Structural basis for the reversible activation of a Rho protein by the bacterial toxin SopE.

The bacterial enteropathogen Salmonella typhimurium employs a type III secretion system to inject bacterial toxins into the host cell cytosol. These toxins transiently activate Rho family GTP-binding protein-dependent signaling cascades to induce cytoskeletal rearrangements. One of these translocated Salmonella toxins, SopE, can activate Cdc42 in a Dbl-like fashion despite its lack of sequence similarity to Dbl-like proteins, the Rho-specific eukaryotic guanine nucleotide exchange factors.

Stability and bifurcations of the figure-8 solution of the three-body problem.

The stability properties of a recently discovered solution of the general three-body problem with equal masses and the shape of a figure 8 are analyzed as the masses are varied. It is shown by numerical continuation and the evaluation of the characteristic multipliers that the solution is stable only in a narrow mass interval. Other less symmetrical and unstable solutions with equal masses in the same homotopy class as the figure-8 orbit have been found.

The bacterial protein SipA polymerizes G-actin and mimics muscle nebulin.

SipA is a Salmonella protein delivered into host cells to promote efficient bacterial entry, which is essential for pathogenicity. SipA exerts its function by binding F-actin, resulting in the stabilization of F-actin and the stimulation of the bundling activity of fimbrin. Here we show that under low salt conditions where spontaneous nucleation and polymerization of actin do not occur, SipA induces extensive polymerization.

Structural studies of metarhodopsin II, the activated form of the G-protein coupled receptor, rhodopsin.

The structural changes that accompany activation of a G-protein coupled receptor (GPCR) are not well understood. To better understand the activation of rhodopsin, the GPCR responsible for visual transduction, we report studies on the three-dimensional structure for the activated state of this receptor, metarhodopsin II. Differences between the three-dimensional structure of ground state rhodopsin and metarhodopsin II, particularly in the cytoplasmic face of the receptor, suggest how the receptor is activated to couple with transducin.

Mutations in the LGI1/Epitempin gene on 10q24 cause autosomal dominant lateral temporal epilepsy.

Autosomal dominant lateral temporal epilepsy (EPT; OMIM 600512) is a form of epilepsy characterized by partial seizures, usually preceded by auditory signs. The gene for this disorder has been mapped by linkage studies to chromosomal region 10q24. Here we show that mutations in the LGI1 gene segregate with EPT in two families affected by this disorder.

Immune response to Salmonella: location, location, location?

Successful immunity against Salmonella infections is dependent on the generation of CD4(+) T helper cells and to a lesser extent on antibody production and CD8(+) T cells. The cells within the lymphatic tissue of the gut are likely to be central for the orchestration of a proper and rapid response. The anatomical restriction of the pathogen may also determine the distribution of effector cells.

RICK/Rip2/CARDIAK mediates signalling for receptors of the innate and adaptive immune systems.

The immune system consists of two evolutionarily different but closely related responses, innate immunity and adaptive immunity. Each of these responses has characteristic receptors-Toll-like receptors (TLRs) for innate immunity and antigen-specific receptors for adaptive immunity. Here we show that the caspase recruitment domain (CARD)-containing serine/threonine kinase Rip2 (also known as RICK, CARDIAK, CCK and Ripk2) transduces signals from receptors of both immune responses.

Cytolethal distending toxin: limited damage as a strategy to modulate cellular functions.

The coevolution of bacterial pathogens and their hosts has contributed to the development of very complex and sophisticated functional pathogen--host interfaces. Thus, well-adapted pathogens have evolved a variety of strategies to manipulate host cell functions precisely. For example, a group of unrelated Gram-negative pathogenic bacteria have evolved a toxin, known as cytolethal distending toxin (CDT), that has the ability to control cell cycle progression in eukaryotic cells.

Salmonella entry into host cells: the work in concert of type III secreted effector proteins.

Upon contact with intestinal epithelial cells, Salmonella enterica serovar spp. inject a set of bacterial proteins into host cells via the bacterial SPI-1 type III secretion system. SopE, SopE2 and SopB, activate CDC42 and Rac to initiate actin cytoskeleton rearrangements.

Role of tyrosine kinases and the tyrosine phosphatase SptP in the interaction of Salmonella with host cells.

Salmonella has evolved an intimate functional interface with its host. Central to this interface is a battery of bacterial proteins delivered into host cells via a specialized organelle termed the type III secretion system. A subset of these bacterial proteins stimulates cellular responses by activating the Rho family GTPases Cdc42 and Rac.

Dynamical mean-field solution of coupled quantum wells: a bifurcation analysis.

The time evolution of a discrete model of three quantum wells with a localized mean-field electrostatic interaction has been analyzed making use of numerical simulation and bifurcation techniques. The discrete Schrödinger equation can be written as a classical Hamiltonian system with two constants of motion. The frequency spectrum and the Lyapunov exponents show that the system is chaotic as its continuum counterpart.

Maintenance of an unfolded polypeptide by a cognate chaperone in bacterial type III secretion.

Many bacterial pathogens use a type III protein secretion system to deliver virulence effector proteins directly into the host cell cytosol, where they modulate cellular processes. A requirement for the effective translocation of several such effector proteins is the binding of specific cytosolic chaperones, which typically interact with discrete domains in the virulence factors. We report here the crystal structure at 1.

Salmonella interactions with host cells: type III secretion at work.

The bacterial pathogen Salmonella enterica has evolved a very sophisticated functional interface with its vertebrate hosts. At the center of this interface is a specialized organelle, the type III secretion system, that directs the translocation of bacterial proteins into the host cell. Salmonella spp.

Induction of specific CD8+ memory T cells and long lasting protection following immunization with Salmonella typhimurium expressing a lymphocytic choriomeningitis MHC class I-restricted epitope.

Numerous studies have shown the potential of Salmonella typhimurium as a vector for delivery of heterologous proteins for vaccination against other pathogens. Earlier studies showed that the inefficient elicitation of MHC class I-restricted responses could limit the use of S. typhimurium as a heterologous antigen delivery vector for vaccination.

Structural mimicry in bacterial virulence.

An important mechanism underlying the strategies used by microbial pathogens to manipulate cellular functions is that of functional mimicry of host activities. In some cases, mimicry is achieved through virulence factors that are direct homologues of host proteins. In others, convergent evolution has produced new effectors that, although having no obvious amino-acid sequence similarity to host factors, are revealed by structural studies to display mimicry at the molecular level.

In vitro activity of telithromycin against Spanish Streptococcus pneumoniae isolates with characterized macrolide resistance mechanisms.

The susceptibilities to telithromycin of 203 Streptococcus pneumoniae isolates prospectively collected during 1999 and 2000 from 14 different geographical areas in Spain were tested and compared with those to erythromycin A, clindamycin, quinupristin-dalfopristin, penicillin G, cefotaxime, and levofloxacin. Telithromycin was active against 98.9% of isolates (MICs, < or =0.

Common and contrasting themes of plant and animal diseases.

Recent studies in bacterial pathogenesis reveal common and contrasting mechanisms of pathogen virulence and host resistance in plant and animal diseases. This review presents recent developments in the study of plant and animal pathogenesis, with respect to bacterial colonization and the delivery of effector proteins to the host. Furthermore, host defense responses in both plants and animals are discussed in relation to mechanisms of pathogen recognition and defense signaling.

CdtA, CdtB, and CdtC form a tripartite complex that is required for cytolethal distending toxin activity.

Campylobacter jejuni encodes a cytolethal distending toxin (CDT) that causes cells to arrest in the G(2)/M transition phase of the cell cycle. Highly related toxins are also produced by other important bacterial pathogens. CDT activity requires the function of three genes: cdtA, cdtB, and cdtC.

Characterization of the mutS-proximal region of the Salmonella typhimurium SPI-1 identifies a group of pathogenicity island-associated genes.

The virulence properties of Salmonella enterica are largely encoded within a set of horizontally acquired gene blocks termed pathogenicity islands. One such pathogenicity island, SPI-1, located at centisome 63 of the Salmonella chromosome between the mutS and fhlA genes, encodes a type III protein secretion system and an iron uptake system. We have characterized the mutS-proximal border of this pathogenicity island and have identified two sets of genes, pigAB and pigCD.

[Comparative analysis of the clinical history and polysomnography in sleep disorders. Diagnostic relevance of polysomnography].

Introduction: The incidence of associate pathologies has been studied during the sleep, as well as the diagnostic efficiency of the clinical history.

Patients And Methods: Patients (n = 136) remitted by diverse services, have been studied. It has been carried out a complete polysomnography, as well as other supplementary studies (anxiety and depression tests, excessive daytime sleepiness Epworth's test, EEG and sleep notebook).

Skp1p and the F-box protein Rcy1p form a non-SCF complex involved in recycling of the SNARE Snc1p in yeast.

Skp1p-cullin-F-box protein (SCF) complexes are ubiquitin-ligases composed of a core complex including Skp1p, Cdc53p, Hrt1p, the E2 enzyme Cdc34p, and one of multiple F-box proteins which are thought to provide substrate specificity to the complex. Here we show that the F-box protein Rcy1p is required for recycling of the v-SNARE Snc1p in Saccharomyces cerevisiae. Rcy1p localized to areas of polarized growth, and this polarized localization required its CAAX box and an intact actin cytoskeleton.

In vitro transposition system for efficient generation of random mutants of Campylobacter jejuni.

Campylobacter jejuni is the most common cause of food-borne illnesses in the United States. Despite the fact that the entire nucleotide sequence of its genome has recently become available, its mechanisms of pathogenicity are poorly understood. This is in part due to the lack of an efficient mutagenesis system.

[Comparison of an auditory evoked potentials index and a bispectral index versus clinical signs for determining the depth of anesthesia produced by propofol or sevoflurane].

Objectives: To evaluate an anesthetic depth index (ADI) obtained from auditory evoked potentials and a bispectral EEG index (BIS) in comparison with clinical assessment of anesthetic depth using the modified observer's assessment of awareness/sedation scale (MOAA/SS), for induction of anesthesia with propofol or sevoflurane as the only agent.

Patients And Methods: The ADI and BIS were recorded simultaneously in this prospective study and compared to the MOAA/SS during the anesthetic induction of 26 adults undergoing elective heart surgery. Assignment of patients to two groups was random.

Modulation of host signaling by a bacterial mimic: structure of the Salmonella effector SptP bound to Rac1.

Salmonella spp. utilize a specialized protein secretion system to deliver a battery of effector proteins into host cells. Several of these effectors stimulate Cdc42- and Rac1-dependent cytoskeletal changes that promote bacterial internalization.