The evolution of the upright posture and gait—a review and a new synthesis

During the last century, approximately 30 hypotheses have been constructed to explain the evolution of the human upright posture and locomotion. The most important and recent ones are discussed here. Meanwhile, it has been established that all main hypotheses published until the last decade of the past century are outdated, at least with respect to some of their main ideas: Firstly, they were focused on only one cause for the evolution of bipedality, whereas the evolutionary process was much more complex. Secondly, they were all placed into a savannah scenario. During the 1990s, the fossil record allowed the reconstruction of emerging bipedalism more precisely in a forested habitat (e.g., as reported by Clarke and Tobias (Science 269:521–524, 1995) and WoldeGabriel et al. (Nature 412:175–178, 2001)). Moreover, the fossil remains revealed increasing evidence that this part of human evolution took place in a more humid environment than previously assumed. The Amphibian Generalist Theory, presented first in the year 2000, suggests that bipedalism began in a wooded habitat. The forests were not far from a shore, where our early ancestor, along with its arboreal habits, walked and waded in shallow water finding rich food with little investment. In contrast to all other theories, wading behaviour not only triggers an upright posture, but also forces the individual to maintain this position and to walk bipedally. So far, this is the only scenario suitable to overcome the considerable anatomical and functional threshold from quadrupedalism to bipedalism. This is consistent with paleoanthropological findings and with functional anatomy as well as with energetic calculations, and not least, with evolutionary psychology. The new synthesis presented here is able to harmonise many of the hitherto competing theories

Imprinted CDKN1C Is a Tumor Suppressor in Rhabdoid Tumor and Activated by Restoration of SMARCB1 and Histone Deacetylase Inhibitors

SMARCB1 is deleted in rhabdoid tumor, an aggressive paediatric malignancy affecting the kidney and CNS. We hypothesized that the oncogenic pathway in rhabdoid tumors involved epigenetic silencing of key cell cycle regulators as a consequence of altered chromatin-remodelling, attributable to loss of SMARCB1, and that this hypothesis if proven could provide a biological rationale for testing epigenetic therapies in this disease. We used an inducible expression system to show that the imprinted cell cycle inhibitor CDKN1C is a downstream target for SMARCB1 and is transcriptionally activated by increased histone H3 and H4 acetylation at the promoter. We also show that CDKN1C expression induces cell cycle arrest, CDKN1C knockdown with siRNA is associated with increased proliferation, and is able to compete against the anti-proliferative effect of restored SMARCB1 expression. The histone deacetylase inhibitor (HDACi), Romidepsin, specifically restored CDKN1C expression in rhabdoid tumor cells through promoter histone H3 and H4 acetylation, recapitulating the effect of SMARCB1 on CDKNIC allelic expression, and induced cell cycle arrest in G401 and STM91-01 rhabdoid tumor cell lines. CDKN1C expression was also shown to be generally absent in clinical specimens of rhabdoid tumor, however CDKN1A and CDKN1B expression persisted. Our observations suggest that maintenance of CDKN1C expression plays a critical role in preventing rhabdoid tumor growth. Significantly, we report for the first time, parallels between the molecular pathways of SMARCB1 restoration and Romidepsin treatment, and demonstrate a biological basis for the further exploration of histone deacetylase inhibitors as relevant therapeutic reagents in the treatment of rhabdoid tumor

Experimental Behavior of Carbon Fiber-Reinforced Polymer (CFRP) Sheets Attached to Concrete Surfaces Using CFRP Anchors

Fiber-reinforced polymer (FRP) composite sheets have gained popularity as a viable strengthening technique for existing reinforced concrete structures. The efficiency of the strengthening system largely depends on adequate bond between FRP sheets and the concrete substrate. In recent years, techniques to anchor FRP sheets have been proposed in applications that have limited distance to develop FRP sheet strength. One promising technique consists of fabricating and bonding FRP anchors during the FRP sheet saturation and embedding them into predrilled holes in the concrete substrate. This paper presents experimental results highlighting the complex behavior between FRP sheets and anchors. The primary failure modes that the sheet-anchor system can experience are identified. The experiments identify the main variables that influence the FRP anchor-sheet system behavior. This research contributes to the needed experimental database that will aid in future development of design recommendations of this anchorage system