TIM-3 functions to enforce CD8+ T cell exhaustion, a dysfunctional state associated with the tolerization of tumor microenvironment. Here we report apoptosis of IFN-γ competent TIM-3+ population of tumor-infiltrating CD8+ T cells in colon cancer. In humans suffering from colorectal cancer, TIM-3+ population is higher in cancer tissue-resident relative to peripheral blood CD8+ T cells. Both the ...

A monomeric variant of triosephosphate isomerase (TIM) with a new engineered binding groove has been characterized further. In this variant (ml8bTIM), the phosphate binding loop had been shortened, causing the binding site to be much more extended. Here, it is reported that in the V233A variant of ml8bTIM (A-TIM), three important properties of the wild-type TIM active site have been restored: (...

The TIM (T cell immunoglobulin mucin) proteins have emerged as key regulators of allergic and autoimmune diseases due to their influence on T helper (Th)-1 and Th-2 responses. On page 955, Chen and colleagues show that one member of this family, TIM-2, multitasks as a receptor for H-ferritin, a component of the iron storage protein ferritin. Ferritin was not what the group expected to find when...

The timeless protein (TIM) is a central component of the circadian pacemaker machinery of the fruitfly Drosophila melanogaster. Both TIM and its partner protein, the period protein PER, show robust circadian oscillations in mRNA and protein levels. Yet the role of TIM in the rhythm generation mechanism is largely unknown. To analyze TIM function, we constructed transgenic flies that carry a hea...

In order to maximize resource utilization as well as providing trust management in P2P computing environments, we propose a novel framework Trust-Incentive Service Management (TIM). Having child model, club model, bid model and trust model, TIM is constructed based on role based price strategy. In this mechanism, providers set the price according to demand and supply, and consumers maximize the...

BACKGROUND T cell immunoglobulin-3 (TIM-3) has been established as a negative regulatory molecule and plays a critical role in immune tolerance. TIM-3 is upregulated in exhausted CD8(+) T cells in both chronic infection and tumor. However, the nature of TIM-3(+)CD4(+) T cells in the tumor microenvironment is unclear. This study is to characterize TIM-3 expressing lymphocytes within human lung c...

OBJECTIVE T cell immunoglobulin- and mucin-domain-containing molecule-4 (Tim-4) receives much attention as a potentially negative regulator of immune responses. However, its modulation on macrophages has not been fully elucidated so far. This study aimed to identify the role of Tim-4 in nitric oxide (NO) modulation. METHODS Macrophages were stimulated with 100 ng/ml LPS or 100 U/ml IFN-γ. RT-...

Regulated nuclear entry of the Period (PER) and Timeless (TIM) proteins, two components of the Drosophila circadian clock, is essential for the generation and maintenance of circadian behavior. PER and TIM shift from the cytoplasm to the nucleus daily, and the length of time that PER and TIM reside in the cytoplasm is an important determinant of the period length of the circadian rhythm. Here w...

T-cell immunoglobulin and mucin domain 3 (Tim-3) is a transmembrane protein that in both mice and humans has been shown to possess various functions in a context-dependent manner. Thus, Tim-3 has been associated with both inhibitory and co-stimulatory function, depending in part on the specific cell type and immune response course. Though originally described on T cells, Tim-3 is now known to b...