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Book ; Online: The Past and the Future of Human Immunity Under Viral Evolutionary Pressure

Magiorkinis, Gkikas / Hurst, Tara P.

2019

Keywords	Medicine ; Immunology ; virus ; evolution ; human immunity ; endogenous retrovirus
Size	1 electronic resource (186 pages)
Publisher	Frontiers Media SA
Document type	Book ; Online
Note	English ; Open Access
HBZ-ID	HT021230832
ISBN	9782889632299 ; 2889632296
Database	ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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Article ; Online: A two-generation study of attachment in mothers and their young adult offspring: Latent classes of attachment and associations with anxiety and depression.

Blake, Julie A / Thomas, Hannah J / Hurst, Cameron P / Pelecanos, Anita M / McGee, Tara Renae / Najman, Jake M / Scott, James G

Journal of affective disorders

2024 Volume 358, Page(s) 361–368

Abstract: Background: Evidence supports the conceptualization of adult attachment as existing along a continuum of attachment security and insecurity; however, ongoing debates persist regarding the use of categorical versus continuous approaches to studying ... ...

Abstract	Background: Evidence supports the conceptualization of adult attachment as existing along a continuum of attachment security and insecurity; however, ongoing debates persist regarding the use of categorical versus continuous approaches to studying attachment. Attachment data collected from a large community sample of mothers and their offspring in young adulthood were used to examine i) latent classes of adult attachment, ii) associations between mother and offspring attachment, iii) the relationship between adult attachment and mental health symptoms. Methods: Mothers and offspring were each administered the Attachment Style Questionnaire when offspring were aged 21-years. Latent class analyses (LCA) were performed to examine response patterns across ASQ items. Associations between mothers' and offspring attachment, and correlations between attachment domains and depression/anxiety subscales were examined. Results: LCA identified four latent classes across a continuum of secure and insecure attachment rather than four distinct adult attachment styles. Anxious attachment subscales correlated strongly with depression/anxiety symptoms in both cohorts. Mothers' attachment was significantly but weakly correlated with their young adult offspring attachment. Limitations: Attachment was measured at one time point and as such, a causal maternal-offspring attachment relationship could not be established. Conclusions: Findings support a dimensional view of attachment security and insecurity over a four-category model of adult attachment. Attachment correlated with anxiety and depressive symptoms and highlights the importance of considering adult attachment when addressing mental health. There was limited evidence of a relationship between middle aged mothers and their offspring in young adulthood, suggesting other factors influence attachment in adulthood.
Language	English
Publishing date	2024-05-10
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	135449-8
ISSN	1573-2517 ; 0165-0327
ISSN (online)	1573-2517
ISSN	0165-0327
DOI	10.1016/j.jad.2024.05.046
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Article ; Online: Epigenetic Control of Human Endogenous Retrovirus Expression: Focus on Regulation of Long-Terminal Repeats (LTRs).

Hurst, Tara P / Magiorkinis, Gkikas

Viruses

2017 Volume 9, Issue 6

Abstract: Transposable elements, including endogenous retroviruses (ERVs), comprise almost 45% of the human genome. This could represent a significant pathogenic burden but it is becoming more evident that many of these elements have a positive contribution to ... ...

Abstract	Transposable elements, including endogenous retroviruses (ERVs), comprise almost 45% of the human genome. This could represent a significant pathogenic burden but it is becoming more evident that many of these elements have a positive contribution to make to normal human physiology. In particular, the contributions of human ERVs (HERVs) to gene regulation and the expression of noncoding RNAs has been revealed with the help of new and emerging genomic technologies. HERVs have the common provirus structure of coding open reading frames (ORFs) flanked by two long-terminal repeats (LTRs). However, over the course of evolution and as a consequence of host defence mechanisms, most of the sequences contain INDELs, mutations or have been reduced to single LTRs by recombination. These INDELs and mutations reduce HERV activity. However, there is a trade-off for the host cells in that HERVs can provide beneficial sources of genetic variation but with this benefit comes the risk of pathogenic activity and spread within the genome. For example, the LTRs are of critical importance as they contain promoter sequences and can regulate not only HERV expression but that of human genes. This is true even when the LTRs are located in intergenic regions or are in antisense orientation to the rest of the gene. Uncontrolled, this promoter activity could disrupt normal gene expression or transcript processing (e.g., splicing). Thus, control of HERVs and particularly their LTRs is essential for the cell to manage these elements and this control is achieved at multiple levels, including epigenetic regulations that permit HERV expression in the germline but silence it in most somatic tissues. We will discuss some of the common epigenetic mechanisms and how they affect HERV expression, providing detailed discussions of HERVs in stem cell, placenta and cancer biology.
MeSH term(s)	Endogenous Retroviruses/genetics ; Epigenesis, Genetic ; Gene Expression Regulation, Viral ; Humans ; Terminal Repeat Sequences
Language	English
Publishing date	2017-05-31
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v9060130
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Article ; Online: Activation of the innate immune response by endogenous retroviruses.

Hurst, Tara P / Magiorkinis, Gkikas

The Journal of general virology

2015 Volume 96, Issue Pt 6, Page(s) 1207–1218

Abstract: The human genome comprises 8 % endogenous retroviruses (ERVs), the majority of which are defective due to deleterious mutations. Nonetheless, transcripts of ERVs are found in most tissues, and these transcripts could either be reverse transcribed to ... ...

Abstract	The human genome comprises 8 % endogenous retroviruses (ERVs), the majority of which are defective due to deleterious mutations. Nonetheless, transcripts of ERVs are found in most tissues, and these transcripts could either be reverse transcribed to generate ssDNA or expressed to generate proteins. Thus, the expression of ERVs could produce nucleic acids or proteins with viral signatures, much like the pathogen-associated molecular patterns of exogenous viruses, which would enable them to be detected by the innate immune system. The activation of some pattern recognition receptors (PRRs) in response to ERVs has been described in mice and in the context of human autoimmune diseases. Here, we review the evidence for detection of ERVs by PRRs and the resultant activation of innate immune signalling. This is an emerging area of research within the field of innate antiviral immunity, showing how ERVs could initiate immune signalling pathways and might have implications for numerous inflammatory diseases.
MeSH term(s)	Animals ; Endogenous Retroviruses/immunology ; Gene Expression ; Humans ; Immunity, Innate ; Mice ; RNA, Viral/immunology ; RNA, Viral/metabolism ; Receptors, Pattern Recognition/metabolism ; Transcription, Genetic ; Viral Proteins/immunology ; Viral Proteins/metabolism
Chemical Substances	RNA, Viral ; Receptors, Pattern Recognition ; Viral Proteins
Language	English
Publishing date	2015-01-27
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	219316-4
ISSN	1465-2099 ; 0022-1317
ISSN (online)	1465-2099
ISSN	0022-1317
DOI	10.1099/jgv.0.000017
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Article ; Online: Perspectives on the future of dysmorphology.

Solomon, Benjamin D / Adam, Margaret P / Fong, Chin-To / Girisha, Katta M / Hall, Judith G / Hurst, Anna C E / Krawitz, Peter M / Moosa, Shahida / Phadke, Shubha R / Tekendo-Ngongang, Cedrik / Wenger, Tara L

American journal of medical genetics. Part A

2022 Volume 191, Issue 3, Page(s) 659–671

Abstract: The field of clinical genetics and genomics continues to evolve. In the past few decades, milestones like the initial sequencing of the human genome, dramatic changes in sequencing technologies, and the introduction of artificial intelligence, have ... ...

Abstract	The field of clinical genetics and genomics continues to evolve. In the past few decades, milestones like the initial sequencing of the human genome, dramatic changes in sequencing technologies, and the introduction of artificial intelligence, have upended the field and offered fascinating new insights. Though difficult to predict the precise paths the field will follow, rapid change may continue to be inevitable. Within genetics, the practice of dysmorphology, as defined by pioneering geneticist David W. Smith in the 1960s as "the study of, or general subject of abnormal development of tissue form" has also been affected by technological advances as well as more general trends in biomedicine. To address possibilities, potential, and perils regarding the future of dysmorphology, a group of clinical geneticists, representing different career stages, areas of focus, and geographic regions, have contributed to this piece by providing insights about how the practice of dysmorphology will develop over the next several decades.
MeSH term(s)	Humans ; Artificial Intelligence ; Genomics ; Genome, Human
Language	English
Publishing date	2022-12-09
Publishing country	United States
Document type	Editorial ; Research Support, N.I.H., Intramural
ZDB-ID	2108614-X
ISSN	1552-4833 ; 0148-7299 ; 1552-4825
ISSN (online)	1552-4833
ISSN	0148-7299 ; 1552-4825
DOI	10.1002/ajmg.a.63060
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Article ; Online: The case for intraocular delivery of PPAR agonists in the treatment of diabetic retinopathy.

Treacy, Maxwell P / Hurst, Tara P

BMC ophthalmology

2012 Volume 12, Page(s) 46

Abstract: Background: Systemic therapeutics targeting the peroxisome proliferator-activated receptors have been found to be beneficial in the treatment of diabetic retinopathy. In this paper, we provide a rationale for the use of these therapeutics as intraocular ...

Abstract	Background: Systemic therapeutics targeting the peroxisome proliferator-activated receptors have been found to be beneficial in the treatment of diabetic retinopathy. In this paper, we provide a rationale for the use of these therapeutics as intraocular agents. In addition, we introduce the peroxisome proliferator-activated receptors and describe their functions in response to the drugs. Discussion: Based on the evidence of large-scale clinical studies investigating the systemic administration of fenofibrate, this ligand for peroxisome proliferator-activated receptor-α is potentially a good candidate for intraocular delivery. Here, we describe the mechanisms by which it might be acting to improve diabetic retinopathy, its relative safety and we speculate on how it could be developed for intraocular delivery. Summary: In this paper, we provide a rationale for the further investigation of peroxisome proliferator-activated receptor-α agonists as intraocular agents for the treatment of diabetic retinopathy.
MeSH term(s)	Diabetic Retinopathy/drug therapy ; Eye ; Fenofibrate/administration & dosage ; Humans ; Hypolipidemic Agents/administration & dosage ; Injections ; PPAR alpha/agonists ; Treatment Outcome
Chemical Substances	Hypolipidemic Agents ; PPAR alpha ; Fenofibrate (U202363UOS)
Language	English
Publishing date	2012-09-02
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2050436-6
ISSN	1471-2415 ; 1471-2415
ISSN (online)	1471-2415
ISSN	1471-2415
DOI	10.1186/1471-2415-12-46
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Article ; Online: Thiazolidinediones in the treatment of HIV/HAART-associated lipodystrophy syndrome.

Edgeworth, Alice / Treacy, Maxwell P / Hurst, Tara P

AIDS reviews

2013 Volume 15, Issue 3, Page(s) 171–180

Abstract: The treatment of HIV-1 infected patients with HAART has resulted in long-term suppression of viral replication and reduced progression to AIDS. However, the use of HAART has been associated with adverse effects, including metabolic dysregulation and ... ...

Abstract	The treatment of HIV-1 infected patients with HAART has resulted in long-term suppression of viral replication and reduced progression to AIDS. However, the use of HAART has been associated with adverse effects, including metabolic dysregulation and changes in body fat deposition. This syndrome, known as HIV/HAART-associated lipodystrophy syndrome, is characterized by insulin resistance, dyslipidemia, lipodystrophy, and increased visceral adiposity, which contribute to an increased risk of cardiovascular disease amongst these patients. The thiazolidinediones are a class of agonists for the nuclear receptors, the peroxisome proliferator-activated receptor. Since peroxisome proliferator-activated receptor is critically involved in the regulation of insulin sensitivity and lipid metabolism, a number of clinical trials have analyzed whether thiazolidinediones could ameliorate the signs of HIV/HAART-associated lipodystrophy syndrome. Based on these trials, thiazolidinediones appear to up-regulate peroxisome proliferator-activated receptor-dependent genes such as adiponectin, an effect that could have important physiological benefits in the long-term for HIV/HAART-associated lipodystrophy syndrome patients. Critically, many of the studies were of short duration and thus the beneficial effects of thiazolidinediones might have been missed. In addition, the few studies on the thiazolidinedione pioglitazone showed a beneficial effect on limb fat mass that was not associated with a pro-atherogenic lipid profile. Based on these studies, a large-scale clinical trial of pioglitazone use in HIV/HAART-associated lipodystrophy syndrome patients is warranted.
MeSH term(s)	Antiretroviral Therapy, Highly Active/adverse effects ; Disease Progression ; Female ; HIV Infections/drug therapy ; HIV Infections/metabolism ; HIV-Associated Lipodystrophy Syndrome/drug therapy ; HIV-Associated Lipodystrophy Syndrome/metabolism ; Humans ; Hypoglycemic Agents/therapeutic use ; Male ; PPAR gamma/drug effects ; Thiazolidinediones/therapeutic use ; Treatment Outcome ; Up-Regulation ; Virus Replication/drug effects
Chemical Substances	Hypoglycemic Agents ; PPAR gamma ; Thiazolidinediones ; pioglitazone (X4OV71U42S)
Language	English
Publishing date	2013-07
Publishing country	Spain
Document type	Journal Article ; Review
ZDB-ID	2086783-9
ISSN	1698-6997 ; 1139-6121
ISSN (online)	1698-6997
ISSN	1139-6121
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Article ; Online: The case for intraocular delivery of PPAR agonists in the treatment of diabetic retinopathy

Treacy Maxwell P / Hurst Tara P

BMC Ophthalmology, Vol 12, Iss 1, p

2012 Volume 46

Abstract: Abstract Background Systemic therapeutics targeting the peroxisome proliferator-activated receptors have been found to be beneficial in the treatment of diabetic retinopathy. In this paper, we provide a rationale for the use of these therapeutics as ... ...

Abstract	Abstract Background Systemic therapeutics targeting the peroxisome proliferator-activated receptors have been found to be beneficial in the treatment of diabetic retinopathy. In this paper, we provide a rationale for the use of these therapeutics as intraocular agents. In addition, we introduce the peroxisome proliferator-activated receptors and describe their functions in response to the drugs. Discussion Based on the evidence of large-scale clinical studies investigating the systemic administration of fenofibrate, this ligand for peroxisome proliferator-activated receptor-α is potentially a good candidate for intraocular delivery. Here, we describe the mechanisms by which it might be acting to improve diabetic retinopathy, its relative safety and we speculate on how it could be developed for intraocular delivery. Summary In this paper, we provide a rationale for the further investigation of peroxisome proliferator-activated receptor-α agonists as intraocular agents for the treatment of diabetic retinopathy.
Keywords	Diabetes ; Diabetic retinopathy ; Intraocular ; Fenofibrate ; TZDs ; PPARs ; Ophthalmology ; RE1-994 ; Medicine ; R ; DOAJ:Ophthalmology ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
Language	English
Publishing date	2012-09-01T00:00:00Z
Publisher	BioMed Central
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Regulated intramembrane proteolysis, innate immunity and therapeutic targets in Alzheimer’s disease

Caroline Coleman-Vaughan / Indu Patwal / Justin V. McCarthy / Tara P. Hurst

AIMS Molecular Science, Vol 3, Iss 2, Pp 138-

2016 Volume 157

Abstract: The critical discovery of the presenilins and their association with familial Alzheimer’s disease (AD) prompted an intensive research effort to understand the molecular mechanisms of that disease. The presenilins were subsequently found to be the ... ...

Abstract	The critical discovery of the presenilins and their association with familial Alzheimer’s disease (AD) prompted an intensive research effort to understand the molecular mechanisms of that disease. The presenilins were subsequently found to be the catalytic component of the multi-protein enzyme complex, γ-secretase, the enzyme that is known to act on the amyloid precursor protein (APP) to generate amyloid beta (Aβ) peptides that comprise the neuritic plaques implicated in AD pathology. Here, we discuss the background of γ-secretase- mediated proteolysis of APP and its association with familial AD. We discuss the association of neuroinflammation with AD, focusing on the link between the innate immune response, the clearance of the Aβ peptides and disease progression. Currently, there are limited treatments for AD that strive to ameliorate the symptoms of the disease but do not address the molecular basis of the disease. The greater understanding of γ- secretase functions has provided new insights into potential therapeutics for AD, a number of which are in clinical trials.
Keywords	Presenilin ; gamma-secretase (γ-secretase) ; regulated intramembrane proteolysis ; Alzheimer’s disease (AD) ; innate immune system ; neuroinflammation ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2016-04-01T00:00:00Z
Publisher	AIMS Press
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The early treatment in diabetic retinopathy study chart compared with the tumbling-E and Landolt-C.

Treacy, Maxwell P / Hurst, Tara P / Conway, Marcus / Duignan, Emma S / Dimitrov, Borislav D / Brennan, Nicholas / Cassidy, Lorraine

Ophthalmology

2015 Volume 122, Issue 5, Page(s) 1062–3.e1

MeSH term(s)	Adolescent ; Adult ; Aged ; Aged, 80 and over ; Diabetic Retinopathy/physiopathology ; Diabetic Retinopathy/therapy ; Female ; Humans ; Male ; Middle Aged ; Vision Tests/instrumentation ; Visual Acuity/physiology
Language	English
Publishing date	2015-05
Publishing country	United States
Document type	Comparative Study ; Journal Article
ZDB-ID	392083-5
ISSN	1549-4713 ; 0161-6420
ISSN (online)	1549-4713
ISSN	0161-6420
DOI	10.1016/j.ophtha.2014.11.024
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