The adaptor protein TRAF3 is an immune checkpoint that inhibits myeloid-derived suppressor cell expansion.

Myeloid-derived suppressor cells (MDSCs) are aberrantly expanded in cancer patients and under other pathological conditions. These cells orchestrate the immunosuppressive and inflammatory network to facilitate cancer metastasis and mediate patient resistance to therapies, and thus are recognized as a prime therapeutic target of human cancers. Here we report the identification of the adaptor protein TRAF3 as a novel immune checkpoint that critically restrains MDSC expansion.

A Posttranscriptional Pathway of CD40 Ligand mRNA Stability Is Required for the Development of an Optimal Humoral Immune Response.

CD40 ligand (CD40L) mRNA stability is dependent on an activation-induced pathway that is mediated by the binding complexes containing the multifunctional RNA-binding protein, polypyrimidine tract-binding protein 1 (PTBP1) to a 3' untranslated region of the transcript. To understand the relationship between regulated CD40L and the requirement for variegated expression during a T-dependent response, we engineered a mouse lacking the CD40L stability element (CD40LΔ5) and asked how this mutation altered multiple aspects of the humoral immunity. We found that CD40LΔ5 mice expressed CD40L at 60% wildtype levels, and lowered expression corresponded to significantly decreased levels of T-dependent Abs, loss of germinal center (GC) B cells and a disorganized GC structure.

Examining variability in the processing of agreement in novice learners: Evidence from event-related potentials.

The present study examines both properties of the language and properties of the learner to better understand variability at the earliest stages of second language (L2) acquisition. We used event-related potentials, an oral production task, and a battery of individual differences measures to examine the processing of number and gender agreement in two groups of low-proficiency English-speaking learners of Spanish who were tested in multiple sessions. The results showed an advantage for number, the feature also instantiated in the native language, as both groups showed a native-like P600 response to subject-verb and noun-adjective number violations across sessions.

Differential Posttreatment Outcomes of Methylphenidate for Smoking Cessation for Individuals With ADHD.

Background And Objectives: In a multisite, randomized study (CTN-0029), a 3-month course of Osmotic-Release Oral System Methylphenidate (OROS-MPH) improved smoking cessation in a group of patients with higher baseline severity in Attention-Deficit/Hyperactivity Disorder (ADHD). This treatment, however, worsened smoking cessation outcome in the group with lower baseline ADHD severity. We want to examine whether this differential treatment effect persisted after OROS-MPH was discontinued.

Individual differences in the processing of referential dependencies: Evidence from event-related potentials.

The present study examines the processing of referential ambiguity and referential failure using event-related potentials (ERPs). Participants read sentences with pronouns (he, she) which contained either one, two, or no potential gender-matching antecedents. Participants also took tests of working memory (Count Span/Reading Span) and attentional control (Number Stroop).