49 research outputs found

    Extracellular Hsp90 and TGFP regulate adhesion, migration and anchorage independent growth in a paired colon cancer cell line model

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    Tumour metastasis remains the major cause of death in cancer patients and, to date, the mechanism and signalling pathways governing this process are not completely understood. The TGF-ß pathway is the most commonly mutated pathway in cancer, however its role in cancer progression is controversial as it can function as both a promoter and a suppressor of metastasis. Although previous studies have suggested a role for the molecular chaperone Hsp90 in regulating the TGF-ß pathway, the level at which this occurs as well as the consequences in terms of colon cancer metastasis are unknown

    Baculovirus Capsid Display Potentiates OVA Cytotoxic and Innate Immune Responses

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    Baculoviruses (BV) are DNA viruses that are pathogenic for insects. Although BV infect a range of mammalian cell types, they do not replicate in these cells. Indeed, the potential effects of these insect viruses on the immune responses of mammals are only just beginning to be studied. We show in this paper that a recombinant Autographa californica multiple nuclear polyhedrosis virus carrying a fragment of ovalbumin (OVA) on the VP39 capsid protein (BV-OVA) has the capacity to act as an adjuvant and vector of antigens in mice, thereby promoting specific CD4 and cytotoxic T cell responses against OVA. BV also induced in vivo maturation of dendritic cells and the production of inflammatory cytokines, thus promoting innate and adaptive immune responses. The OVA-specific response induced by BV-OVA was strong enough to reject a challenge with OVA-expressing melanoma cells (MO5 cells) and effectively prolonged survival of MO5 bearing mice. All these findings, together with the absence of pre-existing immunity to BV in humans and the lack of viral gene expression in mammalian cells, make BV a candidate for vaccination

    Transcriptomic Signatures of Ash (Fraxinus spp.) Phloem

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    Ash (Fraxinus spp.) is a dominant tree species throughout urban and forested landscapes of North America (NA). The rapid invasion of NA by emerald ash borer (Agrilus planipennis), a wood-boring beetle endemic to Eastern Asia, has resulted in the death of millions of ash trees and threatens billions more. Larvae feed primarily on phloem tissue, which girdles and kills the tree. While NA ash species including black (F. nigra), green (F. pennsylvannica) and white (F. americana) are highly susceptible, the Asian species Manchurian ash (F. mandshurica) is resistant to A. planipennis perhaps due to their co-evolutionary history. Little is known about the molecular genetics of ash. Hence, we undertook a functional genomics approach to identify the repertoire of genes expressed in ash phloem.Using 454 pyrosequencing we obtained 58,673 high quality ash sequences from pooled phloem samples of green, white, black, blue and Manchurian ash. Intriguingly, 45% of the deduced proteins were not significantly similar to any sequences in the GenBank non-redundant database. KEGG analysis of the ash sequences revealed a high occurrence of defense related genes. Expression analysis of early regulators potentially involved in plant defense (i.e. transcription factors, calcium dependent protein kinases and a lipoxygenase 3) revealed higher mRNA levels in resistant ash compared to susceptible ash species. Lastly, we predicted a total of 1,272 single nucleotide polymorphisms and 980 microsatellite loci, among which seven microsatellite loci showed polymorphism between different ash species.The current transcriptomic data provide an invaluable resource for understanding the genetic make-up of ash phloem, the target tissue of A. planipennis. These data along with future functional studies could lead to the identification/characterization of defense genes involved in resistance of ash to A. planipennis, and in future ash breeding programs for marker development

    Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

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    This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

    Family Resources in Two Generations and School Readiness Among Children of Teen Parents

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    Overall, children born to teen parents experience disadvantaged cognitive achievement at school entry compared with children born to older parents. However, within this population, there is variation, with a significant fraction of teen parents’ children acquiring adequate preparation for school entry during early childhood. We ask whether the family background of teen parents explains this variation. We use data on children born to teen mothers from three waves of the Early Childhood Longitudinal Study-Birth Cohort (N ~ 700) to study the association of family background with children’s standardized reading and mathematics achievement scores at kindergarten entry. When neither maternal grandparent has completed high school, children’s scores on standardized assessments of math and reading achievement are one-quarter to one-third of a standard deviation lower compared with families where at least one grandparent finished high school. This association is net of teen mothers’ own socioeconomic status in the year prior to children’s school entry

    Transitioning from thoracotomy to thoracoscopy for esophageal atresia in an LMIC setting

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    Introduction: Although the benefits of thoracoscopic esophageal atresia repair (TEAR) are well documented, there has been resistance to the uptake of this approach in low- and middle-income countries. This study reviews a single unit's experience introducing TEAR in a South African state sector tertiary hospital. Method: We describe how we set up MIS for esophageal atresia (EA) at our centre. All neonates with EA managed at our institution from January 2016 to January 2022 were included. Excluded patients included those who were not operated on or if data was missing. We compared the different approaches for managing type C EA in our setting. We analyzed the data using the Mann-Whitney U test. Results: Sixty-five patients were managed with EA over the study duration. There were 54 patients who had type C EA. Thirty-nine patients underwent thoracotomy to repair the defect, and eighteen underwent TEAR, of which sixteen were completed thoracoscopically. There was a statistically significant difference in weight (p-value 0.035), gestational age (p-value 0.002), and age at operation (p-value 0.004) between the groups treated by TEAR and OEAR (open esophageal atresia repair). There was a small median difference in the operative time between TEAR and OEAR of 20 min. The mortality in the OEAR group was higher (20.5 %) compared to the TEAR group (5.5 %), with a p-value of 0.094. Conclusion: A dedicated quality improvement program focused on introducing MIS for EA can produce results comparable to the open procedure in an LMIC setting
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