Combined absence of TRP53 target genes ZMAT3, PUMA and p21 cause a high incidence of cancer in mice.

Transcriptional activation of target genes is essential for TP53-mediated tumour suppression, though the roles of the diverse TP53-activated target genes in tumour suppression remains poorly understood. Knockdown of ZMAT3, an RNA-binding zinc-finger protein involved in regulating alternative splicing, in haematopoietic cells by shRNA caused leukaemia only with the concomitant absence of the PUMA and p21, the critical effectors of TRP53-mediated apoptosis and cell cycle arrest respectively. We were interested to further investigate the role of ZMAT3 in tumour suppression beyond the haematopoietic system.

MARCH1-mediated ubiquitination of MHC II impacts the MHC I antigen presentation pathway.

Major histocompatibility complex class II (MHC II) expression and turn-over are regulated via its ubiquitination by the membrane associated RING-CH 1 (MARCH1) E3 ligase. Unexpectedly, we show that MHC II ubiquitination also impacts MHC I. Lack of MARCH1 in B cells and dendritic cells (DCs) resulted in a significant reduction in surface MHC I expression.

AS-7 improved in vitro quality of red blood cells prepared from whole blood held overnight at room temperature.

Background: Extended room temperature (RT) hold of whole blood (WB) may affect the quality of red blood cell (RBC) components produced from these donations. The availability of better RBC additive solutions (ASs) may help reduce the effects. A new AS, AS-7 (SOLX, Haemonetics Corporation), was investigated for improved in vitro quality of RBCs prepared from WB held overnight at RT.

In vitro measures of membrane changes reveal differences between red blood cells stored in saline-adenine-glucose-mannitol and AS-1 additive solutions: a paired study.

Background: Saline-adenine-glucose-mannitol (SAGM) and a variant solution, AS-1, have been used for more than 30 years to preserve red blood cells (RBCs). Reputedly these RBC components have similar quality, although no paired study has been reported. To determine whether differences exist, a paired study of SAGM RBCs and AS-1 RBCs was conducted to identify membrane changes, including microparticle (MP) quantitation and in vitro RBC-endothelial cell (EC) interaction.

Red blood cell (RBC) age at collection and storage influences RBC membrane-associated carbohydrates and lectin binding.

Background: Membrane-associated carbohydrate changes act as signals for removal of senescent and damaged red blood cells (RBCs) from the circulation and could play a role in the RBC storage lesion and RBC survival after transfusion. In this study, a panel of lectins was used to investigate the expression of carbohydrates on RBCs that had been separated before storage into young and old RBCs.

Study Design And Methods: Leukodepleted RBCs were separated before storage into young and old RBCs (n = 9 paired units) by centrifugation and sampled at nominated time points during 42 days of storage.

A fluorometric quantitative erythrophagocytosis assay using human THP-1 monocytic cells and PKH26-labelled red blood cells.

Removal of senescent, damaged or diseased red blood cells (RBCs) from the circulation in vivo occurs by a process known as erythrophagocytosis. The exact details of the signaling mechanisms that mark RBCs for recognition and influence erythrophagocytosis are still not completely understood. The aim of this study was to develop a quantitative, fluorometric erythrophagocytosis assay for human RBCs and phagocytes to aid elucidation of the biological mechanisms regulating erythrophagocytosis.

Red blood cell age determines the impact of storage and leukocyte burden on cell adhesion molecules, glycophorin A and the release of annexin V.

The influence of the age of the red blood cell (RBC) within its 120-day lifecycle at the time of blood donation on the RBC storage lesion is not well understood. Expression of cell adhesion molecules (CAMs) (CD44, CD47, CD58 and CD147), glycophorin A (GPA) and phosphatidylserine (PS) on young and old RBCs density separated prior to storage of the RBC concentrate was determined by flow cytometry. Older RBCs showed significantly reduced expression of GPA throughout storage and CD44 and CD147 from Day 28 onwards compared to young RBCs.