HSP60 as a Target of Anti-Ergotypic Regulatory T Cells

The 60 kDa heat shock protein (HSP60) has been reported to influence T-cell responses in two ways: as a ligand of toll-like receptor 2 signalling and as an antigen. Here we describe a new mechanism of T-cell immuno-regulation focused on HSP60: HSP60 is up-regulated and presented by activated T cells (HSP60 is an ergotope) to regulatory (anti-ergotypic) T cells. Presentation of HSP60 by activated T cells was found to be MHC-restricted and dependent on accessory molecules - CD28, CD80 and CD86. Anti-ergotypic T cells responded to T-cell HSP60 by proliferation and secreted IFNγ and TGFβ1. In vitro, the anti-ergotypic T cells inhibited IFNγ production by their activated T-cell targets. In vivo, adoptive transfer of an anti-ergotypic HSP60-specific T-cell line led to decreased secretion of IFNγ by arthritogenic T cells and ameliorated adjuvant arthritis (AA). Thus, the presentation of HSP60 by activated T cells turns them into targets for anti-ergotypic regulatory T cells specific for HSP60. However, the direct interaction between the anti-ergotypic T regulators (anti-HSP60) and the activated T cells also down-regulated the regulators. Thus, by functioning as an ergotope, HSP60 can control both the effector T cells and the regulatory HSP60-specific T cells that control them

Agenda pública arquitectura, ciudad, desarrollo

El contenido de “AGENDA PÚBLICA” constituye el cierre del trabajo realizado en Revista Cientodiez entre los años 2006 y 2009. La motivación detrás de este proceso consistió en tender puentes entre problemáticas inicialmente surgidas en el campo disciplinar de la arquitectura, para avanzar hacia la construcción de agendas de desarrollo. El esfuerzo se concentró en dar algunos esbozos de respuesta a las demandas que estas agendas presentan para todos quienes aspiramos a participar y aportar en ellas

Network Theory Analysis of Antibody-Antigen Reactivity Data: The Immune Trees at Birth and Adulthood

Motivation: New antigen microarray technology enables parallel recording of antibody reactivities with hundreds of antigens. Such data affords system level analysis of the immune system’s organization using methods and approaches from network theory. Here we measured the reactivity of 290 antigens (for both the IgG and IgM isotypes) of 10 healthy mothers and their term newborns. We constructed antigen correlation networks (or immune networks) whose nodes are the antigens and the edges are the antigen-antigen reactivity correlations, and we also computed their corresponding minimum spanning trees (MST) – maximal information reduced sub-graphs. We quantify the network organization (topology) in terms of the network theory divergence rate measure and rank the antigen importance in the full antigen correlation networks by the eigen-value centrality measure. This analysis makes possible the characterization and comparison of the IgG and IgM immune networks at birth (newborns) and adulthood (mothers) in terms of topology and node importance. Results: Comparison of the immune network topology at birth and adulthood revealed partial conservation of the IgG immune network topology, and significant reorganization of the IgM immune networks. Inspection of the antigen importance revealed some dominant (in terms of high centrality) antigens in the IgG and IgM networks at birth, which retain their importance at adulthood

Environmentally friendly analysis of emerging contaminants by pressurized hot water extraction-stir bar sorptive extraction-derivatization and gas chromatography-mass spectrometry

This work describes the development, optimiza- tion, and validation of a new method for the simultaneous determination of a wide range of pharmaceuticals (beta- blockers, lipid regulators ... ) and personal care products (fragrances, UV filters, phthalates ... ) in both aqueous and solid environmental matrices. Target compounds were extracted from sediments using pressurized hot water ex- traction followed by stir bar sorptive extraction. The first stage was performed at 1,500 psi during three static extrac- tion cycles of 5 min each after optimizing the extraction temperature (50 – 150 °C) and addition of organic modifiers (% methanol) to water, the extraction solvent. Next, aqueous extracts and water samples were processed using polydime- thylsiloxane bars. Several parameters were optimized for this technique, including extraction and desorption time, ionic strength, presence of organic modifiers, and pH. Fi- nally, analytes were extracted from the bars by ultrasonic irradiation using a reduced amount of solvent (0.2 mL) prior to derivatization and gas chromatography – mass spectrome- try analysis. The optimized protocol uses minimal amounts of organic solvents (<10 mL/sample) and time ( ≈ 8 h/sam- ple) compared to previous ex isting methodologies. Low standard deviation (usually below 10 %) and limits of de- tection (sub-ppb) vouch for the applicability of the method- ology for the analysis of target compounds at trace levels. Once developed, the method was applied to determin

A Ks-band-selected catalogue of objects in the ALHAMBRA survey

The original ALHAMBRA catalogue contained over 400,000 galaxies selected using a synthetic F814W image, to the magnitude limit AB(F814W)$\approx$24.5. Given the photometric redshift depth of the ALHAMBRA multiband data (=0.86) and the approximately $I$-band selection, there is a noticeable bias against red objects at moderate redshift. We avoid this bias by creating a new catalogue selected in the $K_s$ band. This newly obtained catalogue is certainly shallower in terms of apparent magnitude, but deeper in terms of redshift, with a significant population of red objects at $z>1$. We select objects using the $K_s$ band images, which reach an approximate AB magnitude limit $K_s \approx 22$. We generate masks and derive completeness functions to characterize the sample. We have tested the quality of the photometry and photometric redshifts using both internal and external checks. Our final catalogue includes $\approx 95,000$ sources down to $K_s \approx 22$, with a significant tail towards high redshift. We have checked that there is a large sample of objects with spectral energy distributions that correspond to that of massive, passively evolving galaxies at $z > 1$, reaching as far as $z \approx 2.5$. We have tested the possibility of combining our data with deep infrared observations at longer wavelengths, particularly Spitzer IRAC data

Pain Coping Skills Training for African Americans With Osteoarthritis Study: Baseline Participant Characteristics and Comparison to Prior Studies

Background: The Pain Coping Skills Training for African Americans with OsteoaRTthritis (STAART) trial is examining the effectiveness of a culturally enhanced pain coping skills training (CST) program for African Americans with osteoarthritis (OA). This disparities-focused trial aimed to reach a population with greater symptom severity and risk factors for poor pain-related outcomes than previous studies. This paper compares characteristics of STAART participants with prior studies of CST or cognitive behavioral therapy (CBT)-informed training in pain coping strategies for OA. Methods: A literature search identified 10 prior trials of pain CST or CBT-informed pain coping training among individuals with OA. We descriptively compared characteristics of STAART participants with other studies, in 3 domains of the National Institutes of Minority Health and Health Disparities' Research Framework: Sociocultural Environment (e.g., age, education, marital status), Biological Vulnerability and Mechanisms (e.g, pain and function, body mass index), and Health Behaviors and Coping (e.g., pain catastrophizing). Means and standard deviations (SDs) or proportions were calculated for STAART participants and extracted from published manuscripts for comparator studies. Results: The mean age of STAART participants, 59 years (SD = 10.3), was lower than 9 of 10 comparator studies; the proportion of individuals with some education beyond high school, 75%, was comparable to comparator studies (61-86%); and the proportion of individuals who are married or living with a partner, 42%, was lower than comparator studies (62-66%). Comparator studies had less than about 1/3 African American participants. Mean scores on the Western Ontario and McMaster Universities Osteoarthritis Index pain and function scales were higher (worse) for STAART participants than for other studies, and mean body mass index of STAART participants, 35.2 kg/m2 (SD = 8.2), was higher than all other studies (30-34 kg/m2). STAART participants' mean score on the Pain Catastrophizing scale, 19.8 (SD = 12.3), was higher (worse) than other studies reporting this measure (7-17). Conclusions: Compared with prior studies with predominantly white samples, STAART participants have worse pain and function and more risk factors for negative pain-related outcomes across several domains. Given STAART participants' high mean pain catastrophizing scores, this sample may particularly benefit from the CST intervention approach

B-cell-specific checkpoint molecules that regulate anti-tumour immunity.

The role of B cells in anti-tumour immunity is still debated and, accordingly, immunotherapies have focused on targeting T and natural killer cells to inhibit tumour growth1,2. Here, using high-throughput flow cytometry as well as bulk and single-cell RNA-sequencing and B-cell-receptor-sequencing analysis of B cells temporally during B16F10 melanoma growth, we identified a subset of B cells that expands specifically in the draining lymph node over time in tumour-bearing mice. The expanding B cell subset expresses the cell surface molecule T cell immunoglobulin and mucin domain 1 (TIM-1, encoded by Havcr1) and a unique transcriptional signature, including multiple co-inhibitory molecules such as PD-1, TIM-3, TIGIT and LAG-3. Although conditional deletion of these co-inhibitory molecules on B cells had little or no effect on tumour burden, selective deletion of Havcr1 in B cells both substantially inhibited tumour growth and enhanced effector T cell responses. Loss of TIM-1 enhanced the type 1 interferon response in B cells, which augmented B cell activation and increased antigen presentation and co-stimulation, resulting in increased expansion of tumour-specific effector T cells. Our results demonstrate that manipulation of TIM-1-expressing B cells enables engagement of the second arm of adaptive immunity to promote anti-tumour immunity and inhibit tumour growth

Controlling Viral Immuno-Inflammatory Lesions by Modulating Aryl Hydrocarbon Receptor Signaling

Ocular herpes simplex virus infection can cause a blinding CD4+ T cell orchestrated immuno-inflammatory lesion in the cornea called Stromal Keratitis (SK). A key to controlling the severity of SK lesions is to suppress the activity of T cells that orchestrate lesions and enhance the representation of regulatory cells that inhibit effector cell function. In this report we show that a single administration of TCDD (2, 3, 7, 8- Tetrachlorodibenzo-p-dioxin), a non-physiological ligand for the AhR receptor, was an effective means of reducing the severity of SK lesions. It acted by causing apoptosis of Foxp3- CD4+ T cells but had no effect on Foxp3+ CD4+ Tregs. TCDD also decreased the proliferation of Foxp3- CD4+ T cells. The consequence was an increase in the ratio of Tregs to T effectors which likely accounted for the reduced inflammatory responses. In addition, in vitro studies revealed that TCDD addition to anti-CD3/CD28 stimulated naïve CD4+ T cells caused a significant induction of Tregs, but inhibited the differentiation of Th1 and Th17 cells. Since a single TCDD administration given after the disease process had been initiated generated long lasting anti-inflammatory effects, the approach holds promise as a therapeutic means of controlling virus induced inflammatory lesions

Insect-Specific microRNA Involved in the Development of the Silkworm Bombyx mori

MicroRNAs (miRNAs) are endogenous non-coding genes that participate in post-transcription regulation by either degrading mRNA or blocking its translation. It is considered to be very important in regulating insect development and metamorphosis. We conducted a large-scale screening for miRNA genes in the silkworm Bombyx mori using sequence-by-synthesis (SBS) deep sequencing of mixed RNAs from egg, larval, pupal, and adult stages. Of 2,227,930 SBS tags, 1,144,485 ranged from 17 to 25 nt, corresponding to 256,604 unique tags. Among these non-redundant tags, 95,184 were matched to the silkworm genome. We identified 3,750 miRNA candidate genes using a computational pipeline combining RNAfold and TripletSVM algorithms. We confirmed 354 miRNA genes using miRNA microarrays and then performed expression profile analysis on these miRNAs for all developmental stages. While 106 miRNAs were expressed in all stages, 248 miRNAs were egg- and pupa-specific, suggesting that insect miRNAs play a significant role in embryogenesis and metamorphosis. We selected eight miRNAs for quantitative RT-PCR analysis; six of these were consistent with our microarray results. In addition, we searched for orthologous miRNA genes in mammals, a nematode, and other insects and found that most silkworm miRNAs are conserved in insects, whereas only a small number of silkworm miRNAs has orthologs in mammals and the nematode. These results suggest that there are many miRNAs unique to insects