ABSTRACTThe Transfer Code of Practice was launched in 2008 as a set of best‐practice guidelines to be followed when a journal changes publisher, with the aim of ensuring uninterrupted access to content for subscribers. The Code has now been updated to reflect the continued evolution of the academic publishing process driven by new technologies, policies, and publishing practices.

The Transfer Code of Practice, first released in 2008, is a set of recommendations that establishes a baseline level of quality and performance in the event that a journal changes publisher. 2012 will see new developments from the Transfer Working Group, but there is still more work to be done to inform and educate all of the various constituencies involved in the journal transfer process.

The stealthy assassin creeps up to the victim and quickly injects a dose of deadly poison.No, it's not a scene from a spy novel, but one of the ways in which the immune system's natural assassins -cytotoxic T lymphocytes and natural killer cells -can kill their target cells.The deadly poison in this case is a serine protease called granzyme B (GrB), and the killing mechanism is discussed by Christopher Froelich and colleagues in The Journal of Cell Biology.Much is known about GrB -there's evidence that it kills with or without caspase activation, and that it causes mitochondrial permeabilization with or without members of the Bcl-2 family.So Froelich and co-workers set out to assess the relative contributions of these pathways, to come up with a probable scheme for how GrB normally acts.To do this, they measured several different hallmarks of apoptosis -loss of mitochondrial membrane potential (ψ m ), DNA fragmentation and activation of procaspase precursors.Most previous studies have been done on cell lysates, after GrB has been delivered to its target.By contrast, Froelich and colleagues studied whole cells after delivery of the physiological form of GrB, a GrB-Serglycin (SG) complex.Previous studies with lysates had indicated that GrB-treated cells rapidly acquire cleaved (and presumably active) procaspase-3.Mature caspase-3 and GrB then process caspase-7 to complete the initial phase of apoptosis.The authors therefore asked how the absence of procaspase-3 might alter the pattern of apoptosis in whole cells after delivery of GrB-SG.The authors compared MCF-7 cells that lacked procaspase-3 (MCF-7 vec ) with cells that contained a stable transfectant that expressed this zymogen (MCF-7 casp-3 ), after delivery of GrB-SG.They saw DNA fragmentation and a loss of ψ m in the MCF-7 casp-3 cells, but not in MCF-7 vec cells, indicating that caspase-3 is essential for starting apoptosis.The authors also showed that the requirement for caspase-3 was not due simply to the fact that caspase-7 could no longer be activated in the caspase-3-deficient cells.If caspase-3 is the crucial initiator, what's the contribution of the Bcl-2-family members?First, the

The activation of apoptotic cascades triggers a series of events, one of which is the condensation and fragmentation of chromosomal DNA.In mammals, at least three proteins have been implicated in this process -DFF40/CAD, the apoptosis-inducing factor (AIF) and a mitochondrial endonuclease termed endonuclease G (EndoG).How do these proteins work, and are their pro-apoptotic functions conserved in other species?These are the questions tackled by Ding Xue and colleagues, who report their results in Science.The authors started by cloning wah-1, which is the Caenorhabditis elegans homologue of AIF.They then examined the effects of inhibiting the expression of wah-1 using RNA-mediated interference (RNAi) and found that, in wah-1(RNAi)-treated worms, the appearance of embryonic cell corpses during normal development was delayed.This phenotype is similar to that observed in cps-6 mutant worms (CPS-6 is the worm orthologue of mammalian EndoG), and so indicates a role for WAH-1 in the progression of apoptosis.However, a cps-6 mutation did not enhance the wah-1(RNAi) phenotype, indicating that WAH-1 and CPS-6 might function in the same pathway.Xue and co-workers next used TUNEL assays to show that, like AIF, WAH-1 induces chromosome fragmentation.And, using a WAH-1-green fluorescent protein (GFP) fusion protein, they showed that WAH-1 localizes to the mitochondria.So how is WAH-1 activated?The release of apoptogenic factors from mitochondria in response to pro-apoptotic stimuli is triggered by so-called 'BH3-domain-only' proteins.In worms, the most upstream cell-death activator is also a BH3-domain protein, EGL-1.The authors asked whether global expression of egl-1 could release WAH-1 from the mitochondria, and they found that it couldthe punctate mitochondrial staining pattern of WAH-1-GFP became more uniformly spread throughout the cell, and more GFP fluorescence was seen in nuclei,

The activation of apoptotic cascades triggers a series of events, one of which is the condensation and fragmentation of chromosomal DNA.In mammals, at least three proteins have been implicated in this process -DFF40/CAD, the apoptosis-inducing factor (AIF) and a mitochondrial endonuclease termed endonuclease G (EndoG).How do these proteins work, and are their pro-apoptotic functions conserved in other species?These are the questions tackled by Ding Xue and colleagues, who report their results in Science.The authors started by cloning wah-1, which is the Caenorhabditis elegans homologue of AIF.They then examined the effects of inhibiting the expression of wah-1 using RNA-mediated interference (RNAi) and found that, in wah-1(RNAi)-treated worms, the appearance of embryonic cell corpses during normal development was delayed.This phenotype is similar to that observed in cps-6 mutant worms (CPS-6 is the worm orthologue of mammalian EndoG), and so indicates a role for WAH-1 in the progression of apoptosis.However, a cps-6 mutation did not enhance the wah-1(RNAi) phenotype, indicating that WAH-1 and CPS-6 might function in the same pathway.Xue and co-workers next used TUNEL assays to show that, like AIF, WAH-1 induces chromosome fragmentation.And, using a WAH-1-green fluorescent protein (GFP) fusion protein, they showed that WAH-1 localizes to the mitochondria.So how is WAH-1 activated?The release of apoptogenic factors from mitochondria in response to pro-apoptotic stimuli is triggered by so-called 'BH3-domain-only' proteins.In worms, the most upstream cell-death activator is also a BH3-domain protein, EGL-1.The authors asked whether global expression of egl-1 could release WAH-1 from the mitochondria, and they found that it couldthe punctate mitochondrial staining pattern of WAH-1-GFP became more uniformly spread throughout the cell, and more GFP fluorescence was seen in nuclei,

Mutations that activate the Hedgehog (Hh) signalling pathway have been linked to tumour formation, but it's not been clear how.The discovery of a direct link between Hh signalling and key regulators of the cell cycle might now provide the answer.Wei Du and colleagues were studying eye development in Drosophila melanogaster.The expression pattern of Hh during this process, just posterior to cells entering S phase, indicated that