Welfare Issues on Israeli Dairy Farms: Attitudes and Awareness of Farm Workers and Veterinary Practitioners.

Attitudes toward practical dairy cow welfare issues were evaluated based on a questionnaire answered by 500 dairy farm workers and 27 veterinary practitioners. Primarily, the effect of demographic characteristics on attitudes toward cattle welfare was tested. Professionally, five themes were identified: effect of welfare awareness on productivity, knowledge of cattle's senses and social structure, effects of man-animal interactions on milk yield, pain perception and prevention, and knowledge transfer from veterinary practitioners to farm workers.

Computed tomographic analysis of calvarial hyperostosis in captive lions.

Osseous malformations in the skull and cervical vertebrae of lions in captivity are believed to be caused by hypovitaminosis A. These often lead to severe neurologic abnormalities and may result in death. We describe the characterization of these abnormalities based on computed tomography (CT).

Targeting of gp78 for ubiquitin-mediated proteasomal degradation by Hrd1: cross-talk between E3s in the endoplasmic reticulum.

There are an increasing number of ubiquitin ligases (E3s) implicated in endoplasmic reticulum (ER)-associated degradation (ERAD) in mammals. The two for which the greatest amount of information exists are the RING finger proteins gp78 and Hrd1, which are the structural orthologs of the yeast ERAD E3 Hrd1p. We now report that Hrd1, also known as synoviolin, targets gp78 for proteasomal degradation independent of the ubiquitin ligase activity of gp78, without evidence of a reciprocal effect.

Mdm2: p53's lifesaver?

In a recent issue of Molecular Cell, Taira et al. (2007) and Rinaldo et al. (2007) provide insight into the involvement of the DYRK2 kinase and a surprising role of MDM2 in regulation of DNA damage-induced apoptosis via p53 phosphorylation.

E4F1 is an atypical ubiquitin ligase that modulates p53 effector functions independently of degradation.

p53 is regulated by multiple posttranslational modifications, including Hdm2-mediated ubiquitylation that drives its proteasomal degradation. Here, we identify the p53-associated factor E4F1, a ubiquitously expressed zinc-finger protein first identified as a cellular target of the viral oncoprotein E1A, as an atypical ubiquitin E3 ligase for p53 that modulates its effector functions without promoting proteolysis. E4F1 stimulates oligo-ubiquitylation in the hinge region of p53 on lysine residues distinct from those targeted by Hdm2 and previously described to be acetylated by the acetyltransferase PCAF.

A positive feedback loop between the p53 and Lats2 tumor suppressors prevents tetraploidization.

Damage to the mitotic spindle and centrosome dysfunction can lead to cancer. To prevent this, cells trigger a succession of checkpoint responses, where an initial mitotic delay is followed by slippage without cytokinesis, spawning tetraploid G1 cells that undergo a p53-dependent G1/S arrest. We describe the importance of Lats2 (Large Tumor Suppressor 2) in this checkpoint response.

Life, death, and ubiquitin: taming the mule.

Ubiquitin-mediated protein degradation is an efficient way for the cell to get rid of unwanted proteins. A key player in this process is the E3 ubiquitin ligase. In this issue of Cell, and describe a new E3 ligase, ARF-BP1/Mule, which targets two very different substrates, p53 and Mcl-1, with completely different cellular outcomes.

Regulation of p53 by Mdm2: fate is in the numbers.

The p53 tumor suppressor protein is normally restrained by the Mdm2 oncoprotein, which promotes p53 ubiquitination. In a recent issue of Science, report that p53 may face two alternative fates, depending on Mdm2 levels: high Mdm2 drives p53 polyubiquitination and degradation within the cell nucleus, whereas low Mdm2 promotes p53 monoubiquitination and nuclear exclusion.

A novel mammalian endoplasmic reticulum ubiquitin ligase homologous to the yeast Hrd1.

The yeast hHrd1 is a ubiquitin-protein ligase (E3) involved in ER-associated degradation. It was originally identified by genetic methods as an E3 of the yeast cholesterol biosynthetic enzyme HMG-CoA reductase (HMGR). We report the identification and cloning of a human homologue of Hrd1 (hHrd1).

An essential role for tripeptidyl peptidase in the generation of an MHC class I epitope.

Most of the peptides presented by major histocompatibility complex (MHC) class I molecules require processing by proteasomes. Tripeptidyl peptidase II (TPPII), an aminopeptidase with endoproteolytic activity, may also have a role in antigen processing. Here, we analyzed the processing and presentation of the immunodominant human immunodeficiency virus epitope HIV-Nef(73-82) in human dendritic cells.