A total of 192 embalmed cadavers were examined in order to present a detailed study of arterial variations in the upper limb and a meta-analysis of them. The variable terminology previously used was unified into a homogenous and complete classification, with 12 categories covering all the previously reported variant patterns of the arm and forearm.

The INK4a/ARF tumor suppressor locus, a key executor of cellular senescence, is regulated by members of the Polycomb group (PcG) of transcriptional repressors. Here we show that signaling from oncogenic RAS overrides PcG-mediated repression of INK4a by activating the H3K27 demethylase JMJD3 and down-regulating the methyltransferase EZH2. In human fibroblasts, JMJD3 activates INK4a, but not ARF, and causes p16INK4a -dependent arrest. In mouse embryo fibroblasts, Jmjd3 activates both Ink4a and Arf and elicits a p53-dependent arrest, echoing the effects of RAS in this system. Our findings directly implicate JMJD3 in the regulation of INK4a/ARF during oncogene-induced senescence and suggest that JMJD3 has the capacity to act as a tumor suppressor.Supplemental material is available at http://www.genesdev.org.

A total of 112 human embryos (224 upper limbs) between stages 12 and 23 of development were examined. It was observed that formation of the arterial system in the upper limb takes place as a dual process. An initial capillary plexus appears from the dorsal aorta during stage 12 and develops at the same rate as the limb. At stage 13, the capillary plexus begins a maturation process involving the enlargement and differentiation of selected parts. This remodelling process starts in the aorta and continues in a proximal to distal sequence. By stage 15 the differentiation has reached the subclavian and axillary arteries, by stage 17 it has reached the brachial artery as far as the elbow, by stage 18 it has reached the forearm arteries except for the distal part of the radial, and finally by stage 21 the whole arterial pattern is present in its definitive morphology. This differentiation process parallels the development of the skeletal system chronologically. A number of arterial variations were observed, and classified as follows : superficial brachial (7n7 %), accessory brachial (0n6 %), brachioradial (14 %), superficial brachioulnar (4n7 %), superficial brachioulnoradial (0n7%), palmar pattern of the median (18n7 %) and superficial brachiomedian (0n7 %) arteries. They were observed in embryos belonging to stages 17-23 and were not related to a specific stage of development. Statistical comparison with the rates of variations reported in adults did not show significant differences. It is suggested that the variations arise through the persistence, enlargement and differentiation of parts of the initial network which would normally remain as capillaries or even regress.

Variations in connections between the musculocutaneous and median nerves in the arm are not as uncommon as was once thought. This opinion led us to perform a study in 138 cadavers (66 male, 72 female). These variations were seen in 64 cadavers (46.4%), 9 bilaterally and 55 unilaterally (26 right and 29 left); in total, therefore, variations were observed in 73 out of 276 arms (26.4%), 42 male and 31 female. No statistically significant differences by gender and side were observed. We classify the variations in three main patterns: Pattern 1, fusion of both nerves (14 arms, 19.2%); Pattern 2, presence of one supplementary branch between both nerves (53 arms, 72.6%); and Pattern 3, two branches (5 arms, 6.8%). Pattern 2 was further subdivided into a sub-group 2a when a single root from the musculocutaneous nerve contributed to the connection (51 arms, 69.9%), and 2b when there were two roots from the musculocutaneous nerve (2 arms, 2.7%). A combination of Patterns 1 and 2a was observed in one case (1.4%). Further variations are described, published classification systems are reviewed and a meta-analysis of previous results is presented. An overall incidence of 33% of variant arms was observed. Of these variant arms, Pattern 1 represented 13.1%, Pattern 2 represented 75.4%, and Pattern 3, 8.5%, similar to our figures.

Misexpression of Polycomb repressive complex 1 (PRC1) components in human cells profoundly influences the onset of cellular senescence by modulating transcription of the INK4a tumor suppressor gene. Using tandem affinity purification, we find that CBX7 and CBX8, two Polycomb (Pc) homologs that repress INK4a, both participate in PRC1-like complexes with at least two Posterior sex combs (Psc) proteins, MEL18 and BMI1. Each complex contains a single representative of the Pc and Psc families. In primary human fibroblasts, CBX7, CBX8, MEL18 and BMI1 are present at the INK4a locus and shRNA-mediated knockdown of any one of these components results in de-repression of INK4a and proliferative arrest. Sequential chromatin immunoprecipitation (ChIP) reveals that CBX7 and CBX8 bind simultaneously to the same region of chromatin and knockdown of one of the Pc or Psc proteins results in release of the other, suggesting that the binding of PRC1 complexes is interdependent. Our findings provide the first evidence that a single gene can be regulated by several distinct PRC1 complexes and raise important questions about their configuration and relative functions.