ImmunoGlobe: enabling systems immunology with a manually curated intercellular immune interaction network.

Background: While technological advances have made it possible to profile the immune system at high resolution, translating high-throughput data into knowledge of immune mechanisms has been challenged by the complexity of the interactions underlying immune processes. Tools to explore the immune network are critical for better understanding the multi-layered processes that underlie immune function and dysfunction, but require a standardized network map of immune interactions. To facilitate this we have developed ImmunoGlobe, a manually curated intercellular immune interaction network extracted from Janeway's Immunobiology textbook.

Accelerated, but not conventional, radiotherapy of murine B-cell lymphoma induces potent T cell-mediated remissions.

Conventional local tumor irradiation (LTI), delivered in small daily doses over several weeks, is used clinically as a palliative, rather than curative, treatment for chemotherapy-resistant diffuse large B-cell lymphoma (DLBCL) for patients who are ineligible for hematopoietic cell transplantation. Our goal was to test the hypothesis that accelerated, but not conventional, LTI would be more curative by inducing T cell-mediated durable remissions. We irradiated subcutaneous A20 and BL3750 lymphoma tumors in mice with a clinically relevant total radiation dose of 30 Gy LTI, delivered in 10 doses of 3 Gy over 4 days (accelerated irradiation) or as 10 doses of 3 Gy over 12 days (conventional irradiation).

The Predictive Value of Inflammation-Related Peripheral Blood Measurements in Cancer Staging and Prognosis.

In this review, we discuss the interaction between cancer and markers of inflammation (such as levels of inflammatory cells and proteins) in the circulation, and the potential benefits of routinely monitoring these markers in peripheral blood measurement assays. Next, we discuss the prognostic value and limitations of using inflammatory markers such as neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios and C-reactive protein measurements. Furthermore, the review discusses the benefits of combining multiple types of measurements and longitudinal tracking to improve staging and prognosis prediction of patients with cancer, and the ability of novel frameworks to leverage this high-dimensional data.

Longitudinal Monitoring of Antibody Responses against Tumor Cells Using Magneto-nanosensors with a Nanoliter of Blood.

Each immunoglobulin isotype has unique immune effector functions. The contribution of these functions in the elimination of pathogens and tumors can be determined by monitoring quantitative temporal changes in isotype levels. Here, we developed a novel technique using magneto-nanosensors based on the effect of giant magnetoresistance (GMR) for longitudinal monitoring of total and antigen-specific isotype levels with high precision, using as little as 1 nL of serum.

A Robust Protocol for Protein Extraction and Digestion.

Proteins play a key role in all aspects of cellular homeostasis. Proteomics, the large-scale study of proteins, provides in-depth data on protein properties, including abundances and post-translational modification states, and as such provides a rich avenue for the investigation of biological and disease processes. While proteomic tools such as mass spectrometry have enabled exquisitely sensitive sample analysis, sample preparation remains a critical unstandardized variable that can have a significant impact on downstream data readouts.

High-dimensional analysis of the aging immune system: verification of age-associated differences in immune signaling responses in healthy donors.

Background: Single-cell network profiling (SCNP) is a multiparametric flow cytometry-based approach that simultaneously measures evoked signaling in multiple cell subsets. Previously, using the SCNP approach, age-associated immune signaling responses were identified in a cohort of 60 healthy donors.

Methods: In the current study, a high-dimensional analysis of intracellular signaling was performed by measuring 24 signaling nodes in 7 distinct immune cell subsets within PBMCs in an independent cohort of 174 healthy donors [144 elderly (>65 yrs); 30 young (25-40 yrs)].

Genomic relationship between SINE retrotransposons, Pol III-Pol II transcription, and chromatin organization: the journey from junk to jewel.

A typical eukaryotic genome harbors a rich variety of repetitive elements. The most abundant are retrotransposons, mobile retroelements that utilize reverse transcriptase and an RNA intermediate to relocate to a new location within the cellular genomes. A vast majority of the repetitive mammalian genome content has originated from the retrotransposition of SINE (100-300 bp short interspersed nuclear elements that are derived from the structural 7SL RNA or tRNA), LINE (7kb long interspersed nuclear element), and LTR (2-3 kb long terminal repeats) transposable element superfamilies.

Inhibition of activated pericentromeric SINE/Alu repeat transcription in senescent human adult stem cells reinstates self-renewal.

Cellular aging is linked to deficiencies in efficient repair of DNA double strand breaks and authentic genome maintenance at the chromatin level. Aging poses a significant threat to adult stem cell function by triggering persistent DNA damage and ultimately cellular senescence. Senescence is often considered to be an irreversible process.