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Article ; Online: Human adaptive immune receptor repertoire analysis-Past, present, and future.

Nielsen, Sandra C A / Boyd, Scott D

2018 Volume 284, Issue 1, Page(s) 9–23

Abstract: The genes encoding adaptive immune antigen receptors, namely the immunoglobulins expressed in membrane-bound or secreted forms by B cells, and the cell surface T cell receptors, are unique in human biology because they are generated by combinatorial ... ...

Abstract	The genes encoding adaptive immune antigen receptors, namely the immunoglobulins expressed in membrane-bound or secreted forms by B cells, and the cell surface T cell receptors, are unique in human biology because they are generated by combinatorial rearrangement of the genomic DNA. The diversity of receptors so generated in populations of lymphocytes enables the human immune system to recognize antigens expressed by pathogens, but also underlies the pathological specificity of autoimmune diseases and the mistargeted immunity in allergies. Several recent technological developments, foremost among them the invention of high-throughput DNA sequencing instruments, have enabled much deeper and thorough evaluation of clones of human B cells and T cells and the antigen receptors they express during physiological and pathogenic immune responses. The evolutionary struggles between host adaptive immune responses and populations of pathogens are now open to greater scrutiny, elucidation of the underlying reasons for successful or failed immunity, and potential predictive modeling, than ever before. Here we give an overview of the foundations, recent progress, and future prospects in this dynamic area of research.
MeSH term(s)	Adaptive Immunity/genetics ; Adaptive Immunity/immunology ; Antibodies/genetics ; Antibodies/immunology ; Autoimmunity/genetics ; Autoimmunity/immunology ; B-Lymphocytes/immunology ; Genetic Variation/genetics ; High-Throughput Nucleotide Sequencing ; Humans ; Hypersensitivity/genetics ; Hypersensitivity/immunology ; Receptors, Antigen, T-Cell/genetics ; Receptors, Antigen, T-Cell/immunology ; V(D)J Recombination/genetics
Chemical Substances	Antibodies ; Receptors, Antigen, T-Cell
Language	English
Publishing date	2018-09-27
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	391796-4
ISSN	1600-065X ; 0105-2896
ISSN (online)	1600-065X
ISSN	0105-2896
DOI	10.1111/imr.12667
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Article ; Online: North African fox genomes show signatures of repeated introgression and adaptation to life in deserts.

L Rocha, Joana / Silva, Pedro / Santos, Nuno / Nakamura, Mónia / Afonso, Sandra / Qninba, Abdeljebbar / Boratynski, Zbyszek / Sudmant, Peter H / Brito, José C / Nielsen, Rasmus / Godinho, Raquel

Nature ecology & evolution

2023 Volume 7, Issue 8, Page(s) 1267–1286

Abstract: Elucidating the evolutionary process of animal adaptation to deserts is key to understanding adaptive responses to climate change. Here we generated 82 individual whole genomes of four fox species (genus Vulpes) inhabiting the Sahara Desert at different ... ...

Abstract	Elucidating the evolutionary process of animal adaptation to deserts is key to understanding adaptive responses to climate change. Here we generated 82 individual whole genomes of four fox species (genus Vulpes) inhabiting the Sahara Desert at different evolutionary times. We show that adaptation of new colonizing species to a hot arid environment has probably been facilitated by introgression and trans-species polymorphisms shared with older desert resident species, including a putatively adaptive 25 Mb genomic region. Scans for signatures of selection implicated genes affecting temperature perception, non-renal water loss and heat production in the recent adaptation of North African red foxes (Vulpes vulpes), after divergence from Eurasian populations approximately 78 thousand years ago. In the extreme desert specialists, Rueppell's fox (V. rueppellii) and fennec (V. zerda), we identified repeated signatures of selection in genes affecting renal water homeostasis supported by gene expression and physiological differences. Our study provides insights into the mechanisms and genetic underpinnings of a natural experiment of repeated adaptation to extreme conditions.
MeSH term(s)	Animals ; Adaptation, Biological/genetics ; Africa, Northern ; Biological Evolution ; Desert Climate ; Foxes/genetics ; Genomics ; Water ; Homeostasis/genetics ; Homeostasis/physiology
Chemical Substances	Water (059QF0KO0R)
Language	English
Publishing date	2023-06-12
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	2397-334X
ISSN (online)	2397-334X
DOI	10.1038/s41559-023-02094-w
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Article ; Online: Essential omega-3 fatty acids are depleted in sea ice and pelagic algae of the Central Arctic Ocean.

Schmidt, Katrin / Graeve, Martin / Hoppe, Clara J M / Torres-Valdes, Sinhué / Welteke, Nahid / Whitmore, Laura M / Anhaus, Philipp / Atkinson, Angus / Belt, Simon T / Brenneis, Tina / Campbell, Robert G / Castellani, Giulia / Copeman, Louise A / Flores, Hauke / Fong, Allison A / Hildebrandt, Nicole / Kohlbach, Doreen / Nielsen, Jens M / Parrish, Christopher C /

Rad-Menéndez, Cecilia / Rokitta, Sebastian D / Tippenhauer, Sandra / Zhuang, Yanpei

Global change biology

2024 Volume 30, Issue 1, Page(s) e17090

Abstract: Microalgae are the main source of the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), essential for the healthy development of most marine and terrestrial fauna including humans. Inverse correlations of algal EPA and DHA ... ...

Abstract	Microalgae are the main source of the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), essential for the healthy development of most marine and terrestrial fauna including humans. Inverse correlations of algal EPA and DHA proportions (% of total fatty acids) with temperature have led to suggestions of a warming-induced decline in the global production of these biomolecules and an enhanced importance of high latitude organisms for their provision. The cold Arctic Ocean is a potential hotspot of EPA and DHA production, but consequences of global warming are unknown. Here, we combine a full-seasonal EPA and DHA dataset from the Central Arctic Ocean (CAO), with results from 13 previous field studies and 32 cultured algal strains to examine five potential climate change effects; ice algae loss, community shifts, increase in light, nutrients, and temperature. The algal EPA and DHA proportions were lower in the ice-covered CAO than in warmer peripheral shelf seas, which indicates that the paradigm of an inverse correlation of EPA and DHA proportions with temperature may not hold in the Arctic. We found no systematic differences in the summed EPA and DHA proportions of sea ice versus pelagic algae, and in diatoms versus non-diatoms. Overall, the algal EPA and DHA proportions varied up to four-fold seasonally and 10-fold regionally, pointing to strong light and nutrient limitations in the CAO. Where these limitations ease in a warming Arctic, EPA and DHA proportions are likely to increase alongside increasing primary production, with nutritional benefits for a non-ice-associated food web.
MeSH term(s)	Humans ; Fatty Acids, Omega-3 ; Ice Cover ; Diatoms ; Oceans and Seas ; Arctic Regions ; Fatty Acids
Chemical Substances	Fatty Acids, Omega-3 ; Fatty Acids
Language	English
Publishing date	2024-01-25
Publishing country	England
Document type	Journal Article
ZDB-ID	1281439-8
ISSN	1365-2486 ; 1354-1013
ISSN (online)	1365-2486
ISSN	1354-1013
DOI	10.1111/gcb.17090
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Article: Correlates of Risk for Disinhibited Behaviors in the Million Veteran Program Cohort.

Barr, Peter B / Bigdeli, Tim B / Meyers, Jacquelyn L / Peterson, Roseann E / Sanchez-Roige, Sandra / Mallard, Travis T / Dick, Danielle M / Paige Harden, K / Wilkinson, Anna / Graham, David P / Nielsen, David A / Swann, Alan / Lipsky, Rachele K / Kosten, Thomas / Aslan, Mihaela / Harvey, Philip D / Kimbrel, Nathan A / Beckham, Jean C

medRxiv : the preprint server for health sciences

2023

Abstract: ... hepatitis C. Of the significant outcomes 73 (11.9%) and 26 (4.5%) were significant in the African and ... and viral hepatitis C.: Conclusion: Our results demonstrate a shared polygenic basis of EXT across ...

Abstract	Background: Many psychiatric outcomes are thought to share a common etiological pathway reflecting behavioral disinhibition, generally referred to as externalizing disorders (EXT). Recent genome-wide association studies (GWAS) have demonstrated the overlap between EXT and important aspects of veterans' health, such as suicide-related behaviors, substance use disorders, and other medical conditions. Methods: We conducted a series of phenome-wide association studies (PheWAS) of polygenic scores (PGS) for EXT, and comorbid psychiatric problems (depression, schizophrenia, and suicide attempt) in an ancestrally diverse cohort of U.S. veterans ( Results: The EXT PGS was associated with 619 outcomes across all bodily systems, of which, 188 were independent of risk for comorbid problems of PGS. Effect sizes ranged from OR = 1.02 (95% CI = 1.01, 1.03) for overweight/obesity to OR = 1.44 (95% CI = 1.42, 1.47) for viral hepatitis C. Of the significant outcomes 73 (11.9%) and 26 (4.5%) were significant in the African and Hispanic/Latin American results, respectively. Within-family analyses uncovered robust associations between EXT and consequences of substance use disorders, including liver disease, chronic airway obstruction, and viral hepatitis C. Conclusion: Our results demonstrate a shared polygenic basis of EXT across populations of diverse ancestries and independent of risk for other psychiatric problems. The strongest associations with EXT were for diagnoses related to substance use disorders and their sequelae. Overall, we highlight the potential negative consequences of EXT for health and functioning in the US veteran population.
Language	English
Publishing date	2023-07-11
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.03.22.23286865
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Article ; Online: Exploring health and social services in Denmark, Norway, Spain and the United Kingdom for the development of Parkinson's care pathways. A document analysis.

Nielsen, Tove Lise / Kruse, Naja Benigna / Haahr, Anita / Hjelle, Ellen Gabrielsen / Bragstad, Line Kildal / Palmar-Santos, Ana / Navarta-Sánchez, Maria Victoria / Pedraz-Marcos, Azucena / Pires, Sandra Bartolomeu / Roberts, Helen C / Portillo, Mari Carmen

Health & social care in the community

2022 Volume 30, Issue 6, Page(s) e3507–e3518

Abstract: People with Parkinson's disease (PD) may find it difficult to identify and access the wide number of services they need and are entitled to along their complex PD journey. As part of the project OPTIM-PARK - Optimisation of community resources and ... ...

Abstract	People with Parkinson's disease (PD) may find it difficult to identify and access the wide number of services they need and are entitled to along their complex PD journey. As part of the project OPTIM-PARK - Optimisation of community resources and systems of support to enhance the process of living with Parkinson's Disease, document analysis was developed to create overviews of existing resources and systems of support in Denmark, Norway, Spain and the United Kingdom. Documents on community resources, policies, guidelines and professional recommendations were the main sources of information. They were sought systematically at official websites of the public sector (national and regional levels) and websites of non-governmental organisations and scientific societies; searches were performed in October 2020 and updated in September 2021. A higher-level cross-national content analysis integrated all the country-specific information. Data- and concept-driven coding frames were developed; trial coding and peer review strengthened face validity and reliability. The analysis led to overviews of: (1) Key aims at patient and societal levels. (2) Key elements in form of professional approaches. (3) Community resources. (4) Legally anchored services. In general, clear descriptions of how to implement care pathways and tools to facilitate delivery were missing in the included documents, and pathways and guidelines did not include referral to general social support, social security support or labour and employment support. The results shed light on the complex support systems and resources and can inspire the planning of more comprehensive care pathways for people with PD and other long-term conditions.
MeSH term(s)	Humans ; Critical Pathways ; Parkinson Disease/therapy ; Spain ; Reproducibility of Results ; Document Analysis ; Norway ; Social Work ; United Kingdom ; Denmark
Language	English
Publishing date	2022-08-17
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	1155902-0
ISSN	1365-2524 ; 0966-0410
ISSN (online)	1365-2524
ISSN	0966-0410
DOI	10.1111/hsc.13970
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Article ; Online: Prevalence of autoimmune disease among pregnant women and women of reproductive age in New South Wales, Australia: a population-based study.

Nielsen, Timothy C / Nassar, Natasha / Harrison, Christopher / Shand, Antonia / Dale, Russell C / Lowe, Sandra / Lain, Samantha J

The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians

2020 Volume 35, Issue 17, Page(s) 3229–3237

Abstract: Background: Autoimmune diseases disproportionately affect women and have been linked to increased risk of maternal and perinatal mortality and morbidity. Our aim was to determine the prevalence of autoimmune disease among pregnant women and women of ... ...

Abstract	Background: Autoimmune diseases disproportionately affect women and have been linked to increased risk of maternal and perinatal mortality and morbidity. Our aim was to determine the prevalence of autoimmune disease among pregnant women and women of reproductive age (WRA), which is not well described. Materials and methods: A population-based study was conducted using data from a survey of general practitioner (GP) encounters and state-wide hospital admissions in New South Wales (NSW). A list of 29 conditions and relevant diagnosis codes was used to identify autoimmune disease. Prevalence estimates and trends were calculated using population denominators for GP encounters for WRA in 2011-2015 and hospital admissions for WRA and pregnant women in 2013-2017. Results: A total 31,065 GP encounters for WRA were identified and 607 (2.0%) reported an autoimmune disease, equivalent to 1.1 GP encounters per 10 WRA each year when extrapolating to NSW population figures. For WRA admitted to hospital, 2.6% had an autoimmune diagnosis recorded each year equivalent to a population prevalence of 0.5%. A total 477,243 births were identified, of which 4230 mothers (0.9%) had at least one autoimmune disease recorded during a 1-year pregnancy lookback period. Autoimmune disease prevalence among both pregnant women and WRA either attending GP or hospital increased, on average, 2-4% per year over the study period. Conclusions: A small, but potentially growing proportion of reproductive age and pregnant women have a diagnosed autoimmune disease, and this may impact their health outcomes.
MeSH term(s)	Australia ; Autoimmune Diseases/epidemiology ; Female ; Humans ; New South Wales/epidemiology ; Pregnancy ; Pregnant Women ; Prevalence
Language	English
Publishing date	2020-09-13
Publishing country	England
Document type	Journal Article
ZDB-ID	2077261-0
ISSN	1476-4954 ; 1057-0802 ; 1476-7058
ISSN (online)	1476-4954
ISSN	1057-0802 ; 1476-7058
DOI	10.1080/14767058.2020.1817893
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Article ; Online: Correlates of Risk for Disinhibited Behaviors in the Million Veteran Program Cohort.

Barr, Peter B / Bigdeli, Tim B / Meyers, Jacquelyn L / Peterson, Roseann E / Sanchez-Roige, Sandra / Mallard, Travis T / Dick, Danielle M / Harden, K Paige / Wilkinson, Anna / Graham, David P / Nielsen, David A / Swann, Alan C / Lipsky, Rachele K / Kosten, Thomas R / Aslan, Mihaela / Harvey, Philip D / Kimbrel, Nathan A / Beckham, Jean C

JAMA psychiatry

2023 Volume 81, Issue 2, Page(s) 188–197

Abstract: ... 95% CI, 1.42-1.47 for viral hepatitis C). Of the significant outcomes, 73 (11.9%) were significant ... chronic airway obstruction, and viral hepatitis C.: Conclusions and relevance: Results ...

Abstract	Importance: Many psychiatric outcomes share a common etiologic pathway reflecting behavioral disinhibition, generally referred to as externalizing (EXT) disorders. Recent genome-wide association studies (GWASs) have demonstrated the overlap between EXT disorders and important aspects of veterans' health, such as suicide-related behaviors and substance use disorders (SUDs). Objective: To explore correlates of risk for EXT disorders within the Veterans Health Administration (VA) Million Veteran Program (MVP). Design, setting, and participants: A series of phenome-wide association studies (PheWASs) of polygenic risk scores (PGSs) for EXT disorders was conducted using electronic health records. First, ancestry-specific PheWASs of EXT PGSs were conducted in the African, European, and Hispanic or Latin American ancestries. Next, a conditional PheWAS, covarying for PGSs of comorbid psychiatric problems (depression, schizophrenia, and suicide attempt; European ancestries only), was performed. Lastly, to adjust for unmeasured confounders, a within-family analysis of significant associations from the main PheWAS was performed in full siblings (European ancestries only). This study included the electronic health record data from US veterans from VA health care centers enrolled in MVP. Analyses took place from February 2022 to August 2023 covering a period from October 1999 to January 2020. Exposures: PGSs for EXT, depression, schizophrenia, and suicide attempt. Main outcomes and measures: Phecodes for diagnoses derived from the International Statistical Classification of Diseases, Ninth and Tenth Revisions, Clinical Modification, codes from electronic health records. Results: Within the MVP (560 824 patients; mean [SD] age, 67.9 [14.3] years; 512 593 male [91.4%]), the EXT PGS was associated with 619 outcomes, of which 188 were independent of risk for comorbid problems or PGSs (from odds ratio [OR], 1.02; 95% CI, 1.01-1.03 for overweight/obesity to OR, 1.44; 95% CI, 1.42-1.47 for viral hepatitis C). Of the significant outcomes, 73 (11.9%) were significant in the African results and 26 (4.5%) were significant in the Hispanic or Latin American results. Within-family analyses uncovered robust associations between EXT PGS and consequences of SUDs, including liver disease, chronic airway obstruction, and viral hepatitis C. Conclusions and relevance: Results of this cohort study suggest a shared polygenic basis of EXT disorders, independent of risk for other psychiatric problems. In addition, this study found associations between EXT PGS and diagnoses related to SUDs and their sequelae. Overall, this study highlighted the potential negative consequences of EXT disorders for health and functioning in the US veteran population.
MeSH term(s)	Humans ; Male ; Aged ; Veterans ; Cohort Studies ; Genome-Wide Association Study ; Schizophrenia ; Substance-Related Disorders ; Hepatitis, Viral, Human
Language	English
Publishing date	2023-11-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	2701203-7
ISSN	2168-6238 ; 2168-622X
ISSN (online)	2168-6238
ISSN	2168-622X
DOI	10.1001/jamapsychiatry.2023.4141
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Article ; Online: Gastrointestinal γδ T cells reveal differentially expressed transcripts and enriched pathways during peanut oral immunotherapy.

Zhang, Wenming / Dhondalay, Gopal Krishna / Liu, Taryn Audrey / Kaushik, Abhinav / Hoh, Ramona / Kwok, Shirley / Kambham, Neeraja / Fernandez-Becker, Nielsen Q / Andorf, Sandra / Desai, Manisha / Galli, Stephen J / Boyd, Scott D / Nadeau, Kari C / Manohar, Monali / DeKruyff, Rosemarie H / Chinthrajah, R Sharon

Allergy

2022 Volume 77, Issue 5, Page(s) 1606–1610

MeSH term(s)	Arachis ; Humans ; Immunologic Factors ; Immunotherapy ; Peanut Hypersensitivity/therapy ; Receptors, Antigen, T-Cell, gamma-delta ; T-Lymphocytes
Chemical Substances	Immunologic Factors ; Receptors, Antigen, T-Cell, gamma-delta
Language	English
Publishing date	2022-02-18
Publishing country	Denmark
Document type	Letter ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	391933-x
ISSN	1398-9995 ; 0105-4538
ISSN (online)	1398-9995
ISSN	0105-4538
DOI	10.1111/all.15250
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Article ; Online: Risk and Resilience: How Is the Health of Older Adults and Immigrant People Living in Canada Impacted by Climate- and Air Pollution-Related Exposures?

Tilstra, McKenzie H / Tiwari, Ishwar / Niwa, Leigh / Campbell, Sandra / Nielsen, Charlene C / Jones, C Allyson / Osornio Vargas, Alvaro / Bulut, Okan / Quemerais, Bernadette / Salma, Jordana / Whitfield, Kyle / Yamamoto, Shelby S

International journal of environmental research and public health

2021 Volume 18, Issue 20

Abstract: Background: In the rapidly shifting Canadian climate, an ageing population, and increased migration, a greater understanding of how local climate and air pollution hazards impact older adults and immigrant populations will be necessary for mitigating ... ...

Abstract	Background: In the rapidly shifting Canadian climate, an ageing population, and increased migration, a greater understanding of how local climate and air pollution hazards impact older adults and immigrant populations will be necessary for mitigating and adapting to adverse health impacts. Objectives: To explore the reported health impacts of climate change and air pollution exposures in older adults and immigrant people living in Canada, identify known factors influencing risk and resilience in these populations and gaps in the literature. Methods: We searched for research focused on older adults and immigrants living in Canada, published from 2010 onward, where the primary exposures were related to climate or air pollution. We extracted data on setting, exposures, health outcomes, and other relevant contextual factors. Results and discussion: We identified 52 eligible studies, most focused in Ontario and Quebec. Older people in Canada experience health risks due to climate and air pollution exposures. The extent of the risk depends on multiple factors. We found little information about the climate- and air pollution-related health impacts experienced by immigrant communities. Conclusions: Further research about climate- and air pollution-related exposures, health, and which factors promote or reduce resiliency in Canada's older adults and immigrant communities is necessary.
MeSH term(s)	Aged ; Aging ; Air Pollutants/analysis ; Air Pollution/adverse effects ; Air Pollution/analysis ; Canada/epidemiology ; Climate Change ; Emigrants and Immigrants ; Humans ; Ontario/epidemiology
Chemical Substances	Air Pollutants
Language	English
Publishing date	2021-10-09
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2175195-X
ISSN	1660-4601 ; 1661-7827
ISSN (online)	1660-4601
ISSN	1661-7827
DOI	10.3390/ijerph182010575
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Article: Supramolecular Complexes of Plant Neurotoxin Veratridine with Cyclodextrins and Their Antidote-like Effect on Neuro-2a Cell Viability.

Uribe, Laura A / Leonardo, Sandra / Nielsen, Thorbjørn Terndrup / Steinmann, Casper / Campàs, Mònica / Fragoso, Alex

Pharmaceutics

2022 Volume 14, Issue 3

Abstract: Veratridine (VTD) is a plant neurotoxin that acts by blocking the voltage-gated sodium channels (VGSC) of cell membranes. Symptoms of VTD intoxication include intense nausea, hypotension, arrhythmia, and loss of consciousness. The treatment for the ... ...

Abstract	Veratridine (VTD) is a plant neurotoxin that acts by blocking the voltage-gated sodium channels (VGSC) of cell membranes. Symptoms of VTD intoxication include intense nausea, hypotension, arrhythmia, and loss of consciousness. The treatment for the intoxication is mainly focused on treating the symptoms, meaning there is no specific antidote against VTD. In this pursuit, we were interested in studying the molecular interactions of VTD with cyclodextrins (CDs). CDs are supramolecular macrocycles with the ability to form host-guest inclusion complexes (ICs) inside their hydrophobic cavity. Since VTD is a lipid-soluble alkaloid, we hypothesized that it could form stable inclusion complexes with different types of CDs, resulting in changes to its physicochemical properties. In this investigation, we studied the interaction of VTD with β-CD, γ-CD and sulfobutyl ether β-CD (SBCD) by isothermal titration calorimetry (ITC) and nuclear magnetic resonance (NMR) spectroscopy. Docking and molecular dynamics studies confirmed the most stable configuration for the inclusion complexes. Finally, with an interest in understanding the effects of the VTD/CD molecular interactions, we performed cell-based assays (CBAs) on Neuro-2a cells. Our findings reveal that the use of different amounts of CDs has an antidote-like concentration-dependent effect on the cells, significantly increasing cell viability and thus opening opportunities for novel research on applications of CDs and VTD.
Language	English
Publishing date	2022-03-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527217-2
ISSN	1999-4923
ISSN	1999-4923
DOI	10.3390/pharmaceutics14030598
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