Recognition of specific sialoglycan structures by oral streptococci impacts the severity of endocardial infection.

Streptococcus gordonii and Streptococcus sanguinis are primary colonizers of the tooth surface. Although generally non-pathogenic in the oral environment, they are a frequent cause of infective endocarditis. Both streptococcal species express a serine-rich repeat surface adhesin that mediates attachment to sialylated glycans on mucin-like glycoproteins, but the specific sialoglycan structures recognized can vary from strain to strain. Previous studies have shown that sialoglycan binding is clearly important for aortic valve infections caused by some S. gordonii, but this process did not contribute to the virulence of a strain of S. sanguinis. However, these streptococci can bind to different subsets of sialoglycan structures. Here we generated isogenic strains of S. gordonii that differ only in the type and range of sialoglycan structures to which they adhere and examined whether this rendered them more or less virulent in a rat model of endocarditis. The findings indicate that the recognition of specific sialoglycans can either enhance or diminish pathogenicity. Binding to sialyllactosamine reduces the initial colonization of mechanically-damaged aortic valves, whereas binding to the closely-related trisaccharide sialyl T-antigen promotes higher bacterial densities in valve tissue 72 hours later. A surprising finding was that the initial attachment of streptococci to aortic valves was inversely proportional to the affinity of each strain for platelets, suggesting that binding to platelets circulating in the blood may divert bacteria away from the endocardial surface. Importantly, we found that human and rat platelet GPIbα (the major receptor for S. gordonii and S. sanguinis on platelets) display similar O-glycan structures, comprised mainly of a di-sialylated core 2 hexasaccharide, although the rat GPIbα has a more heterogenous composition of modified sialic acids. The combined results suggest that streptococcal interaction with a minor O-glycan on GPIbα may be more important than the over-all affinity for GPIbα for pathogenic effects

Anomalous cosmic rays in the heliosheath

We report on Voyager 1 and 2 observations of anomalous cosmic rays in the outer heliosphere. The energy spectrum of anomalous cosmic ray helium as each spacecraft crossed the solar wind termination shock into the heliosheath remained modulated. Assuming the intensity gradient between the two spacecraft is purely radial, we find that radial gradients in the heliosheath of He with 11.6–22.3 MeV/nuc and with ∼61–73MeV/nuc∼61–73 MeV/nuc are 4.9±1.2%/AU4.9±1.2%/AU and 0.0±0.5%/AU,0.0±0.5%/AU, respectively. Strong temporal variations of the 11.6–22.3 MeV/nuc He intensity at both spacecraft were observed in 2005 just after Voyager 1 crossed the termination shock and while Voyager 2 was upstream. After 2006.0, the intensity variations are more moderate and likely due to a combination of spatial and temporal variations. As of early 2008, the anomalous cosmic ray He energy spectrum has unfolded to what may be a source spectrum. The spectrum at Voyager 2 remains modulated. We examine three recent models of the origin of anomalous cosmic rays in light of these observations

Abundances and energy spectra of corotating interaction region heavy ions

We have surveyed He-Fe spectra for 41 Corotating Interaction Regions (CIRs) from 1998–2007 observed on ACE. The spectra are similar for all species, and have the form of broken power laws with the spectral break occurring at a few MeV/nucleon. Except for overabundances of He and Ne, the abundances are close to those of the solar wind. We find the rare isotope ^3He is enhanced in ~40% of the events. In individual CIRs the Fe/O ratio correlates strongly with the solar wind Fe/O ratio measured 2–4 days prior to the CIR passage. Taken together with previously reported observations of pick-up He^+ in CIRs, these observations provide evidence that CIRs are accelerated out of a suprathermal ion pool of heated solar wind ions, pick-up ions, and remnant suprathermal ions from impulsive solar energetic particle (SEP) events

How efficient are coronal mass ejections at accelerating solar energetic particles?

The largest solar energetic particle (SEP) events are thought to be due to particle acceleration at a shock driven by a fast coronal mass ejection (CME). We investigate the efficiency of this process by comparing the total energy content of energetic particles with the kinetic energy of the associated CMEs. The energy content of 23 large SEP events from 1998 through 2003 is estimated based on data from ACE, GOES, and SAMPEX, and interpreted using the results of particle transport simulations and inferred longitude distributions. CME data for these events are obtained from SOHO. When compared to the estimated kinetic energy of the associated coronal mass ejections (CMEs), it is found that large SEP events can extract ~10% or more of the CME kinetic energy. The largest SEP events appear to require massive, very energetic CMEs

Caenorhabditis elegans methionine/S-adenosylmethionine cycle activity is sensed and adjusted by a nuclear hormone receptor

Vitamin B12 is an essential micronutrient that functions in two metabolic pathways: the canonical propionate breakdown pathway and the methionine/S-adenosylmethionine (Met/SAM) cycle. In Caenorhabditis elegans, low vitamin B12, or genetic perturbation of the canonical propionate breakdown pathway results in propionate accumulation and the transcriptional activation of a propionate shunt pathway. This propionate-dependent mechanism requires nhr-10 and is referred to as \u27B12-mechanism-I\u27. Here, we report that vitamin B12 represses the expression of Met/SAM cycle genes by a propionate-independent mechanism we refer to as \u27B12-mechanism-II\u27. This mechanism is activated by perturbations in the Met/SAM cycle, genetically or due to low dietary vitamin B12. B12-mechanism-II requires nhr-114 to activate Met/SAM cycle gene expression, the vitamin B12 transporter, pmp-5, and adjust influx and efflux of the cycle by activating msra-1 and repressing cbs-1, respectively. Taken together, Met/SAM cycle activity is sensed and transcriptionally adjusted to be in a tight metabolic regime

STEREO and ACE observations of CIR particles

In the present solar minimum, corotating interaction regions (CIRs) produce frequent particle enhancements at 1 AU as observed at STEREO and ACE. As the two STEREO spacecraft move apart, differences in CIR time profiles observed at each spacecraft are becoming large. The timing differences are often roughly similar to the corotation time lag between the two spacecraft, however many of the features seen at Ahead and Behind require more than just a time shift. Perhaps transient disturbances in the solar wind affect connection to or transport from the shock, or temporal changes occur in the CIR shock itself. Additional timing differences of >1 day result from the different heliographic latitudes of the two STEREO spacecraf

The Arabidopsis Chromatin-Modifying Nuclear siRNA Pathway Involves a Nucleolar RNA Processing Center

SummaryIn Arabidopsis thaliana, small interfering RNAs (siRNAs) direct cytosine methylation at endogenous DNA repeats in a pathway involving two forms of nuclear RNA polymerase IV (Pol IVa and Pol IVb), RNA-DEPENDENT RNA POLYMERASE 2 (RDR2), DICER-LIKE 3 (DCL3), ARGONAUTE4 (AGO4), the chromatin remodeler DRD1, and the de novo cytosine methyltransferase DRM2. We show that RDR2, DCL3, AGO4, and NRPD1b (the largest subunit of Pol IVb) colocalize with siRNAs within the nucleolus. By contrast, Pol IVa and DRD1 are external to the nucleolus and colocalize with endogenous repeat loci. Mutation-induced loss of pathway proteins causes downstream proteins to mislocalize, revealing their order of action. Pol IVa acts first, and its localization is RNA dependent, suggesting an RNA template. We hypothesize that maintenance of the heterochromatic state involves locus-specific Pol IVa transcription followed by siRNA production and assembly of AGO4- and NRPD1b-containing silencing complexes within nucleolar processing centers

REFERENTIAL HAEMATOLOGICAL VALUES IN AGOUTIS (DASYPROCTA FULIGINOSA) KEPT IN CAPTIVITY

El objetivo del presente estudio fue determinar los valores hematológicos del añuje (Dasyprocta fuliginosa) criado en cautiverio en el Zoológico Patronato Parque Las Leyendas (PATPAL). Se utilizaron 23 animales (11 machos y 12 hembras; 13 juveniles y 10 adultos). Los animales fueron anestesiados con una combinación de Ketamina (10 mg/kg peso vivo) y Xilacina (1 mg/kg peso vivo) i.m. El análisis hematológico incluyó hemoglobina (Hb), hematocrito (Ht), contaje de eritrocitos y leucocitos, Volumen Corpuscular Medio (VGM), Concentración de Hemoglobina Corpuscular Media (CHGM) y Hemoglobina Corpuscular Media (HCM), y el diferencial de leucocitos. Los resultados fueron: 6.17 x 106/μl eritrocitos, 5,739 x 103/μl leucocitos, 40.4% Ht, 12.42 g/dl Hb, 66.56 fl VGM, 20.56 pg HCM, 30.88 g/dl CHGM; y 67.1% neutrófilos, 29.6% linfocitos, 2.39% eosinófilos, 0.26% monocitos y 0.56% abastonados. Los valores encontrados son similares a otros valores reportados en la literatura.The purpose of the present study was to determine the haematologic values of agoutis (Dasyprocta fuliginosa) bred in captivity at the Patronato Parque Las Leyendas zoo (PATPAL). Twenty three animals were used (11 males and 12 females; 13 juvenile and 10 adults). They were anesthetized with a combination of Ketamine (10 mg/kg BW) and Xilacine (1 mg/kg BW) i.m. The haemathological analysis included haemoglobin (Hb), hematocrit (Ht), count of erythrocytes (RBC) and leucocytes (WBC), mean cell volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), and the leukocyte differential. The obtained values were: 6.17 x 106/μl RBC, 5,739 x 103/μl WBC, 40.4% Ht, 12.42 g/dl Hb, 66.56 fl MCV, 20.56 pg MCH, 30.88 g/dl MCHC; and 67.1% neutrophils, 29.6% lymphocytes, 2.39% eosinophils, 0.26% monocytes and 0.56% band neutrophils. The encountered values were similar to those reported in the literature

Ticagrelor Reduces Thromboinflammatory Markers in Patients With Pneumonia

Despite treatment advances for sepsis and pneumonia, significant improvements in outcome have not been realized. Antiplatelet therapy may improve outcome in pneumonia and sepsis. In this study, the authors show that ticagrelor reduced leukocytes with attached platelets as well as the inflammatory biomarker interleukin (IL)-6. Pneumonia patients receiving ticagrelor required less supplemental oxygen and lung function tests trended toward improvement. Disruption of the P2Y12 receptor in a murine model protected against inflammatory response, lung permeability, and mortality. Results indicate a mechanistic link between platelets, leukocytes, and lung injury in settings of pneumonia and sepsis, and suggest possible therapeutic approaches to reduce complications. (Targeting Platelet-Leukocyte Aggregates in Pneumonia With Ticagrelor [XANTHIPPE]; NCT01883869

BdlA, DipA and Induced Dispersion Contribute to Acute Virulence and Chronic Persistence of Pseudomonas aeruginosa

The human pathogen Pseudomonas aeruginosa is capable of causing both acute and chronic infections. Differences in virulence are attributable to the mode of growth: bacteria growing planktonically cause acute infections, while bacteria growing in matrix-enclosed aggregates known as biofilms are associated with chronic, persistent infections. While the contribution of the planktonic and biofilm modes of growth to virulence is now widely accepted, little is known about the role of dispersion in virulence, the active process by which biofilm bacteria switch back to the planktonic mode of growth. Here, we demonstrate that P. aeruginosa dispersed cells display a virulence phenotype distinct from those of planktonic and biofilm cells. While the highest activity of cytotoxic and degradative enzymes capable of breaking down polymeric matrix components was detected in supernatants of planktonic cells, the enzymatic activity of dispersed cell supernatants was similar to that of biofilm supernatants. Supernatants of non-dispersing Delta bdlA biofilms were characterized by a lack of many of the degradative activities. Expression of genes contributing to the virulence of P. aeruginosa was nearly 30-fold reduced in biofilm cells relative to planktonic cells. Gene expression analysis indicated dispersed cells, while dispersing from a biofilm and returning to the single cell lifestyle, to be distinct from both biofilm and planktonic cells, with virulence transcript levels being reduced up to 150-fold compared to planktonic cells. In contrast, virulence gene transcript levels were significantly increased in non-dispersing Delta bdlA and Delta dipA biofilms compared to wild-type planktonic cells. Despite this, bdlA and dipA inactivation, resulting in an inability to disperse in vitro, correlated with reduced pathogenicity and competitiveness in cross-phylum acute virulence models. In contrast, bdlA inactivation rendered P. aeruginosa more persistent upon chronic colonization of the murine lung, overall indicating that dispersion may contribute to both acute and chronic infections