The efficiency of CD4 recruitment to ligand-engaged TCR controls the agonist/partial agonist properties of peptide-MHC molecule ligands.

One hypothesis seeking to explain the signaling and biological properties of T cell receptor for antigen (TCR) partial agonists and antagonists is the coreceptor density/kinetic model, which proposes that the pharmacologic behavior of a TCR ligand is largely determined by the relative rates of (a) dissociation ofligand from an engaged TCR and (b) recruitment oflck-linked coreceptors to this ligand-engaged receptor. Using several approaches to prevent or reduce the association of CD4 with occupied TCR, we demonstrate that consistent with this hypothesis, the biological and biochemical consequence of limiting this interaction is to convert typical agonists into partial agonist stimuli. Thus, adding anti-CD4 antibody to T cells recognizing a wild-type peptide-MHC class II ligand leads to disproportionate inhibition of interleukin-2 (IL-2) relative to IL-3 production, the same pattern seen using a TCR partial agonist/antagonist. In addition, T cells exposed to wild-type ligand in the presence of anti-CD4 antibodies show a pattern of TCR signaling resembling that seen using partial agonists, with predominant accumulation of the p21 tyrosine-phosphorylated form of TCR-zeta, reduced tyrosine phosphorylation of CD3epsilon, and no detectable phosphorylation of ZAP-70. Similar results are obtained when the wild-type ligand is presented by mutant class II MHC molecules unable to bind CD4. Likewise, antibody coligation of CD3 and CD4 results in an agonist-like phosphorylation pattern, whereas bivalent engagement of CD3 alone gives a partial agonist-like pattern. Finally, in accord with data showing that partial agonists often induce T cell anergy, CD4 blockade during antigen exposure renders cloned T cells unable to produce IL-2 upon restimulation. These results demonstrate that the biochemical and functional responses to variant TCR ligands with partial agonist properties can be largely reproduced by inhibiting recruitment of CD4 to a TCR binding a wild-type ligand, consistent with the idea that the relative rates of TCR-ligand disengagement and of association of engaged TCR with CD4 may play a key role in determining the pharmacologic properties of peptide-MHC molecule ligands. Beyond this insight into signaling through the TCR, these results have implications for models of thymocyte selection and the use of anti-coreceptor antibodies in vivo for the establishment ofimmunological tolerance

SYNTHESIS OF SULFUR-CONTAINED MICROCAPSULES AND POTENTIAL APPLICATION IN RUBBER

Microcapsule-based material is potentially utilized in a variety of fields such as pharmaceuticals, food, biology, self-healing materials, etc. More remarkedly, in the rubber-related fields, this outstanding material is able to have a crucial role to play as an alternative of sulfur in compounding and vulcanizing process with regard to the self-healing ability after cracking. In this research, the interface polymerization was applied to generate microcapsules, whose shell was synthesized from Urea-formaldehyde pre-polymer modified by 0.25 wt% melamine containing sulfur (S) as a core substance. When the synthesizing process was carried out at 80 C and stirring rate of 300 rpm in 2 hours, the microcapsule product was spherical with the average size of 115 m and contained 60% of core content that was examined by FTIR, DLS, SEM, TGA and experimented the potential application. As a result, the amount of 8 phr of produced microcapsules utilized in NBR rubber compounds necessitated a longer time to vulcanize rubber at 160 C  compared to using 5 phr free S. Besides, the mechanical strength of the microcapsules-contained product was insignificantly changed but bloom-like phenomenon on the rubber surface was markedly improved. It is noticeable that the vulcanized NBR rubber with the presence of these microcapsules are well able to heal its crack or cut when heated up to 150 C in 10 minutes while the free S-vulcanized NBR rubber is definitely unable to be self-healing in the same conditions

An imaging interferometry capability for the EISCAT Svalbard Radar.

Interferometric imaging (aperture synthesis imaging) is a technique used by radio astronomers to achieve angular resolution that far surpasses what is possible with a single large aperture. A similar technique has been used for radar imaging studies of equatorial ionospheric phenomena at the Jicamarca Radio Observatory. We present plans for adding an interferometric imaging capability to the EISCAT Svalbard Radar (ESR), a capability which will contribute significantly to several areas of active research, including naturally and artificially enhanced ion-acoustic echoes and their detailed relation in space and time to optical phenomena, polar mesospheric summer echoes (PMSE), and meteor studies. Interferometry using the two antennas of the ESR has demonstrated the existence of extremely narrow, fieldaligned scattering structures, but having only a single baseline is a severe limitation for such studies. Building additional IS-class antennas at the ESR is not a trivial task. However, the very high scattering levels in enhanced ion-acoustic echoes and PMSE means that a passive receiver antenna of more modest gain should still be capable of detecting these echoes. In this paper we present simulations of what an imaging interferometer will be capable of observing for different antenna configurations and brightness distributions, under ideal conditions, using two different image inversion algorithms. We also discuss different antenna and receiver technologies

Temporal fluctuation of multidrug resistant salmonella typhi haplotypes in the mekong river delta region of Vietnam.

BACKGROUND: typhoid fever remains a public health problem in Vietnam, with a significant burden in the Mekong River delta region. Typhoid fever is caused by the bacterial pathogen Salmonella enterica serovar Typhi (S. Typhi), which is frequently multidrug resistant with reduced susceptibility to fluoroquinolone-based drugs, the first choice for the treatment of typhoid fever. We used a GoldenGate (Illumina) assay to type 1,500 single nucleotide polymorphisms (SNPs) and analyse the genetic variation of S. Typhi isolated from 267 typhoid fever patients in the Mekong delta region participating in a randomized trial conducted between 2004 and 2005. PRINCIPAL FINDINGS: the population of S. Typhi circulating during the study was highly clonal, with 91% of isolates belonging to a single clonal complex of the S. Typhi H58 haplogroup. The patterns of disease were consistent with the presence of an endemic haplotype H58-C and a localised outbreak of S. Typhi haplotype H58-E2 in 2004. H58-E2-associated typhoid fever cases exhibited evidence of significant geo-spatial clustering along the Sông H u branch of the Mekong River. Multidrug resistance was common in the established clone H58-C but not in the outbreak clone H58-E2, however all H58 S. Typhi were nalidixic acid resistant and carried a Ser83Phe amino acid substitution in the gyrA gene. SIGNIFICANCE: the H58 haplogroup dominates S. Typhi populations in other endemic areas, but the population described here was more homogeneous than previously examined populations, and the dominant clonal complex (H58-C, -E1, -E2) observed in this study has not been detected outside Vietnam. IncHI1 plasmid-bearing S. Typhi H58-C was endemic during the study period whilst H58-E2, which rarely carried the plasmid, was only transient, suggesting a selective advantage for the plasmid. These data add insight into the outbreak dynamics and local molecular epidemiology of S. Typhi in southern Vietnam

The environmental impacts of different mask options for healthcare settings in the UK

During the COVID-19 pandemic, different strategies emerged to combat shortages of certified face masks used in the healthcare sector. These strategies included increasing production from the original manufacturing sites, commissioning new production facilities locally, exploring and allowing the reuse of single-use face masks via various decontamination methods, and developing reusable mask alternatives that meet the health and safety requirements set out in European Standards. In this article, we quantify and evaluate the life-cycle environmental impacts of selected mask options available for use by healthcare workers in the UK, with the objective of supporting decision- and policy-making. We investigate alternatives to traditional single-use face masks like surgical masks and respirators (or FFP3 masks), including cloth masks decontaminated in washing machines; FFP3 masks decontaminated via vapour hydrogen peroxide, and rigid half masks cleaned with antibacterial wipes. Our analysis demonstrates that: (1) the reuse options analysed are environmentally preferential to the traditional “use then dispose” of masks; (2) the environmental benefits increase with the number of reuses; and (3) the manufacturing location and the material composition of the masks have great influence over the life-cycle environmental impacts of each mask use option, in particular for single-use options

SYNTHESIS AND ANTIBACTERIAL ACTIVITY OF COMPOSITE BASED ON CHITOSAN-GRAFTED-(N-BUTYL ACRYLATE) AND SILVER NANOPARTICLES

It has been found for a long time that chitosan (CS) and silver nanoparticles (AgNPs) have outstanding antibacterial activities but there were some drawbacks restricting their wide utilization. In this research, CS modified is combined with AgNPs to expand applications and enhance the antibacterial activities. The colloid of CS and AgNPs (CS/Ag) was synthesized via chemical reduction while grafting copolymerization was carried out with monomer n-butyl acrylate (BA) and initiator tert-butyl hydroperoxide (TBHP) generating composite between CS-g-BA/Ag. The effects of parameters on synthesizing CS-g-BA/Ag composite were studied by determining the grafting percentage (G%) and grafting efficiency (E%)

The phase diagram of water from quantum simulations

The phase diagram of water has been calculated for the TIP4PQ/2005 model, an empirical rigid non-polarisable model. The path integral Monte Carlo technique was used, permitting the incorporation of nuclear quantum effects. The coexistence lines were traced out using the Gibbs-Duhem integration method, once having calculated the free energies of the liquid and solid phases in the quantum limit, which were obtained via thermodynamic integration from the classical value by scaling the mass of the water molecule. The resulting phase diagram is qualitatively correct, being displaced to lower temperatures by 15-20K. It is found that the influence of nuclear quantum effects are correlated to the tetrahedral order parameter.Comment: 10 pages, 6 figures, 1 tabl

Plasma cholesterol levels and brain development in preterm newborns.

BackgroundTo assess whether postnatal plasma cholesterol levels are associated with microstructural and macrostructural regional brain development in preterm newborns.MethodsSixty preterm newborns (born 24-32 weeks gestational age) were assessed using MRI studies soon after birth and again at term-equivalent age. Blood samples were obtained within 7 days of each MRI scan to analyze for plasma cholesterol and lathosterol (a marker of endogenous cholesterol synthesis) levels. Outcomes were assessed at 3 years using the Bayley Scales of Infant Development, Third Edition.ResultsEarly plasma lathosterol levels were associated with increased axial and radial diffusivities and increased volume of the subcortical white matter. Early plasma cholesterol levels were associated with increased volume of the cerebellum. Early plasma lathosterol levels were associated with a 2-point decrease in motor scores at 3 years.ConclusionsHigher early endogenous cholesterol synthesis is associated with worse microstructural measures and larger volumes in the subcortical white matter that may signify regional edema and worse motor outcomes. Higher early cholesterol is associated with improved cerebellar volumes. Further work is needed to better understand how the balance of cholesterol supply and endogenous synthesis impacts preterm brain development, especially if these may be modifiable factors to improve outcomes