to dissociate and move away from the site to deliver an electron to cyt c₁ and liberate the H⁺. When oxidation of the semiquinone is prevented, it participates in bypass reactions, including superoxide generation if O₂ is available. When the b-heme chain is available as an acceptor, the semiquinone is oxidized in a process in which the proton is passed to the glutamate of the conserved -PEWY- sequence, and the semiquinone anion passes its electron to heme b_L to form the product ubiquinone. The rate is rapid compared to the limiting reaction, and would require movement of the semiquinone closer to heme b_L to enhance the rate constant. The acceptor reactions at the Q_i-site are still controversial, but likely involve a “two-electron gate” in which a stable semiquinone stores an electron. Possible mechanisms to explain the cyt b₁₅₀ phenomenon are discussed, and the information from pulsed-EPR studies about the structure of the intermediate state is reviewed.The mechanism discussed is applicable to a monomeric bc₁ complex. We discuss evidence in the literature that has been interpreted as shown that the dimeric structure participates in a more complicated mechanism involving electron transfer across the dimer interface. We show from myxothiazol titrations and mutational analysis of Tyr-199, which is at the interface between monomers, that no such inter-monomer electron transfer is detected at the level of the b_L hemes. We show from analysis of strains with mutations at Asn-221 that there are coulombic interactions between the b-hemes in a monomer. The data can also be interpreted as showing similar coulombic interaction across the dimer interface, and we discuss mechanistic implications.     

Inhibition Effect of a Custom Peptide on Lung Tumors

Cecropin B is a natural antimicrobial peptide and CB1a is a custom, engineered modification of it. In vitro, CB1a can kill lung cancer cells at concentrations that do not kill normal lung cells. Furthermore, in vitro, CB1a can disrupt cancer cells from adhering together to form tumor-like spheroids. Mice were xenografted with human lung cancer cells; CB1a could significantly inhibit the growth of tumors in this in vivo model. Docetaxel is a drug in present clinical use against lung cancers; it can have serious side effects because its toxicity is not sufficiently limited to cancer cells. In our studies in mice: CB1a is more toxic to cancer cells than docetaxel, but dramatically less toxic to healthy cells.     

Orientation of chlorophyll in vivo. Studies with magnetic field oriented chlorella

The streptomycetes have a bacterial-type cell wall and a mycelial growth habit. Although the exact taxonomic relationship to yeasts or fungi and the bacteria is unknown, a great similarity to bacteria is assumed. $\text{Streptomyces erythreus}$ CA340 (Abbott) is found to possess a multienzyme complex making fatty acids. The crude enzyme complex is stimulated by FMN; is inhibited by iodoacetamide; is excluded and partially purified (ca. 70-fold) by Sephadex G-200; is most active at pH 7.5; is most stable in 0.5 M phosphate buffer. Thus, $\text{S. erythreus}$ CA340 and possibly all streptomycetes have a major biochemical similarity to yeasts and fungi.     

Physio-chemical mathematical theory for transitions in cellular metabolism: An aspect of carcinogenesis

It is pointed out that the non-monotonic character of the chemical reaction rate expressions, together with the relative magnitude of the diffusivity constants, is likely to engender a multiplicity of locally stable steady-state solutions to the system of reaction-diffusion equations for the concentration distributions of molecular species through the volume of a living cell. A transition in cellular metabolism, i.e., the dynamical evolution from an initial locally stable steady-state solution for the concentration distributions to another distinct locally stable steady-state solution, can be induced by an etiologic agent which modifies the rate expressions significantly during an interval of time. Global inequality analysis is employed to derive a condition on the modified rate expressions that is sufficient to guarantee the occurrence of such a transition in cellular metabolism. The possibility of a transition induced by a chemical carcinogen is investigated by applying the latter sufficient condition, and it is found that the statistical frequency of carcinogenesis should depend essentially on the magnitude of the grouping (T ^{2 − α} D ^α) for a total doseD of carcinogen administered to an animal at a uniform rate (D/T) over a time interval of durationT, where α is a certain positive number less than 1. This theoretical result is shown to be supported by the available experimental evidence.     

The regulation of urease activity in Aspergillus nidulans

Aspergillus nidulans can utilize urea as a sole source of nitrogen but not as a carbon source. Urea is degraded by a urease. Mutation at any one of three genes, ureB, ureC, and ureD, may result in deficient urease activity. The ureB gene is closely linked to ureA, the structural gene for the urea transport protein. The heat lability of a ureB ^– revertant strain, intragenic complementation tests, and the linkage of ureB to ureA suggest that ureB is the urease structural gene. The ureD gene is probably involved in the synthesis or incorporation of a nickel cofactor essential for urease activity. The function of the ureC gene is not known. Urease is not induced but is subject to nitrogen regulation. The urease activities of ammonium-derepressed mutants show that the effector of nitrogen regulation is more likely to be glutamine than ammonium. When glutamine is present in the medium, urease appears to be inactivated by some means which does not involve a newly synthesized protease or a direct interaction between glutamine and urease.     

The phylogenetic position of the bumble bee inquiline Bombus inexspectatus and implications for the evolution of social parasitism

The high alpine European bumble bee Bombus (Thoracobombus) inexspectatus is one of three taxa in which obligate social parasitism has evolved in bumble bees. Until now, the phylogenetic placement of this species has not been analyzed quantitatively because it is rare in nature. Here a specimen of B. inexspectatus is sequenced for five genes to assess its phylogenetic position relative to other bumble bee species. Phylogenetic estimation of B. inexspectatus places this species within the subgenus Thoracobombus, as expected based on morphology. This provides strong support for the acquisition of social parasitism in B. inexspectatus separate from that found in the bumble bees of the subgenus Psithyrus and B. (Alpinobombus) hyperboreus. Furthermore, B. inexspectatus is not the sister taxon of its host but is a near relative, suggesting a loose but not strict adherence to Emery’s rule. B. inexspectatus is a sister taxon to a clade including B. veteranus, a frequent nest usurper that has been suggested to be a facultative social parasite. The phylogenetic placement of all bumble bee social parasites relative to their hosts is discussed.     

Place du scanner dans l’imagerie de l’hyperparathyroïdie primaire

Primary hyperparathyroidism is a biological diagnosis. The reference treatment is surgery. When minimally invasive surgery is considered, it is recommended to perform a cervical ultrasound and a scintigraphic examination to localize the hypertrophied parathyroid glands. The multiphasic scanner (4D CT) is a very effective examination to detect and locate precisely the parathyroid adenomas. The study of densities makes it possible to differentiate the adenoma from the thyroid and the lymph nodes that are the differential diagnoses. Without injection, the adenoma is more hypodense than the thyroid with a threshold set at 75 UH. On the early phase after injection, the adenoma appears very hypervascularized with a density > 114 UH. The ganglion appears hypovascularized with a density < 114 UH. In the late phase, there is a decrease in the density within the adenoma, while density within the ganglion increases. The parathyroid scan is indicated in case of negativity or discordance of the couple ultrasound scintigraphy. It is also strongly recommended, in case of persistence or recurrence of hyperparathyroidism after surgery, as well as to better study a parathyroid ectopy.     

Description of Goffartia phalacra n. sp. (Diplogastridae: Nematoda) from India

A new species, Goffartia phalacra n. sp. is described and illustrated. The body is thin and slender with L = 511 to 646 μm; a = 37.1 to 47.4; b = 4.8 to 6; c = 2.6 to 4.8; c′ = 13.6 to 32.8; V = 40% to 49% in females. Males are smaller but similar to females and the posterior region is strongly curved. The species is characterized by a tubular stoma, a smooth round lip region, anterior pharynx much smaller than posterior pharynx, two pairs of unicellular glands associated with the vagina, and males with a broad keel-shaped gubernaculum. G. phalacra n. sp. can be differentiated from all other species of the genus by its lip region and the structure of the gubernaculum. This is the first instance of a species of Goffartia occurring in a terrestrial habitat and the first report of a species from India.     

Age- and density-dependent population dynamics in static and variable environments

We consider a general model of a single-species population with age- and density-dependent per capita birth and death rates. In a static environment we show that if the per capita death rate is independent of age, then the local stability of any stationary state is guaranteed by the requirement that, in the region of the steady state, the density dependence of the birth rate should be negative and that of the death rate positive. In a variable environment we show that, provided the system is locally stable, small environmental fluctuations will give rise to small age structure and population fluctuations which are related to the driving environmental fluctuations by a simple “transfer function.” We illustrate our general theory by examining a model with a per capita death rate which is age and density independent and a per capita birth rate which is zero up to some threshold age a₀, adopts a finite density-dependent value up to a maximum age a_o + α, and is zero thereafter. We conclude from this model that resonance due specifically to single-species age-structure effects will only be of practical importance in populations whose members have a life cycle consisting of a long immature phase followed by a short burst of intense reproductive effort (α a_o).     

The chromosomes of the Filariae

An understanding of the nature of the chromosomes of the filariae is expected to greatly assist the future interpretation of genome data. Filarial development is not eutelic, and there does not seem to be a fixed number of cell divisions in the way that there is in Caenorhabditis. It is not clear whether the chromosomes of the filariae have localized centromeres or whether they are holocentric. Sex determination is by a chromosomal "balance" X0 system in most filariae, but in some Onchocercidae there has been a chromosomal fusion to create a neo-XY system. It is presumed that the molecular basis of sex determination in filariae is similar to Caenorhabditis. The ancestral karyotype of the filariae is probably 5A+X0, but in some Onchocercidae this has been reduced to 4A+XY, and in O. volvulus and O. gibsoni it has been further reduced to 3A+XY. Onchocerca volvulus and O. gibsoni both have supernumary (B-) chromosomes and in O. volvulus there is a single active nucleolus organising region near the middle of the long autosome.     

Predictive feedback control and Fitts–law

Fitts’ law is a well established empirical formula, known for encapsulating the “speed-accuracy trade-off”. For discrete, manual movements from a starting location to a target, Fitts’ law relates movement duration to the distance moved and target size. The widespread empirical success of the formula is suggestive of underlying principles of human movement control. There have been previous attempts to relate Fitts’ law to engineering-type control hypotheses and it has been shown that the law is exactly consistent with the closed-loop step-response of a time-delayed, first-order system. Assuming only the operation of closed-loop feedback, either continuous or intermittent, this paper asks whether such feedback should be predictive or not predictive to be consistent with Fitts law. Since Fitts’ law is equivalent to a time delay separated from a first-order system, known control theory implies that the controller must be predictive. A predictive controller moves the time-delay outside the feedback loop such that the closed-loop response can be separated into a time delay and rational function whereas a non- predictive controller retains a state delay within feedback loop which is not consistent with Fitts’ law. Using sufficient parameters, a high-order non-predictive controller could approximately reproduce Fitts’ law. However, such high-order, “non-parametric” controllers are essentially empirical in nature, without physical meaning, and therefore are conceptually inferior to the predictive controller. It is a new insight that using closed-loop feedback, prediction is required to physically explain Fitts’ law. The implication is that prediction is an inherent part of the “speed-accuracy trade-off”.     

Optimal patch use in a stochastic environment

This paper considers an animal foraging on prey which are distributed in well-defined patches. It is assumed that the environment may be stochastic and that the animal can gain information on patch type as it forages. The foraging policy which maximises mean reward rate for the environment is characterised in terms of a function of state called the potential function. This policy is shown to be given by the rule: continue foraging on the present patch while the potential is positive, when the potential falls to zero move on to the next patch. Let r denote the current reward rate on a patch and let γ denote the maximum mean reward rate for the environment. It is shown that r ? γ if it is optimal to leave. Conditions which ensure r < γ are also given. For a large class of environments the optimal policy is stated in terms of a revised reward rate r?, and is given by the rule: continue on the present patch while $\text{r}\text{?}\text{> γ}$, when r? falls to γ move on to the next patch. Finally, it is shown that the stay time on a patch is a decreasing function of γ.     

Tests of Independence and Zero Correlations Among P Random Variables

Suppose it is desired to determine whether there is an association between any pair of p random variables. A common approach is to test H₀ : R = I, where R is the usual population correlation matrix. A closely related approach is to test H₀ : R_pb = I, where R_pb is the matrix of percentage bend correlations. In so far as type I errors are a concern, at a minimum any test of H₀ should have a type I error probability close to the nominal level when all pairs of random variables are independent. Currently, the Gupta-Rathie method is relatively successful at controlling the probability of a type I error when testing H₀: R = I, but as illustrated in this paper, it can fail when sampling from nonnormal distributions. The main goal in this paper is to describe a new test of H₀: R_pb = I that continues to give reasonable control over the probability of a type I error in the situations where the Gupta-Rathie method fails. Even under normality, the new method has advantages when the sample size is small relative to p. Moreover, when there is dependence, but all correlations are equal to zero, the new method continues to give good control over the probability of a type I error while the Gupta-Rathie method does not. The paper also reports simulation results on a bootstrap confidence interval for the percentage bend correlation.     

A note on the structure of system state spaces and its implications on the existence of non-repeatable experiments

The implication of state space structure on the existence of a repeatable experimentE designed to determine if a states∈L has propertyP or notP is investigated. It is shown that if a state spaceL is connected, then no experimentE is repeatable. This formalism is used to demonstrate that if a propertyP has an associated set of points inL which is dense with dense complement inL, then there exists no repeatable experimentE which can be used to test whethers has propertyP or notP. Other consequences of this formalization are discussed.     

On the evolution of dominance modifiers I. A nonlinear analysis

A well known mathematical model of evolution of dominance is subjected to a nonlinear analysis. For the case where the primary locus and the modifying locus are completely linked (r = 0) a global Ljapunov function is given. This proves that selection of dominance modifiers entirely due to their modifying effect is possible. This result is also extended to small recombination fractions r by using the method of Ljapunov functions in a more sophisticated way. For r = 0 and μ = 0 a lower bound for the success of selection of the modifier is given. Furthermore, the influence of the dominance relations between the alleles (measured by the parameters h and k) is investigated. Finally it is shown that differential and difference equations lead to the same results (which need not be the case in general). As a by-product we obtain a new equilibrium point in the classical one locus selection-mutation model.