Engagement of OX40 enhances antigen-specific CD4(+) T cell mobilization/memory development and humoral immunity: comparison of alphaOX-40 with alphaCTLA-4.

Increasing the long-term survival of memory T cells after immunization is key to a successful vaccine. In the past, the generation of large numbers of memory T cells in vivo has been difficult because Ag-stimulated T cells are susceptible to activation-induced cell death. Previously, we reported that OX40 engagement resulted in a 60-fold increase in the number of Ag-specific CD4(+) memory T cells that persisted 60 days postimmunization. In this report, we used the D011.10 adoptive transfer model to examine the kinetics of Ag-specific T cell entry into the peripheral blood, the optimal route of administration of Ag and alphaOX40, and the Ag-specific Ab response after immunization with soluble OVA and alphaOX40. Finally, we compared the adjuvant properties of alphaOX40 to those of alphaCTLA-4. Engagement of OX-40 in vivo was most effective when the Ag was administered s.c. Time course studies revealed that it was crucial for alphaOX40 to be delivered within 24-48 h after Ag exposure. Examination of anti-OVA Ab titers revealed a 10-fold increase in mice that received alphaOX40 compared with mice that received OVA alone. Both alphaOX40 and alphaCTLA-4 increased the percentage of OVA-specific CD4(+) T cells early after immunization (day 4), but alphaOX40-treated mice had much higher percentages of OVA-specific memory CD4(+) T cells from days 11 to 29. These studies demonstrate that OX40 engagement early after immunization with soluble Ag enhances long-term T cell and humoral immunity in a manner distinct from that provided by blocking CTLA-4.     

The activity of ant product of the Salmonella phage P22 against the closely related but heteroimmune phage L.

Summary P22 mutants defective in the early gene 24 are complemented by phage L in mixed infection. P22 12 ^- and P22 23 ^- mutants are not complemented by phage L. Gene function 24 of an L prophage is turned on by a superinfecting P22 24 ^- mutant and complements the missing function of the defective P22 phage. Since this transactivation of prophage gene 24 depends on a functional gene ant in the superinfecting P22 mutant, it indicates derepression for leftward directed gene expression in prophage L. On the contrary neither the rightward directed expression of gene 12 nor of gene 23 in prophage L can be turned on by superinfecting P22 24 ^- 12 ^- or P22 24 ^- 23 ^- mutants (and also not by P22 12 ^- and P22 23 ^-) to a degree sufficient for complementation of simultaneously superinfecting L virB 12 ^- or L virB 23 ^- mutants. The failure to detect release of repression for rightward directed gene expression of prophage L corresponds to the earlier observation (Prell, 1975) that P22 superinfecting L lysogens cannot release replication inhibition for simultaneously infecting phage L. The results are discussed with respect to the mechanism underlying the different action of P22 antirepressor in L and in P22 lysogens.     

Impact of bio-augmentation with Sphingomonas sp. strain TTNP3 in membrane bioreactors degrading nonylphenol

This study evaluates the potential of bio-augmentation to improve the degradation of recalcitrant nonylphenol during the wastewater treatment in membrane bioreactors (MBR). One MBR containing activated sludge was bio-augmented using multistep inoculation with freeze dried Sphingomonas sp. strain TTNP3, whereas a second control reactor contained activated sludge solely. The ¹⁴C-labeled-nonylphenol isomer (4-[1-ethyl-1,3-dimethylpentyl]phenol) was applied as a single pulse. Bio-augmentation resulted in an immediate increase of dissolved radioactivity in the effluent in comparison to the control reactor (13% and 2% of initially applied radioactivity after 1 day, respectively). After 5 days of operation, the retentate of the bio-augmented reactor contained only 7% of the initial radioactivity in contrast to 50% in the control reactor. The radioactivity associated to the mixed liquor suspended solids, i.e., the suspension of biomass and other solids on the retentate side of the membrane, was mainly found as non-extractable residues that were increasingly formed during prolonged reactor operation, especially for the control MBR. HPLC-LSC and GC-MSⁿ analyses revealed that the bio-augmented reactor produced more polar hydroquinone as main degradation intermediate, whereas the control reactor effluent contained a complex mixture of apolar compounds with shortened oxidized alkyl chains. Thus, the apparent differences in the behavior of nonylphenol between the reactors were due to the catabolism of nonylphenol conferred by bio-augmentation with Sphingomonas sp. strain TTNP3. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Relation between Px phages and generalised transducing particles of phage P22

Summary P22 mutants with an altered ability to form generalised transducing particles were tested for their ability to form the hybrid Px phages during growth on Py-lysogenic strains of Salmonella typhimurium. The mutant which produces more (less) transducing particles produces also more (less) Px phages. It is suggested that Px particles might be regarded as self-replicating generalised transducing particles.     

Direct utilization of mannose for mammalian glycoprotein biosynthesis

Direct utilization of mannose for glycoprotein biosynthesis has not been studied because cellular mannose is assumed to be derived entirely from glucose. However, animal sera contain sufficient mannose to force uptake through glucose-tolerant, mannose-specific transporters. Under physiological conditions this transport system provides 75% of the mannose for protein glycosylation in human hepatoma cells despite a 50- to 100-fold higher concentration of glucose. This suggests that direct use of mannose is more important than conversion from glucose. Consistent with this finding the liver is low in phosphomannose isomerase activity (fructose-6-P<->mannose-6-P), the key enzyme for supplying glucose-derived mannose to the N-glycosylation pathway. [2- 3H] Mannose is rapidly absorbed from the intestine of anesthetized rats and cleared from the blood with a t1/2of 30 min. After a 30 min lag, label is incorporated into plasma glycoproteins, and into glycoproteins of all organs during the first hour. Most (87%) of the initial incorporation occurs in the liver, but this decreases as radiolabeled plasma glycoproteins increase. Radiolabel in glycoproteins also increases 2- to 6-fold in other organs between 1-8 h, especially in lung, skeletal muscle, and heart. These organs may take up hepatic- derived radiolabeled plasma glycoproteins. Significantly, the brain, which is not exposed to plasma glycoproteins, shows essentially no increase in radiolabel. These results suggest that mammals use mannose transporters to deliver mannose from blood to the liver and other organs for glycoprotein biosynthesis. Additionally, contrary to expectations, most of the mannose for glycoprotein biosynthesis in cultured hepatoma cells is derived from mannose, not glucose. Extracellular mannose may also make a significant contribution to glycoprotein biosynthesis in the intact organism.      

Ant-mediated inactivation of Salmonella phage L-specified repression at OR of prophage L.

Summary Ant product of phage P22 inactivates repression of prophage L at the right-hand operator o_R and allows for transactivation of prophage gene 12. The transactivation efficiency observed with a series of phage and prophage recombinants, using single superinfection of a lysogenic bacterium, is about the same as that recently observed at o_L of prophage L. This finding is in contrast to the failure to demonstrate derepression at o_R of prophage L in an experimental system employing double superinfection (Prell, 1978a). The reasons for the differing results are discussed and it is shown that derepression by the ant product in trans at o_R of the prophage is not modified to any significant degree by the immunity specificity (L or P22) of the prophage or of the superinfecting phage.     

Inequalities in Global Trade: A Cross-Country Comparison of Trade Network Position,Economic Wealth,Pollution and Mortality

In this paper we investigate how structural patterns of international trade give rise to emissions inequalities across countries, and how such inequality in turn impact countries’ mortality rates. We employ Multi-regional Input-Output analysis to distinguish between sulfur-dioxide (SO2) emissions produced within a country’s boarders (production-based emissions) and emissions triggered by consumption in other countries (consumption-based emissions). We use social network analysis to capture countries’ level of integration within the global trade network. We then apply the Prais-Winsten panel estimation technique to a panel data set across 172 countries over 20 years (1990–2010) to estimate the relationships between countries’ level of integration and SO2 emissions, and the impact of trade integration and SO2 emission on mortality rates. Our findings suggest a positive, (log-) linear relationship between a country’s level of integration and both kinds of emissions. In addition, although more integrated countries are mainly responsible for both forms of emissions, our findings indicate that they also tend to experience lower mortality rates. Our approach offers a unique combination of social network analysis with multiregional input-output analysis, which better operationalizes intuitive concepts about global trade and trade structure.     

Susceptibility-Weighted Imaging Provides Insight into White Matter Damage in Amyotrophic Lateral Sclerosis

Background

Amyotrophic lateral sclerosis (ALS) is a fatal, progressive neurodegenerative disorder, characterised by widespread white matter damage. There is growing evidence that disturbances in iron metabolism contribute to white matter alterations.

Materials & Methods

We analysed the data of susceptibility-weighted imaging (SWI) of white matter in a cohort of 27 patients with ALS and 30 healthy age-matched controls.

Results

Signal alterations were found on SWI in the corpus callosum; along the corticospinal tract (subcortical motor cortex, posterior limb of the internal capsule and brainstem levels) and in the subgyral regions of frontal, parietal, temporal, occipital and limbic lobes. Alterations of white matter in the corpus callosum correlated with disease severity as assessed by the revised ALS functional rating scale.

Conclusion

SWI is capable of indicating iron and myelin disturbances in white matter of ALS patients. The SWI patterns observed in this study suggest that widespread alterations due to iron disturbances occur in patients with ALS and correlate with disease severity.