IL-10 production in macrophages is regulated by a TLR-driven CREB-mediated mechanism that is linked to genes involved in cell metabolism

IL-10 is produced by macrophages in diverse immune settings and is critical in limiting immune-mediated pathology. In helminth infections, macrophages are an important source of IL-10; however, the molecular mechanism underpinning production of IL-10 by these cells is poorly characterized. In this study, bone marrow–derived macrophages exposed to excretory/secretory products released by Schistosoma mansoni cercariae rapidly produce IL-10 as a result of MyD88-mediated activation of MEK/ERK/RSK and p38. The phosphorylation of these kinases was triggered by TLR2 and TLR4 and converged on activation of the transcription factor CREB. Following phosphorylation, CREB is recruited to a novel regulatory element in the Il10 promoter and is also responsible for regulating a network of genes involved in metabolic processes, such as glycolysis, the tricarboxylic acid cycle, and oxidative phosphorylation. Moreover, skin-resident tissue macrophages, which encounter S. mansoni excretory/secretory products during infection, are the first monocytes to produce IL-10 in vivo early postinfection with S. mansoni cercariae. The early and rapid release of IL-10 by these cells has the potential to condition the dermal microenvironment encountered by immune cells recruited to this infection site, and we propose a mechanism by which CREB regulates the production of IL-10 by macrophages in the skin, but also has a major effect on their metabolic state

Rotation and mass of the sa galaxy, ngc 681

Rotation curve, mass distribution, and mass density of SA galaxy, NGC 68

CD4+ T cell hyporesponsiveness after repeated exposure to Schistosoma mansoni larvae is dependent upon interleukin-10

The effect that multiple percutaneous exposures to Schistosoma larvae has on the development of early CD4+ lymphocyte reactivity is unclear, yet it is important in the context of humans living in areas where schistosomiasis is endemic. In a murine model of multiple infections, we show that exposure of mice to repeated doses (4×) of Schistosoma mansoni cercariae, compared to a single dose (1×), results in CD4+ T cell hyporesponsiveness within the skin-draining lymph nodes (sdLN), manifested as reduced CD4+ cell proliferation and cytokine production. FoxP3+ CD4+ regulatory T cells were present in similar numbers in the sdLN of 4× and 1× mice and thus are unlikely to have a role in effecting hyporesponsiveness. Moreover, anergy of the CD4+ cell population from 4× mice was slight, as proliferation was only partly circumvented through the in vitro addition of exogenous interleukin-2 (IL-2), and the in vivo blockade of the regulatory molecule PD1 had a minimal effect on restoring responsiveness. In contrast, IL-10 was observed to be critical in mediating hyporesponsiveness, as CD4+ cells from the sdLN of 4× mice deficient for IL-10 were readily able to proliferate, unlike those from 4× wild-type cohorts. CD4+ cells from the sdLN of 4× mice exhibited higher levels of apoptosis and cell death, but in the absence of IL-10, there was significantly less cell death. Combined, our data show that IL-10 is a key factor in the development of CD4+ T cell hyporesponsiveness after repeated parasite exposure involving CD4+ cell apoptosis

Young Children with ASD Use Lexical and Referential Information During On-line Sentence Processing

Research with adults and older children indicates that verb biases are strong influences on listeners’ interpretations when processing sentences, but they can be overruled. In this paper, we ask two questions: (i) are children with Autism Spectrum Disorder (ASD) who are high functioning sensitive to verb biases like their same age typically developing peers?, and (ii) do young children with ASD and young children with typical development (TD) override strong verb biases to consider alternative interpretations of ambiguous sentences? Participants were aged 5–9 years (mean age 6.65 years): children with ASD who were high functioning and children with TD. In task 1, biasing and neutral verbs were included (e.g., eat cake versus move cake). In task 2, the focus was on whether the prepositional phrase occurring with an instrument biasing verb (e.g., ‘Chop the tree with the axe’) was interpreted as an instrument even if the named item was an implausible instrument (e.g., candle in ‘Cut the cake with the candle’). Overall, the results showed similarities between groups but the ASD group was generally slower. In task 1, both groups looked at the named object faster in the biasing than the non-biasing condition, and in the biasing condition the ASD group looked away from the target more quickly than the TD group. In task 2, both groups identified the target in the prepositional phrase. They were more likely to override the verb instrument bias and consider the alternative (modification) interpretation in the implausible condition (e.g., looking at the picture of a cake with a candle on it’). Our findings indicate that children of age 5 years and above can use context to override verb biases. Additionally, an important component of the sentence processing mechanism is largely intact for young children with ASD who are high functioning. Like children with TD, they draw on verb semantics and plausibility in integrating information. However, they are likely to be slower in processing the language they hear. Based on previous findings of associations between processing speed and cognitive functioning, the implication is that their understanding will be negatively affected, as will their academic outcomes

Characterization of the sources of protein-ligand affinity: 1-sulfonato-8-(1')anilinonaphthalene binding to intestinal fatty acid binding protein

1-Sulfonato-8-(1')anilinonaphthalene (1,8-ANS) was employed as a fluorescent probe of the fatty acid binding site of recombinant rat intestinal fatty acid binding protein (1-FABP). The enhancement of fluorescence upon binding allowed direct determination of binding affinity by fluorescence titration experiments, and measurement of the effects on that affinity of temperature, pH, and ionic strength. Solvent isotope effects were also determined. These data were compared to results from isothermal titration calorimetry. We obtained values for the enthalpy and entropy of this interaction at a variety of temperatures, and hence determined the change in heat capacity of the system consequent upon binding. The ANS-1-FABP is enthalpically driven; above approximately 14 degrees C it is entropically opposed, but below this temperature the entropy makes a positive contribution to the binding. The changes we observe in both enthalpy and entropy of binding with temperature can be derived from the change in heat capacity upon binding by integration, which demonstrates the internal consistency of our results. Bound ANS is displaced by fatty acids and can itself displace fatty acids bound to I-FABP. The binding site for ANS appears to be inside the solvent-containing cavity observed in the x-ray crystal structure, the same cavity occupied by fatty acid. From the fluorescence spectrum and from an inversion of the Debye-Hueckel formula for the activity coefficients as a function of added salt, we inferred that this cavity is fairly polar in character, which is in keeping with inferences drawn from the x-ray structure. The binding affinity of ANS is considered to be a consequence of both electrostatic and conditional hydrophobic effects. We speculate that the observed change in heat capacity is produced mainly by the displacement of strongly hydrogen-bonded waters from the protein cavity

Unexpected benefits of pre-university skills training for A-level students

First-year undergraduates can find the transition from the prescriptive learning environment at school to one of self-directed learning at university, a considerable challenge. A Pre-university Skills Course (PSC) was developed to address this issue by preparing sixth formers for the university learning style. It was piloted with students in the year prior to A-level examinations at a selective state-funded school in East Anglia. The present paper examines the effect of the course on the students’ A-level tariff. Chi-squared analysis of A-level grades of students with comparable GCSE results, indicate that students who undertook the PSC performed significantly better in their A-level results than those who did not. These data demonstrate how skills training might improve A-level performance and assist in the transition to university

Nurses\u27 Alumnae Association Bulletin - Volume 5 Number 8

Calling All Nurses Financial Report Calendar of Events Lest You Forget! Attention Review of the Alumnae Association Meetings President\u27s Report Barton Memorial Division Oxygen Therapy Welcome, White Haven Alumnae Clinical Use of Penicillin in Infections of the Ears, Nose and Throat Address - Graduation of Nurses, 1945 Miscellaneous Items The Blood that Kills The Story of Malaria Program Prizes - May, 1946 Capping Exercises The Economic Security Program of the Pennsylvania State Nurses\u27 Association The Clara Melville Scholarship Fund Card of Thanks The Poet\u27s Corner The Hospital Pharmacy Jefferson Medical College Hospital School of Nursing Faculty Jefferson Hospital Gray Lady Unite, A.R.R. The Volunteer Nurses\u27 Aides Salute Jefferson Nurses Changes in the Staff at Jefferson Hospital Red Cross Recruits Did You Know That The Pennsylvania Nurse Medical College News Magazine and Newspaper Items Central Dressing Room and Transfusion Unit Rules Concerning Central Dressing Room Radios and Electrical Appliances Attending College Nurses in Anesthesia Condolences Marriages New Arrivals Deaths The Bulletin Committee Attention, Alumnae New Addresse

Nurses\u27 Alumnae Association Bulletin, April 1961

Alumnae Meetings 1960 Social Committee Clara Melville Scholarship Fund Bulletin Committee Private Duty Nurse\u27s Section Report of the School of Nursing and Nursing Service Staff Nurses Association Student Activities Personal Items of Interest Expansion of Jefferson Artificial Kidney Unit Medical Work in the Congo Marriages New Arrivals Necrology Annual Giving Fun