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  1. Article ; Online: Hair and salivary cortisol and their relationship with lifestyle, mood and cognitive outcomes in premanifest Huntington’s disease

    Travis Cruickshank / Tenielle Porter / Simon M. Laws / Mel Ziman / Danielle M. Bartlett

    Scientific Reports, Vol 11, Iss 1, Pp 1-

    2021  Volume 8

    Abstract: Abstract Salivary cortisol dysrhythmias have been reported in some, but not all studies assessing hypothalamic–pituitary–adrenal (HPA) axis function in Huntington’s disease (HD). These differences are presumed to be due to environmental influences on ... ...

    Abstract Abstract Salivary cortisol dysrhythmias have been reported in some, but not all studies assessing hypothalamic–pituitary–adrenal (HPA) axis function in Huntington’s disease (HD). These differences are presumed to be due to environmental influences on temporal salivary cortisol measurement. Further exploration of HPA-axis function using a more stable and longer-term measure, such as hair cortisol, is needed to confirm earlier findings. This study aimed to evaluate hair and salivary cortisol concentrations and their associations with clinical and lifestyle outcomes in individuals with premanifest HD (n = 26) compared to healthy controls (n = 14). Participants provided saliva and hair samples and data were collected on clinical disease outcomes, mood, cognition, physical activity, cognitive reserve, sleep quality and social network size to investigate relationships between clinical and lifestyle outcomes and cortisol concentrations. Hair and salivary cortisol concentrations did not significantly differ between the premanifest HD and control groups. No significant associations were observed between hair or salivary cortisol concentrations and cognitive, mood or lifestyle outcomes. However, hair cortisol concentrations were significantly associated with disease outcomes in individuals with premanifest HD. Significant associations between hair cortisol concentrations and measures of disease burden and onset may suggest a potential disease marker and should be explored longitudinally in a larger sample of individuals with HD.
    Keywords Medicine ; R ; Science ; Q
    Subject code 333
    Language English
    Publishing date 2021-03-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: TNF -Block Genotypes Influence Susceptibility to HIV-Associated Sensory Neuropathy in Indonesians and South Africans

    Jessica Gaff / Fitri Octaviana / Prinisha Pillay / Huguette Gaelle Ngassa Mbenda / Ibnu A. Ariyanto / June Anne Gan / Catherine L. Cherry / Peter Kamerman / Simon M. Laws / Patricia Price

    International Journal of Molecular Sciences, Vol 21, Iss 2, p

    2020  Volume 380

    Abstract: HIV-associated sensory neuropathy (HIV-SN) is a disabling complication of HIV disease and antiretroviral therapies (ART). Since stavudine was removed from recommended treatment schedules, the prevalence of HIV-SN has declined and associated risk factors ... ...

    Abstract HIV-associated sensory neuropathy (HIV-SN) is a disabling complication of HIV disease and antiretroviral therapies (ART). Since stavudine was removed from recommended treatment schedules, the prevalence of HIV-SN has declined and associated risk factors have changed. With stavudine, rs1799964*C (TNF-1031) associated with HIV-SN in Caucasians and Indonesians but not in South Africans. Here, we investigate associations between HIV-SN and rs1799964*C and 12 other polymorphisms spanning TNF and seven neighboring genes (the TNF -block) in Indonesians ( n = 202; 34/168 cases) and South Africans ( n = 75; 29/75 cases) treated without stavudine. Haplotypes were derived using fastPHASE and haplotype networks built with PopART. There were no associations with rs1799964*C in either population. However, rs9281523*C in intron 10 of BAT1 (alternatively DDX39B ) independently associated with HIV-SN in Indonesians after correcting for lower CD4 T-cell counts and >500 copies of HIV RNA/mL (model p = 0.0011, Pseudo R 2 = 0.09). rs4947324*T (between NFKBIL1 and LTA ) independently associated with reduced risk of HIV-SN and shared haplotype 1 (containing no minor alleles) associated with increased risk of HIV-SN after correcting for greater body weight, a history of tuberculosis and nadir CD4 T-cell counts (model: p = 0.0003, Pseudo R 2 = 0.22). These results confirm TNF -block genotypes influence susceptibility of HIV-SN. However, critical genotypes differ between ethnicities and with stavudine use.
    Keywords hiv ; sensory neuropathy ; tnf -block ; 8.1 ancestral haplotype ; ddx39b and bat1 ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 310
    Language English
    Publishing date 2020-01-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Validation of a priori candidate Alzheimer’s disease SNPs with brain amyloid-beta deposition

    Michael Vacher / Tenielle Porter / Victor L. Villemagne / Lidija Milicic / Madeline Peretti / Christopher Fowler / Ralph Martins / Stephanie Rainey-Smith / David Ames / Colin L. Masters / Christopher C. Rowe / James D. Doecke / Simon M. Laws

    Scientific Reports, Vol 9, Iss 1, Pp 1-

    2019  Volume 8

    Abstract: Abstract The accumulation of brain amyloid β (Aβ) is one of the main pathological hallmarks of Alzheimer’s disease (AD). However, the role of brain amyloid deposition in the development of AD and the genetic variants associated with this process remain ... ...

    Abstract Abstract The accumulation of brain amyloid β (Aβ) is one of the main pathological hallmarks of Alzheimer’s disease (AD). However, the role of brain amyloid deposition in the development of AD and the genetic variants associated with this process remain unclear. In this study, we sought to identify associations between Aβ deposition and an a priori evidence based set of 1610 genetic markers, genotyped from 505 unrelated individuals (258 Aβ+ and 247 Aβ−) enrolled in the Australian Imaging, Biomarker & Lifestyle (AIBL) study. We found statistically significant associations for 6 markers located within intronic regions of 6 genes, including AC103796.1-BDNF, PPP3R1, NGFR, KL, ABCA7 & CALHM1. Although functional studies are required to elucidate the role of these genes in the accumulation of Aβ and their potential implication in AD pathophysiology, our findings are consistent with results obtained in previous GWAS efforts.
    Keywords Medicine ; R ; Science ; Q
    Subject code 616
    Language English
    Publishing date 2019-11-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Using imputation to provide harmonized longitudinal measures of cognition across AIBL and ADNI

    Rosita Shishegar / Timothy Cox / David Rolls / Pierrick Bourgeat / Vincent Doré / Fiona Lamb / Joanne Robertson / Simon M. Laws / Tenielle Porter / Jurgen Fripp / Duygu Tosun / Paul Maruff / Greg Savage / Christopher C. Rowe / Colin L. Masters / Michael W. Weiner / Victor L. Villemagne / Samantha C. Burnham

    Scientific Reports, Vol 11, Iss 1, Pp 1-

    2021  Volume 11

    Abstract: Abstract To improve understanding of Alzheimer’s disease, large observational studies are needed to increase power for more nuanced analyses. Combining data across existing observational studies represents one solution. However, the disparity of such ... ...

    Abstract Abstract To improve understanding of Alzheimer’s disease, large observational studies are needed to increase power for more nuanced analyses. Combining data across existing observational studies represents one solution. However, the disparity of such datasets makes this a non-trivial task. Here, a machine learning approach was applied to impute longitudinal neuropsychological test scores across two observational studies, namely the Australian Imaging, Biomarkers and Lifestyle Study (AIBL) and the Alzheimer's Disease Neuroimaging Initiative (ADNI) providing an overall harmonised dataset. MissForest, a machine learning algorithm, capitalises on the underlying structure and relationships of data to impute test scores not measured in one study aligning it to the other study. Results demonstrated that simulated missing values from one dataset could be accurately imputed, and that imputation of actual missing data in one dataset showed comparable discrimination (p < 0.001) for clinical classification to measured data in the other dataset. Further, the increased power of the overall harmonised dataset was demonstrated by observing a significant association between CVLT-II test scores (imputed for ADNI) with PET Amyloid-β in MCI APOE-ε4 homozygotes in the imputed data (N = 65) but not for the original AIBL dataset (N = 11). These results suggest that MissForest can provide a practical solution for data harmonization using imputation across studies to improve power for more nuanced analyses.
    Keywords Medicine ; R ; Science ; Q
    Subject code 310
    Language English
    Publishing date 2021-12-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: The acceleration of aging and Alzheimer’s disease through the biological mechanisms behind obesity and type II diabetes

    Ralph Nigel Martins / Simon M. Laws / Wei Ling Florence Lim / Andrea C. Wilson / Ian James Martins

    Health, Vol 05, Iss 05, Pp 913-

    2013  Volume 920

    Abstract: The incidence of diabetes is predicted to increase to 21% by 2050. Currently, one third of US adults are obese and over 11% of these individuals have diabetes. Due to the growing need for therapeutic intervention to control and/or stabilize this increase ...

    Abstract The incidence of diabetes is predicted to increase to 21% by 2050. Currently, one third of US adults are obese and over 11% of these individuals have diabetes. Due to the growing need for therapeutic intervention to control and/or stabilize this increase in the incidence of diabetes in Western communities, gaining a comprehensive understanding of the association between obesity and Type 2 diabetes has become increasingly important to diabetes research. The increased cell senescence associated with diabetes has been associated with the limited ability of cells to divide, with indication of telomere shortening and genomic instability of the cells. Obese individuals have shorter telomeres suggesting an inverse relationship between adiposity and telomere length. The implication that Type 2 diabetes has on biological aging is of particular interest since telomere shortening in obesity and diabetes has been associated with an early risk for dementia and even progression to Alzheimer’s disease (AD). Lifestyle, nutrition and longevity are closely related and cellular senescence has been associated with telomere shortening and connected to longevity. Diet, cholesterol lowering drugs and exercise that control food intake and glucose tolerance in aging and diabetic individuals, via connections between liver circadian clocks and the suprachiasmatic nucleus in the brain, also have been shown to alter telomere lengths. Lifestyle interventions, such as diets low in fat and exercise, target the rise in obesity and associated telomere shortening by delaying or preventing the onset of Type 2 diabetes. The implementation of these anti-aging therapies early in life may prevent calorie overload and activation of calorie sensitive genes such as Sirtuin 1 (Sirt1). This may maintain telomere length and the control of obesity, which is linked to cardiovascular disease, diabetes and accelerates aging and AD.
    Keywords Telomere ; Sirtuin 1 ; Lifestyle ; Nutrition ; Diabetes ; Obesity ; Alzheimer’s Disease ; Medicine (General) ; R5-920 ; Medicine ; R ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
    Subject code 571
    Language English
    Publishing date 2013-05-01T00:00:00Z
    Publisher Scientific Research Publishing
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Comprehensive genetic analysis of the human lipidome identifies loci associated with lipid homeostasis with links to coronary artery disease

    Gemma Cadby / Corey Giles / Phillip E. Melton / Kevin Huynh / Natalie A. Mellett / Thy Duong / Anh Nguyen / Michelle Cinel / Alex Smith / Gavriel Olshansky / Tingting Wang / Marta Brozynska / Mike Inouye / Nina S. McCarthy / Amir Ariff / Joseph Hung / Jennie Hui / John Beilby / Marie-Pierre Dubé /
    Gerald F. Watts / Sonia Shah / Naomi R. Wray / Wei Ling Florence Lim / Pratishtha Chatterjee / Ian Martins / Simon M. Laws / Tenielle Porter / Michael Vacher / Ashley I. Bush / Christopher C. Rowe / Victor L. Villemagne / David Ames / Colin L. Masters / Kevin Taddei / Matthias Arnold / Gabi Kastenmüller / Kwangsik Nho / Andrew J. Saykin / Xianlin Han / Rima Kaddurah-Daouk / Ralph N. Martins / John Blangero / Peter J. Meikle / Eric K. Moses

    Nature Communications, Vol 13, Iss 1, Pp 1-

    2022  Volume 17

    Abstract: Dysregulation of lipid metabolism is associated with coronary artery disease (CAD). Here, the authors perform GWAS of the serum lipidome to identify variants associated with lipid species that are putatively in the mechanistic pathway to CAD. ...

    Abstract Dysregulation of lipid metabolism is associated with coronary artery disease (CAD). Here, the authors perform GWAS of the serum lipidome to identify variants associated with lipid species that are putatively in the mechanistic pathway to CAD.
    Keywords Science ; Q
    Language English
    Publishing date 2022-06-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Risk prediction of late-onset Alzheimer’s disease implies an oligogenic architecture

    Qian Zhang / Julia Sidorenko / Baptiste Couvy-Duchesne / Riccardo E. Marioni / Margaret J. Wright / Alison M. Goate / Edoardo Marcora / Kuan-lin Huang / Tenielle Porter / Simon M. Laws / Australian Imaging Biomarkers and Lifestyle (AIBL) Study / Perminder S. Sachdev / Karen A. Mather / Nicola J. Armstrong / Anbupalam Thalamuthu / Henry Brodaty / Loic Yengo / Jian Yang / Naomi R. Wray /
    Allan F. McRae / Peter M. Visscher

    Nature Communications, Vol 11, Iss 1, Pp 1-

    2020  Volume 11

    Abstract: Despite the identification of genetic risk loci for late-onset Alzheimer’s disease (LOAD), the genetic architecture and prediction remains unclear. Here, the authors use genetic risk scores for prediction of LOAD across three datasets and show evidence ... ...

    Abstract Despite the identification of genetic risk loci for late-onset Alzheimer’s disease (LOAD), the genetic architecture and prediction remains unclear. Here, the authors use genetic risk scores for prediction of LOAD across three datasets and show evidence suggesting oligogenic variant architecture for this disease.
    Keywords Science ; Q
    Language English
    Publishing date 2020-09-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Concordant peripheral lipidome signatures in two large clinical studies of Alzheimer’s disease

    Kevin Huynh / Wei Ling Florence Lim / Corey Giles / Kaushala S. Jayawardana / Agus Salim / Natalie A. Mellett / Adam Alexander T. Smith / Gavriel Olshansky / Brian G. Drew / Pratishtha Chatterjee / Ian Martins / Simon M. Laws / Ashley I. Bush / Christopher C. Rowe / Victor L. Villemagne / David Ames / Colin L. Masters / Matthias Arnold / Kwangsik Nho /
    Andrew J. Saykin / Rebecca Baillie / Xianlin Han / Rima Kaddurah-Daouk / Ralph N. Martins / Peter J. Meikle

    Nature Communications, Vol 11, Iss 1, Pp 1-

    2020  Volume 11

    Abstract: The onset and pathology of Alzheimer’s disease (AD) is associated with changes to lipid metabolism. Here, the authors analysed 569 lipids from 32 classes and subclasses in two independent patient cohorts to identify key lipid pathways to link the plasma ... ...

    Abstract The onset and pathology of Alzheimer’s disease (AD) is associated with changes to lipid metabolism. Here, the authors analysed 569 lipids from 32 classes and subclasses in two independent patient cohorts to identify key lipid pathways to link the plasma lipidome with AD and the future onset of AD.
    Keywords Science ; Q
    Language English
    Publishing date 2020-11-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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    Inter-library loan at ZB MED

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  9. Article ; Online: Risk prediction of late-onset Alzheimer’s disease implies an oligogenic architecture

    Qian Zhang / Julia Sidorenko / Baptiste Couvy-Duchesne / Riccardo E. Marioni / Margaret J. Wright / Alison M. Goate / Edoardo Marcora / Kuan-lin Huang / Tenielle Porter / Simon M. Laws / Australian Imaging Biomarkers and Lifestyle (AIBL) Study / Perminder S. Sachdev / Karen A. Mather / Nicola J. Armstrong / Anbupalam Thalamuthu / Henry Brodaty / Loic Yengo / Jian Yang / Naomi R. Wray /
    Allan F. McRae / Peter M. Visscher

    Nature Communications, Vol 11, Iss 1, Pp 1-

    2020  Volume 11

    Abstract: Despite the identification of genetic risk loci for late-onset Alzheimer’s disease (LOAD), the genetic architecture and prediction remains unclear. Here, the authors use genetic risk scores for prediction of LOAD across three datasets and show evidence ... ...

    Abstract Despite the identification of genetic risk loci for late-onset Alzheimer’s disease (LOAD), the genetic architecture and prediction remains unclear. Here, the authors use genetic risk scores for prediction of LOAD across three datasets and show evidence suggesting oligogenic variant architecture for this disease.
    Keywords Science ; Q
    Language English
    Publishing date 2020-09-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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    Inter-library loan at ZB MED

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  10. Article ; Online: Concordant peripheral lipidome signatures in two large clinical studies of Alzheimer’s disease

    Kevin Huynh / Wei Ling Florence Lim / Corey Giles / Kaushala S. Jayawardana / Agus Salim / Natalie A. Mellett / Adam Alexander T. Smith / Gavriel Olshansky / Brian G. Drew / Pratishtha Chatterjee / Ian Martins / Simon M. Laws / Ashley I. Bush / Christopher C. Rowe / Victor L. Villemagne / David Ames / Colin L. Masters / Matthias Arnold / Kwangsik Nho /
    Andrew J. Saykin / Rebecca Baillie / Xianlin Han / Rima Kaddurah-Daouk / Ralph N. Martins / Peter J. Meikle

    Nature Communications, Vol 11, Iss 1, Pp 1-

    2020  Volume 11

    Abstract: The onset and pathology of Alzheimer’s disease (AD) is associated with changes to lipid metabolism. Here, the authors analysed 569 lipids from 32 classes and subclasses in two independent patient cohorts to identify key lipid pathways to link the plasma ... ...

    Abstract The onset and pathology of Alzheimer’s disease (AD) is associated with changes to lipid metabolism. Here, the authors analysed 569 lipids from 32 classes and subclasses in two independent patient cohorts to identify key lipid pathways to link the plasma lipidome with AD and the future onset of AD.
    Keywords Science ; Q
    Language English
    Publishing date 2020-11-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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    Inter-library loan at ZB MED

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