81 research outputs found

    DDR2 controls breast tumor stiffness and metastasis by regulating integrin mediated mechanotransduction in CAFs

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    Biomechanical changes in the tumor microenvironment influence tumor progression and metastases. Collagen content and fiber organization within the tumor stroma are major contributors to biomechanical changes (e., tumor stiffness) and correlated with tumor aggressiveness and outcome. What signals and in what cells control collagen organization within the tumors, and how, is not fully understood. We show in mouse breast tumors that the action of the collagen receptor DDR2 in CAFs controls tumor stiffness by reorganizing collagen fibers specifically at the tumor-stromal boundary. These changes were associated with lung metastases. The action of DDR2 in mouse and human CAFs, and tumors in vivo, was found to influence mechanotransduction by controlling full collagen-binding integrin activation via Rap1-mediated Talin1 and Kindlin2 recruitment. The action of DDR2 in tumor CAFs is thus critical for remodeling collagen fibers at the tumor-stromal boundary to generate a physically permissive tumor microenvironment for tumor cell invasion and metastases

    The economic impacts of blackbird (Icteridae) damage to sunflower in the USA

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    BACKGROUND: Blackbird (Icteridae) damage to ripening sunflower (Helianthus annuus L.) has been a persistent economic issue in the USA for the last five decades. To quantify losses, we surveyed blackbird damage from 2001 to 2013 (excluding 2004) to physiologically mature sunflower in eight states: North Dakota, South Dakota, Texas, Nebraska, Minnesota, Colorado, Kansas, and Vermont. RESULTS:We pooled data gathered during the most recent 5 years (2009 to 2013) of the survey and found losses averaged US2.5millionandUS2.5 million and US11.3 million for confectionery and oilseed hybrids, respectively. Three states, North Dakota, South Dakota, and Nebraska, had sufficient acreage and bird damage to warrant economic analyses using a regional economic model. The average annual total (direct plus indirect) economic impact of bird damage to sunflower production for North Dakota, South Dakota, and Nebraska was US18.7million,US18.7million, US7.3 million, and $US2.6million, respectively. CONCLUSION: This study provides a better understanding of the broader economic implications of bird damage to sunflower by estimating the macroeconomic impacts of lost sunflower production in the region. Additionally, the findings of this study may be used to inform decisions regarding bird management policy by providing policymakers with information to determine the downstream value of bird management and the possible benefits of improved methods that further mitigate losses

    fMRI predictors of treatment outcome in pediatric anxiety disorders

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    A growing number of studies have found evidence that anxiety and depressive disorders are associated with atypical amygdala hyperactivation, which decreases with effective treatment. Interest has emerged in this phenomenon as a possible biological marker for individuals who are likely to benefit from tailored treatment approaches. The present study was designed to examine relationships between pre-treatment amygdala activity and treatment response in a sample of anxious children and adolescents. Participants, who were diagnosed predominantly with Generalized Anxiety Disorder (GAD), underwent functional magnetic resonance imaging (fMRI) scanning prior to treatment with fluoxetine or cognitive behavioral therapy (CBT). Results indicated significant negative associations between degree of left amygdala activation and measures of post-treatment symptom improvement in the group as a whole. Taken together with research on associations between adult amygdala activation and treatment response, these findings suggest that patients whose pre-treatment amygdala activity is the strongest may be particularly likely to respond well to such widely used treatments as selective serotonin reuptake inhibitor (SSRI) medications and CBT

    Systems biology via redescription and ontologies (I): finding phase changes with applications to malaria temporal data

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    Biological systems are complex and often composed of many subtly interacting components. Furthermore, such systems evolve through time and, as the underlying biology executes its genetic program, the relationships between components change and undergo dynamic reorganization. Characterizing these relationships precisely is a challenging task, but one that must be undertaken if we are to understand these systems in sufficient detail. One set of tools that may prove useful are the formal principles of model building and checking, which could allow the biologist to frame these inherently temporal questions in a sufficiently rigorous framework. In response to these challenges, GOALIE (Gene ontology algorithmic logic and information extractor) was developed and has been successfully employed in the analysis of high throughput biological data (e.g. time-course gene-expression microarray data and neural spike train recordings). The method has applications to a wide variety of temporal data, indeed any data for which there exist ontological descriptions. This paper describes the algorithms behind GOALIE and its use in the study of the Intraerythrocytic Developmental Cycle (IDC) of Plasmodium falciparum, the parasite responsible for a deadly form of chloroquine resistant malaria. We focus in particular on the problem of finding phase changes, times of reorganization of transcriptional control

    The Grizzly, April 5, 2007

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    Two Ursinus Seniors Win Watson Fellowship • Ursinus Hillel: Current Events and Future Plans • Edible Books Festival a Success • USGA Update • Situation in Darfur • Back on the Shelves: Contraceptive Sponge • Nutrition Tips: Tea Time • Seeing Double a Musical for Peace • UC Spotlight: The Lantern • Opinions: Concerning Bong Hits for Jesus • Ursinus Athletics Prosper in 2006-2007https://digitalcommons.ursinus.edu/grizzlynews/1736/thumbnail.jp

    The mental health effects of pet death during childhood: Is it better to have loved and lost than never to have loved at all?

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    Pet ownership is common. Growing evidence suggests children form deep emotional attachments to their pets. Yet, little is known about children’s emotional reactions to a pet’s death. The goal of this study was to describe the relationship between experiences of pet death and risk of childhood psychopathology and determine if it was “better to have loved and lost than never to have loved at all”. Data came from the Avon Longitudinal Study of Parents and Children, a UK-based prospective birth cohort (n = 6260). Children were characterized based on their exposure to pet ownership and pet death from birth to age 7 (never loved;loved without loss; loved with loss). Psychopathology symptoms at age 8 were compared across groups using multivariable linear regression. Psychopathology symptoms were higher among children who had loved with loss compared to those who had loved without loss (β = 0.35, p = 0.013; 95% CI = 0.07, 0.63), even after adjustment for other adversities. This group effect was more pronounced in males than in females. There was no difference in psychopathology symptoms between children who had loved with loss and those who had never loved (β = 0.20, p = 0.31, 95% CI = −0.18–0.58). The developmental timing, recency, or accumulation of pet death was unassociated with psychopathology symptoms. Pet death may be traumatic for children and associated with subsequent mental health difficulties. Where childhood pet ownership and pet bereavement is concerned, Tennyson’s pronouncement may not apply to children’s grief responses: it may not be “better to have loved and lost than never to have loved at all”

    Systematic analysis of membrane contact sites in Saccharomyces cerevisiae uncovers modulators of cellular lipid distribution

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    Actively maintained close appositions, or contact sites, between organelle membranes, enable the efficient transfer of biomolecules between the various cellular compartments. Several such sites have been described together with their tethering machinery. Despite these advances we are still far from a comprehensive understanding of the function and regulation of most contact sites. To systematically characterize the proteome of contact sites and support the discovery of new tethers and functional molecules, we established a high throughput screening approach in Saccharomyces cerevisiae based on co-localization imaging. We imaged split fluorescence reporters for six different contact sites, two of which have never been studied before, on the background of 1165 strains expressing a mCherry-tagged yeast protein that have a cellular punctate distribution (a hallmark of contact sites). By scoring both co-localization events and effects on reporter size and abundance, we discovered over 100 new potential contact site residents and effectors in yeast. Focusing on several of the newly identified residents, we identified one set of hits as previously unrecognized homologs to Vps13 and Atg2. These proteins share their lipid transport domain, thus expanding this family of lipid transporters. Analysis of another candidate, Ypr097w, which we now call Lec1 (Lipid-droplet Ergosterol Cortex 1), revealed that this previously uncharacterized protein dynamically shifts between lipid droplets and the cell cortex, and plays a role in regulation of ergosterol distribution in the cell

    Systematic analysis of membrane contact sites in Saccharomyces cerevisiae uncovers modulators of cellular lipid distribution

    Get PDF
    Actively maintained close appositions between organelle membranes, also known as contact sites, enable the efficient transfer of biomolecules between cellular compartments. Several such sites have been described as well as their tethering machineries. Despite these advances we are still far from a comprehensive understanding of the function and regulation of most contact sites. To systematically characterize contact site proteomes, we established a high-throughput screening approach in Saccharomyces cerevisiae based on co-localization imaging. We imaged split fluorescence reporters for six different contact sites, several of which are poorly characterized, on the background of 1165 strains expressing a mCherry-tagged yeast protein that has a cellular punctate distribution (a hallmark of contact sites), under regulation of the strong TEF2 promoter. By scoring both co-localization events and effects on reporter size and abundance, we discovered over 100 new potential contact site residents and effectors in yeast. Focusing on several of the newly identified residents, we identified three homologs of Vps13 and Atg2 that are residents of multiple contact sites. These proteins share their lipid transport domain, thus expanding this family of lipid transporters. Analysis of another candidate, Ypr097w, which we now call Lec1 (Lipid-droplet Ergosterol Cortex 1), revealed that this previously uncharacterized protein dynamically shifts between lipid droplets and the cell cortex, and plays a role in regulation of ergosterol distribution in the cell. Overall, our analysis expands the universe of contact site residents and effectors and creates a rich database to mine for new functions, tethers, and regulators
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