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Search Results: 1 - 10 of 297787 matches for " Carrie J Shawber "
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Notch regulates the angiogenic response via induction of VEGFR-1
Yasuhiro Funahashi, Carrie J Shawber, Marina Vorontchikhina, Anshula Sharma, Hasina H Outtz, Jan Kitajewski
Vascular Cell , 2010, DOI: 10.1186/2040-2384-2-3
Abstract: Vascular endothelial growth factor-A (VEGF-A) is essential to the multistep process of vascular development, and proper vessel formation in a variety of settings is exquisitely sensitive to levels of VEGF-A [1-4]. VEGF-A signals through two receptor tyrosine kinases: VEGFR-1 (flt1) and VEGFR-2 (flk1), while placenta growth factor (PlGF) signals exclusively through VEGFR-1. Both VEGF-A and PlGF induce endothelial cell proliferation, survival, and migration [3,5,6]. The role of VEGFR-1 in angiogenesis has largely been defined in terms of its opposition to VEGFR-2. VEGFR-2 is considered the primary VEGF-A receptor that drives angiogenesis, while VEGFR-1 has high binding affinity for VEGF-A but weak kinase activity. Thus, VEGFR-1 is thought to function mainly as a decoy receptor that sequesters VEGF-A [7-11]. This concept is supported by analysis of mouse models where deletion of flt1 led to vessel overgrowth and disruption of vascular patterning [12]. In addition, mice expressing a mutant allele of flt1 that lacks the tyrosine kinase domain (flt1TK-/-) did not exhibit the vascular patterning defects seen in flt1-/-mice, suggesting that in embryonic development, the kinase activity of VEGFR-1 was dispensable and that its predominant function is via its high affinity binding to VEGF-A [9]. Despite this, a positive function for VEGFR-1 in angiogenesis has been demonstrated in a variety of settings. flt1TK-/- mice displayed defects in tumor vessel formation and metastasis [13,14], and inhibition of VEGFR-1 led to defects in neovascularization of the eye [15]. The signaling pathways that regulate VEGFR-1 expression in endothelial cells remain unclear.Notch, a receptor that functions in cell fate decisions, has been shown to be downstream of VEGF-A in endothelial sprouting [16,17] and arterial specification [18,19]. The Notch proteins are highly conserved trans-membrane receptors that are required for normal embryonic development. In mammals, there are four Notch proteins (N
Notch modulates VEGF action in endothelial cells by inducing Matrix Metalloprotease activity
Yasuhiro Funahashi, Carrie J Shawber, Anshula Sharma, Emi Kanamaru, Yun K Choi, Jan Kitajewski
Vascular Cell , 2011, DOI: 10.1186/2045-824x-3-2
Abstract: We assessed the relationship between VEGF and Notch signaling in cultured human umbilical vein endothelial cells. Overexpression of VEGF-induced Notch4 and the Notch ligand, Dll4, activated Notch signaling, and altered endothelial cell morphology in a fashion similar to that induced by Notch activation. Expression of a secreted Notch antagonist (Notch1 decoy) suppressed VEGF-mediated activation of endothelial Notch signaling and endothelial morphogenesis. We demonstrate that Notch mediates VEGF-induced matrix metalloprotease activity via induction of MMP9 and MT1-MMP expression and activation of MMP2. Introduction of a MMP inhibitor blocked Notch-mediated endothelial morphogenesis. In mice, analysis of VEGF-induced dermal angiogenesis demonstrated that the Notch1 decoy reduced perivascular MMP9 expression.Taken together, our data demonstrate that Notch signaling can act downstream of VEGF signaling to regulate endothelial cell morphogenesis via induction and activation of specific MMPs. In a murine model of VEGF-induced dermal angiogenesis, Notch inhibition led to reduced MMP9 expression.Angiogenesis, the formation of new blood vessels from existing vasculature, is a multi-step process that plays a central role in embryogenesis and pathological phenomena. Vascular Endothelial Growth Factor (VEGF) is a key regulator of angiogenesis and is important for the degradation of extracellular matrix (ECM), as well as the subsequent proliferation, migration, and survival of endothelial cells. ECM components, including fibrins, collagens, and laminins, form a lamina around existing vasculature that must be degraded in order to form new vessels.VEGF signaling via VEGFR-2 induces the expression of endothelial cell-derived matrix metalloproteases (MMPs), including MMP2 [1], MMP9 [2], and MT1-MMP [3], which degrade the matrix to allow for endothelial sprouting. MMPs are thus essential for angiogenesis, and their loss from either endothelium or inflammatory cells has been associate
Z-Structures on Product Groups
Carrie J. Tirel
Mathematics , 2010,
Abstract: A Z-structure on a group G, defined by M. Bestvina, is a pair (\hat{X}, Z) of spaces such that \hat{X} is a compact ER, Z is a Z-set in \hat{X}, G acts properly and cocompactly on X=\hat{X}\Z, and the collection of translates of any compact set in X forms a null sequence in \hat{X}. It is natural to ask whether a given group admits a Z-structure. In this paper, we will show that if two groups each admit a Z-structure, then so do their free and direct products.
Adolescent Adjustment: The Hazards of Conflict Avoidance and the Benefits of Conflict Resolution  [PDF]
Megan E. Ubinger, Paul J. Handal, Carrie E. Massura
Psychology (PSYCH) , 2013, DOI: 10.4236/psych.2013.41007

Current literature provides strong support for the relationship between perceived family conflict (i.e., disagreements, expressed anger, and/or aggression) and adolescent maladjustment (i.e., internalizing, externalizing, and/or physiological symptoms). Moreover, research indicates that successful conflict resolution (i.e., “behaviors that regulate, reduce, or terminate conflicts,” Davies & Cummings, 1994) decreases the adverse impact family conflict has on children. Many researchers have treated conflict resolution as a dichotomous variable (e.g., resolved or unresolved), but there may be different approaches to conflict resolution. Only one dimensional measure of conflict resolution has been developed in the literature, and it has only been used in a sample of young adults. Recent research has also underscored the importance of assessing conflict avoidance (i.e., indirect efforts to alter stressful situations). Unfortunately, there are limited studies on conflict avoidance and its impact on psychological adjustment, none of which use an adolescent sample. The primary purpose of the current study was to determine whether the relationship between conflict resolution, conflict avoidance, and adjustment would extend to adolescents using a dimensional measure of conflict resolution. Second, the current study aimed to develop and pilot a dimensional measure of conflict avoidance. One hundred two adolescents between the ages of 14 and 19 were recruited from four parochial high schools in a large Midwestern city. The participants completed self-report measures regarding perceived family conflict, conflict resolution, avoidant behaviors, and psychological adjustment. Results paralleled the findings of previous research in a young adult sample regarding the impact of conflict resolution on adjustment. In addition, after considering perceived family conflict, the presence of conflict avoidance added significantly to the prediction of adolescents’ psychological symptoms. These findings suggest that assessing for conflict avoidance in addition to family conflict and conflict resolution may have important implications for the screening and assessment of adolescent psychological health.

The Effects of Rearing Temperature on American Glass Eels  [PDF]
Carrie J. Blakeslee, Heather S. Galbraith, Robert M. Deems
Agricultural Sciences (AS) , 2018, DOI: 10.4236/as.2018.98074
Abstract: American eels are declining throughout their range requiring a better understanding of physiological requirements of all life stages and optimal conditions for laboratory rearing and aquaculture. American glass eels (Anguilla rostrata) were housed for 3 weeks at 14°C, 18°C, 22°C, or 26°C to determine optimal juvenile rearing temperature in the laboratory. All treatments exhibited weight gain over the course of the study except the 14°C treatment; however, there were only marginal differences in final weight between the 18°C and 14°C treatments and no differences in length. Variation in length and weight generally increased as temperature increased with significant differences in the standard error of weight between 14°C and the 22°C and 26°C treatments and between 18°C and 26°
ZIP4H (TEX11) Deficiency in the Mouse Impairs Meiotic Double Strand Break Repair and the Regulation of Crossing Over
Carrie A. Adelman,John H. J. Petrini
PLOS Genetics , 2008, DOI: 10.1371/journal.pgen.1000042
Abstract: We have recently shown that hypomorphic Mre11 complex mouse mutants exhibit defects in the repair of meiotic double strand breaks (DSBs). This is associated with perturbation of synaptonemal complex morphogenesis, repair and regulation of crossover formation. To further assess the Mre11 complex's role in meiotic progression, we identified testis-specific NBS1-interacting proteins via two-hybrid screening in yeast. In this screen, Zip4h (Tex11), a male germ cell specific X-linked gene was isolated. Based on sequence and predicted structural similarity to the S. cerevisiae and A. thaliana Zip4 orthologs, ZIP4H appears to be the mammalian ortholog. In S. cerevisiae and A. thaliana, Zip4 is a meiosis-specific protein that regulates the level of meiotic crossovers, thus influencing homologous chromosome segregation in these organisms. As is true for hypomorphic Nbs1 (Nbs1ΔB/ΔB) mice, Zip4h?/Y mutant mice were fertile. Analysis of spermatocytes revealed a delay in meiotic double strand break repair and decreased crossover formation as inferred from DMC1 and MLH1 staining patterns, respectively. Achiasmate chromosomes at the first meiotic division were also observed in Zip4h?/Y mutants, consistent with the observed reduction in MLH1 focus formation. These results indicate that meiotic functions of Zip4 family members are conserved and support the view that the Mre11 complex and ZIP4H interact functionally during the execution of the meiotic program in mammals.
Mechanisms Underlying the Link between Cannabis Use and Prospective Memory
Carrie Cuttler, Ryan J. McLaughlin, Peter Graf
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0036820
Abstract: While the effects of cannabis use on retrospective memory have been extensively examined, only a limited number of studies have focused on the links between cannabis use and prospective memory. We conducted two studies to examine the links between cannabis use and both time-based and event-based prospective memory as well as potential mechanisms underlying these links. For the first study, 805 students completed an online survey designed to assess cannabis consumption, problems with cannabis use indicative of a disorder, and frequency of experiencing prospective memory failures. The results showed small to moderate sized correlations between cannabis consumption, problems with cannabis use, and prospective memory. However, a series of mediation analyses revealed that correlations between problems with cannabis use and prospective memory were driven by self-reported problems with retrospective memory. For the second study, 48 non-users (who had never used cannabis), 48 experimenters (who had used cannabis five or fewer times in their lives), and 48 chronic users (who had used cannabis at least three times a week for one year) were administered three objective prospective memory tests and three self-report measures of prospective memory. The results revealed no objective deficits in prospective memory associated with chronic cannabis use. In contrast, chronic cannabis users reported experiencing more internally-cued prospective memory failures. Subsequent analyses revealed that this effect was driven by self-reported problems with retrospective memory as well as by use of alcohol and other drugs. Although our samples were not fully characterized with respect to variables such as neurological disorders and family history of substance use disorders, leaving open the possibility that these variables may play a role in the detected relationships, the present findings indicate that cannabis use has a modest effect on self-reported problems with prospective memory, with a primary problem with retrospective memory appearing to underlie this relationship.
The Role of Protein Crystallography in Defining the Mechanisms of Biogenesis and Catalysis in Copper Amine Oxidase
Valerie J. Klema,Carrie M. Wilmot
International Journal of Molecular Sciences , 2012, DOI: 10.3390/ijms13055375
Abstract: Copper amine oxidases (CAOs) are a ubiquitous group of enzymes that catalyze the conversion of primary amines to aldehydes coupled to the reduction of O 2 to H 2O 2. These enzymes utilize a wide range of substrates from methylamine to polypeptides. Changes in CAO activity are correlated with a variety of human diseases, including diabetes mellitus, Alzheimer’s disease, and inflammatory disorders. CAOs contain a cofactor, 2,4,5-trihydroxyphenylalanine quinone (TPQ), that is required for catalytic activity and synthesized through the post-translational modification of a tyrosine residue within the CAO polypeptide. TPQ generation is a self-processing event only requiring the addition of oxygen and Cu(II) to the apoCAO. Thus, the CAO active site supports two very different reactions: TPQ synthesis, and the two electron oxidation of primary amines. Crystal structures are available from bacterial through to human sources, and have given insight into substrate preference, stereospecificity, and structural changes during biogenesis and catalysis. In particular both these processes have been studied in crystallo through the addition of native substrates. These latter studies enable intermediates during physiological turnover to be directly visualized, and demonstrate the power of this relatively recent development in protein crystallography.
Considering Other Consumers: Fisheries, Predators, and Atlantic Herring in the Gulf of Maine
Andrew J. Read,Carrie R. Brownstein
Ecology and Society , 2003,
Abstract: After decades of overexploitation and severe depletion, Atlantic herring stocks in waters of the northeastern United States have recovered. Fishery managers now consider the herring resource to be underexploited. Nevertheless, some fishery managers and sustainable fishery advocates in New England have expressed concern that the fishery management plan may not adequately consider the importance of herring as prey for marine mammals, seabirds, and piscivorous fish. Several studies suggest that consumption by these predators is significant, yet trophic interactions are not explicitly considered in stock assessment models. Instead, as in most fisheries stock assessments, predation is subsumed within the natural mortality rate, and no empirical estimates of herring consumption are used in the models. The goal of the present study was to assess the consumption of herring by marine mammals and to compare this level of consumption with estimates of natural mortality derived from herring stock assessment models. Using the most recent estimates of abundance and the best available data on diet, we estimated total annual consumption of herring by eight marine mammal species in the Gulf of Maine. Our results indicate that marine mammals consume 93,802–189,898 metric tons (mt; 1 metric ton = 1000 kg) of herring annually. In addition, piscivorous fish and seabirds are important predators of herring. We estimate that the consumption of herring by these upper trophic level predators may have exceeded the estimate of natural mortality used in stock assessment models by more than fourfold in 1991. We suggest that fisheries management must move beyond a single-species approach to one that includes formal consideration of trophic relationships.
Strange Bedfellows: Youth Activists, Government Sponsorship, and the Company of Young Canadians (CYC), 1965-1970
William J. Campbell,Carrie A. Dickenson
European Journal of American Studies , 2008, DOI: 10.4000/ejas.2862
Abstract: 1. IntroductionThroughout the 1950s small groups of anti-conformists from Greenwich Village, New York City left the east coast and relocated to the North Beach area of San Francisco. Influenced by the writings of Jack Kerouac, Allen Ginsberg and William S. Burroughs, The Beats often chose to settle in rundown neighborhoods that had been in decline since the Depression called The Haight. By the summer of 1967 it was not the cheap rent that lured many prominent activists and hordes of youth to ...
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