Insufficient protection by Neisseria meningitidis vaccination alone during eculizumab therapy

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Baryon-Baryon Interactions

After a short survey of some topics of interest in the study of baryon-baryon scattering, the recent Nijmegen energy dependent partial wave analysis (PWA) of the nucleon-nucleon data is reviewed. In this PWA the energy range for both pp and np is now 0 < Tlab < 350 MeV and a chi^2_{d.o.f.}=1.08 was reached. The implications for the pion-nucleon coupling constants are discussed. Comments are made with respect to recent discussions around this coupling constant in the literature. In the second part, we briefly sketch the picture of the baryon in several, more or less QCD-based, quark-models that have been rather prominent in the literature. Inspired by these pictures we constructed a new soft-core model for the nucleon-nucleon interaction and present the first results of this model in a chi^2 -fit to the new multi-energy Nijmegen PWA. With this new model we succeeded in narrowing the gap between theory and experiment at low energies. For the energies Tlab = 25-320 MeV we reached a record low chi^2_{p.d.p.} = 1.16. We finish the paper with some conclusions and an outlook describing the extension of the new model to baryon-baryon scattering.Comment: 12 pages LaTeX and one postscript figure included. Invited talk presented at the XIVth European Conference of Few-Body Problems in Physics, Amsterdam, August 23-28, 199

Long-Range Rapidity Correlations in Heavy Ion Collisions at Strong Coupling from AdS/CFT

We use AdS/CFT correspondence to study two-particle correlations in heavy ion collisions at strong coupling. Modeling the colliding heavy ions by shock waves on the gravity side, we observe that at early times after the collision there are long-range rapidity correlations present in the two-point functions for the glueball and the energy-momentum tensor operators. We estimate rapidity correlations at later times by assuming that the evolution of the system is governed by ideal Bjorken hydrodynamics, and find that glueball correlations in this state are suppressed at large rapidity intervals, suggesting that late-time medium dynamics can not "wash out" the long-range rapidity correlations that were formed at early times. These results may provide an insight on the nature of the "ridge" correlations observed in heavy ion collision experiments at RHIC and LHC, and in proton-proton collisions at LHC.Comment: 32 pages, 2 figures; v2: typos corrected, references adde

Insulin-Stimulated Degradation of Apolipoprotein B100: Roles of Class II Phosphatidylinositol-3-Kinase and Autophagy

Both in humans and animal models, an acute increase in plasma insulin levels, typically following meals, leads to transient depression of hepatic secretion of very low density lipoproteins (VLDL). One contributing mechanism for the decrease in VLDL secretion is enhanced degradation of apolipoprotein B100 (apoB100), which is required for VLDL formation. Unlike the degradation of nascent apoB100, which occurs in the endoplasmic reticulum (ER), insulin-stimulated apoB100 degradation occurs post-ER and is inhibited by pan-phosphatidylinositol (PI)3-kinase inhibitors. It is unclear, however, which of the three classes of PI3-kinases is required for insulin-stimulated apoB100 degradation, as well as the proteolytic machinery underlying this response. Class III PI3-kinase is not activated by insulin, but the other two classes are. By using a class I-specific inhibitor and siRNA to the major class II isoform in liver, we now show that it is class II PI3-kinase that is required for insulin-stimulated apoB100 degradation in primary mouse hepatocytes. Because the insulin-stimulated process resembles other examples of apoB100 post-ER proteolysis mediated by autophagy, we hypothesized that the effects of insulin in autophagy-deficient mouse primary hepatocytes would be attenuated. Indeed, apoB100 degradation in response to insulin was significantly impaired in two types of autophagy-deficient hepatocytes. Together, our data demonstrate that insulin-stimulated apoB100 degradation in the liver requires both class II PI3-kinase activity and autophagy. © 2013 Andreo et al

The Suppressor of AAC2 Lethality SAL1 Modulates Sensitivity of Heterologously Expressed Artemia ADP/ATP Carrier to Bongkrekate in Yeast

The ADP/ATP carrier protein (AAC) expressed in Artemia franciscana is refractory to bongkrekate. We generated two strains of Saccharomyces cerevisiae where AAC1 and AAC3 were inactivated and the AAC2 isoform was replaced with Artemia AAC containing a hemagglutinin tag (ArAAC-HA). In one of the strains the suppressor of ΔAAC2 lethality, SAL1, was also inactivated but a plasmid coding for yeast AAC2 was included, because the ArAACΔsal1Δ strain was lethal. In both strains ArAAC-HA was expressed and correctly localized to the mitochondria. Peptide sequencing of ArAAC expressed in Artemia and that expressed in the modified yeasts revealed identical amino acid sequences. The isolated mitochondria from both modified strains developed 85% of the membrane potential attained by mitochondria of control strains, and addition of ADP yielded bongkrekate-sensitive depolarizations implying acquired sensitivity of ArAAC-mediated adenine nucleotide exchange to this poison, independent from SAL1. However, growth of ArAAC-expressing yeasts in glycerol-containing media was arrested by bongkrekate only in the presence of SAL1. We conclude that the mitochondrial environment of yeasts relying on respiratory growth conferred sensitivity of ArAAC to bongkrekate in a SAL1-dependent manner. © 2013 Wysocka-Kapcinska et al

Detection of group A Streptococcus in tonsils from pediatric patients reveals high rate of asymptomatic streptococcal carriage

<p>Abstract</p> <p>Background</p> <p>Group A <it>Streptococcus </it>(GAS) causes acute tonsillopharyngitis in children, and approximately 20% of this population are chronic carriers of GAS. Antibacterial therapy has previously been shown to be insufficient at clearing GAS carriage. Bacterial biofilms are a surface-attached bacterial community that is encased in a matrix of extracellular polymeric substances. Biofilms have been shown to provide a protective niche against the immune response and antibiotic treatments, and are often associated with recurrent or chronic bacterial infections. The objective of this study was to test the hypothesis that GAS is present within tonsil tissue at the time of tonsillectomy.</p> <p>Methods</p> <p>Blinded immunofluorescent and histological methods were employed to evaluate palatine tonsils from children undergoing routine tonsillectomy for adenotonsillar hypertrophy or recurrent GAS tonsillopharyngitis.</p> <p>Results</p> <p>Immunofluorescence analysis using anti-GAS antibody was positive in 11/30 (37%) children who had tonsillectomy for adenotonsillar hypertrophy and in 10/30 (33%) children who had tonsillectomy for recurrent GAS pharyngitis. Fluorescent microscopy with anti-GAS and anti-cytokeratin 8 & 18 antibodies revealed GAS was localized to the tonsillar reticulated crypts. Scanning electron microscopy identified 3-dimensional communities of cocci similar in size and morphology to GAS. The characteristics of these communities are similar to GAS biofilms from <it>in vivo </it>animal models.</p> <p>Conclusion</p> <p>Our study revealed the presence of GAS within the tonsillar reticulated crypts of approximately one-third of children who underwent tonsillectomy for either adenotonsillar hypertrophy or recurrent GAS tonsillopharyngitis at the Wake Forest School of Medicine.</p> <p>Trial Registration</p> <p>The tissue collected was normally discarded tissue and no patient identifiers were collected. Thus, no subjects were formally enrolled.</p

Paroxysmal nocturnal hemoglobinuria (PNH): higher sensitivity and validity in diagnosis and serial monitoring by flow cytometric analysis of reticulocytes

Flow cytometric analysis of GPI-anchored proteins (GPI-AP) is the gold standard for diagnosis of paroxysmal nocturnal hemoglobinuria (PNH). Due to therapy options and the relevance of GPI-deficient clones for prognosis in aplastic anaemia detection of PNH is gaining importance. However, no generally accepted standard has been established. This study analysed the usefulness of a flow cytometric panel with CD58, CD59 on reticulocytes and erythrocytes, CD24/CD66b and CD16, FLAER on granulocytes and CD14, and CD48 on monocytes. Actual cut-off (mean + 2 SD) for GPI-deficient cells was established in healthy blood donors. We studied 1,296 flow cytometric results of 803 patients. Serial monitoring was analysed during a median follow-up of 1,039 days in 155 patients. Of all, 22% and 48% of 155 follow-up patients. showed significant GPI-AP-deficiency at time of initial analyses. During follow-up in 9%, a new PNH diagnosis, and in 28%, a significant change of size or lineage involvement was demonstrated. Highly significant correlations for GPI-AP deficiency were found within one cell lineage (r2 = 0.61–0.95, p < 0.0001) and between the different cell lineages (r2 = 0.49–0.88, p < 0.0001). Especially for detection of small GPI-deficient populations, reticulocytes and monocytes proved to be sensitive diagnostic tools. Our data showed superiority of reticulocyte analyses compared with erythrocyte analyses due to transfusion and hemolysis independency especially in cases with small GPI-deficient populations. In conclusion, a screening panel of at least two different GPI-AP markers on granulocytes, erythrocytes, and reticulocytes provides a simple and rapid method to detect even small GPI-deficient populations. Among the markers in our panel, CD58 and CD59 on reticulocytes, CD24/66b, and eventually FLAER on granulocytes as well as CD14 on monocytes were most effective for flow cytometric diagnosis of GPI deficiency

Heterochromatic Genome Stability Requires Regulators of Histone H3 K9 Methylation

Heterochromatin contains many repetitive DNA elements and few protein-encoding genes, yet it is essential for chromosome organization and inheritance. Here, we show that Drosophila that lack the Su(var)3-9 H3K9 methyltransferase display significantly elevated frequencies of spontaneous DNA damage in heterochromatin, in both somatic and germ-line cells. Accumulated DNA damage in these mutants correlates with chromosomal defects, such as translocations and loss of heterozygosity. DNA repair and mitotic checkpoints are also activated in mutant animals and are required for their viability. Similar effects of lower magnitude were observed in animals that lack the RNA interference pathway component Dcr2. These results suggest that the H3K9 methylation and RNAi pathways ensure heterochromatin stability

Hearing Loss in Stranded Odontocete Dolphins and Whales

The causes of dolphin and whale stranding can often be difficult to determine. Because toothed whales rely on echolocation for orientation and feeding, hearing deficits could lead to stranding. We report on the results of auditory evoked potential measurements from eight species of odontocete cetaceans that were found stranded or severely entangled in fishing gear during the period 2004 through 2009. Approximately 57% of the bottlenose dolphins and 36% of the rough-toothed dolphins had significant hearing deficits with a reduction in sensitivity equivalent to severe (70–90 dB) or profound (>90 dB) hearing loss in humans. The only stranded short-finned pilot whale examined had profound hearing loss. No impairments were detected in seven Risso's dolphins from three different stranding events, two pygmy killer whales, one Atlantic spotted dolphin, one spinner dolphin, or a juvenile Gervais' beaked whale. Hearing impairment could play a significant role in some cetacean stranding events, and the hearing of all cetaceans in rehabilitation should be tested