SCALiR: A Web Application for Automating Absolute Quantification of Mass Spectrometry-Based Metabolomics Data.

Quantitative liquid chromatography-mass spectrometry (LC-MS)-based metabolomics is becoming an important approach for studying complex biological systems but presents several technical challenges that limit its widespread use. Computing metabolite concentrations using standard curves generated from standard mixtures of known concentrations is a labor-intensive process that is often performed manually. Currently, there are few options for open-source software tools that can automatically calculate metabolite concentrations.

Predicting a Stable Dimeric Form of the PD1-PDL1 Complex: Implications for Understanding the PD1 Activation Mechanism.

The activation of T cells is typically accompanied by inhibitory mechanisms within which the programmed cell death (PD1) receptor stands out. Upon binding the ligands PDL1 and PDL2, PD1 drives T cells to an unresponsive state called exhaustion, characterized by a markedly decreased capacity to exert effector functions. For this reason, PD1 has become one of the most important targets in cancer immunotherapy.

Methods for Quantifying the Metabolic Boundary Fluxes of Cell Cultures in Large Cohorts by High-Resolution Hydrophilic Liquid Chromatography Mass Spectrometry.

Metabolomics is a mainstream approach for investigating the metabolic underpinnings of complex biological phenomena and is increasingly being applied to large-scale studies involving hundreds or thousands of samples. Although metabolomics methods are robust in smaller-scale studies, they can be challenging to apply to larger cohorts due to the inherent variability of liquid chromatography mass spectrometry (LC-MS). Much of this difficulty results from the time-dependent changes in the LC-MS system, which affects both the qualitative and quantitative performances of the instrument.

Unraveling a Conserved Conformation of the FG Loop upon the Binding of Natural Ligands to the Human and Murine PD1.

The activation of T cells is normally accompanied by inhibitory mechanisms within which the PD1 receptor stands out. PD1 drives T cells to an unresponsive state called exhaustion, characterized by a markedly decreased capacity to exert effector functions upon binding the ligands PDL1 and PDL2. For this reason, PD1 has become one of the most important targets in cancer immunotherapy.

Differential Effects of IL2Rα and IL15Rα over the Stability of the Common Beta-Gamma Signaling Subunits of the IL2 and IL15 Receptors.

Interleukin (IL) 2 and IL15 are two members of the common gamma chain cytokine family, involved in the regulation of the T cell differentiation process. Both molecules use a specific alpha subunit, IL2Rα and IL15Rα, and share the same beta and gamma chains signaling receptors. The presence of the specific alpha subunit modulates the T cell ability to compete for both soluble cytokines while the beta and gamma subunits are responsible for the signal transduction.

Exploring the conformational dynamics of PD1 in complex with different ligands: What we can learn for designing novel PD1 signaling blockers?

Activation of T cells triggers the expression of regulatory molecules like the programmed cell death 1 (PD1) protein. The association of PD1 with the natural ligands PDL1 and PDL2 induces an inhibitory signal that prevents T cells from proliferating and exerting effector functions. However, little is known about how the binding of the ligands induce the PD1 inhibitory signal over T cells effector functions.

Affinity-matured variants derived from nimotuzumab keep the original fine specificity and exhibit superior biological activity.

Nimotuzumab is a humanized monoclonal antibody against the Epidermal Growth Factor Receptor with a long history of therapeutic use, recognizing an epitope different from the ones targeted by other antibodies against the same antigen. It is also distinguished by much less toxicity resulting in a better safety profile, which has been attributed to its lower affinity compared to these other antibodies. Nevertheless, the ideal affinity window for optimizing the balance between anti-tumor activity and toxic effects has not been determined.

Quantitative assessment of extracellular IL-1 regulation.

IL-1 system is involved in the induction and maintenance of chronic inflammation associated with several autoimmune diseases and cancer, mainly due to its capacity to promote the secretion of inflammatory mediators. For this reason, several intracellular and extracellular mechanisms for this system have been fixed during the evolution. In spite of the large description of molecular interactions between IL-1 ligands and receptors, little is known about the relevance and limits of the extracellular regulatory mechanims in different scenarios.

Quantitative Contribution of IL2Rγ to the Dynamic Formation of IL2-IL2R Complexes.

Interleukin-2 (IL2) is a growth factor for several immune cells and its function depends on its binding to IL2Rs in the cell membrane. The most accepted model for the assembling of IL2-IL2R complexes in the cell membrane is the Affinity Conversion Model (ACM). This model postulates that IL2R receptor association is sequential and dependent on ligand binding.