Adenosine Uptake through the Nucleoside Transporter ENT1 Suppresses Antitumor Immunity and T Cell Pyrimidine Synthesis.

Immunosuppression by adenosine is an important cancer immune checkpoint. Extracellular adenosine signals through specific receptors and can be transported across the cell membrane through nucleoside transporters. While adenosine receptors are well-known to regulate tumor immunity, the impact of adenosine transporters remains unexplored.

Automated informatics may increase the detection rate of suspicious cases of human trafficking-a preliminary study.

Objectives: Worldwide, there is an estimated 40.3 million victims trapped in modern day slavery, including 24.9 million in forced labor and 15.

Adenosine A2A receptor is a tumor suppressor of NASH-associated hepatocellular carcinoma.

Inhibition of adenosine A2A receptor (A2AR) is a promising approach for cancer immunotherapy currently evaluated in several clinical trials. We here report that anti-obesogenic and anti-inflammatory functions of A2AR, however, significantly restrain hepatocellular carcinoma (HCC) development. Adora2a deletion in mice triggers obesity, non-alcoholic steatohepatitis (NASH), and systemic inflammation, leading to spontaneous HCC and promoting dimethylbenzyl-anthracene (DMBA)- or diethylnitrosamine (DEN)-induced HCC.

The CD73 immune checkpoint promotes tumor cell metabolic fitness.

CD73 is an ectonucleotidase overexpressed on tumor cells that suppresses anti-tumor immunity. Accordingly, several CD73 inhibitors are currently being evaluated in the clinic, including in large randomized clinical trials. Yet, the tumor cell-intrinsic impact of CD73 remain largely uncharacterized.

Immunogen-Specific Strengths and Limitations of the Activation-Induced Marker Assay for Assessing Murine Antigen-Specific CD4+ T Cell Responses.

The activation-induced marker (AIM) assay is a cytokine-independent technique to identify Ag-specific T cells based on the upregulated expression of activation markers after Ag restimulation. The method offers an alternative to intracellular cytokine staining in immunological studies, in which limited cytokine production makes the cell subsets of interest difficult to detect. Studies of lymphocytes in human and nonhuman primates have used the AIM assay to detect Ag-specific CD4+ and CD8+ T cells.

Vitamin B-12 Intake from Dairy but Not Meat Is Associated with Decreased Risk of Low Vitamin B-12 Status and Deficiency in Older Adults from Quebec, Canada.

Background: Vitamin B-12 deficiency can result in irreversible neurologic damages. It is most prevalent among older adults (∼5%-15%), mainly due to impaired absorption. Vitamin B-12 bioavailability varies between food sources, so their importance in preventing deficiency may also vary.

Increased TCR signaling in regulatory T cells is disengaged from TCR affinity.

Foxp3+ regulatory T cells (Tregs) are capable suppressors of aberrant self-reactivity. However, TCR affinity and specificities that support Treg function, and how these compare to autoimmune T cells remain unresolved. In this study, we used antigen agnostic and epitope-focused analyses to compare TCR repertoires of regulatory and effector T cells that spontaneously infiltrate pancreatic islets of non-obese diabetic mice.

and Are Involved in Cell Sensitivity to LiCl by Regulating the Translation of mRNA.

Lithium chloride (LiCl) has been widely researched and utilized as a therapeutic option for bipolar disorder (BD). Several pathways, including cell signaling and signal transduction pathways in mammalian cells, are shown to be regulated by LiCl. LiCl can negatively control the expression and activity of , a phosphoglucomutase that influences sugar metabolism in yeast.

Assessing the Efficacy of Immune Checkpoint Inhibitors in Preclinical Tumor Models.

The identification of novel immune-related targets that can reactivate or enhance antitumor immunity is a very active field of cancer research. In this context, syngeneic tumor models are often used during the preclinical development of immunotherapies to assess their efficacy and analyze the immune system and tumor cell interaction. Here, we present the practical procedures to generate subcutaneous tumors and experimental lung metastases used to evaluate the antitumor activity of your immunotherapy of interest.

IRES-mediated translation in bacteria.

Despite the similarity in fundamental goals of translation initiation between different domains of life, it is one of the most phylogenetically diverse steps of the central dogma of molecular biology. In a classical view, the translation signals for prokaryotes and eukaryotes are distinct from each other. This idea was challenged by the finding that the Internal Ribosome Entry Site (IRES) belonging to Plautia stali intestine virus (PSIV) could bypass the domain-specific boundaries and effectively initiate translation in E.

CD73 Inhibits cGAS-STING and Cooperates with CD39 to Promote Pancreatic Cancer.

The ectonucleotidases CD39 and CD73 catalyze extracellular ATP to immunosuppressive adenosine, and as such, represent potential cancer targets. We investigated biological impacts of CD39 and CD73 in pancreatic ductal adenocarcinoma (PDAC) by studying clinical samples and experimental mouse tumors. Stromal CD39 and tumoral CD73 expression significantly associated with worse survival in human PDAC samples and abolished the favorable prognostic impact associated with the presence of tumor-infiltrating CD8+ T cells.

Nature vs. nurture: FOXP3, genetics, and tissue environment shape Treg function.

The importance of regulatory T cells (Tregs) in preventing autoimmunity has been well established; however, the precise alterations in Treg function in autoimmune individuals and how underlying genetic associations impact the development and function of Tregs is still not well understood. Polygenetic susceptibly is a key driving factor in the development of autoimmunity, and many of the pathways implicated in genetic association studies point to a potential alteration or defect in regulatory T cell function. In this review transcriptomic control of Treg development and function is highlighted with a focus on how these pathways are altered during autoimmunity.

Residential Homes with Extremely High Indoor Radon Concentrations in Southern Lehigh County, Pennsylvania.

A housing development of 87 new homes on approximately 300 acres of former farm land was found to have 19 homes with basement radon-222 ( 222 Rn) concentrations greater than 37,000 Bq m -3 , with the highest recorded result to date being 648,000 +/- 1,031 Bq m -3 , based upon the diffusion barrier charcoal canister result. The US Environmental Protection Agency (EPA) Action Level for 222 Rn is 148 Bq m -3 . This single-family housing development is in the southeast corner of Lehigh County, Pennsylvania, about 58 km northwest of Philadelphia, in a geologic unit known as the Epler Formation.

CD73 Promotes Chronic Lymphocytic Leukemia.

The ecto-nucleotidase CD73 is an important immune checkpoint in tumor immunity that cooperates with CD39 to hydrolyze pro-inflammatory extracellular ATP into immunosuppressive adenosine. While the role of CD73 in immune evasion of solid cancers is well established, its role in leukemia remains unclear. To investigate the role of CD73 in the pathogenesis of chronic lymphocytic leukemia (CLL), Eµ-TCL1 transgenic mice that spontaneously develop CLL were crossed with CD73 mice.

Methylmalonic acid analysis using urine filter paper samples to screen for metabolic vitamin B deficiency in older adults.

Methylmalonic acid (MMA) analysis in urine represents a noninvasive approach to screening for vitamin B deficiency in older adults. A method allowing the analysis of MMA/creatinine in fasting urine collected on filter paper was developed/validated. Dry urine specimens were eluted using a solution containing internal standards, filtrated and analyzed by ultra-performance LC-MS/MS.

Amniocentesis to diagnose congenital cytomegalovirus infection following maternal primary infection.

Background: Congenital cytomegalovirus infection following maternal primary cytomegalovirus infection affects approximately 0.4% of newborns in the United States but may be hard to diagnose prenatally.

Objective: To evaluate the current sensitivity and specificity of amniocentesis in detecting congenital cytomegalovirus infection.

A dormant T-cell population with autoimmune potential exhibits low self-reactivity and infiltrates islets in type 1 diabetes.

The contribution of low-affinity T cells to autoimmunity in the context of polyclonal T-cell responses is understudied due to the limitations in their capture by tetrameric reagents and low level of activation in response to antigenic stimulation. As a result, low-affinity T cells are often disregarded as nonantigen-specific cells irrelevant to the immune response. Our study aimed to assess how the level of self-antigen reactivity shapes T-cell lineage and effector responses in the context of spontaneous tissue-specific autoimmunity observed in NOD mice.

A Review of the EUSO-Balloon Pathfinder for the JEM-EUSO Program.

is a pathfinder for , the mission concept of a spaceborne observatory which is designed to observe Ultra-High Energy Cosmic Ray (UHECR)-induced Extensive Air Showers (EAS) by detecting their UltraViolet (UV) light tracks "from above." On August 25, 2014, was launched from Timmins Stratospheric Balloon Base (Ontario, Canada) by the balloon division of the French Space Agency CNES. After reaching a floating altitude of 38 km, imaged the UV light in the wavelength range ∼290-500 nm for more than 5 hours using the key technologies of .

Noninvasive Prediction of Congenital Cytomegalovirus Infection After Maternal Primary Infection.

Objective: To develop and internally validate a noninvasive method for the prediction of congenital cytomegalovirus (CMV) infection after primary maternal CMV infection.

Methods: We conducted a secondary analysis of a multicenter randomized placebo-controlled trial of CMV hyperimmune globulin to prevent congenital infection. Women were eligible if they had primary CMV infection, defined as detectable plasma CMV-specific immunoglobulin (Ig)M and CMV-specific IgG with avidity less than 50% before 24 weeks of gestation or IgG seroconversion before 28 weeks, and were carrying a singleton fetus without ultrasonographic findings suggestive of CMV infection.

Discussion on "Competition on Spatial Statistics for Large Datasets".

Unlabelled: We discuss the methods and results of the RESSTE team in the competition on spatial statistics for large datasets. In the first sub-competition, we implemented block approaches both for the estimation of the covariance parameters and for prediction using ordinary kriging. In the second sub-competition, a two-stage procedure was adopted.

A Trial of Hyperimmune Globulin to Prevent Congenital Cytomegalovirus Infection.

Background: Primary cytomegalovirus (CMV) infection during pregnancy carries a risk of congenital infection and possible severe sequelae. There is no established intervention for preventing congenital CMV infection.

Methods: In this multicenter, double-blind trial, pregnant women with primary CMV infection diagnosed before 24 weeks' gestation were randomly assigned to receive a monthly infusion of CMV hyperimmune globulin (at a dose of 100 mg per kilogram of body weight) or matching placebo until delivery.