Dendritic Cell PD-L1 Limits Autoimmunity and Follicular T Cell Differentiation and Function.

The programmed death (PD)-1 coinhibitory receptor regulates the balance between T cell activation and tolerance. Although the PD-1 ligands, PD-L1 and PD-L2, are expressed on a variety of cell types, the cell type-specific functions of PD-1 ligands in inducing signals through PD-1 are unknown. In this study, we use PD-L1 conditional knockout mice to investigate the cell type-specific functions of PD-L1.

Using a modified Delphi methodology to gain consensus on the use of dressings in chronic wounds management.

Objective: Managing chronic wounds is associated with a burden to patients, caregivers, health services and society and there is a lack of clarity regarding the role of dressings in improving outcomes. This study aimed to provide understanding on a range of topics, including: the definition of chronicity in wounds, the burden of illness, clinical outcomes of reducing healing time and the impact of early interventions on clinical and economic outcomes and the role of matrix metalloproteinases (MMPs) in wound healing.

Method: A systematic review of the literature was carried out on the role of dressings in diabetic foot ulcer (DFU), and venous leg ulcer (VLU) management strategies, their effectiveness, associated resource use/cost, and quality of life (QoL) impact on patients.

Society of Behavioral Medicine (SBM) position statement: Increasing funding for the NIH OBSSR to promote timely and effective behavioral medicine research.

Chronic diseases are a leading cause of morbidity and mortality in the USA. Most chronic diseases have behavioral risk factors that can improve health and quality of life and reduce financial burdens. Improved methods of measurement and behavioral interventions are rapidly progressing.

High-density genetic mapping of a major QTL for resistance to multiple races of loose smut in a tetraploid wheat cross.

Loose smut, caused by Ustilago tritici (Pers.) Rostr., is a systemic disease of tetraploid durum wheat (Triticum turgidum L.

Genome re-sequencing and simple sequence repeat markers reveal the existence of divergent lineages in the Canadian Puccinia striiformis f. sp. tritici population with extensive DNA methylation.

Wheat stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), is an important disease in Canada.

Correlation between MEK signature and Ras gene alteration in advanced gastric cancer.

MEK inhibitor (selumetinib) is a potent, orally active inhibitor of MAPK/ERK pathway. It is important to develop an accurate and robust method indicative of RAS pathway activity to stratify potential patients who can benefit from selumetinib treatment in gastric cancer (GC). First, we surveyed the sensitivity to selumetinib in a panel of 22 GC cell lines and correlated with MEK signature to selumetinib sensitivity.

Antagonism of Neurotensin Receptors in the Ventral Tegmental Area Decreases Methamphetamine Self-Administration and Methamphetamine Seeking in Mice.

Background: Neurotensin is a peptide that modulates central dopamine neurotransmission and dopamine-related behaviors. Methamphetamine self-administration increases neurotensin levels in the ventral tegmental area, but the consequences for self-administration behavior have not been described. Here we test the hypothesis that antagonizing neurotensin receptors in the ventral tegmental area attenuates the acquisition of methamphetamine self-administration and methamphetamine intake.

PD-L1 Prevents the Development of Autoimmune Heart Disease in Graft-versus-Host Disease.

Effector memory T cells (T) are less capable of inducing graft-versus-host disease (GVHD) compared with naive T cells (T). Previously, in the TS1 TCR transgenic model of GVHD, wherein TS1 CD4 cells specific for a model minor histocompatibility Ag (miHA) induce GVHD in miHA-positive recipients, we found that cell-intrinsic properties of TS1 T reduced their GVHD potency relative to TS1 T Posttransplant, TS1 T progeny expressed higher levels of PD-1 than did TS1 T progeny, leading us to test the hypothesis that T induce less GVHD because of increased sensitivity to PD-ligands. In this study, we tested this hypothesis and found that indeed TS1 T induced more severe skin and liver GVHD in the absence of PD-ligands.

Correction to: Abstracts : 29th European Congress of Pathology.

Due to an error with the registration system, the following abstract was regrettably omitted from the Poster Sessions. The abstract should have been included as PS-10-021 and displayed on page S166.

B Cells Drive Autoimmunity in Mice with CD28-Deficient Regulatory T Cells.

Follicular regulatory T (T) cells are a newly defined regulatory T cell (Treg) subset that suppresses follicular helper T cell-mediated B cell responses in the germinal center reaction. The precise costimulatory signal requirements for proper T cell differentiation and function are still not known. Using conditional knockout strategies of CD28, we previously demonstrated that loss of CD28 signaling in Tregs caused autoimmunity in mice (termed CD28-ΔTreg mice), characterized by lymphadenopathy, accumulation of activated T cells, and cell-mediated inflammation of the skin and lung.

Experimental measurement-device-independent quantum digital signatures.

The development of quantum networks will be paramount towards practical and secure telecommunications. These networks will need to sign and distribute information between many parties with information-theoretic security, requiring both quantum digital signatures (QDS) and quantum key distribution (QKD). Here, we introduce and experimentally realise a quantum network architecture, where the nodes are fully connected using a minimum amount of physical links.

The diverse functions of the PD1 inhibitory pathway.

T cell activation is a highly regulated process involving peptide-MHC engagement of the T cell receptor and positive costimulatory signals. Upon activation, coinhibitory 'checkpoints', including programmed cell death protein 1 (PD1), become induced to regulate T cells. PD1 has an essential role in balancing protective immunity and immunopathology, homeostasis and tolerance.

Targeted reconstruction of T cell receptor sequence from single cell RNA-seq links CDR3 length to T cell differentiation state.

The T cell compartment must contain diversity in both T cell receptor (TCR) repertoire and cell state to provide effective immunity against pathogens. However, it remains unclear how differences in the TCR contribute to heterogeneity in T cell state. Single cell RNA-sequencing (scRNA-seq) can allow simultaneous measurement of TCR sequence and global transcriptional profile from single cells.

Workshop on challenges, insights, and future directions for mouse and humanized models in cancer immunology and immunotherapy: a report from the associated programs of the 2016 annual meeting for the Society for Immunotherapy of cancer.

Understanding how murine models can elucidate the mechanisms underlying antitumor immune responses and advance immune-based drug development is essential to advancing the field of cancer immunotherapy. The Society for Immunotherapy of Cancer (SITC) convened a workshop titled, "Challenges, Insights, and Future Directions for Mouse and Humanized Models in Cancer Immunology and Immunotherapy" as part of the SITC 31st Annual Meeting and Associated Programs on November 10, 2016 in National Harbor, MD. The workshop focused on key issues in optimizing models for cancer immunotherapy research, with discussions on the strengths and weaknesses of current models, approaches to improve the predictive value of mouse models, and advances in cancer modeling that are anticipated in the near future.

The temperature of storage of a batch of wheat distillers dried grains with solubles samples on their nutritive value for broilers.

1. A batch of wheat distillers dried grains with solubles (DDGS) was obtained immediately after production and was separated into 5 equal parts and placed in woven polypropylene sacks. The samples were stored under 5 different temperature conditions for 1 year as follows: kept at a constant -20°C; kept at -20°C for 24 h period and after that kept at a constant +4°C; kept at a constant +4°C only; kept at a constant +15°C; stored at ambient temperature (range of weekly mean temperatures was from +4 to +22°C).

Quantitative trait loci for resistance to stripe rust of wheat revealed using global field nurseries and opportunities for stacking resistance genes.

Quantitative trait loci controlling stripe rust resistance were identified in adapted Canadian spring wheat cultivars providing opportunity for breeders to stack loci using marker-assisted breeding. Stripe rust or yellow rust, caused by Puccinia striiformis Westend. f.

In vivo CRISPR screening identifies Ptpn2 as a cancer immunotherapy target.

Immunotherapy with PD-1 checkpoint blockade is effective in only a minority of patients with cancer, suggesting that additional treatment strategies are needed. Here we use a pooled in vivo genetic screening approach using CRISPR-Cas9 genome editing in transplantable tumours in mice treated with immunotherapy to discover previously undescribed immunotherapy targets. We tested 2,368 genes expressed by melanoma cells to identify those that synergize with or cause resistance to checkpoint blockade.

Systemic PD149163, a neurotensin receptor 1 agonist, decreases methamphetamine self-administration in DBA/2J mice without causing excessive sedation.

Methamphetamine (METH) is a psychostimulant that exhibits significant abuse potential. Although METH addiction is a major health and societal concern, no drug is currently approved for its therapeutic management. METH activates the central dopaminergic "reward" circuitry, and with repeated use increases levels of the neuromodulatory peptide neurotensin in the nucleus accumbens and ventral tegmental area.

Wild emmer genome architecture and diversity elucidate wheat evolution and domestication.

Wheat ( spp.) is one of the founder crops that likely drove the Neolithic transition to sedentary agrarian societies in the Fertile Crescent more than 10,000 years ago. Identifying genetic modifications underlying wheat's domestication requires knowledge about the genome of its allo-tetraploid progenitor, wild emmer ( ssp.

Nucleic acid extraction from formalin-fixed paraffin-embedded cancer cell line samples: a trade off between quantity and quality?

Background: Advanced genomic techniques such as Next-Generation-Sequencing (NGS) and gene expression profiling, including NanoString, are vital for the development of personalised medicines, as they enable molecular disease classification. This has become increasingly important in the treatment of cancer, aiding patient selection. However, it requires efficient nucleic acid extraction often from formalin-fixed paraffin-embedded tissue (FFPE).

Reproductive outcome following pre-implantation genetic diagnosis (PGD) in the UK.

In 2013, the National Health Service Commissioning board centralized the funding in England for up to three cycles of pre-implantation genetic diagnosis (PGD) for couples who have, or are carriers of, a specific genetic disorder. This study presents the historical data of PGD cycles and their clinical outcomes in UK as extrapolated from the national data registry. Retrospective analysis of outcome of cycles undergoing pre-implantation genetic diagnosis in the UK over the past 20 years was performed from the Human Fertilisation and Embryology Authority database (n = 2974).

The microRNA miR-31 inhibits CD8 T cell function in chronic viral infection.

During infection, antigen-specific T cells undergo tightly regulated developmental transitions controlled by transcriptional and post-transcriptional regulation of gene expression. We found that the microRNA miR-31 was strongly induced by activation of the T cell antigen receptor (TCR) in a pathway involving calcium and activation of the transcription factor NFAT. During chronic infection with lymphocytic choriomeningitis virus (LCMV) clone 13, miR-31-deficent mice recovered from clinical disease, while wild-type mice continued to show signs of disease.