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Angiocidin, a tumor-associated peptide, has been previously shown to inhibit tumor progression by blocking angiogenesis. We now show that angiocidin has a direct inhibitory effect on tumor cell proliferation. MDA-MB-231 breast cancer cells were inhibited from proliferating in the presence of epidermal growth factor (EGF) and angiocidin. Angiocidin transfected breast cancer cells also displayed growth inhibition in vitro and failed to develop significant tumors in mice as compared to vector controls. The anti-proliferative effect of angiocidin was reversed by treating the cells with the epidermal growth factor receptor (EGFR) inhibitor 4557W, a potent tyrosine kinase inhibitor. Consistent with these results, we found that treatment of breast cancer cells with angiocidin induced a 2.3 fold increase in EGFR tyrosine 845 phosphorylation while no change in phosphorylation was observed in the remaining 16 phosphorylation sites of EGFR and those of its family members as measured by a human EGFR phosphorylation array. Treatment of breast cancer cells with angiocidin also resulted in the activation of nuclear factor ĸB (Nf-ĸB) and the de novo up-regulation of many down-stream genes transcribed by Nf-ĸB, including cytokines, inflammatory mediators and the cell cycle inhibitor p21(waf1). Therefore, angiocidin is a peptide that not only inhibits tumor angiogenesis but also directly induces inhibition of tumor growth progression through the activation of EGFR and down-stream genes transcribed by Nf-ĸB., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The temporal and spatial control of organ-specific endoderm progenitor development is poorly understood. miRNAs affect cell function by regulating programmatic changes in protein expression levels. We show that the miR302/367 cluster is a target of the transcription factor Gata6 in mouse lung endoderm and regulates multiple aspects of early lung endoderm progenitor development. miR302/367 is expressed at early stages of lung development, but its levels decline rapidly as development proceeds. Gain- and loss-of-function studies show that altering miR302/367 expression disrupts the balance of lung endoderm progenitor proliferation and differentiation, as well as apical-basal polarity. Increased miR302/367 expression results in the formation of an undifferentiated multi-layered lung endoderm, whereas loss of miR302/367 activity results in decreased proliferation and enhanced lung endoderm differentiation. miR302/367 coordinates the balance between proliferation and differentiation, in part, through direct regulation of Rbl2 and Cdkn1a, whereas apical-basal polarity is controlled by regulation of Tiam1 and Lis1. Thus, miR302/367 directs lung endoderm development by coordinating multiple aspects of progenitor cell behavior, including proliferation, differentiation and apical-basal polarity.

Objectives: Previous research has demonstrated that ligands for the gamma subtype of peroxisome proliferator-activated receptors (PPARs) reduce inflammation in two different murine models of colitis. This study was designed to examine the potential efficacy of rosiglitazone, a ligand for the gamma subtype of PPARs, as a therapy for active ulcerative colitis., Methods: Fifteen patients with mild to moderately active ulcerative colitis despite therapy with 5-aminosalicylic acid compounds were enrolled in an open-label study of rosiglitazone (4 mg b.i.d. p.o.) for 12 wk. Thirteen of 15 patients were receiving concomitant therapy with corticosteroids and/or immunomodulator medications. Disease activity was measured with the Disease Activity Index., Results: After 12 wk of therapy, four patients (27%) had achieved clinical remission, of whom three (20%) also had an endoscopic remission. Four additional patients (27%) had a clinical response without achieving remission. Two patients were hospitalized with worsened disease activity, and one patient was withdrawn for nephrotic syndrome., Conclusions: These data suggest that ligands for the gamma subtype of PPARs may represent a novel therapy for ulcerative colitis. A double blind, placebo-controlled, randomized trial is warranted.

Rab8 is a GTPase involved in membrane trafficking. In photoreceptor cells, rab8 is proposed to participate in the late stages of delivery of rhodopsin-containing post-Golgi membranes to the plasma membrane near the base of the connecting cilium. To test the function of rab8 in vivo, we generated transgenic Xenopus laevis expressing wild-type, constitutively active (Q67L), and dominant negative (T22N) forms of canine rab8 in their rod photoreceptors as green fluorescent protein (GFP) fusion proteins. Wild-type and constitutively active GFP-rab8 proteins were primarily associated with Golgi and post-Golgi membranes, whereas the dominant negative protein was primarily cytoplasmic. Expression of wild-type GFP-rab8 had minimal effects on cell survival and intracellular structures. In contrast, GFP-rab8T22N caused rapid retinal degeneration. In surviving peripheral rods, tubulo-vesicular structures accumulated at the base of the connecting cilium. Expression of GFP-rab8Q67L induced a slower retinal degeneration in some tadpoles. Transgene effects were transmitted to F1 offspring. Expression of the GFP-rab8 fusion proteins appears to decrease the levels of endogenous rab8 protein. Our results demonstrate a role for rab8 in docking of post-Golgi membranes in rods, and constitute the first report of a transgenic X. laevis model of retinal degenerative disease.

Mislocalization of the photopigment rhodopsin may be involved in the pathology of certain inherited retinal degenerative diseases. Here, we have elucidated rhodopsin's targeting signal which is responsible for its polarized distribution to the rod outer segment (ROS). Various green fluorescent protein (GFP)/rhodopsin COOH-terminal fusion proteins were expressed specifically in the major red rod photoreceptors of transgenic Xenopus laevis under the control of the Xenopus opsin promoter. The fusion proteins were targeted to membranes via lipid modifications (palmitoylation and myristoylation) as opposed to membrane spanning domains. Membrane association was found to be necessary but not sufficient for efficient ROS localization. A GFP fusion protein containing only the cytoplasmic COOH-terminal 44 amino acids of Xenopus rhodopsin localized exclusively to ROS membranes. Chimeras between rhodopsin and alpha adrenergic receptor COOH-terminal sequences further refined rhodopsin's ROS localization signal to its distal eight amino acids. Mutations/deletions of this region resulted in partial delocalization of the fusion proteins to rod inner segment (RIS) membranes. The targeting and transport of endogenous wild-type rhodopsin was unaffected by the presence of mislocalized GFP fusion proteins.

This paper presents and analyzes findings from unstructured interviews with women aged 61 to 92 regarding their perceptions and feelings about their aging bodies. The data are discussed in light of the existing literature on women's body image which has largely ignored the experiences of women in later life and which has tended to focus on adolescent and middle-aged women. Given the fact that beauty is equated with youthfulness and thinness in our society, older women face unique challenges as they strive to construct and maintain positive evaluations of self. The women in the study exhibit the internalization of ageist beauty norms even as they assert that health is more important to them than physical attractiveness and comment on the 'naturalness' of the aging process.

Traditional treatment approaches for patients with inflammatory bowel disease involve 1) pharmacologic management with aminosalicylates, corticosteroids, immunomodulatory agents, and antibiotics; and 2) nonpharmacologic management by surgical and dietary means. Complications and inadequate responses to current treatment modalities have resulted in the development of new and more specific biologic therapies. The proinflammatory cytokine tumor necrosis factor alpha (TNF alpha) is present in elevated concentrations in patients with inflammatory bowel disease; therefore, it has been targeted for treatment approaches. Infliximab is a chimeric, monoclonal antibody to TNF alpha developed to inhibit the interaction of TNF alpha with its receptor, to result in amelioration of inflammation. This biologic agent has received the most attention and is the most studied of those for the treatment of patients with Crohn's disease. This article reviews the symptoms of inflammatory bowel disease, the traditional treatment approaches used, the role of TNF alpha in disease pathogenesis, and the value of infliximab in treatment.

Labeling cochlear nerve fibers in the inner ear of chinchillas with biotinylated dextran polyamine was used to trace the thin fibers (Type II), which likely innervate outer hair cells. These axons, 0. 1-0.5 microm in diameter, were distinguished from the thicker Type I, fibers innervating inner hair cells, and traced to small-cell clusters in the cochlear nucleus. This study provided two major new insights into the outer hair cell connections in the cochlear nucleus and the potential significance of very thin axons and synaptic nests, which are widespread in the CNS. 1) EM serial reconstructions of labeled and unlabeled material revealed that Type II axons rarely formed synapses with conventional features (vesicles gathered at junctions). Rather, their endings contained arrays of endoplasmic reticulum and small spherical vesicles without junctions. 2) Type II axons projected predominantly to synaptic nests, where they contacted other endings and dendrites of local interneurons (small stellate and mitt cells, but not granule cells). Synaptic nests lacked intrinsic glia and, presumably, their high-affinity amino acid transporters. As functional units, nests and their Type II inputs from outer hair cells may contribute to an analog processing mode, which is slower, more diffuse, longer-lasting, and potentially more plastic than the digital processors addressed by inner hair cells., (Copyright 1999 Wiley-Liss, Inc.)

We tested the hypothesis that a generalist arthropod predator, Tenodera sinensis Saussure, could trigger a trophic cascade in an old-field ecosystem. These mantids had relatively weak effects on abundance and biomass of other carnivorous arthropods as a group. The effect of mantids on herbivores was stronger than on carnivores, mainly concentrated in Homoptera and Diptera. Herbivore load was reduced by mantids with the consequence that overall plant biomass (mainly grasses) was increased. Percapita interaction strengths between mantids and other arthropod taxa were, for the most part, weakly negative. Our study demonstrates that a significant trophic cascade can be triggered by a generalist predator even within the framework of a diverse community with relatively diffuse interactions.

We undertook a preliminary investigation of the cuticular extracts of five common mantid species in the eastern United States: Tenodera sinensis (Saussure), T. angustipennis (Saussure) and Mantis religiosa (Linnaeus) introduced from the Old World and Stagmomantis carolina (Johannson) and Bruneria borealis (Scudder), which are New World species. The major components of these mixtures were normal alkanes, predominately hentriacontane, or in the case of the parthenogenic species B. borealis, tritriacontane. Tricontanal was detected in the extracts of all five species, and smaller amounts of other aldehydes and n-tricontanol were detected in some species. Complex mixtures of methyl and dimethylalkanes also were present in these extracts. The composition of the cuticular hydrocarbons of these mantids may be an adaptation for reduction of evaporative water loss in these insects that inhabit open fields.

Relative timing of egg hatch between two cooccurring, congeneric mantids, Tenodera angustipennis and T. sinensis, was experimentally manipulated in replicated field enclosures to test the importance of intraguild predation to survivorship and development of T. angustipennis. T. angustipennis is normally smaller than its congener because of later egg-hatch. Delaying introduction of T. sinensis relative to normal egg hatch phenology reduced mortality for T. angustipennis, but did not affect its rate of development. The results indicate that intraguild predation by normally earlierhatching T. sinensis can be an important factor in the early life history of T. angustipennis, but that interspecific competition is not a strong selective factor in developmental asynchrony between these two species.

We investigated the short-term response of an arthropod assemblage to elevated generalist predator densities by introducing Chinese mantids (Tenodera sinensis) to field plots in a replicated, controlled experiment. Abundances of carnivorous arthropods were reduced by mantids to a greater extent than herbivores, and cursorial spiders emigrated from treatment plots in greater numbers than from controls. Initially, this emigration consisted only of small spiders that were demonstrated in the laboratory to be prey for mantids. Thus, the initial response of an arthropod assemblage to increased predators, densities was increased interactions among predators, which caused decline in predator population densities in a shorter time than competition for prey would require. Predator avoidance behavior must be considered together with intraguild predation and competition when interpreting the outcome of predator manipulations. Shortterm experiments may be more valuable than longer term studies in detecting this effect.

Although serotonin is thought to be a neurotransmitter in a number of retinal systems, much of the precise synaptic connectivity of serotonergic neurons is unknown. To address this issue, we used an antiserum directed against serotonin to label serotonergic bipolar and amacrine cells in the turtle retina. Light-microscopic analysis of labeled amacrine and bipolar cells indicated that both had bistratified dendritic arborizations primarily in stratum 1 and in strata 4/5 of the inner plexiform layer. Ultrastructural analysis of the neurocircuitry of these cells indicated that the processes of labeled bipolar cells in the outer plexiform layer made basal junction contacts with photoreceptor terminals. Only in rare instances did labeled bipolar cells processes invaginate near photoreceptor ribbon synapses. Processes of labeled bipolar cells received both conventional and small ribbon synaptic contacts in the outer plexiform layer. Bipolar cell processes in stratum 1 of the inner plexiform layer synapsed onto either amacrine/amacrine or amacrine/ganglion cell dyads, and made rare ribbon synaptic contacts onto labeled amacrine cell processes. Synaptic inputs to serotonergic bipolar cells in stratum 1 were from unlabeled bipolar and amacrine cells. Bipolar cell contacts in strata 4/5 were similar to those in stratum 1, but were fewer in number and no bipolar cell inputs were seen. Labeled amacrine cell output in both strata was onto other unlabeled amacrine cells and ganglion cells; but synaptic outputs to unlabeled bipolar cells were only seen in strata 4/5. In both strata 1 and 4/5, synaptic inputs to labeled amacrine cells were from both unlabeled amacrine cells and labeled bipolar cells. The serotonergic amacrine cells had many more synaptic interactions in stratum 1 than in strata 4/5 which supports the role of serotonergic bipolar cells in the OFF pathway of retinal processing. Interactions between serotonergic bipolar and amacrine cells may play an important role in visual processing.

The structure of cursorial spider assemblages was examined along a gradient of four temperature successional communities. Species diversity (H'), richness (S), and evenness (J') exhibited a dichotomy between herbaceous and woody communities rather than a progressive change with community age: all three parameters were higher in the two younger fields than in the two older woodlands, which is contrary to conventional successional theory. Species importance curves were steeper in the two woody communities. The breadth of the distribution of adult body lengths was greater in the two herbaceous communities. Indices of community similarity revealed neither a successional trend nor the vegetative dichotomy. We suggest the hypothesis that habitat structure is a more important determinant of cursorial spider diversity than successional age per se, and that the switch in dominance from herbaceous to woody vegetation is the critical change. We further suggest that competition for prey is more important to cursorial spiders in early successional (herbaceous) communities, because of a switch in the limiting resource from prey in these communities to the amount of accumulating litter (a spatial resource) in older woody stands. This may explain the greater variation in adult body size of these generalist predators in the two younger communities.

Experiments were performed to determine if earlier colonists inhibited, enhanced, or were necessary for establishment of later colonists during development of an estuarine fouling community at Lewes, Delaware. We determined the significance of earlier stages on the successional process by functionally removing early colonizing species. Since settlement of sessile invertebrates onto our experimental test plates was seasonal, we were able to accomplish functional removal of early colonists by putting out clean test panels after these species had ceased settling. Comparisons between panels initially submerged at three different times in 1974 and 1975, and between panels put out at one-month intervals throughout the study (to describe seasonal settlement patterns) allowed us to determine interactions between adult populations of earlier colonists and colonizing individuals of later arriving species.The dominant sessile species in our system and their times of settlement were: a barnacle (Balanus improvisus) - April through June, a polychaete (Hydroides dianthus) - July and August, a tunicate (Molgula manhatensis) - June through October, a hydroid (Tubularia crocea) - July through October, and a mussel (Mytilus edulis) - November through April. All successional series eventually came to be dominated by M. edulis, and it persisted as the dominant for over a year.A variety of species interactions were observed. M. edulis inhibited colonization by all other dominants and B. improvisus partially inhibited settlement of M. manhattensis. The presence of adult M. manhattensis had no influence on summer settlement of T. crocea, but the hydroids enhanced settlement of tunicates in the fall. During both years of our study, larger settlements of mussels were noted on panels harboring tunicates and hydroids than on bare surfaces. H. dianthus, on the other hand, became established only on bare substrates, and colonization was almost totally inhibited by other dominants.Development in our fouling community did not conform to any single model of community development presented to date. Instead, components of several models were observed within our relatively simple (in terms of number of species) system. For example, facilitation (enhancement of later colonists by earlier ones) and inhibition (resistance of earlier colonists to invasion by later colonists) were both observed. However, we found no evidence earlier colonists were essential for establishment of the next developmental stage. In fact, inhibitory interactions appeared to be much more prevalent than facilitative interactions. The former may also have more profound effects on community development since they more often determine eventual species compositions.

gamma-aminobutyric acid (GABA) has been reported to be an important neurotransmitter in the retinas of many species. This immunocytochemical study detailed the localization of antigens resembling GABA and glutamic acid decarboxylase (GAD, an enzyme involved in the synthesis of GABA), in retinal neurons in the turtle, Pseudemys scripta elegans. GABA-like immunoreactivity was present within somata in the inner and outer regions of the inner nuclear layer, within somata in the ganglion cell layer, and in processes in the outer plexiform layer, inner plexiform layer, and ganglion cell axon layer. GAD-like immunoreactivity was found in somata in the inner and outer regions of the inner nuclear layer and in processes in the inner and outer plexiform layers. Cell counts indicated more somata with GABA-like than GAD-like immunoreactivity in the inner nuclear layer. Double-label studies showed that every somata in the inner nuclear layer which had GAD-like immunoreactivity also had GABA-like immunoreactivity, but that many somata had only GABA-like immunoreactivity. The stratification of immunoreactivity within the inner plexiform layer was analyzed using a scanning densitometer. We described the strate within the inner plexiform layer such that S0 represented the inner nuclear layer/inner plexiform layer border and S100 represented the inner plexiform layer/ganglion cell layer border. Analysis of GAD-like labeling yielded seven distinct strata with peak densities at positions S8, S19, S28, S42, S59, S75, and S93. GABA-like labeling provided five distinct strata with peak densities at positions S17, S28, S67, S84, and S95. The strata with peaks of GABA-like immunoreactivity at S17 and S28 were in statistically identical locations to corresponding strata with GAD-like immunoreactivity. The strata with GABA-like immunoreactivity at S67, S84, and S95 did not have statistically identical peaks of correlated GAD-like immunoreactivity, although there were corresponding strata with GAD-like immunoreactivity nearby. Antiserum directed against GABA failed to produce labeled strata at positions corresponding to the strata with GAD-like immunoreactivity at S8 and S42. In summary, our results indicated that the antisera we used, which were directed against GABA and GAD, produced significantly different labeling in the inner nuclear layer, inner plexiform layer, and the ganglion cell body and axon layers of the turtle retina. Until the physiological significance of these differences is resolved, studies employing these markers to investigate the function of GABA in the turtle retina should be interpreted with caution.

A guild of cellular slime molds (CSM) consisting of two isolates from each of five species, representing two genera, and obtained from the same square meter of forest soil exhibited extensive growth rate variation when tested on a suite of 18 bacteria isolated from the same soil. Significant growth rate differences were found at each taxonomic level examined: among species of different genera, between genera, among species within genera, and between isolates (=clones) within species. The type of bacteria used as prey determined the relative rank of the growth rates in different CSM isolates, as well as the taxonomic level at which significant differences were found. We suggest a possible reconciliation between a previous hypothesis, based on competition, and contradictory experimental work on resource partitioning in this guild of bacterial predators. Our results raise a question about the efficacy of using single genotypes to represent a species when ecological ideas are developed through laboratory investigations.

The hypothesis that carrion provides a source of nutrition important to reproduction in the omnivorous neogastropod, Ilyanassa obsoleta (Say), was tested by collecting snails during winter, prior to reproductive season, and allowing them to feed ad libitum on three replicated diets (with starvation control) in the laboratory: vegetable, meat, and a mixture of meat and vegetable.The results indicate that, while a mixed diet is necessary for growth, meat may be the most important dietary constituent in terms of sexual condition and reproductive output of I. obsoleta. It is suggested that the chemotactic response to meat may be strongest for both sexes during the reproductive season, and may be responsible for some of the marked spatial heterogeneity in natural populations.

A new method for measuring structural change in sets of species which have been subjected to natural or experimental perturbation is developed and is shown to be superior to static diversity and evenness measures for this purpose. Three parameters, HΔ', JΔ', and XΔ;} are shown to provide necessary and sufficient information on the severity of a perturbation as well as the uniformity of its effect on all species in the set. When positive and negative changes in species abundance are considered separately, the method is sensitive to compensatory changes which are not detected by static measures.The parameters are then calculated for some data sets on polluted and unpolluted fish communities in second and third order streams from the Clemons Fork watershed in eastern Kentucky. Results indicate that HΔ', the diversity of change over two sampling seasons, is high for perturbed and unperturbed systems, but JΔ' the eveness of change is lower for the communities which were polluted in the second sampling season. Severe pollution results in the suppression of most major fish species, whereas more moderate pollution results in a large number of compensatory changes. The biological basis for such an outcome is discussed, and the notion of these three parameters as the "vital signs" of a healthy ecosystem is presented.

Two sympatric, congeneric mantid species, Tenodera sinensis (Saussure) and t. angustipennis (Saussure) exhibit intrinsically different temporal patterns of egg hatch in the spring. Tenodera sinensis hatches first, and begins to enter second instar by the time T. angustipennis starts to hatch. As a result, there is asynchrony in developmental times such that several different instars may be present during the first crucial month of life when mantid population densities are high and prey availability is low. The body length ratio of larger to smaller nymphs is most commonly ≥1.37, in favor of T. sinensis. This character divergence suggests allochronic niche separation which may alleviate competition for prey. However this same ratio appears to be the threshold for both interspecific predation and cannibalism among these bitrophic generalist predators. Therefore T. sinensis, which is nearly always larger, may have a selective advantage by utilizing its smaller congener and later-hatching conspecifics as prey in a food limited environment.

An ecosystem perturbation experiment in which inorganic fertilizer was added to two successional old fields of different ages indicated that stability, expressed as resistance to modification by enrichment, increased during succession only at the primary trophic level. The perturbation was propagated throughout the arthropod herbivores and carnivores. Both herbivores and carnivores were less stable in the older field. In contrast to current ecological theory, greater diversity at a trophic level was accompanied by lower stability at the next higher level.

The principal raw material of modern U.S. agriculture is fossil fuel, whereas the labor input is relatively small (about 9 hours per crop acre). As agriculture is dependent upon fossil energy, crop production costs will also soar when fuel costs increase two- to fivefold. A return of 2.8 kcal of corn per 1 kcal of fuel input may then be uneconomical. Green revolution agriculture also uses high energy crop production technology, especially with respect to fertilizers and pesticides. While one may not doubt the sincerity of the U.S. effort to share its agricultural technology so that the rest of the world can live and eat as it does, one must be realistic about the resources available to accomplish this mission. In the United States we are currently using an equivalent of 80 gallons of gasoline to produce an acre of corn. With fuel shortages and high prices to come, we wonder if many developing nations will be able to afford the technology of U.S. agriculture. Problems have already occurred with green revolution crops, particularly problems related to pests (57). More critical problems are expected when there is a world energy crisis. A careful assessment should be made of the benefits, costs, and risks of high energy-demand green revolution agriculture in order to be certain that this program will not aggravate the already serious world food situation (58). To reduce energy inputs, green revolution and U.S. agriculture might employ such alternatives as rotations and green manures to reduce the high energy demand of chemical fertilizers and pesticides. U.S. agriculture might also reduce energy expenditures by substituting some manpower currently displaced by mechanization. While no one knows for certain what changes will have to be made, we can be sure that when conventional energy resources become scarce and expensive, the impact on agriculture as an industry and a way of life will be significant. This analysis is but a preliminary investigation of a significant agricultural problem that deserves careful attention and greater study before the energy situation becomes more critical.