Inflammasome-dependent IFN-γ drives pathogenesis in Streptococcus pneumoniae meningitis

The pathology associated with Streptococcus pneumoniae meningitis results largely from activation of immune-associated pathways. We systematically investigated the production of IFN subtypes, as well as their influence on pathology, in a mouse model of S. pneumoniae meningitis. Despite the occurrence of a mixed IFN type I/II gene signature, no evidence for production or involvement of type I IFNs in disease progression was found. In contrast, type II IFN (IFN-γ) was strongly induced, and IFN-γ(-/-) mice were significantly protected from severe disease. Using intracellular cytokine staining and targeted cell-depletion approaches, NK cells were found to be the dominant source of IFN-γ. Furthermore, production of IFN-γ was found to be dependent upon ASC and IL-18, indicating that an ASC-dependent inflammasome pathway was responsible for mediating IFN-γ induction. The influence of IFN-γ gene deletion on a range of processes known to be involved in bacterial meningitis pathogenesis was examined. Although neutrophil numbers in the brain were similar in infected wild-type and IFN-γ(-/-) mice, both monocyte recruitment and CCL2 production were less in infected IFN-γ(-/-) mice compared with infected wild-type controls. Additionally, gene expression of NO synthase was strongly diminished in infected IFN-γ(-/-) mice compared with infected controls. Finally, bacterial clearance was enhanced in IFN-γ(-/-) mice, although the underlying mechanism remains unclear. Together, these data suggest that inflammasome-dependent IFN-γ contributes via multiple pathways to pathology during S. pneumoniae meningitis.

Interaction of the solar wind with them Moon: An overview on the results from the SARA experiment aboard Chandrayaan-1

The results from the Sub-keV Atom Reflecting Analyzer (SARA) experiment onboard Chandrayaan-1 have revealed several hitherto unknown and interesting aspects about the interaction of solar wind with the Moon. The SARA experiment had two sensors — CENA and SWIM. The Chandrayaan-1 energetic neutrals analyzer (CENA), detected energetic neutral atoms (ENAs), and the Solar Wind Monitor (SWIM) measured ions of solar wind origin. In this review, we summarize the observations made by the SARA experiment, which are: (1) substantial (~20%) and sustained backscattering of solar wind protons from lunar surface as energetic neutral hydrogen,1 (2) minimagnetosphere around magnetic anomalies on Moon using the backscattered ENAs,2 (3) reflection of solar wind protons from the Moon surface,3 (4) huge (~50%) deflection of solar wind protons over strong magnetic anomalies,4 and (5) presence of protons in the near-lunar plasma wake.5 These results have implications on the lunar plasma environment, implantation of solar wind hydrogen on lunar surface, and behavior of small scale magnetic anomalies on planetary bodies. The SARA observations suggest that similar processes may happen on other airless bodies covered with regolith in the solar system as well as in extra-solar system. This paper presents a review of the results obtained from the SARA observation.

Ctp1 and the MRN-complex are required for endonucleolytic Rec12 removal with release of a single class of oligonucleotides in fission yeast

DNA double-strand breaks (DSBs) are formed during meiosis by the action of the topoisomerase-like Spo11/Rec12 protein, which remains covalently bound to the 5' ends of the broken DNA. Spo11/Rec12 removal is required for resection and initiation of strand invasion for DSB repair. It was previously shown that budding yeast Spo11, the homolog of fission yeast Rec12, is removed from DNA by endonucleolytic cleavage. The release of two Spo11 bound oligonucleotide classes, heterogeneous in length, led to the conjecture of asymmetric cleavage. In fission yeast, we found only one class of oligonucleotides bound to Rec12 ranging in length from 17 to 27 nucleotides. Ctp1, Rad50, and the nuclease activity of Rad32, the fission yeast homolog of Mre11, are required for endonucleolytic Rec12 removal. Further, we detected no Rec12 removal in a rad50S mutant. However, strains with additional loss of components localizing to the linear elements, Hop1 or Mek1, showed some Rec12 removal, a restoration depending on Ctp1 and Rad32 nuclease activity. But, deletion of hop1 or mek1 did not suppress the phenotypes of ctp1Delta and the nuclease dead mutant (rad32-D65N). We discuss what consequences for subsequent repair a single class of Rec12-oligonucleotides may have during meiotic recombination in fission yeast in comparison to two classes of Spo11-oligonucleotides in budding yeast. Furthermore, we hypothesize on the participation of Hop1 and Mek1 in Rec12 removal.

Laribacter hongkongensis: a potential cause of infectious diarrhea

In this study, we describe the isolation of Laribacter hongkongensis, a recently described genus and species of bacterium, in pure culture on charcoal cefoperazone deoxycholate agar from the stool of six patients with diarrhea. Three patients were residents of Hong Kong, and three of Switzerland. In none of the stool samples obtained from these six patients was Salmonella, Shigella, enterohemorrhagic Escherichia coli, Vibrio, Aeromonas, Plesiomonas, or Campylobacter recovered. Rotavirus antigen detection, electron microscopic examination for viruses, and microscopic examinations for ova and cysts were all negative for the stool samples obtained from the three patients in Hong Kong. Enterotoxigenic E. coli was recovered from one of the patients in Hong Kong. Unlike L. hongkongensis type strain HKU1, all the six strains were motile with bipolar flagellae. Sequencing of the 16S ribosomal RNA genes of the six strains showed that they all had sequences with only 0-2 base differences to that of the type strain. Pulsed field gel electrophoresis of the SpeI digested genomic DNA of the six isolates and that of the type strain revealed that the seven isolates were genotypically unrelated strains. More extensive epidemiologic studies should be carried out to ascertain the causative association between L. hongkongensis and diarrhea and to define the reservoir and modes of transmission of L. hongkongensis.

Corporate dividencs and seasoned equity issues: an empirical investigation

This paper investigates whether managers rely on dividends to obtain a higher price in a stock offering and whether the stock price reaction to dividend and offering announcements justifies such a coordination. The evidence does not support either conjecture. Issuing firms are not more likely to pay or increase dividends than nonissuing forms. Moreover, there is little evidence that firms time stock offering announcements right after dividend declarations to befefit from the attendant information disclosure. The analysis of dividend and stock offering announcement effects suggests few if any benefits from linking divbidend and stock offering announcements.

Is there a ‚Depth versus Participation‘ Dilemma in International Cooperation?

Much of the International Relations literature assumes that there is a “depth versus participation” dilemma in international politics: shallower international agreements attract more countries and greater depth is associated with less participation. We argue that this conjecture is too simple and probably misleading because the depth of any given cooperative effort is in fact multidimensional. This multidimensionality manifests itself in the design characteristics of international agreements: in particular, the specificity of obligations, monitoring and enforcement mechanisms, dispute settlement mechanisms, positive incentives (assistance), and organizational structures (secretariats). We theorize that the first three of these design characteristics have negative and the latter three have positive effects on participation in international cooperative efforts. Our empirical testing of these claims relies on a dataset that covers more than 200 global environmental treaties. We find a participation-limiting effect for the specificity of obligations, but not for monitoring and enforcement. In contrast, we observe that assistance provisions in treaties have a significant and substantial positive effect on participation. Similarly, dispute settlement mechanisms tend to promote treaty participation. The main implication of our study is that countries do not appear to stay away from agreements with monitoring and enforcement provisions, but that the inclusion of positive incentives and dispute settlement mechanisms can promote international cooperation. In other words, our findings suggest that policymakers do not necessarily need to water down global treaties in order to obtain more participation.

Evidence of species-specific neighborhood effects in the dipterocarpaceae of a Bornean rain forest

Although accumulating evidence indicates that local intraspecific density-dependent effects are not as rare in species-rich communities as previously suspected, there are still very few detailed and systematic neighborhood analyses of species-rich communities. Here, we provide such an analysis with the overall goal of quantifying the relative importance of inter- and intraspecific interaction strength in a primary, lowland dipterocarp forest located at Danum, Sabah, Malaysia. Using data on 10 abundant overstory dipterocarp species from two 4-ha permanent plots, we evaluated the effects of neighbors on the absolute growth rate of focal trees (from 1986 to 1996) over increasing neighborhood radii (from 1 to 20 m) with multiple regressions. Only trees 10 cm to < 100 cm girth at breast height in 1986 were considered as focal trees. Among neighborhood models with one neighbor term, models including only conspecific larger trees performed best in five out of 10 species. Negative effects of conspecific larger neighbors were most apparent in large overstory species such as those of the genus Shorea. However, neighborhood models with separate terms and radii for heterospecific and conspecific neighbors accounted for more variability in absolute growth rates than did neighborhood models with one neighbor term. The conspecific term was significant for nine out of 10 species. Moreover, in five out of 10 species, trees without conspecific neighbors had significantly higher absolute growth rates than trees with conspecific neighbors. Averaged over the 10 species, trees without conspecific neighbors grew 32.4 cm(2) in basal area from 1986 to 1996, whereas trees with conspecific neighbors only grew 14.7 cm(2) in basal area, although there was no difference in initial basal area between trees in the two groups. Averaged across the six species of the genus Shorea, negative effects of conspecific larger trees were significantly stronger than for heterospecific larger neighbors. Thus, high local densities within neighborhoods of 20 m may lead to strong intraspecific negative and, hence, density-dependent, effects even in species rich communities with low overall densities at larger spatial scales. We conjecture that the strength of conspecific effects may be correlated with the degree of host specificity of ectomycorrhizae.

Loose but normal: a semantic association study.

An abnormal facilitation of the spreading activation within semantic networks is thought to under-lie schizophrenics' remote associations and referential ideas. In normal subjects, elevated magical ideation (MI) has also been associated with a style of thinking similar to that of schizotypal subjects. We thus wondered whether normal subjects with a higher MI score would judge "loose associations" as being more closely related than do subjects with a lower MI score. In two experiments, we investigated whether judgments of the semantic distance between stimulus words varied as a function of MI. In the first experiment, random word pairs of two word classes, animals and fruits, were presented. Subjects had to judge the semantic distance between word pairs. In the second experiment, sets of three words were presented, consisting of a pair of indirectly related, or unrelated nouns plus a third noun. Subjects had to judge the semantic distance of the third noun to the word pair The results of both experiments showed that higher MI subjects considered unrelated words as more closely associated than did lower MI subjects. We conjecture that for normal subjects high on MI "loose associations" may not be loose after all. We also note that the tendency to link uncommon, nonobvious, percepts may not only be the basis of paranormal and paranoid ideas of reference, but also a prerequisite of creative thinking.

Brain damage and addictive behavior: a neuropsychological and electroencephalogram investigation with pathologic gamblers.

BACKGROUND Gambling is a form of nonsubstance addiction classified as an impulse control disorder. Pathologic gamblers are considered healthy with respect to their cognitive status. Lesions of the frontolimbic systems, mostly of the right hemisphere, are associated with addictive behavior. Because gamblers are not regarded as "brain-lesioned" and gambling is nontoxic, gambling is a model to test whether addicted "healthy" people are relatively impaired in frontolimbic neuropsychological functions. METHODS Twenty-one nonsubstance dependent gamblers and nineteen healthy subjects underwent a behavioral neurologic interview centered on incidence, origin, and symptoms of possible brain damage, a neuropsychological examination, and an electroencephalogram. RESULTS Seventeen gamblers (81%) had a positive medical history for brain damage (mainly traumatic head injury, pre- or perinatal complications). The gamblers, compared with the controls, were significantly more impaired in concentration, memory, and executive functions, and evidenced a higher prevalence of non-right-handedness (43%) and, non-left-hemisphere language dominance (52%). Electroencephalogram (EEG) revealed dysfunctional activity in 65% of the gamblers, compared with 26% of controls. CONCLUSIONS This study shows that the "healthy" gamblers are indeed brain-damaged. Compared with a matched control population, pathologic gamblers evidenced more brain injuries, more fronto-temporo-limbic neuropsychological dysfunctions and more EEG abnormalities. The authors thus conjecture that addictive gambling may be a consequence of brain damage, especially of the frontolimbic systems, a finding that may well have medicolegal consequences.

Invitation à la topologie algébrique. Tome II. Cohomologie, variétés

Ce Tome II introduit la cohomologie, qui est une théorie duale de l'homologie, et examine les liens avec cette dernière ainsi que les divers produits construits sur les modules d'homologie et de cohomologie. Nous étudions en détail les variétés topologiques avec ou sans bord, définissons sur celles-ci au moyen de l'homologie une notion d'orientation et la comparons avec les définitions classiques d'orientation pour les variétés différentiables ou triangulables. Nous exposons les théorèmes de dualité de Poincaré, Alexander et Lefschetz et en déduisons les propriétés des formes d'intersection et de la signature des variétés. Le dernier chapitre du livre présente les résultats fondamentaux concernant la différentiabilité et la triangulabilité des variétés, obtenus depuis les années soixante du siècle dernier, tant en grandes dimensions qu'en dimension quatre. Nous discutons également la conjecture de Poincaré classique et ses généralisations. Bien que des démonstrations complètes de ces résultats soient hors de portée d'un ouvrage tel que le nôtre, nous nous sommes attachés à rendre leurs énoncés compréhensibles. Cette vue d'ensemble, et les références à la littérature qui l'accompagnent, fournissent une introduction aux développements récents dans ce riche domaine de la topologie.

Guaranteed resonance enclosures and exclosures for atoms and molecules

In this paper, we confirm, with absolute certainty, a conjecture on a certain oscillatory behaviour of higher auto-ionizing resonances of atoms and molecules beyond a threshold. These results not only definitely settle a more than 30 year old controversy in Rittby et al. (1981 Phys. Rev. A 24, 1636–1639 (doi:10.1103/PhysRevA.24.1636)) and Korsch et al. (1982 Phys. Rev. A 26, 1802–1803 (doi:10.1103/PhysRevA.26.1802)), but also provide new and reliable information on the threshold. Our interval-arithmetic-based method allows one, for the first time, to enclose and to exclude resonances with guaranteed certainty. The efficiency of our approach is demonstrated by the fact that we are able to show that the approximations in Rittby et al. (1981 Phys. Rev. A 24, 1636–1639 (doi:10.1103/PhysRevA.24.1636)) do lie near true resonances, whereas the approximations of higher resonances in Korsch et al. (1982 Phys. Rev. A 26, 1802–1803 (doi:10.1103/PhysRevA.26.1802)) do not, and further that there exist two new pairs of resonances as suggested in Abramov et al. (2001 J. Phys. A 34, 57–72 (doi:10.1088/0305-4470/34/1/304)).

Yang-Baxter deformations of Minkowski spacetime

We study Yang-Baxter deformations of 4D Minkowski spacetime. The Yang-Baxter sigma model description was originally developed for principal chiral models based on a modified classical Yang-Baxter equation. It has been extended to coset curved spaces and models based on the usual classical Yang-Baxter equation. On the other hand, for flat space, there is the obvious problem that the standard bilinear form degenerates if we employ the familiar coset Poincaré group/Lorentz group. Instead we consider a slice of AdS5 by embedding the 4D Poincaré group into the 4D conformal group SO(2, 4) . With this procedure we obtain metrics and B-fields as Yang-Baxter deformations which correspond to well-known configurations such as T-duals of Melvin backgrounds, Hashimoto-Sethi and Spradlin-Takayanagi-Volovich backgrounds, the T-dual of Grant space, pp-waves, and T-duals of dS4 and AdS4. Finally we consider a deformation with a classical r-matrix of Drinfeld-Jimbo type and explicitly derive the associated metric and B-field which we conjecture to correspond to a new integrable system.

Why Do Some International Institutions Contain Strong Dispute Settlement Provisions: New Evidence from Preferential Trade Agreements

To understand why some international institutions have stronger dispute settlement mechanisms (DSMs) than others, we investigate the dispute settlement provisions of nearly 600 preferential trade agreements (PTAs), which possess several desirable case-selection features and are evoked more than is realized. We broaden the study of dispute settlement design beyond “legalization” and instead reorient theorizing around a multi-faceted conceptualization of the strength of DSMs. We posit that strong DSMs are first and foremost a rational response to features of agreements that require stronger dispute settlement, such as depth and large memberships. Multivariate empirical tests using a new data set on PTA design confirm these expectations and reveal that depth – the amount of policy change specified in an agreement – is the most powerful and consistent predictor of DSM strength, providing empirical support to a long-posited but controversial conjecture. Yet power also plays a sizeable role, since agreements among asymmetric members are more likely to have strong DSMs due to their mutual appeal, as are those involving the United States. Important regional differences also emerge, as PTAs across the Americas are designed with strong dispute settlement, as are Asian PTAs, which contradicts the conventional wisdom about Asian values and legalization. Our findings demonstrate that rationalism explains much of international institutional design, yet it can be enhanced by also incorporating power-based and regional explanations.