The influence of masticatory loading on craniofacial morphology: A test case across technological transitions in the Ohio valley

Masticatory loading is one of the main environmental stimuli that generate craniofacial variation among recent humans. Experimental studies on a wide variety of mammals, including those with retrognathic postcanine teeth, predict that responses to masticatory loading will be greater in the occlusal plane, the inferior rostrum, and regions associated with the attachments of the temporalis and masseter muscles. Here we test these experimentally‐derived predictions on an extinct human population from the middle and upper Ohio valley that underwent a marked shift from hunting‐gathering to extensive farming during the last 3,000 years and for which we have good archaeological evidence about diet and food processing technology. Geometric morphometric methods were used to detect and measure the putative effect of diet changes on cranial shape independent of size. Our results partially confirm only some of the experimental predictions. The effect of softer and/or less tough diets on craniofacial shape seem to be concentrated in the relative reduction of the temporal fossa and in a displacement of the attachment of the temporal muscle. However, there were few differences in craniofacial shape in regions closer to the occlusal plane. These results highlight the utility of exploring specific localized morphological shifts using a hierarchical model of craniofacial integration. Am J Phys Anthropol, 2010. © 2009 Wiley‐Liss, Inc.     

Metalloprotease-induced ectodomain shedding of neural cell adhesion molecule (NCAM)

Transmembrane forms of neural cell adhesion molecule (NCAM140, NCAM180(1)) are key regulators of neuronal development. The extracellular domain of NCAM can occur as a soluble protein in normal brain, and its levels are elevated in neuropsychiatric disorders, such as schizophrenia; however the mechanism of ectodomain release is obscure. Ectodomain shedding of NCAM140, releasing a fragment of 115 kD, was found to be induced in NCAM-transfected L-fibroblasts by the tyrosine phosphatase inhibitor pervanadate, but not phorbol esters. Pervanadate-induced shedding was mediated by a disintegrin metalloprotease (ADAM), regulated by ERK1/2 MAP kinase. In primary cortical neurons, NCAM was shed at high levels, and the metalloprotease inhibitor GM6001 significantly increased NCAM-dependent neurite branching and outgrowth. Moreover, NCAM-dependent neurite outgrowth and branching were inhibited in neurons isolated from a transgenic mouse model of NCAM shedding. These results suggest that regulated metalloprotease-induced ectodomain shedding of NCAM down-regulates neurite branching and neurite outgrowth. Thus, increased levels of soluble NCAM in schizophrenic brain have the potential to impair neuronal connectivity.     

Distribution of binding sites for human chorionic gonadotropin in the preovulatory follicle of the rat

The distribution of binding sites for human chorionic gonadotropin (hCG) in the preovulatory follicle was studied by autoradiography. An ovulatory dose (10 IU/rat) of [125I]hCG (1.4 muCi/IU) was administered intravenously, and large Graafian follicles were isolated 3 h later by microdissection. Injection of excess unlabeled hCG (500 IU/rat) prevented uptake of radioactivity by the follicle, indicating that binding of iodinated hormone was confined to specific and saturable receptor sites. The density of bound hormone molecules was highest in the theca interna and in three to four layers of mural granulosa cells adjacent to the basement membrane; labeling was chiefly associated with the cell borders. No significant binding could be detected either on the oocyte or on the cumulus cells surrounding the oocyte. We therefore suggest that the induction of ovum maturation does not require attachment of the hormone to the oocyte itself or to follicle cells in its immediate vicinity.     

Myosin mediates contractile force generation by hepatic stellate cells in response to endothelin-1

Although endothelin-1-stimulated contractile force generation by stellate cells is believed to play an important role in hepatic pathophysiology, the molecular signals that mediate this process are incompletely understood. The aim of this study was to test the hypothesis that myosin mediates the contractile force generated by stellate cells in response to endothelin-1. Contractile force generation by primary and immortalized stellate cells was directly and quantitatively measured. Myosin phosphorylation and reorganization, and actin stress fiber formation were investigated in immortalized stellate cells. Endothelin-1 stimulated a rapid and robust generation of contractile force by primary and immortalized stellate cells with a similar dose dependence. Myosin phosphorylation, actin stress fiber assembly, and reorganization of myosin to stress fibers were induced by concentrations of endothelin-1 that also stimulated stellate cell contraction. BQ-123, a selective endothelin receptor antagonist, inhibited myosin phosphorylation and contractile force generation. Y-27632, which selectively inhibits rho-associated kinase, also blocked endothelin-1-stimulated myosin phosphorylation and contractile force generation with a similar dose dependence. These results suggest that endothelin-1-stimulated contractile force generation by stellate cells is mediated by myosin.