| Records |
| Author |
Fogel, O.; Richard-Miceli, C.; Tost, J. |
Title  |
Epigenetic Changes in Chronic Inflammatory Diseases |
Type |
Journal Article |
| Year |
2017 |
Publication |
Advances in Protein Chemistry and Structural Biology |
Abbreviated Journal |
Adv Protein Chem Struct Biol |
| Volume |
106 |
Issue |
|
Pages |
139-189 |
| Keywords |
Behcet's disease; Crohn's disease; DNA methylation; Ewas; Epigenetics; Histone modifications; Inflammatory bowel disease; Psoriasis; Spondyloarthritis; Ulcerative colitis |
| Abstract |
The number of people diagnosed with chronic inflammatory diseases has increased noteworthy in the last 40 years. Spondyloarthritis (SpA), inflammatory bowel diseases (IBD), and psoriasis are the most frequent chronic inflammatory diseases, resulting from a combination of genetic predisposition and environmental factors. Epigenetic modifications include DNA methylation, histone modifications, and small and long noncoding RNAs. They are influenced by environmental exposure, life-style, and aging and have recently been shown to be altered in many complex diseases including inflammatory diseases. While epigenetic modifications have been well characterized in other diseases such as cancer and autoimmune diseases, knowledge on changes in inflammatory diseases is lagging behind with some disease-specific differences. While the DNA methylation profile of different cell types in patients with IBD has been relatively well described, less is known on changes implicated in psoriasis, and no systematic genome-wide studies have so far been performed in SpA. In this chapter, we review in detail the reported changes in patterns of DNA methylation and posttranslational histone modifications in chronic inflammatory diseases highlighting potential connections between disease-associated pathophysiological changes such as the dysbiosis of the microbiome or genetic variations associated with disease susceptibility and the epigenome. We also discuss important parameters of meaningful epigenetic studies such as the use of well defined, disease-relevant cell populations, and elude on the potential future of engineering of the epigenome in inflammatory diseases. |
| Address |
Laboratory for Epigenetics and Environment, Centre National de Genotypage, CEA-Institut de Genomique, Evry, France. Electronic address: tost@cng.fr |
| Corporate Author |
|
Thesis |
|
| Publisher |
|
Place of Publication |
|
Editor |
|
| Language |
English |
Summary Language |
|
Original Title |
|
| Series Editor |
|
Series Title |
|
Abbreviated Series Title |
|
| Series Volume |
|
Series Issue |
|
Edition |
|
| ISSN |
1876-1623 |
ISBN |
|
Medium |
|
| Area |
|
Expedition |
|
Conference |
|
| Notes |
PMID:28057210 |
Approved |
no |
| Call Number |
ref @ user @ |
Serial |
96374 |
| Permanent link to this record |
| |
|
| |
| Author |
Zapotoczna, M.; Forde, E.; Hogan, S.; Humphreys, H.; O'Gara, J.P.; Fitzgerald-Hughes, D.; Devocelle, M.; O'Neill, E. |
| Title |
Eradication of Staphylococcus aureus Biofilm Infections Using Synthetic Antimicrobial Peptides |
Type |
Journal Article |
| Year |
2017 |
Publication |
The Journal of Infectious Diseases |
Abbreviated Journal |
J Infect Dis |
| Volume |
215 |
Issue |
6 |
Pages |
975-983 |
| Keywords |
Animals; Anti-Bacterial Agents/*pharmacology; Biofilms/*drug effects; Catheter-Related Infections/*drug therapy; Cytokines/blood; Disease Models, Animal; Humans; Methicillin-Resistant Staphylococcus aureus/*drug effects; Microbial Sensitivity Tests; Peptides/*pharmacology; Peptides, Cyclic/pharmacology; Rats; Rats, Sprague-Dawley; Staphylococcal Infections/*drug therapy; Vancomycin/administration & dosage; *Staphylococcus aureus; *antimicrobial peptides (AMPs); *biofilm; *catheter lock solution (CLS) |
| Abstract |
Here, we demonstrate that antimicrobial peptides (AMPs) are an effective antibiofilm treatment when applied as catheter lock solutions (CLSs) against S. aureus biofilm infections. The activity of synthetic AMPs (Bac8c, HB43, P18, Omiganan, WMR, Ranalexin, and Polyphemusin) was measured against early and mature biofilms produced by methicillin-resistant S. aureus and methicillin-susceptible S. aureus isolates from patients with device-related infections grown under in vivo-relevant biofilm conditions. The cytotoxic and hemolytic activities of the AMPs against human cells and their immunomodulatory potential in human blood were also characterized. The D-Bac8c2,5Leu variant emerged as the most effective AMP during in vitro studies and was also highly effective in eradicating S. aureus biofilm infection when used in a CLS rat central venous catheter infection model. These data support the potential use of D-Bac8c2,5Leu, alone or in combination with other AMPs, in the treatment of S. aureus intravenous catheter infections. |
| Address |
Department of Microbiology, School of Natural Sciences, National University of Ireland, Galway, Ireland |
| Corporate Author |
|
Thesis |
|
| Publisher |
|
Place of Publication |
|
Editor |
|
| Language |
English |
Summary Language |
|
Original Title |
|
| Series Editor |
|
Series Title |
|
Abbreviated Series Title |
|
| Series Volume |
|
Series Issue |
|
Edition |
|
| ISSN |
0022-1899 |
ISBN |
|
Medium |
|
| Area |
|
Expedition |
|
Conference |
|
| Notes |
PMID:28453851 |
Approved |
no |
| Call Number |
ref @ user @ |
Serial |
99511 |
| Permanent link to this record |
| |
|
| |
| Author |
Zapotoczna, M.; Forde, E.; Hogan, S.; Humphreys, H.; O'Gara, J.P.; Fitzgerald-Hughes, D.; Devocelle, M.; O'Neill, E. |
| Title |
Eradication of Staphylococcus aureus Biofilm Infections Using Synthetic Antimicrobial Peptides |
Type |
Journal Article |
| Year |
2017 |
Publication |
The Journal of Infectious Diseases |
Abbreviated Journal |
J Infect Dis |
| Volume |
215 |
Issue |
6 |
Pages |
975-983 |
| Keywords |
Animals; Anti-Bacterial Agents/*pharmacology; Biofilms/*drug effects; Catheter-Related Infections/*drug therapy; Cytokines/blood; Disease Models, Animal; Humans; Methicillin-Resistant Staphylococcus aureus/*drug effects; Microbial Sensitivity Tests; Peptides/*pharmacology; Peptides, Cyclic/pharmacology; Rats; Rats, Sprague-Dawley; Staphylococcal Infections/*drug therapy; Vancomycin/administration & dosage; *Staphylococcus aureus; *antimicrobial peptides (AMPs); *biofilm; *catheter lock solution (CLS) |
| Abstract |
Here, we demonstrate that antimicrobial peptides (AMPs) are an effective antibiofilm treatment when applied as catheter lock solutions (CLSs) against S. aureus biofilm infections. The activity of synthetic AMPs (Bac8c, HB43, P18, Omiganan, WMR, Ranalexin, and Polyphemusin) was measured against early and mature biofilms produced by methicillin-resistant S. aureus and methicillin-susceptible S. aureus isolates from patients with device-related infections grown under in vivo-relevant biofilm conditions. The cytotoxic and hemolytic activities of the AMPs against human cells and their immunomodulatory potential in human blood were also characterized. The D-Bac8c2,5Leu variant emerged as the most effective AMP during in vitro studies and was also highly effective in eradicating S. aureus biofilm infection when used in a CLS rat central venous catheter infection model. These data support the potential use of D-Bac8c2,5Leu, alone or in combination with other AMPs, in the treatment of S. aureus intravenous catheter infections. |
| Address |
Department of Microbiology, School of Natural Sciences, National University of Ireland, Galway, Ireland |
| Corporate Author |
|
Thesis |
|
| Publisher |
|
Place of Publication |
|
Editor |
|
| Language |
English |
Summary Language |
|
Original Title |
|
| Series Editor |
|
Series Title |
|
Abbreviated Series Title |
|
| Series Volume |
|
Series Issue |
|
Edition |
|
| ISSN |
0022-1899 |
ISBN |
|
Medium |
|
| Area |
|
Expedition |
|
Conference |
|
| Notes |
PMID:28453851 |
Approved |
no |
| Call Number |
ref @ user @ |
Serial |
100541 |
| Permanent link to this record |
| |
|
| |
| Author |
Li, M.; Zhao, H.; Ananiev, G.E.; Musser, M.T.; Ness, K.H.; Maglaque, D.L.; Saha, K.; Bhattacharyya, A.; Zhao, X. |
| Title |
Establishment of Reporter Lines for Detecting Fragile X Mental Retardation (FMR1) Gene Reactivation in Human Neural Cells |
Type |
Journal Article |
| Year |
2017 |
Publication |
Stem Cells (Dayton, Ohio) |
Abbreviated Journal |
Stem Cells |
| Volume |
35 |
Issue |
1 |
Pages |
158-169 |
| Keywords |
Drug discovery; Fmr1; Fmrp; Fragile X syndrome; High throughput; Induced pluripotent stem cells; Luciferase |
| Abstract |
Human patient-derived induced pluripotent stem cells (hiPSCs) provide unique opportunities for disease modeling and drug development. However, adapting hiPSCs or their differentiated progenies to high throughput assays for phenotyping or drug screening has been challenging. Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability and a major genetic cause of autism. FXS is caused by mutational trinucleotide expansion in the FMR1 gene leading to hypermethylation and gene silencing. One potential therapeutic strategy is to reactivate the silenced FMR1 gene, which has been attempted using both candidate chemicals and cell-based screening. However, molecules that effectively reactivate the silenced FMR1 gene are yet to be identified; therefore, a high throughput unbiased screen is needed. Here we demonstrate the creation of a robust FMR1-Nluc reporter hiPSC line by knocking in a Nano luciferase (Nluc) gene into the endogenous human FMR1 gene using the CRISPR/Cas9 genome editing method. We confirmed that luciferase activities faithfully report FMR1 gene expression levels and showed that neural progenitor cells derived from this line could be optimized for high throughput screening. The FMR1-Nluc reporter line is a good resource for drug screening as well as for testing potential genetic reactivation strategies. In addition, our data provide valuable information for the generation of knockin human iPSC reporter lines for disease modeling, drug screening, and mechanistic studies. Stem Cells 2017;35:158-169. |
| Address |
Department of Neuroscience, University of Wisconsin-Madison, Madison, Wisconsin, USA |
| Corporate Author |
|
Thesis |
|
| Publisher |
|
Place of Publication |
|
Editor |
|
| Language |
English |
Summary Language |
|
Original Title |
|
| Series Editor |
|
Series Title |
|
Abbreviated Series Title |
|
| Series Volume |
|
Series Issue |
|
Edition |
|
| ISSN |
1066-5099 |
ISBN |
|
Medium |
|
| Area |
|
Expedition |
|
Conference |
|
| Notes |
PMID:27422057 |
Approved |
no |
| Call Number |
ref @ user @ |
Serial |
95937 |
| Permanent link to this record |
| |
|
| |
| Author |
Canario Guzman, J.A.; Espinal, R.; Baez, J.; Melgen, R.E.; Rosario, P.A.P.; Mendoza, E.R. |
| Title |
Ethical challenges for international collaborative research partnerships in the context of the Zika outbreak in the Dominican Republic: a qualitative case study |
Type |
Journal Article |
| Year |
2017 |
Publication |
Health Research Policy and Systems |
Abbreviated Journal |
Health Res Policy Syst |
| Volume |
15 |
Issue |
1 |
Pages |
82 |
| Keywords |
Capacity-building; Caribbean region; Developing countries; Disease outbreaks; Dominican Republic; Health equity; Health research systems; Research ethics; Research networks; Zika virus |
| Abstract |
BACKGROUND: The establishment of international collaborative research partnerships in times of infectious disease outbreaks of international importance has been considered an ethical imperative. Frail health research systems in low- and middle-income countries can be an obstacle to achieve the goal of knowledge generation and the search for health equity before, during and after infectious disease outbreaks. METHODS: A qualitative case study was conducted to identify the challenges and opportunities facing the Dominican Republic with regards to developing international collaborative research partnerships in the context of the Zika outbreak and its ethical implications. Researchers conducted 34 interviews (n = 30 individual; n = 4 group) with 39 participants (n = 23 males; n = 16 females) representing the government, universities, international donor agencies, non-governmental organisations, community-based organisations and medical societies, in two metropolitan cities. RESULTS: Five international collaborative research projects related to the Zika virus were identified. Major ethical challenges were linked to the governance of health research, training of human resources, the institutionalisation of scientific activity, access to research funds and cultural aspects. Capacity-building was not necessarily a component of some partnership agreements. With few exceptions, local researchers were merely participating in data collection and less on defining the problem. Opportunities for collaborative work included the possibility of participation in international research consortiums through calls for proposals. CONCLUSIONS: The Dominican government and research stakeholders can contribute to the international response to the Zika virus through active participation in international collaborative research partnerships; however, public recognition of the need to embrace health research as part of public policy efforts is warranted. A working group led by the government and formed by national and international research stakeholders will be key to identify ways in which the country could respond to the ethical demand of generating new knowledge in times of outbreaks. |
| Address |
Centro Nacional de Investigaciones en Salud Materno Infantil Dr. Hugo Mendoza (CENISMI), Centro Los Heroes, Santo Domingo, Republica Dominicana |
| Corporate Author |
|
Thesis |
|
| Publisher |
|
Place of Publication |
|
Editor |
|
| Language |
English |
Summary Language |
|
Original Title |
|
| Series Editor |
|
Series Title |
|
Abbreviated Series Title |
|
| Series Volume |
|
Series Issue |
|
Edition |
|
| ISSN |
1478-4505 |
ISBN |
|
Medium |
|
| Area |
|
Expedition |
|
Conference |
|
| Notes |
PMID:28946911 |
Approved |
no |
| Call Number |
ref @ user @ |
Serial |
97182 |
| Permanent link to this record |
