Although Apc mutation is widely considered an initiating event in colorectal cancer, little is known about the earliest stages of tumorigenesis following sporadic Apc loss. Therefore, we have utilized a novel mouse model that facilitates the sporadic inactivation of Apc via frameshift reversion of Cre in single, isolated cells and subsequently tracks the fates of Apc-deficient intestinal cells....

UNLABELLED Activated protein C (APC) has cytoprotective effects on liver ischemia-reperfusion injury (IRI). However, it is unclear whether APC is beneficial in steatotic liver IRI. We compared the cytoprotective effects of APC in nonsteatotic and steatotic liver IRI. METHODS Mice fed either normal diets (ND mice) or high fat diets (HF mice), were treated with APC or saline (control) and were ...

Adenomatous polyposis coli (APC) is inactivated in familial adenomatous polyposis and sporadic colorectal cancer. Mice carrying defective APC (apc(Min/+)) spontaneously develop gastrointestinal tumors. APC binds GSK3beta, which phosphorylates beta-catenin thus fostering its degradation. beta-catenin upregulates the serum- and glucocorticoid-inducible kinase Sgk1, which inhibits GSK3beta. The pr...

The control of inflammatory diseases requires functional regulatory T cells (Tregs) with significant Gata-3 expression. Here we address the inhibitory role of Tregs on intestinal tumorigenesis in the Apc (/Min+) mouse model that resembles human familial adenomatous polyposis (FAP). Apc (/Min+) mice had a markedly increased frequency of Foxp3+ Tregs and yet decreased Gata-3 expression in the lam...

Emi2 (also called Erp1) inhibits the anaphase-promoting complex/cyclosome (APC/C) and thereby causes metaphase II arrest in unfertilized vertebrate eggs. Both the D-box and the zinc-binding region (ZBR) of Emi2 have been implicated in APC/C inhibition. However, it is not well known how Emi2 interacts with and hence inhibits the APC/C. Here we show that Emi2 binds the APC/C via the C-terminal ta...

Mechanistic and structural studies of large multi-subunit assemblies are greatly facilitated by their reconstitution in heterologous recombinant systems. In the present paper, we describe the generation of recombinant human APC/C (anaphase-promoting complex/cyclosome), an E3 ubiquitin ligase that regulates cell-cycle progression. Human APC/C is composed of 14 distinct proteins that assemble int...

BACKGROUND Acute traumatic coagulopathy (ATC) has been linked to an increase in activated protein C (aPC) from 40 pM in healthy individuals to 175 pM. aPC exerts its activity primarily through cleavage of active coagulation factor Va (fVa). Platelets reportedly possess fVa which is more resistant to aPC cleavage than plasma fVa; this work examines the hypothesis that normal platelets are suffic...

The distribution systems and microgrids in remote, rural areas are often of a single-phase nature due to economic viability. Fixed frequency three-phase induction generators (IGs) popular such applications their competitive performance features, utility. This article proposes control approach for injecting power grid from an active phase converter (APC) assisted IG. presented ensures balanced o...

Mutations resulting in the truncation of the adenomatous polyposis coli (APC) protein are common to most colonic tumours. The APC protein has emerged as a multifunctional protein that contributes to cytoskeletal organisation and is involved in the regulation of beta-catenin. Both, changes in transcription due to increases in beta-catenin, as well as defects in directed cell migration and cell d...

Casein Kinase 1δ (CK1δ) is a serione/threonine kinase required for cell cycle progression, circadian rhythm, vesicle trafficking, and neurite outgrowth [1]. CK1δ is also a therapeutic target in various cancers, Alzheimer’s disease, alcoholism, and sleep disorders [1]. To examine the role of CK1δ in brain development, we used cerebellar granule cell progenitors (GCPs) as a model system. GCPs are...