Pattern and inhibition-dependent invasion of pyramidal cell dendrites by fast spikes in the hippocampus in vivo.

The invasion of sodium spikes from the soma into dendrites was studied in hippocampal pyramidal cells by simultaneous extracellular and intracellular recordings in anesthetized rats and by simultaneous extracellular recordings of the somatic and dendritic potentials in freely behaving animals. During complex-spike patterns, recorded in the immobile or sleeping animal, dendritic invasion of successive spikes was substantially attenuated. Complex-spike bursts occurred in association with population discharge of CA3-CA1 pyramidal cells (sharp wave field events). Synaptic inhibition reduced the amplitude of sodium spikes in the dendrites and prevented the occurrence of calcium spikes. These findings indicate that (i) the voltage-dependent calcium influx into the dendrites is under the control of inhibitory neurons and (ii) the temporal coincidence of synaptic depolarization and activation of voltage-dependent calcium conductances by the backpropagating spikes during sharp wave bursts may be critical for synaptic plasticity in the intact hippocampus.

Toxoplasma invasion: the parasitophorous vacuole is formed from host cell plasma membrane and pinches off via a fission pore.

Most intracellular pathogens avoid lysing their host cells during invasion by wrapping themselves in a vacuolar membrane. This parasitophorous vacuole membrane (PVM) is often retained, serving as a critical transport interface between the parasite and the host cell cytoplasm. To test whether the PVM formed by the parasite Toxoplasma gondii is derived from host cell membrane or from lipids secreted by the parasite, we used time-resolved capacitance measurements and video microscopy to assay host cell surface area during invasion. We observed no significant change in host cell surface area during PVM formation, demonstrating that the PVM consists primarily of invaginated host cell membrane. Pinching off of the PVM from the host cell membrane occurred after an unexpected delay (34-305 sec) and was seen as a 0.219 +/- 0.006 pF drop in capacitance, which corresponds well to the predicted surface area of the entire PVM (30-33 microns2). The formation and closure of a fission pore connecting the extracellular medium and the vacuolar space was detected as the PVM pinched off. This final stage of parasite entry was accomplished without any breach in cell membrane integrity.

Low molecular weight EPS II of Rhizobium meliloti allows nodule invasion in Medicago sativa.

Effective invasion of alfalfa by Rhizobium meliloti Rm1021 normally requires the presence of succinoglycan, an exopolysaccharide (EPS) produced by the bacterium. However, Rm1021 has the ability to produce a second EPS (EPS II) that can suppress the symbiotic defects of succinoglycan-deficient strains. EPS II is a polymer of modified glucose-(beta-1,3)-galactose subunits and is produced by Rm1021 derivatives carrying either an expR101 or mucR mutation. If the ability to synthesize succinoglycan is blocked genetically, expR101 derivatives of Rm1021 are nodulation-proficient, whereas mucR derivatives of Rm1021 are not. The difference in nodulation proficiency between these two classes of EPS II-producing strains is due to the specific production of a low molecular weight form of EPS II by expR101 strains. A low molecular weight EPS II fraction consisting of 15-20 EPS II disaccharide subunits efficiently allows nodule invasion by noninfective strains when present in amounts as low as 7 pmol per plant, suggesting that low molecular weight EPS II may act as a symbiotic signal during infection.

Antisense RNA to the type I insulin-like growth factor receptor suppresses tumor growth and prevents invasion by rat prostate cancer cells in vivo.

Prostate carcinoma is the second leading cause of death from malignancy in men in the United States. Prostate cancer cells express type I insulin-like growth factor receptor (IGF-IR) and prostate cancer selectively metastazises to bone, which is an environment rich in insulin-like growth factors (IGFs), thereby supporting a paracrine action for cancer cell proliferation. We asked whether the IGF-IR is coupled to tumorigenicity and invasion of prostate cancer. When rat prostate adenocarcinoma cells (PA-III) were stably transfected with an antisense IGF-IR expression construct containing the ZnSO4-inducible metallothionein-1 transcriptional promoter, the transfectants expressed high levels of IGF-IR antisense RNA after induction with ZnSO4, which resulted in dramatically reduced levels of endogenous IGF-IR mRNA. A significant reduction in expression both of tissue-type plasminogen activator and of urokinase-type plasminogen activator occurred in PA-III cells accompanying inhibition of IGF-IR. Subcutaneous injection of either nontransfected PA-III or PA-III cells transfected with vector minus the IGF-IR insert into nude mice resulted in large tumors after 4 weeks. However, mice injected with IGF-IR antisense-transfected PA-III cells either developed tumors 90% smaller than controls or remained tumor-free after 60 days of observation. When control-transfected PA-III cells were inoculated over the abraded calvaria of nude mice, large tumors formed with invasion of tumor cells into the brain parenchyma. In contrast, IGF-IR antisense transfectants formed significantly smaller tumors with no infiltration into brain. These results indicate an important role for the IGF/IGF-IR pathway in metastasis and provide a basis for targeting IGF-IR as a potential treatment for prostate cancer.

Metalloelastase is required for macrophage-mediated proteolysis and matrix invasion in mice.

Macrophages secrete a variety of proteinases that are thought to participate in remodeling of the extracellular matrix associated with inflammatory processes. We have eliminated expression of the macrophage metalloelastase (MME) gene by targeted disruption to assess the role of this protein in macrophage-mediated proteolysis. We found that the macrophages of MME-deficient (MME-/-) mice have a markedly diminished capacity to degrade extracellular matrix components. In addition, MME-/- macrophages are essentially unable to penetrate reconstituted basement membranes in vitro and in vivo. MME is therefore required for macrophage-mediated extracellular matrix proteolysis and tissue invasion.

Relationship between evolutionary rate and cellular location among the Inv/Spa invasion proteins of Salmonella enterica.

For 21 strains of Salmonella enterica, nucleotide sequences were obtained for three invasion genes, spaO, spaP, and spaQ, of the chromosomal inv/spa complex, the products of which form a protein export system required for entry of the bacteria into nonphagocytic host cells. These genes are present in all eight subspecies of the salmonellae, and homologues occur in a variety of other bacteria, including the enteric pathogens Shigella and Yersinia, in which they are plasmid borne. Evolutionary diversification of the invasion genes among the subspecies of S. enterica has been generally similar in pattern and average rate to that of housekeeping genes. However, the range of variation in evolutionary rate among the invasion genes is unusually large, and there is a relationship between the evolutionary rate and cellular location of the invasion proteins, possibly reflecting diversifying selection on exported proteins in adaptation to variable host factors in extracellular environments. The SpaO protein, which is hypervariable in S. enterica and exhibits only 24% sequence identity with its homologues in Shigella and Yersinia, is secreted. In contrast, the membrane-associated proteins SpaP, SpaQ, and InvA are weakly polymorphic and have > 60% sequence identity with the corresponding proteins of other enteric bacteria. Acquisition of the inv/spa genes may have been a key event in the evolution of the salmonellae as pathogens, following which the invention of flagellar phase shifting facilitated niche expansion to include warm-blooded vertebrates.

Silencing of the E-cadherin invasion-suppressor gene by CpG methylation in human carcinomas.

E-Cadherin, a cell adhesion molecule, which plays a key role in maintaining the epithelial phenotype, is regarded as an invasion-suppressor gene in light of accumulating evidence from in vitro experiments and clinical observations. In an attempt to clarify the mechanism responsible for inactivation of this gene in carcinomas, we investigated the methylation state around the promoter region by digestion of DNA with the methylation-sensitive restriction enzyme Hpa II, as CpG methylation of the promoter has been postulated to be a mechanism of transcriptional inactivation of some genes. We found that E-cadherin expression-negative carcinoma cell lines were accompanied by the hypermethylation state, whereas E-cadherin-positive cell lines were not. Furthermore, treatment of E-cadherin-negative carcinoma cells with the demethylating agent 5-azacytidine resulted in reexpression of the gene and reversion of scattered spindle-shaped cells to cells with epithelial morphology. These results suggest that hypermethylation around the promoter may be a mechanism of E-cadherin inactivation in human carcinomas and that treatment of E-cadherin-inactivated cells with a demethylating agent may cause gene expression reversion leading to epithelial morphogenesis with acquisition of the homophilic cell-cell adhesive property.

Disulfide oxidoreductase activity of Shigella flexneri is required for release of Ipa proteins and invasion of epithelial cells.

Secretion of IpaB, IpaC, and IpaD proteins of Shigella flexneri, essential for the invasion of epithelial cells, requires a number of proteins encoded by the spa and mxi loci on the large plasmid. Introduction of dsbA::Tn5 into S.flexneri from Escherichia coli K-12 reduced invasiveness, which resulted from a decrease in the capacity to release IpaB, IpaC, and IpaD proteins into the external medium. Examination of the surface-presented Ipa proteins of the dsbA mutant, however, revealed Ipa proteins at levels similar to those on wild-type cells. Since the defective phenotype was similar to that of the spa32 mutant of S. flexneri and the Spa32 sequence possessed two Cys residues, the effect of dsbA mutation of the folding structure of Spa32 under reducing conditions and on the surface expression of Spa32 was investigated. The results indicated that Spa32 was a disulfide-containing protein whose correctly folded structure was required for its presentation on the outer membrane. Indeed, replacing either one of the two Cys residues in Spa32 with Ser by site-directed mutagenesis reduced its capacity to release Ipa proteins into the external medium and led to the accumulation of Spa32 protein in the periplasm. These results indicated that the DsbA protein performs an essential function during the invasion of mammalian cells, by facilitating transport of the Spa32 protein across the outer membrane.

Ecological chaos in the wake of invasion.

Irregularities in observed population densities have traditionally been attributed to discretization of the underlying dynamics. We propose an alternative explanation by demonstrating the evolution of spatiotemporal chaos in reaction-diffusion models for predator-prey interactions. The chaos is generated naturally in the wake of invasive waves of predators. We discuss in detail the mechanism by which the chaos is generated. By considering a mathematical caricature of the predator-prey models, we go on to explain the dynamical origin of the irregular behavior and to justify our assertion that the behavior we present is a genuine example of spatiotemporal chaos.

Invasion, Proliferation and Control of Invasive Aquatic Plants in Colorado State Parks

Nonnative aquatic species are invasive worldwide. These species adversely affect natural aquatic ecosystems in a variety of ways and can negatively affect agriculture, recreation and industry. This study addresses identification and control of aquatic plant species of concern in Colorado State Parks. Seventeen species identified as potential threats to the parks and safe, effective chemical control methodologies were determined for each species. A matrix was developed to include the plants, appropriate chemical controls and the type of aquatic habitat where chemical use would be safe and effective. The matrix and recommendations for its use will be provided to the Colorado Division of Parks and Outdoor Recreation to develop a management plan under Section 1204 of the National Invasive Species Act.

Genetic signature of a recent invasion: The ragged sea hare Bursatella leachii in Mar Menor (SE Spain)

This study received partial financial support from the Séneca Foundation, Agencia Regional de Ciencia y Tecnología de la Región de Murcia, Spain (11881/PI/09). The first author (MGW) was supported by Fundação para a Ciência e Tecnologia (FCT, Portugal) postdoctoral grant (SFRH/BPD/70689/2010). JD was supported through an Erasmus grant (2011–2013) of the European MSc in Marine Biodiversity and Conservation (EMBC).

Saint Mathew Law and Bonini Paradox in Textual Theory of Complex Models

The mathematical models of the complex reality are texts belonging to a certain literature that is written in a semi-formal language, denominated L(MT) by the authors whose laws linguistic mathematics have been previously defined. This text possesses linguistic entropy that is the reflection of the physical entropy of the processes of real world that said text describes. Through the temperature of information defined by Mandelbrot, the authors begin a text-reality thermodynamic theory that drives to the existence of information attractors, or highly structured point, settling down a heterogeneity of the space text, the same one that of ontologic space, completing the well-known law of Saint Mathew, of the General Theory of Systems and formulated by Margalef saying: “To the one that has more he will be given, and to the one that doesn't have he will even be removed it little that it possesses.

The European Elections in France: The paradox of a more European yet more eurosceptic campaign. EPIN Commentaries No. 16, 6 February 2014

Despite the probable shift towards European rather than national issues in the European election campaign in France, the combined effects of the economic crisis and the unpopularity of political leaders could crystallise a ‘protest’ vote for both national and European leaders, and for the EU as a whole, explain the authors in this EPIN Commentary.

European Corporate Governance Reform and the German Party Paradox. CES Germany & Europe Working Papers, No. 03.1, 2003

This paper addresses the current discussion on links between party politics and production regimes. Why do German Social Democrats opt for more corporate governance liberalization than the CDU although, in terms of the distributional outcomes of such reforms, one would expect the situation to be reversed? I divide my analysis into three stages. First, I use the European Parliament’s crucial vote on the European takeover directive in July 2001 as a test case to show that the left-right dimension does indeed matter in corporate governance reform, beside cross-class and cross-party nation-based interests. In a second step, by analyzing the party positions in the main German corporate governance reforms in the 1990s, I show that the SPD and the CDU behave “paradoxically” in the sense that the SPD favored more corporate governance liberalization than the CDU, which protected the institutions of “Rhenish,” “organized” capitalism. This constellation occurred in the discussions on company disclosure, management accountability, the power of banks, network dissolution, and takeover regulation. Third, I offer two explanations for this paradoxical party behavior. The first explanation concerns the historical conversion of ideas. I show that trade unions and Social Democrats favored a high degree of capital organization in the Weimar Republic, but this ideological position was driven in new directions at two watersheds: one in the late 1940s, the other in the late 1950s. My second explanation lies in the importance of conflicts over managerial control, in which both employees and minority shareholders oppose managers, and in which increased shareholder power strengthens the position of works councils.