Relationship of cranial robusticity to cranial form,geography and climate in Homo sapiens

Variation in cranial robusticity among modern human populations is widely acknowledged but not well‐understood. While the use of “robust” cranial traits in hominin systematics and phylogeny suggests that these characters are strongly heritable, this hypothesis has not been tested. Alternatively, cranial robusticity may be a response to differences in diet/mastication or it may be an adaptation to cold, harsh environments. This study quantifies the distribution of cranial robusticity in 14 geographically widespread human populations, and correlates this variation with climatic variables, neutral genetic distances, cranial size, and cranial shape. With the exception of the occipital torus region, all traits were positively correlated with each other, suggesting that they should not be treated as individual characters. While males are more robust than females within each of the populations, among the independent variables (cranial shape, size, climate, and neutral genetic distances), only shape is significantly correlated with inter‐population differences in robusticity. Two‐block partial least‐squares analysis was used to explore the relationship between cranial shape (captured by three‐dimensional landmark data) and robusticity across individuals. Weak support was found for the hypothesis that robusticity was related to mastication as the shape associated with greater robusticity was similar to that described for groups that ate harder‐to‐process diets. Specifically, crania with more prognathic faces, expanded glabellar and occipital regions, and (slightly) longer skulls were more robust than those with rounder vaults and more orthognathic faces. However, groups with more mechanically demanding diets (hunter‐gatherers) were not always more robust than groups practicing some form of agriculture. Am J Phys Anthropol, 2010. © 2009 Wiley‐Liss, Inc.     

Slit-Robo signaling mediates lymphangiogenesis and promotes tumor lymphatic metastasis

The Slit family of guidance cues binds to Roundabout (Robo) receptors to modulate neuronal, leukocytic, and endothelial migration. Slit-Robo signaling had been reported to function as chemoattractive signal for vascular endothelial cells during angiogenesis. In this study, we found that Robo1 was expressed in lymphatic endothelial cells to mediate the migration and tube formation of these cells upon Slit2 stimulation, which were specifically inhibited by the function-blocking antibody R5 to Slit2/Robo1 interaction. To further explore the lymphangiogenic effect and significance mediated by Slit-Robo signaling, we intercrossed Slit2 transgenic mice with a non-metastatic RIP1-Tag2 mouse tumor model, and found that transgenic overexpression of Slit2 significantly enhanced tumor lymphangiogenesis and subsequently promoted mesenteric lymph node metastasis of pancreatic islet tumors. Taken together, our findings reveal that through interacting with Robo1, Slit2 is a novel and potent lymphangiogenic factor and contributes to tumor lymphatic metastasis.     

Effects of protons on macroscopic and single-channel currents mediated by the human P2X7 receptor

Human P2X7 receptors (hP2X7Rs) belong to the P2X family, which opens an intrinsic cation channel when challenged by extracellular ATP. hP2X7Rs are expressed in cells of the inflammatory and immune system. During inflammation, ATP and protons are secreted into the interstitial fluid. Therefore, we investigated the effect of protons on the activation of hP2X7Rs. hP2X7Rs were expressed in Xenopus laevis oocytes and activated by the agonists ATP or benzoyl-benzoyl-ATP (BzATP) at different pH values. The protons reduced the hP2X7R-dependent cation current amplitude and slowed the current deactivation depending on the type and concentration of the agonist used. These effects can be explained by (i) the protonation of ATP, which reduces the effective concentration of the agonist ATP⁴⁻ at the high- and low-affinity ATP activation site of the hP2XR, and (ii) direct allosteric inhibition of the hP2X7R channel opening that follows ATP⁴⁻ binding to the low-affinity activation site. Due to the hampered activation via the low-affinity activation site, a low pH (as observed in inflamed tissues) leads to a relative increase in the contribution of the high-affinity activation site for hP2X7R channel opening.     

Structural flexibility and the positive charges are the key factors in bacterial cell selectivity and membrane penetration of peptoid-substituted analog of Piscidin 1

Piscidin 1 (Pis-1) is a novel cytotoxic peptide with a cationic α-helical structure isolated from the mast cells of hybrid striped bass. In our previous study, we showed that Pis-1[PG] with a substitution of Pro⁸ for Gly⁸ in Pis-1 had higher bacterial cell selectivity than Pis-1. We designed peptoid residue-substituted peptide, Pis-1[NkG], in which Gly⁸ of Pis-1 was replaced with Nlys (Lys peptoid residue). Pis-1[NkG] had higher antibacterial activity and lower cytotoxicity against mammalian cells than Pis-1 and Pis-1[PG]. We determined the tertiary structure of Pis-1[PG] and Pis-1[NkG] in the presence of DPC micelles by NMR spectroscopy. Both peptides had a three-turn helix in the C-terminal region and a bent structure in the center. Pis-1[PG] has a rigid bent structure at Pro⁸ whereas Pis-1[NkG] existed as a dynamic equilibrium of two conformers with a flexible hinge structure at Nlys⁸. Depolarization of the membrane potential of Staphylococcus aureus and confocal laser-scanning microscopy study revealed that Pis-1[NkG] effectively penetrated the bacterial cell membrane and accumulated in the cytoplasm, whereas Pis-1[PG] did not penetrate the membrane but remained outside or on the cell surface. Introduction of a lysine peptoid at position 8 of Pis-1 provided conformational flexibility and increased the positive charge at the hinge region; both factors facilitated penetration of the bacterial cell membrane and conferred bacterial cell selectivity on Pis-1[NkG].     

Overexpression of stearoyl-CoA desaturase-1 results in an increase of conjugated linoleic acid (CLA) and n-7 fatty acids in 293 cells

The effect of human SCD1 heterologous expression on cellular fatty acid synthesis was investigated in the current study. The SCD1 gene expression cassette and PGK-neomycin-selectable marker cassette were co-introduced into HEK 293 cells by electroporation, and subsequently, SCD1 expression was evaluated by fatty acid analysis. RT-PCR analysis indicated that the foreign SCD1 gene could be expressed in transformed cell lines. Total lipid analysis of the transformed cells fed with vaccenic acid (t11-18:1) as a substrate showed that SCD1 expression resulted in an increase in c9t11-CLA from 0.73-1.03% to 2.69-2.86% (p < 0.05) and that the conversion efficiency was elevated from 5.11-6.88% to 16.49-20.06% (p < 0.05). Surprisingly, the concentration of t10c12-CLA was also increased, from 0.10-0.41% to 1.35-1.69% in SCD1 cells (p < 0.05). SCD1 expression also resulted in a significant (p < 0.05) increase in palmitoleic acid (16:1 n-7) from 1.56-2.26% to 3.47-4.04% and cis-vaccenic acid (18:1 n-7) from 2.42-3.97% to 6.20-7.22%, and the corresponding conversion ratio of n-7 fatty acid was elevated from 12.01-16.70% to 22.62-24.13% (p < 0.05). This study demonstrates that the foreign SCD1 gene was expressed with high efficiency and induced elevated c9t11-CLA, t10c12-CLA, and n-7 fatty acid levels in mammalian cells.     

DRR1 is expressed in the developing nervous system and downregulated during neuroblastoma carcinogenesis

Down-regulated in renal cell carcinoma 1 (DRR1) is mapped at 3p21.1, and is a candidate tumor suppressor gene. However, its biological roles have yet to be elucidated. Here, we developed polyclonal antibodies against DRR1 protein, and examined its expression during embryogenesis and carcinogenesis. The DRR1 protein was preferentially expressed in axonal projections of the central and peripheral nervous system of mice during embryonic days 10.5-16.5. Consistent with this expression pattern, the protein was detected in the neurites of primary cultured cortical neurons of rats at embryonic day 18.5. Survival of these cells was significantly inhibited by RNAi-induced downregulation of DRR1 expression. DRR1 was poorly expressed in established cancer cell lines, including neuroblastoma cells, whereas strong expression was observed in normal cells. A neuroblastoma model, MYCN transgenic mice, revealed that DRR1 protein was expressed in the celiac ganglion 2 weeks after birth when neuroblast hyperplasia was also observed; however, there was no longer any expression of DRR1 protein in tumors originating from the ganglion 8 weeks after birth. Together, our data indicate that DRR1 protein is expressed in normal cells, particularly in the nervous system during embryogenesis, is involved in neuronal cell survival, and is downregulated during neuroblastoma carcinogenesis.     

Human Y‐chromosome short tandem repeats: A tale of acculturation and migrations as mechanisms for the diffusion of agriculture in the Balkan Peninsula

Southeastern Europe and, particularly, the Balkan Peninsula are especially useful when studying the mechanisms responsible for generating the current distribution of Paleolithic and Neolithic genetic signals observed throughout Europe. In this study, 404 individuals from Montenegro and 179 individuals from Serbia were typed for 17 Y‐STR loci and compared across 9 Y‐STR loci to geographically targeted previously published collections to ascertain the phylogenetic relationships of populations within the Balkan Peninsula and beyond. We aim to provide information on whether groups in the region represent an amalgamation of Paleolithic and Neolithic genetic substrata, or whether acculturation has played a critical role in the spread of agriculture. We have found genetic markers of Middle Eastern, south Asian and European descent in the area, however, admixture analyses indicate that over 80% of the Balkan gene pool is of European descent. Altogether, our data support the view that the diffusion of agriculture into the Balkan region was mostly a cultural phenomenon although some genetic infiltration from Africa, the Levant, the Caucasus, and the Near East has occurred. Am J Phys Anthropol, 2010. © 2010 Wiley‐Liss, Inc.