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Claes P.,Future Health | Liberton D.K.,Pennsylvania State University | Daniels K.,Future Health | Rosana K.M.,Pennsylvania State University | And 23 more authors.
PLoS Genetics | Year: 2014

Human facial diversity is substantial, complex, and largely scientifically unexplained. We used spatially dense quasi-landmarks to measure face shape in population samples with mixed West African and European ancestry from three locations (United States, Brazil, and Cape Verde). Using bootstrapped response-based imputation modeling (BRIM), we uncover the relationships between facial variation and the effects of sex, genomic ancestry, and a subset of craniofacial candidate genes. The facial effects of these variables are summarized as response-based imputed predictor (RIP) variables, which are validated using self-reported sex, genomic ancestry, and observer-based facial ratings (femininity and proportional ancestry) and judgments (sex and population group). By jointly modeling sex, genomic ancestry, and genotype, the independent effects of particular alleles on facial features can be uncovered. Results on a set of 20 genes showing significant effects on facial features provide support for this approach as a novel means to identify genes affecting normal-range facial features and for approximating the appearance of a face from genetic markers. © 2014 Claes et al.


News Article | February 16, 2017
Site: www.eurekalert.org

Scientists at Trinity College Dublin have discovered how certain cancers hijack the immune system for their benefit, tricking it into helping rather than harming them. While most of us are aware that our immune system protects us from infection, we may be less aware of the key role that cells of the immune system also play in coordinating the repair of damaged tissue. This 'wound-healing' aspect of the immune response stimulates growth of new cells within damaged tissue and brings extra nutrients and oxygen into the injured tissue. However, cancers frequently exploit the wound-healing side of the immune system for their own ends. Indeed, cancers have been described as 'wounds that do not heal' due to their ability to masquerade as damaged tissue in order to receive help from the immune system. But just how cancers switch on this wound-healing response is not well understood. However, scientists from the Smurfit Institute of Genetics at Trinity College Dublin, led by Smurfit Professor of Medical Genetics, Seamus Martin, have just found that a molecule called TRAIL -- which is frequently found in high concentrations on many cancers -- can become 're-wired' in certain tumours to send an inflammatory 'wound-healing' signal. Ironically, TRAIL normally delivers a signal for cells to die, but the Trinity scientists found that this molecule can also send a wound-healing message from tumour cells. The research, conducted by Research Fellow at Trinity, Dr Conor Henry, has just been published in the internationally renowned journal, Molecular Cell. Commenting on the findings, Professor Martin said: "Understanding how cancers turn on the wound-healing response has been mysterious, so we are very excited to find that certain cancers exploit TRAIL for that purpose." "This suggests ways in which we can turn off this reaction in cancers that use TRAIL to hoodwink the immune system into helping rather than harming them." Work in the Martin laboratory at Trinity College Dublin is supported by Science Foundation Ireland and Worldwide Cancer Research.


News Article | February 20, 2017
Site: www.medicalnewstoday.com

Scientists at Trinity College Dublin have discovered how certain cancers hijack the immune system for their benefit, tricking it into helping rather than harming them. While most of us are aware that our immune system protects us from infection, we may be less aware of the key role that cells of the immune system also play in coordinating the repair of damaged tissue. This 'wound-healing' aspect of the immune response stimulates growth of new cells within damaged tissue and brings extra nutrients and oxygen into the injured tissue. However, cancers frequently exploit the wound-healing side of the immune system for their own ends. Indeed, cancers have been described as 'wounds that do not heal' due to their ability to masquerade as damaged tissue in order to receive help from the immune system. But just how cancers switch on this wound-healing response is not well understood. However, scientists from the Smurfit Institute of Genetics at Trinity College Dublin, led by Smurfit Professor of Medical Genetics, Seamus Martin, have just found that a molecule called TRAIL - which is frequently found in high concentrations on many cancers - can become 're-wired' in certain tumours to send an inflammatory 'wound-healing' signal. Ironically, TRAIL normally delivers a signal for cells to die, but the Trinity scientists found that this molecule can also send a wound-healing message from tumour cells. The research, conducted by Research Fellow at Trinity, Dr Conor Henry, has just been published in the internationally renowned journal, Molecular Cell. Commenting on the findings, Professor Martin said: "Understanding how cancers turn on the wound-healing response has been mysterious, so we are very excited to find that certain cancers exploit TRAIL for that purpose." "This suggests ways in which we can turn off this reaction in cancers that use TRAIL to hoodwink the immune system into helping rather than harming them." Work in the Martin laboratory at Trinity College Dublin is supported by Science Foundation Ireland and Worldwide Cancer Research. Article: Caspase-8 Acts in a Non-enzymatic Role as a Scaffold for Assembly of a Pro-inflammatory "FADDosome" Complex upon TRAIL Stimulation, Conor M. Henry, Seamus J. Martin, Molecular Cell, doi: 10.1016/j.molcel.2017.01.022, published 9 February 2017.


PubMed | Lund University, Smurfit Institute of Genetics, University College Dublin and St Vincents University Hospital
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2017

43 Background: Predicting the risk of tumour recurrence, and thus the need for chemotherapy, for lymph node-negative breast cancer patients is a significant problem for clinicians and patients.We have identified a core proliferation signature, which is consistently high in proliferating primary cultures, and is downregulated during cellular senescence. Using a reverse engineering approach on a breast cancer-specific regulatory network, and confirmed by ChIP-seq analysis, we have identified a hierarchy of several highly interconnected Master Transcriptional Regulators upstream of these core proliferation genes.Further analysis of the expression of these factors in breast cancer cohorts at the mRNA and protein levels reveals a remarkable ability to reliably predict recurrence risk for early-stage breast cancer. Strikingly, in our analyses, a combination of just two of these factors outperforms the currently used clinical biomarkers for breast cancer recurrence risk, as well as recently developed multi-gene prognostic assays. Moreover, the addition of the senescence regulator p16We propose that this novel approach has succeeded in identifying drivers of breast cancer proliferation which, when combined with a marker of senescence such as p16


Campbell M.,Smurfit Institute of Genetics | Doyle S.L.,Trinity College Dublin | Doyle S.L.,Our Ladys Childrens Hospital | Ozaki E.,Smurfit Institute of Genetics | And 4 more authors.
Advances in Experimental Medicine and Biology | Year: 2014

Age-related macular degeneration (AMD) is the leading cause of central vision loss worldwide and while polymorphisms in genes associated with the immune system have been identified as risk factors for disease development, the underlying pathways and mechanisms involved in disease progression have remained unclear. In AMD, localised inflammatory responses related to particulate matter accumulation and subsequent “sterile” inflammation has recently gained considerable interest amongst basic researchers and clinicians alike. Typically, inflammatory responses in the human body are caused as a result of bacterial or viral infection, however in chronic conditions such as AMD, extracellular particulate matter such as drusen can be “sensed” by the NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome, culminating in the release of the two pro-inflammatory cytokines IL-1β and IL-18 in the delicate local tissue of the retina. Identification at the molecular level of mediators of the inflammatory response in AMD may yield novel therapeutic approaches to this common and often severe form of blindness. Here, we will describe the role of IL-18 in AMD and other forms of retinal disorders. We will outline some of the key functions of IL-18 as it pertains to maintaining tissue homeostasis in a healthy and degenerating/ diseased retina. © Springer Science+Business Media, LLC 2014.


Kroger C.,Moyne Institute of Preventive Medicine | Colgan A.,Moyne Institute of Preventive Medicine | Srikumar S.,Moyne Institute of Preventive Medicine | Handler K.,Moyne Institute of Preventive Medicine | And 8 more authors.
Cell Host and Microbe | Year: 2013

Bacterial transcriptional networks consist of hundreds of transcription factors and thousands of promoters. However, the true complexity of transcription in a bacterial pathogen and the effect of the environments encountered during infection remain to be established. We present a simplified approach for global promoter identification in bacteria using RNA-seq-based transcriptomic analyses of 22 distinct infection-relevant environmental conditions. Individual RNA samples were combined to identify most of the 3,838 Salmonella enterica serovar Typhimurium promoters in just two RNA-seq runs. Individual in vitro conditions stimulated characteristic transcriptional signatures, and the suite of 22 conditions induced transcription of 86% of all S. Typhimurium genes. We highlight the environmental conditions that induce the Salmonella pathogenicity islands and present a small RNA expression landscape of 280 sRNAs. This publicly available compendium of environmentally controlled expression of every transcriptional feature of S. Typhimurium constitutes a useful resource for the bacterial research community. © 2013 Elsevier Inc.


Graciet E.,Smurfit Institute of Genetics | O'Maoileidigh D.S.,Smurfit Institute of Genetics | Wellmer F.,Smurfit Institute of Genetics
Methods in Molecular Biology | Year: 2014

Over the past 20 years, classic genetic approaches have shown that the developmental program underlying flower formation involves a large number of transcriptional regulators. However, the target genes of these transcription factors, as well as the gene regulatory networks they control, remain largely unknown. Chromatin immunoprecipitation coupled to next-generation sequencing (ChIP-Seq), which allows the identification of transcription factor binding sites on a genome-wide scale, has been successfully applied to a number of transcription factors in Arabidopsis. The ChIP-Seq procedure involves chemical cross-linking of proteins to DNA, followed by chromatin fragmentation and immunoprecipitation of specific protein-DNA complexes. The regions of the genome bound by a specific transcription factor can then be identified after next-generation sequencing. © Springer Science+Business Media, New York 2014.

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