Actomyosin Regulation and Symmetry Breaking in a Model of Polarization in the Early Caenorhabditis elegans Embryo

Polarization, whereby a cell defines a spatial axis by segregating specific determinants to distinct regions, is an essential and highly conserved biological process. The process of polarization is initiated by a cue that breaks an initially symmetric distribution of determinants, allowing for a spatially asymmetric redistribution. The nature of this cue is currently not well understood. Utilizing the conservation of polarization process and its determinants, we theoretically investigate the nature of the cue and the regulation of contractility that enables the establishment of polarity in early embryos of the nematode worm Caenorhabditis elegans (C. elegans). Our biologically based model, which consists of coupled partial differential equations, suggests that a biochemical but not mechanical cue is sufficient for symmetry breaking, and inhibition of contractile elements by specific determinants is needed for sustained spatial redistribution.     

A tetravalent dengue nanoparticle stimulates antibody production in mice

Background

Dengue is a major public health problem worldwide, especially in the tropical and subtropical regions of the world. Infection with a single Dengue virus (DENV) serotype causes a mild, self-limiting febrile illness called dengue fever. However, a subset of patients experiencing secondary infection with a different serotype progresses to the severe form of the disease, dengue hemorrhagic fever/dengue shock syndrome. Currently, there are no licensed vaccines or antiviral drugs to prevent or treat dengue infections. Biodegradable nanoparticles coated with proteins represent a promising method for in vivo delivery of vaccines.

Findings

Here, we used a murine model to evaluate the IgG production after administration of inactivated DENV corresponding to all four serotypes adsorbed to bovine serum albumin nanoparticles. This formulation induced a production of anti-DENV IgG antibodies (p < 0.001). However, plaque reduction neutralization assays with the four DENV serotypes revealed that these antibodies have no neutralizing activity in the dilutions tested.

Conclusions

Our results show that while the nanoparticle system induces humoral responses against DENV, further investigation with different DENV antigens will be required to improve immunogenicity, epitope specicity, and functional activity to make this platform a viable option for DENV vaccines.     

The freeze-thaw stress response of the yeast Saccharomyces cerevisiae is growth phase specific and is controlled by nutritional state via the RAS-cyclic AMP signal transduction pathway.

The ability of cells to survive freezing and thawing is expected to depend on the physiological conditions experienced prior to freezing. We examined factors affecting yeast cell survival during freeze-thaw stress, including those associated with growth phase, requirement for mitochondrial functions, and prior stress treatment(s), and the role played by relevant signal transduction pathways. The yeast Saccharomyces cerevisiae was frozen at -20 degrees C for 2 h (cooling rate, less than 4 degrees C min-1) and thawed on ice for 40 min. Supercooling occurred without reducing cell survival and was followed by freezing. Loss of viability was proportional to the freezing duration, indicating that freezing is the main determinant of freeze-thaw damage. Regardless of the carbon source used, the wild-type strain and an isogenic petite mutant ([rho 0]) showed the same pattern of freeze-thaw tolerance throughout growth, i.e., high resistance during lag phase and low resistance during log phase, indicating that the response to freeze-thaw stress is growth phase specific and not controlled by glucose repression. In addition, respiratory ability and functional mitochondria are necessary to confer full resistance to freeze-thaw stress. Both nitrogen and carbon source starvation led to freeze-thaw tolerance. The use of strains affected in the RAS-cyclic AMP (RAS-cAMP) pathway or supplementation of an rca1 mutant (defective in the cAMP phosphodiesterase gene) with cAMP showed that the freeze-thaw response of yeast is under the control of the RAS-cAMP pathway. Yeast did not adapt to freeze-thaw stress following repeated freeze-thaw treatment with or without a recovery period between freeze-thaw cycles, nor could it adapt following pretreatment by cold shock. However, freeze-thaw tolerance of yeast cells was induced during fermentative and respiratory growth by pretreatment with H2O2, cycloheximide, mild heat shock, or NaCl, indicating that cross protection between freeze-thaw stress and a limited number of other types of stress exists.     

The effects of alpha-methylnoradrenaline on protein and electrolyte secretion by rat submandibular and parotid glands

alpha-Methylnoradrenaline (alpha-mNA) is a potent secretagogue for the parotid and submandibular glands of rats. With regard to the parotid glands, alpha-mNA activates mainly beta-adrenoceptors. In the submandibular glands, alpha-mNA activates alpha-adrenoceptors at higher doses whereas at relatively lower doses it activates beta-adrenoceptors. alpha-mNA may not stimulate the specific alpha 2-adrenoceptors of the salivary glands of rats.     

Biosynthesis and composition of bacterial poly(hydroxyalkanoates)

It is well established that Alcaligenes eutrophus can accumulate a copolymer containing 3-hydroxybutyrate and 3-hydroxyvalerate, but longer 3-hydroxyacid monomers have not been reported to occur in this organism. The properties of the enzymes of poly(hydroxyalkanoate) (PHA) biosynthesis are discussed and it is proposed that the substrate specificity of the polymerizing enzyme restricts the range of monomer units incorporated into PHA. Various other bacteria produce similar copolymers from propionic acid and/or valeric acid. A number of Pseudomonas species accumulate PHAs containing longer-chain monomer units from linear alkanoic acids, alkanes and alcohols.     

The regulation of transport of glucose, gluconate and 2-oxogluconate and of glucose catabolism in Pseudomonas aeruginosa.

1. The induction by glucose and gluconate of the transport systems and catabolic enzymes for glucose, gluconate and 2-oxogluconate was studied with Pseudomonas aeruginosa PAO1 growing in a chemostat under conditions of nitrogen limitation with citrate as the major carbon source. 2. In the presence of a residual concentration of 30mM-citrate an inflowing glucose concentration of 6-8 mM was required to induce the glucose-transport system and associated catabolic enzymes. When the glucose concentration was raised to 20mM the glucose-transport system was repressed, but the transport system for gluconate, and at higher glucose concentrations, that for 2-oxogluconate, were induced. No repression of the glucose-catabolizing enzymes occurred at the higher inflowing glucose concentrations. 3. In the presence of 30mM-citrate no marked threshold concentration was required for the induction of the gluconate-transport system by added gluconate. 4. In the presence of 30mM-citrate and various concentrations of added glucose and gluconate, the activity of the glucose-transport system accorded with the proposal that a major factor concerned in the repression of this system was the concentration of gluconate, produced extracellularly by glucose dehydrogenase. 5. This proposal was supported by chemostat experiments with mutants defective in glucose dehydrogenase. Such mutants showed no repression of the glucose-transport system by high inflowing concentrations, but with a mutant apparently defective only in glucose dehydrogenase, the addition of gluconate caused repression of the glucose-transport system. 6. Studies with the mutants showed that both glucose and gluconate can induce the enzymes of the Entner-Doudoroff system, whereas for the induction of the gluconate-transport system glucose must be converted into gluconate.     

Invasions Slow Down or Collapse in the Presence of Reactive Boundaries

Motivated by the propagation of thin bacterial films around planar obstacles, this paper considers the dynamics of travelling wave solutions to the Fisher–KPP equation \(u_t = u(1-u) + u_{xx} + u_{yy}\) in a planar strip \(-\infty< x < \infty \), \(0 \le y \le L\). We examine the propagation of fronts in the presence of a mixed boundary condition (also referred to as a ‘partially absorbing’ or ‘reactive’ boundary) \(u_y = \alpha u\), with \(\alpha >0\), at \(y=0\). The presence of boundary conditions of this kind leads to the development of front solutions that propagate in x but contain transverse structure in y. Motivated by the observation that the speed of propagation in the Fisher–KPP equation is determined (for exponentially decaying initial conditions) by the behaviour at the leading edge, we analyse the linearised Fisher–KPP equation in order to estimate the speed of the stable travelling front, a function of the width L and the imposed boundary conditions. For wide strips the speed estimate based on the linearised equation agrees well with the results of numerical simulations. For narrow channels numerical simulations indicate that the stable front propagates more slowly, and for sufficiently small L or sufficiently large \(\alpha \) the front speed falls to zero and the front collapses. The reason for the collapse is the non-existence, far behind the front, of a stable positive equilibrium solution u(x, y). While existence of these equilibrium states can be demonstrated via phase plane arguments, the investigation of stability is similar to calculations of critical patch sizes carried out in similar ecological models.