Augmenting Endogenous Wnt Signaling Improves Skin Wound Healing

Wnt signaling is required for both the development and homeostasis of the skin, yet its contribution to skin wound repair remains controversial. By employing Axin2^LacZ/+ reporter mice we evaluated the spatial and temporal distribution patterns of Wnt responsive cells, and found that the pattern of Wnt responsiveness varies with the hair cycle, and correlates with wound healing potential. Using Axin2^LacZ/LacZ mice and an ear wound model, we demonstrate that amplified Wnt signaling leads to improved healing. Utilizing a biochemical approach that mimics the amplified Wnt response of Axin2^LacZ/LacZ mice, we show that topical application of liposomal Wnt3a to a non-healing wound enhances endogenous Wnt signaling, and results in better skin wound healing. Given the importance of Wnt signaling in the maintenance and repair of skin, liposomal Wnt3a may have widespread application in clinical practice.     

Competition over Personal Resources Favors Contribution to Shared Resources in Human Groups

Members of social groups face a trade-off between investing selfish effort for themselves and investing cooperative effort to produce a shared group resource. Many group resources are shared equitably: they may be intrinsically non-excludable public goods, such as vigilance against predators, or so large that there is little cost to sharing, such as cooperatively hunted big game. However, group members'' personal resources, such as food hunted individually, may be monopolizable. In such cases, an individual may benefit by investing effort in taking others'' personal resources, and in defending one''s own resources against others. We use a game theoretic “tug-of-war” model to predict that when such competition over personal resources is possible, players will contribute more towards a group resource, and also obtain higher payoffs from doing so. We test and find support for these predictions in two laboratory economic games with humans, comparing people''s investment decisions in games with and without the options to compete over personal resources or invest in a group resource. Our results help explain why people cooperatively contribute to group resources, suggest how a tragedy of the commons may be avoided, and highlight unifying features in the evolution of cooperation and competition in human and non-human societies.     

Integration of Motion Responses Underlying Directional Motion Anisotropy in Human Early Visual Cortical Areas

Recent imaging studies have reported directional motion biases in human visual cortex when perceiving moving random dot patterns. It has been hypothesized that these biases occur as a result of the integration of motion detector activation along the path of motion in visual cortex. In this study we investigate the nature of such motion integration with functional MRI (fMRI) using different motion stimuli. Three types of moving random dot stimuli were presented, showing either coherent motion, motion with spatial decorrelations or motion with temporal decorrelations. The results from the coherent motion stimulus reproduced the centripetal and centrifugal directional motion biases in V1, V2 and V3 as previously reported. The temporally decorrelated motion stimulus resulted in both centripetal and centrifugal biases similar to coherent motion. In contrast, the spatially decorrelated motion stimulus resulted in small directional motion biases that were only present in parts of visual cortex coding for higher eccentricities of the visual field. In combination with previous results, these findings indicate that biased motion responses in early visual cortical areas most likely depend on the spatial integration of a simultaneously activated motion detector chain.     

A REAPPRAISAL OF PORPHYRA AND BANGIA (BANGIOPHYCIDAE, RHODOPHYTA) IN THE NORTHEAST ATLANTIC BASED ON THE rbcL–rbcS INTERGENIC SPACER

Sequence data of the rbc L –rbc S noncoding intergenic spacer of the plastid genome for 47 specimens of Porphyra and Bangia from the northeast Atlantic reveal that they fall into 11 distinct sequences: P. purpurea, P. dioica (includes a sample of P. "ochotensis" from Helgoland), P. amplissima (includes P. thulaea and British records of P. "miniata" ), P. linearis, P. umbilicalis, P. "miniata", B. atropurpurea s.l. from Denmark and B. atropurpurea s.l. from Wales, P. drachii, P. leucosticta (includes a British record of P. "miniata var. abyssicola" ), and P. "insolita" (includes P. "yezoensis" from Helgoland). Of these, data obtained for P. purpurea , P. dioica, P. amplissima, P. linearis, P. umbilicalis, P. drachii, and P. leucosticta were based on type specimens or material compared with types. Comparison of sequence data for Porphyra spp. and Bangia atropurpurea s.l. (including B. fuscopurpurea, the type species of Bangia ) confirms that the species are congeneric. The data also confirm that the number of layers that make up the Porphyra thallus are not taxonomically significant. Comparison of sequence data for species from the northeast Atlantic with those for material of two species from the Pacific reveals that the species fall into two distinct groupings: an Atlantic group, containing P. purpurea, P. dioica, P. amplissima, P. linearis, P. umbilicalis, P. "miniata", and B. atropurpurea, and a Pacific group, containing P. "pseudolinearis", P. drachii, P. leucosticta, P. "yezoensis" (including a sample of P. "tenera" ), and P. "insolita" (including P. "yezoensis" from Helgoland). The possibility of alien species in the northeast Atlantic is discussed.     

Terpenoids from Zingiber officinale (Ginger) Induce Apoptosis in Endometrial Cancer Cells through the Activation of p53

Novel strategies are necessary to improve chemotherapy response in advanced and recurrent endometrial cancer. Here, we demonstrate that terpenoids present in the Steam Distilled Extract of Ginger (SDGE) are potent inhibitors of proliferation of endometrial cancer cells. SDGE, isolated from six different batches of ginger rhizomes, consistently inhibited proliferation of the endometrial cancer cell lines Ishikawa and ECC-1 at IC₅₀ of 1.25 µg/ml. SDGE also enhanced the anti-proliferative effect of radiation and cisplatin. Decreased proliferation of Ishikawa and ECC-1 cells was a direct result of SDGE-induced apoptosis as demonstrated by FITC-Annexin V staining and expression of cleaved caspase 3. GC/MS analysis identified a total of 22 different terpenoid compounds in SDGE, with the isomers neral and geranial constituting 30–40%. Citral, a mixture of neral and geranial inhibited the proliferation of Ishikawa and ECC-1 cells at an IC₅₀ 10 µM (2.3 µg/ml). Phenolic compounds such as gingerol and shogaol were not detected in SDGE and 6-gingerol was a weaker inhibitor of the proliferation of the endometrial cancer cells. SDGE was more effective in inducing cancer cell death than citral, suggesting that other terpenes present in SDGE were also contributing to endometrial cancer cell death. SDGE treatment resulted in a rapid and strong increase in intracellular calcium and a 20–40% decrease in the mitochondrial membrane potential. Ser-15 of p53 was phosphorylated after 15 min treatment of the cancer cells with SDGE. This increase in p53 was associated with 90% decrease in Bcl2 whereas no effect was observed on Bax. Inhibitor of p53, pifithrin-α, attenuated the anti-cancer effects of SDGE and apoptosis was also not observed in the p53^neg SKOV-3 cells. Our studies demonstrate that terpenoids from SDGE mediate apoptosis by activating p53 and should be therefore be investigated as agents for the treatment of endometrial cancer.     

Interaction of gravi- and phototropic stimulation in the response of maize (Zea mays L.) coleoptiles

The influence of gravitropic stimulation upon blue-light-induced first positive phototropism for stimulations in the same (light source and center of gravity opposite to each other) and in opposing directions was investigated in maize cole-optiles by measuring fluence-response patterns. As a result of gravitropic counterstimulation, phototropic bending was transient with maximum curvature occurring 100 min after stimulation. On a horizontal clinostat, however, the seedlings curved for 20 h. Gravistimulation in the opposite direction acted additively upon blue-light curvature. Gravistimulation in the same direction as phototropic stimulation produced a complex behaviour deviating from simple additivity. This pattern can be explained by a gravitropically mediated sensitization of the phototropic reaction, an optimal dependence of differential growth on the sum of photo-and gravistimulation, and blue-light-induced inhibition of gravitropic curvature at high fluences. These findings indicate that several steps of photo-and gravitransduction are separate. Preirradiation with red light desensitized the system independently of applied gravity-treatment, indicating that the site of red-light interaction is common to both transduction chains.Abbreviations BL blue light - G⁺ stimulation by light and gravity in the same direction (i.e. light source and center of gravity opposite to each other) - G^- stimulation by light and gravity in opposing directions     

Generation of the truncated form of the nerve growth factor receptor by rat Schwann cells. Evidence for post-translational processing.

These studies were initiated to determine whether the soluble, truncated form of the nerve growth factor (NGF) receptor arises from post-translational processing of the intact, membrane-bound receptor or from an alternatively spliced mRNA. Pulse-chase analysis of cultured primary rat Schwann cells coupled with immunoprecipitations using antibodies to the intracellular and extracellular domains of the receptor were used to monitor receptor production. Three forms of the NGF receptor (80, 83, and 85 kDa) displaying a precursor product relationship were detected over the 2-h chase period; only the 85-kDa species was detected on the cell surface. Truncated receptors (50 and 52 kDa) were detected in conditioned media 5 h after cell labeling but were never observed intracellularly. Polymerase chain reaction and RNase protection analyses of NGF receptor mRNA targeted toward the coding region for the transmembrane domain detected no splice variants that could generate truncated receptor, and media conditioned by fibroblasts transfected with rat receptor cDNA, in which splicing cannot occur, nonetheless contained the truncated receptor protein. Taken together, these results suggest that the truncated NGF receptor does not arise as a distinct translation product but rather from a post-translational modification of the intact, surface-bound form of the protein.