The influences of low protein diet on the intestinal microbiota of mice
- Authors: Masuoka, Hiroaki , Suda, Wataru , Tomitsuka, Eriko , Shindo, Chie , Takayasu, Lena , Horwood, Paul , Greenhill, Andrew , Hattori, Masahira , Umezaki, Masahiro , Hirayama, Kazuhiro
- Date: 2020
- Type: Text , Journal article
- Relation: Scientific Reports Vol. 10, no. 1 (2020), p.
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- Description: Recent research suggests that protein deficiency symptoms are influenced by the intestinal microbiota. We investigated the influence of low protein diet on composition of the intestinal microbiota through animal experiments. Specific pathogen-free (SPF) mice were fed one of four diets (3, 6, 9, or 12% protein) for 4 weeks (n = 5 per diet). Mice fed the 3% protein diet showed protein deficiency symptoms such as weight loss and low level of blood urea nitrogen concentration in their serum. The intestinal microbiota of mice in the 3% and 12% protein diet groups at day 0, 7, 14, 21 and 28 were investigated by 16S rRNA gene sequencing, which revealed differences in the microbiota. In the 3% protein diet group, a greater abundance of urease producing bacterial species was detected across the duration of the study. In the 12% diet protein group, increases of abundance of Streptococcaceae and Clostridiales families was detected. These results suggest that protein deficiency may be associated with shifts in intestinal microbiota. © 2020, The Author(s).
Reduced renal function may explain the higher prevalence of hyperuricemia in older people
- Authors: Wang, Yutang , Zhang, Wanlin , Qian, Tingting , Sun, Hui , Xu, Qun , Hou, Xujuan , Hu, Wenqi , Zhang, Guang , Drummond, Grant , Sobey, Chris , Charchar, Fadi , Golledge, Jonathan , Yang, Guang
- Date: 2021
- Type: Text , Journal article
- Relation: Scientific Reports Vol. 11, no. 1 (2021), p.
- Relation: https://purl.org/au-research/grants/nhmrc/1062671
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- Description: This study aimed to investigate the contribution of renal dysfunction to enhanced hyperuricemia prevalence in older people. A cohort of 13,288 Chinese people aged between 40 and 95 years were recruited from January to May 2019. Serum uric acid concentration and estimated glomerular filtration rate [eGFR] were measured. The associations between age or eGFR and serum uric acid or hyperuricemia were analyzed using linear or binary logistic regression adjusting for risk factors. Uric acid concentration and prevalence of hyperuricemia were greater in older participants. Adjustment for reduced renal function (eGFR < 60 mL/min/1.73 m2) eliminated the associations between older age and higher uric acid concentration and between older age and higher prevalence of hyperuricemia diagnosis, whereas adjustment for other risk factors did not change those associations. Lower eGFR was associated with higher uric acid concentration both before (β = − 0.296, P < 0.001) and after adjustment for age (β = − 0.313, P < 0.001). Reduced renal function was associated with hyperuricemia diagnosis both before (odds ratio, OR, 3.64; 95% CI 3.10–4.28; P < 0.001) and after adjustment for age (adjusted OR, 3.82; 95% CI 3.22–4.54; P < 0.001). Mean serum uric acid and prevalence of hyperuricemia were higher in people with eGFR < 60 mL/min/1.73 m2 than those with eGFR ≥ 60 mL/min/1.73 m2. The prevalence of reduced renal function increased with older age (P < 0.001). This study suggests that reduced renal function can explain the increased uric acid levels and hyperuricemia diagnoses in older people. © 2021, The Author(s).
Genetic aetiology of self-harm ideation and behaviour
- Authors: Campos, Adrian , Verweij, Karin , Statham, Dixie , Madden, Pamela , Maciejewski, Dominique , Davis, Katrina , John, Ann , Hotopf, Matthew , Heath, Andrew , Martin, Nicholas , Rentería, Miguel
- Date: 2020
- Type: Text , Journal article
- Relation: Scientific Reports Vol. 10, no. 1 (2020), p.
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- Description: Family studies have identified a heritable component to self-harm that is partially independent from comorbid psychiatric disorders. However, the genetic aetiology of broad sense (non-suicidal and suicidal) self-harm has not been characterised on the molecular level. In addition, controversy exists about the degree to which suicidal and non-suicidal self-harm share a common genetic aetiology. In the present study, we conduct genome-wide association studies (GWAS) on lifetime self-harm ideation and self-harm behaviour (i.e. any lifetime self-harm act regardless of suicidal intent) using data from the UK Biobank (n > 156,000). We also perform genome wide gene-based tests and characterize the SNP heritability and genetic correlations between these traits. Finally, we test whether polygenic risk scores (PRS) for self-harm ideation and self-harm behaviour predict suicide attempt, suicide thoughts and non-suicidal self-harm (NSSH) in an independent target sample of 8,703 Australian adults. Our GWAS results identified one genome-wide significant locus associated with each of the two phenotypes. SNP heritability (hsnp2) estimates were ~10%, and both traits were highly genetically correlated (LDSC rg > 0.8). Gene-based tests identified seven genes associated with self-harm ideation and four with self-harm behaviour. Furthermore, in the target sample, PRS for self-harm ideation were significantly associated with suicide thoughts and NSSH, and PRS for self-harm behaviour predicted suicide thoughts and suicide attempt. Follow up regressions identified a shared genetic aetiology between NSSH and suicide thoughts, and between suicide thoughts and suicide attempt. Evidence for shared genetic aetiology between NSSH and suicide attempt was not statistically significant. © 2020, The Author(s).
- Description: This research was conducted using data from the UK Biobank resource under application number 25331. AC-G is supported by a UQ Research Training Scholarship from The University of Queensland (UQ). MER thanks the support of the NHMRC and Australian Research Council (ARC), and National Health and Medical Research Council (NHMRC) through a Research Fellowship (GNT1102821) and NHMRC Centre for Research Excellence in Suicide Prevention (GNT1042580). This research was made possible thanks to support from the US National Institutes of Health (grants AA013326, AA07535, AA0758O, AA07728, AA10249, AA13320, AA13321, AA14041, AA11998, AA17688, DA00272, DA012854, DA07261, DA018267, DA018660, DA23668 and DA019951); the Australian National Health and Medical Research Council (241944, 339462, 389927, 389875, 389891, 389892, 389938, 442915, 442981, 496739, 552485, 552498, 628911 1047956); the Australian Research Council (A7960034, A79906588, A79801419, DP0770096, DP0212016 and DP0343921).
Aberrant pregnancy-associated plasma protein-A expression in breast cancers prognosticates clinical outcomes
- Authors: Prithviraj, Prashanth , Anaka, Matthew , Thompson, Erik , Sharma, Revati , Walkiewicz, Marzena , Tutuka, Candani , Behren, Andreas , Kannourakis, George , Jayachandran, Aparna
- Date: 2020
- Type: Text , Journal article
- Relation: Scientific Reports Vol. 10, no. 1 (2020), p.
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- Description: Elevated levels of pregnancy-associated plasma protein-A (PAPP-A) have been implicated in the pathogenesis of various malignancies, including breast cancers. Breast cancer is one of the most frequent carcinomas and is the second most common cancer type detected in women of child-bearing age. Throughout pregnancy PAPP-A is produced and secreted by the placental syncytiotrophoblast cells; co-incidentally pregnancy-associated breast cancers often have an aggressive clinical course. The components of the PAPP-A/IGF axis was assessed in a panel of breast cancer cell lines. Using neutralising antibodies the impact of PAPP-A/IGF axis on cell motility was evaluated. PAPP-A was expressed in four of the twelve breast cancer cell lines tested. Blocking PAPP-A and IGFBP4 with neutralising antibodies significantly decreased motiliy of MDA-MB-231 cells. Upregulation of PAPP-A expression in breast tumours resulted in a trend towards worse overall survival. Notably, PAPP-A expression also positively correlated with epithelial-to-mesenchymal transition markers. In conclusion, these results indicate that PAPP-A plays an important role in breast cancer progression and it may be a promising therapeutic target in breast cancer. © 2020, The Author(s).
A field investigation of the relationship between rotating shifts, sleep, mental health and physical activity of Australian paramedics
- Authors: Khan, Wahaj , Jackson, Melinda , Kennedy, Gerard , Conduit, Russell
- Date: 2021
- Type: Text , Journal article
- Relation: Scientific Reports Vol. 11, no. 1 (2021), p.
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- Description: Paramedics working on a rotating shift are at an increased risk of developing chronic health issues due to continuous circadian rhythm disruption. The acute effects of shift rotation and objectively measured sleep have rarely been reported in paramedics. This study investigated the relationships between a rotating shift schedule and sleep (using actigraphy), subjective reports of sleepiness, mood, stress and fatigue. Galvanic Skin Response, energy expenditure and physical activity (BodyMedia SenseWear Armband) were also recorded across the shift schedule. Paramedics were monitored for a period of eight consecutive days across pre-shift, day shift, night shift, and 2 days off. Fifteen paramedics (M age = 39.5 and SD = 10.7 years) who worked rotational shifts experienced sleep restriction during night shift compared to pre-shift, day shift and days off (p < 0.001). Night shift was also associated with higher levels of stress (p < 0.05), fatigue (p < 0.05), and sleepiness (p < 0.05). One day off was related to a return to pre-shift functioning. Such shift-related issues have a compounding negative impact on an already stressful occupation with high rates of physical and mental health issues. Therefore, there is an urgent need to investigate methods to reduce rotating shift burden on the health of paramedics. This could be through further research aimed at providing recommendations for shift work schedules with sufficient periods for sleep and recovery from stress. © 2021, The Author(s).
Uncovering genetic mechanisms of hypertension through multi-omic analysis of the kidney
- Authors: Eales, James , Jiang, Xiao , Xu, Xiaoguang , Prestes, Priscilla , Charchar, Fadi
- Date: 2021
- Type: Text , Journal article
- Relation: Nature Genetics Vol. 53, no. 5 (2021), p. 630-637
- Full Text: false
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- Description: The kidney is an organ of key relevance to blood pressure (BP) regulation, hypertension and antihypertensive treatment. However, genetically mediated renal mechanisms underlying susceptibility to hypertension remain poorly understood. We integrated genotype, gene expression, alternative splicing and DNA methylation profiles of up to 430 human kidneys to characterize the effects of BP index variants from genome-wide association studies (GWASs) on renal transcriptome and epigenome. We uncovered kidney targets for 479 (58.3%) BP-GWAS variants and paired 49 BP-GWAS kidney genes with 210 licensed drugs. Our colocalization and Mendelian randomization analyses identified 179 unique kidney genes with evidence of putatively causal effects on BP. Through Mendelian randomization, we also uncovered effects of BP on renal outcomes commonly affecting patients with hypertension. Collectively, our studies identified genetic variants, kidney genes, molecular mechanisms and biological pathways of key relevance to the genetic regulation of BP and inherited susceptibility to hypertension. © 2021, Crown.
Blood–brain barrier disruption and ventricular enlargement are the earliest neuropathological changes in rats with repeated sub-concussive impacts over 2 weeks
- Authors: Hiles-Murison, Bailey , Lavender, Andrew , Hackett, Mark , Armstrong, Joshua , Nesbit, Michael
- Date: 2021
- Type: Text , Journal article
- Relation: Scientific Reports Vol. 11, no. 1 (2021), p.
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- Description: Repeated sub-concussive impact (e.g. soccer ball heading), a significantly lighter form of mild traumatic brain injury, is increasingly suggested to cumulatively alter brain structure and compromise neurobehavioural function in the long-term. However, the underlying mechanisms whereby repeated long-term sub-concussion induces cerebral structural and neurobehavioural changes are currently unknown. Here, we utilised an established rat model to investigate the effects of repeated sub-concussion on size of lateral ventricles, cerebrovascular blood–brain barrier (BBB) integrity, neuroinflammation, oxidative stress, and biochemical distribution. Following repeated sub-concussion 3 days per week for 2 weeks, the rats showed significantly enlarged lateral ventricles compared with the rats receiving sham-only procedure. The sub-concussive rats also presented significant BBB dysfunction in the cerebral cortex and hippocampal formation, whilst neuromotor function assessed by beamwalk and rotarod tests were comparable to the sham rats. Immunofluorescent and spectroscopic microscopy analyses revealed no significant changes in neuroinflammation, oxidative stress, lipid distribution or protein aggregation, within the hippocampus and cortex. These data collectively indicate that repeated sub-concussion for 2 weeks induce significant ventriculomegaly and BBB disruption, preceding neuromotor deficits. © 2021, The Author(s). *Please note that there are multiple authors for this article therefore only the name of the first 5 including Federation University Australia affiliate “Andrew Lavender” is provided in this record**
Evaluating the holistic costs and benefits of corn production systems in Minnesota, US
- Authors: Sandhu, Harpinder , Scialabba, Nadia , Warner, Chris , Behzadnejad, Fatemeh , Keohane, Kieran
- Date: 2020
- Type: Text , Journal article
- Relation: Scientific Reports Vol. 10, no. 1 (2020), p.
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- Description: Global agriculture aims to minimize its impacts on environment and human health while maintaining its productivity. This requires a comprehensive understanding of its benefits and costs to ecosystems and society. Here, we apply a new evaluation framework developed by the Economics of Ecosystems and Biodiversity for Agriculture and Food (TEEBAgriFood) to assess key benefits and costs on the production side of genetically modified (GM) and organic corn systems in Minnesota, USA. The market value of GM corn is $4.5 billion, and only $31.8 million for organic corn using production data and market prices of 2017. GM corn generates revenue of $1488 per hectare (at $121 per MT), which is significantly lower than the organic corn at $2793 per hectare (at $294 per MT). Using a novel three-stage wellbeing valuation, analysis of the associations between corn production intensity and subjective measures of general health and wellbeing indicates that the total non-financial health cost associated with GM corn is $427.50 per hectare or $1.3 billion annually. We also find that the total annual environmental cost associated with GM corn production is $179 per hectare or $557.65 million within Minnesota. The use of the evaluation framework can help to improve decision making at farm and policy level to develop sustainable agriculture in order to minimize environmental and health related costs to society and economy. © 2020, The Author(s). **Please note that there are multiple authors for this article therefore only the name of the first 5 including Federation University Australia affiliate “Harpinder Sandhu” is provided in this record**
- Description: Global agriculture aims to minimize its impacts on environment and human health while maintaining its productivity. This requires a comprehensive understanding of its benefits and costs to ecosystems and society. Here, we apply a new evaluation framework developed by the Economics of Ecosystems and Biodiversity for Agriculture and Food (TEEBAgriFood) to assess key benefits and costs on the production side of genetically modified (GM) and organic corn systems in Minnesota, USA. The market value of GM corn is $4.5 billion, and only $31.8 million for organic corn using production data and market prices of 2017. GM corn generates revenue of $1488 per hectare (at $121 per MT), which is significantly lower than the organic corn at $2793 per hectare (at $294 per MT). Using a novel three-stage wellbeing valuation, analysis of the associations between corn production intensity and subjective measures of general health and wellbeing indicates that the total non-financial health cost associated with GM corn is $427.50 per hectare or $1.3 billion annually. We also find that the total annual environmental cost associated with GM corn production is $179 per hectare or $557.65 million within Minnesota. The use of the evaluation framework can help to improve decision making at farm and policy level to develop sustainable agriculture in order to minimize environmental and health related costs to society and economy. © 2020, The Author(s). **Please note that there are multiple authors for this article therefore only the name of the first 5 including Federation University Australia affiliate “________________” is provided in this record**
The oligomeric assembly of galectin-11 is critical for anti-parasitic activity in sheep (Ovis aries)
- Authors: Sakthivel, Dhanasekaran , Preston, Sarah , Gasser, Robin , Meeusen, Els , Piedrafita, David
- Date: 2020
- Type: Text , Journal article
- Relation: Communications Biology Vol. 3, no. 1 (2020), p.
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- Description: Galectins are a family of glycan-binding molecules with a characteristic affinity for ß-D-glycosides that mediate a variety of important cellular functions, including immune and inflammatory responses. Galectin-11 (LGALS-11) has been recently identified as a mediator induced specifically in animals against gastrointestinal nematodes and can interfere with parasite growth and development. Here, we report that at least two natural genetic variants of LGALS-11 exist in sheep, and demonstrate fundamental differences in anti-parasitic activity, correlated with their ability to dimerise. This study improves our understanding of the role of galectins in the host immune and inflammatory responses against parasitic nematodes and provides a basis for genetic studies toward selective breeding of animals for resistance to parasites. © 2020, The Author(s). **Please note that there are multiple authors for this article therefore only the name of the first 5 including Federation University Australia affiliate “Dhanasekaran Sakthivel, Sarah Preston, Robin Gasser, Els Meeusen, David Piedrafita” is provided in this record**
Thymic development of unconventional T cells: how NKT cells, MAIT cells and γδ T cells emerge
- Authors: Pellicci, Daniel , Koay, Hui-Fern , Berzins, Stuart
- Date: 2020
- Type: Text , Journal article , Review
- Relation: Nature Reviews Immunology Vol. 20, no. 12 (2020), p. 756-770
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- Description: T cell lineages are defined by specialized functions and differential expression of surface antigens, cytokines and transcription factors. Conventional CD4+ and CD8+ T cells are the best studied of the T cell subsets, but ‘unconventional’ T cells have emerged as being more abundant and influential than has previously been appreciated. Key subsets of unconventional T cells include natural killer T (NKT) cells, mucosal-associated invariant T (MAIT) cells and γδ T cells; collectively, these make up ~10% of circulating T cells, and often they are the majority of T cells in tissues such as the liver and gut mucosa. Defects and deficiencies in unconventional T cells are associated with autoimmunity, chronic inflammation and cancer, so it is important to understand how their development is regulated. In this Review, we describe the thymic development of NKT cells, MAIT cells and γδ T cells and highlight some of the key differences between conventional and unconventional T cell development. © 2020, Springer Nature Limited.
Plasma lipocalin-2/NGAL is stable over 12 weeks and is not modulated by exercise or dieting
- Authors: Nakai, Michael , Prestes, Priscilla , O’Brien, Brendan , Charchar, Fadi , Marques, Francine
- Date: 2021
- Type: Text , Journal article
- Relation: Scientific Reports Vol. 11, no. 1 (2021), p.
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- Description: Amongst other immune cells, neutrophils play a key role in systemic inflammation leading to cardiovascular disease and can release inflammatory factors, including lipocalin-2 (LCN2). LCN2 drives cardiac hypertrophy and plays a role in maladaptive remodelling of the heart and has been associated with renal injury. While lifestyle factors such as diet and exercise are known to attenuate low-grade inflammation, their ability to modulate plasma LCN2 levels is unknown. Forty-eight endurance athletes and 52 controls (18–55 years) underwent measurement for various cardiovascular health indicators, along with plasma LCN2 concentration. No significant difference in LCN2 concentration was seen between the two groups. LCN2 was a very weak predictor or absent from models describing blood pressures or predicting athlete status. In another cohort, 57 non-diabetic overweight or obese men and post-menopausal women who fulfilled Adult Treatment Panel III metabolic syndrome criteria were randomly allocated into either a control, modified Dietary Approaches to Stop Hypertension (DASH) diet, or DASH and exercise group. Pre- and post-intervention demographic, cardiovascular health indicators, and plasma LCN2 expression were measured in each individual. While BMI fell in intervention groups, LCN2 levels remained unchanged within and between all groups, as illustrated by strong correlations between LCN2 concentrations pre- and 12 weeks post-intervention (r = 0.743, P < 0.0001). This suggests that circulating LCN2 expression are stable over a period of at least 12 weeks and is not modifiable by diet and exercise. © 2021, The Author(s). *Please note that there are multiple authors for this article therefore only the name of the first 5 including Federation University Australia affiliate “Priscilla Prestes, Brendan O'Brien, Fadi Charchar and Francine Marques” is provided in this record** .
Association between nocturnal activity of the sympathetic nervous system and cognitive dysfunction in obstructive sleep apnoea
- Authors: Alomri, Ridwan , Kennedy, Gerard , Wali, Siraj , Alhejaili, Faris , Robinson, Stephen
- Date: 2021
- Type: Text , Journal article
- Relation: Scientific Reports Vol. 11, no. 1 (2021), p. 11990-11990.
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- Description: Obstructive sleep apnoea (OSA) is associated with repetitive breathing obstructions during sleep. These episodes of hypoxia and associated arousals from sleep induce physiological stress and nocturnal over-activation of the sympathetic nervous system (SNS). One consequence of OSA is impairment in a range of cognitive domains. Previous research into cognitive impairment in OSA have focussed on intermittent hypoxia and disrupted sleep, but not nocturnal over-activation of the SNS. Therefore, we investigated whether nocturnal over-activity of the SNS was associated with cognitive impairments in OSA. The extent of nocturnal SNS activation was estimated from heart rate variability (HRV), pulse wave amplitude (PWA) and stress response biomarkers (cortisol and glucose levels). OSA severity was significantly associated with PWA indices and the HRV low frequency/ high frequency ratio (p < 0.05). Morning blood glucose levels were significantly associated with the duration of a blood oxygen saturation (SaO2) < 90% (p < 0.01). PWA and HRV were significantly associated with the time taken to perform a task involving visuospatial functioning (p < 0.05), but not with impairments in sustained attention, reaction time or autobiographical memory. These results suggest that the visuospatial dysfunction observed in people with OSA is associated with increased nocturnal activity of the SNS. © 2021, The Author(s).
Integration of palaeo-and-modern food webs reveal slow changes in a river floodplain wetland ecosystem
- Authors: Kattel, Giri , Eyre, Bradley , Gell, Peter
- Date: 2020
- Type: Text , Journal article
- Relation: Scientific Reports Vol. 10, no. 1 (2020), p.
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- Description: Large rivers, including the Murray River system in southeast Australia, are disturbed by many activities. The arrival of European settlers to Australia by the mid-1800s transformed many floodplain wetlands of the lower Murray River system. River impoundment and flow regulation in the late 1800s and, from the 1930s, resulted in species invasion, and elevated nutrient concentrations causing widespread eutrophication. An integrated palaeoecology, and palaeo-and-modern food web approach, incorporating mixing models, was undertaken to reveal changes in a regulated wetland (i.e. Kings Billabong). The lack of preserved sediment suggests the wetland was naturally intermittent before 1890. After this time, when used as a water retention basin, the wetland experienced net sediment accumulation. Subfossil cladocerans, and δ13C of Daphnia, chironomid, and bulk sediment, all reflected an early productive, likely clear water state and shifts in trophic state following river regulation in the 1930s. Food web mixing models, based on δ13C and δ15N in subfossil and modern Daphnia, fish, and submerged and emergent macrophytes, also indicated a shift in the trophic relationships between fish and Daphnia. By the 1970s, a new state was established but a further significant alteration of nitrogen and carbon sources, and trophic interactions, continued through to the early 2000s. A possible switch from Daphnia as a prey of Australian Smelt could have modified the food web of the wetland by c. 2006. The timing of this change corresponded to the expansion of emergent macrophytes possibly due to landscape level disruptions. The evidence of these changes suggests a need for a broader understanding of the evolution of wetlands for the management of floodplains in the region. © 2020, The Author(s).
- Description: Funding details: National Key Research and Development Program of China Stem Cell and Translational Research, #2016YFC0402900 Funding details: National Key Research and Development Program of China Stem Cell and Translational Research, #2016YFE0201900 Funding details: Centre of Excellence for Electromaterials Science, Australian Research Council, ARC;ACES, DP160100248 Funding details: Centre of Excellence for Electromaterials Science, Australian Research Council, ARC;ACES, LE0668495
Establishment of sex difference in circulating uric acid is associated with higher testosterone and lower sex hormone-binding globulin in adolescent boys
- Authors: Wang, Yutang , Charchar, Fadi
- Date: 2021
- Type: Text , Journal article
- Relation: Scientific Reports Vol. 11, no. 1 (2021), p.
- Relation: https://purl.org/au-research/grants/nhmrc/1062671
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- Description: Men have higher circulating levels of uric acid than women. This sex difference is suspected to be a result of suppressive effects of estradiol on uric acid. If so, estradiol would be inversely associated with circulating uric acid. This study aimed to test this hypothesis. This cross-sectional study included 9472 participants (weighted sample size of 184,342,210) aged 12–80 years from the 2013 to 2016 US National Health and Nutrition Examination Survey. Associations of sex hormones with uric acid were analyzed using weighted least squares regression, adjusting for demographic characteristics, lifestyle risk factors, and comorbidities. Neither free nor bioavailable estradiol was inversely associated with circulating uric acid in adolescent boys or girls, or adult men or women, or perimenopausal women after full adjustment. The sex difference in uric acid was established during adolescence as a result of a dramatic increase in uric acid in adolescent boys. During adolescence, the increase in estradiol in girls over time was accompanied by a relatively unchanged level of uric acid. All three fractions of estradiol (free, bioavailable, and total) were positively associated with uric acid in adolescent boys and girls after full adjustment. In adolescent boys, all three fractions of testosterone were positively associated with serum uric acid, and sex hormone-binding globulin was inversely associated with uric acid after full adjustment. These results suggest that estradiol is not inversely associated with circulating uric acid in adolescents and the establishment of sex difference in circulating uric acid during adolescence is associated with higher testosterone and lower sex hormone-binding globulin in adolescent boys. © 2021, The Author(s).
Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals
- Authors: Surendran, Praveen , Feofanova, Elena , Lahrouchi, Najim , Ntalla, Ionna , Karthikeyan, Savita , Cook, James , Chen, Lingyan , Mifsud, Borbala , Yao, Chen , Kraja, Aldi , Cartwright, James , Hellwege, Jacklyn , Giri, Ayush , Tragante, Vinicius , Thorleifsson, Gudmar , Liu, Dajiang , Prins, Bram , Stewart, Isobel , Cabrera, Claude , Eales, James , Akbarov, Artur , Auer, Paul , Charchar, Fadi , Howson, Joanna , LifeLines Cohort, Study , Epic, C. V. D. , Epic InterAct , Understanding Society Scientific, Group , Million Veteran, Program
- Date: 2020
- Type: Text , Journal article
- Relation: Nature Genetics Vol. 52, no. 12 (2020), p. 1314-1332
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- Description: Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to ~1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency ≤ 0.01) variant BP associations (P < 5 × 10−8), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were ~8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets. © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc. There are 286 authors of this articles not all are listed in this record.
AusTraits, a curated plant trait database for the Australian flora
- Authors: Falster, Daniel , Gallagher, Rachael , Wenk, Elizabeth , Wright, Ian , Cheal, David
- Date: 2021
- Type: Text , Journal article , Data article
- Relation: Scientific Data Vol. 8, no. 1 (2021), p.
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- Description: We introduce the AusTraits database - a compilation of values of plant traits for taxa in the Australian flora (hereafter AusTraits). AusTraits synthesises data on 448 traits across 28,640 taxa from field campaigns, published literature, taxonomic monographs, and individual taxon descriptions. Traits vary in scope from physiological measures of performance (e.g. photosynthetic gas exchange, water-use efficiency) to morphological attributes (e.g. leaf area, seed mass, plant height) which link to aspects of ecological variation. AusTraits contains curated and harmonised individual- and species-level measurements coupled to, where available, contextual information on site properties and experimental conditions. This article provides information on version 3.0.2 of AusTraits which contains data for 997,808 trait-by-taxon combinations. We envision AusTraits as an ongoing collaborative initiative for easily archiving and sharing trait data, which also provides a template for other national or regional initiatives globally to fill persistent gaps in trait knowledge. © 2021, The Author(s). **Please note that there are multiple authors for this article therefore only the name of the first 5 including Federation University Australia affiliate “David Cheal" is provided in this record**
Kallistatin limits abdominal aortic aneurysm by attenuating generation of reactive oxygen species and apoptosis
- Authors: Krishna, Smriti , Li, Jiaze , Wang, Yutang , Moran, Corey , Trollope, Alexandra
- Date: 2021
- Type: Text , Journal article
- Relation: Scientific Reports Vol. 11, no. 1 (2021), p.
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- Description: Inflammation, vascular smooth muscle cell apoptosis and oxidative stress are believed to play important roles in abdominal aortic aneurysm (AAA) pathogenesis. Human kallistatin (KAL; gene SERPINA4) is a serine proteinase inhibitor previously shown to inhibit inflammation, apoptosis and oxidative stress. The aim of this study was to investigate the role of KAL in AAA through studies in experimental mouse models and patients. Serum KAL concentration was negatively associated with the diagnosis and growth of human AAA. Transgenic overexpression of the human KAL gene (KS-Tg) or administration of recombinant human KAL (rhKAL) inhibited AAA in the calcium phosphate (CaPO4) and subcutaneous angiotensin II (AngII) infusion mouse models. Upregulation of KAL in both models resulted in reduction in the severity of aortic elastin degradation, reduced markers of oxidative stress and less vascular smooth muscle apoptosis within the aorta. Administration of rhKAL to vascular smooth muscle cells incubated in the presence of AngII or in human AAA thrombus-conditioned media reduced apoptosis and downregulated markers of oxidative stress. These effects of KAL were associated with upregulation of Sirtuin 1 activity within the aortas of both KS-Tg mice and rodents receiving rhKAL. These results suggest KAL-Sirtuin 1 signalling limits aortic wall remodelling and aneurysm development through reductions in oxidative stress and vascular smooth muscle cell apoptosis. Upregulating KAL may be a novel therapeutic strategy for AAA. © 2021, The Author(s).
Molecular insights into genome-wide association studies of chronic kidney disease-defining traits
- Authors: Xu, Xiaoguang , Eales, James , Akbarov, Artur , Guo, Hui , Becker, Lorenz , Talavera, David , Ashraf, Fehzan , Nawaz, Jabran , Pramanik, Sanjeev , Bowes, John , Jiang, Xiao , Dormer, John , Denniff, Matthew , Antczak, Andrzej , Szulinska, Monika , Wise, Ingrid , Prestes, Priscilla , Glyda, Maciej , Bogdanski, Pawel , Zukowska-Szczechowska, Ewa , Berzuini, Carlo , Woolf, Adrian , Samani, Nilesh , Charchar, Fadi , Tomaszewski, Maciej
- Date: 2018
- Type: Text , Journal article
- Relation: Nature communications Vol. 9, no. 1 (2018), p. 1-12
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- Description: Genome-wide association studies (GWAS) have identified >100 loci of chronic kidney disease-defining traits (CKD-dt). Molecular mechanisms underlying these associations remain elusive. Using 280 kidney transcriptomes and 9958 gene expression profiles from 44 non-renal tissues we uncover gene expression partners (eGenes) for 88.9% of CKD-dt GWAS loci. Through epigenomic chromatin segmentation analysis and variant effect prediction we annotate functional consequences to 74% of these loci. Our colocalisation analysis and Mendelian randomisation in >130,000 subjects demonstrate causal effects of three eGenes (NAT8B, CASP9 and MUC1) on estimated glomerular filtration rate. We identify a common alternative splice variant in MUC1 (a gene responsible for rare Mendelian form of kidney disease) and observe increased renal expression of a specific MUC1 mRNA isoform as a plausible molecular mechanism of the GWAS association signal. These data highlight the variants and genes underpinning the associations uncovered in GWAS of CKD-dt.
Modulation of TCR signalling components occurs prior to positive selection and lineage commitment in iNKT cells
- Authors: Dinh, Xuyen , Stanley, Dragana , Smith, Letitia , Moreau, Morgane , Berzins, Stuart
- Date: 2021
- Type: Text , Journal article
- Relation: Scientific Reports Vol. 11, no. 1 (2021), p.
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- Description: iNKT cells play a critical role in controlling the strength and character of adaptive and innate immune responses. Their unique functional characteristics are induced by a transcriptional program initiated by positive selection mediated by CD1d expressed by CD4+CD8+ (double positive, DP) thymocytes. Here, using a novel Vα14 TCR transgenic strain bearing greatly expanded numbers of CD24hiCD44loNKT cells, we examined transcriptional events in four immature thymic iNKT cell subsets. A transcriptional regulatory network approach identified transcriptional changes in proximal components of the TCR signalling cascade in DP NKT cells. Subsequently, positive and negative selection, and lineage commitment, occurred at the transition from DP NKT to CD4 NKT. Thus, this study introduces previously unrecognised steps in early NKT cell development, and separates the events associated with modulation of the T cell signalling cascade prior to changes associated with positive selection and lineage commitment. © 2021, The Author(s). **Please note that there are multiple authors for this article therefore only the name of the first 5 including Federation University Australia affiliate “Stuart Berzins” is provided in this record**
Drivers of seedling establishment success in dryland restoration efforts
- Authors: Shackelford, Nancy , Paterno, Gustavo , Winkler, Daniel , Erickson, Todd , Wong, Megan
- Date: 2021
- Type: Text , Journal article
- Relation: Nature Ecology and Evolution Vol. 5, no. 9 (2021), p. 1283-1290
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- Description: Restoration of degraded drylands is urgently needed to mitigate climate change, reverse desertification and secure livelihoods for the two billion people who live in these areas. Bold global targets have been set for dryland restoration to restore millions of hectares of degraded land. These targets have been questioned as overly ambitious, but without a global evaluation of successes and failures it is impossible to gauge feasibility. Here we examine restoration seeding outcomes across 174 sites on six continents, encompassing 594,065 observations of 671 plant species. Our findings suggest reasons for optimism. Seeding had a positive impact on species presence: in almost a third of all treatments, 100% of species seeded were growing at first monitoring. However, dryland restoration is risky: 17% of projects failed, with no establishment of any seeded species, and consistent declines were found in seeded species as projects matured. Across projects, higher seeding rates and larger seed sizes resulted in a greater probability of recruitment, with further influences on species success including site aridity, taxonomic identity and species life form. Our findings suggest that investigations examining these predictive factors will yield more effective and informed restoration decision-making. © 2021, The Author(s), under exclusive licence to Springer Nature Limited. **Please note that there are multiple authors for this article therefore only the name of the first 5 including Federation University Australia affiliate “Megan Wong” is provided in this record** Author Correction: Drivers of seedling establishment success in dryland restoration efforts (Nature Ecology & Evolution, (2021), 5, 9, (1283-1290), 10.1038/s41559-021-01510-3). https://doi.org/10.1038/s41559-021-01544-7
- Description: Restoration of degraded drylands is urgently needed to mitigate climate change, reverse desertification and secure livelihoods for the two billion people who live in these areas. Bold global targets have been set for dryland restoration to restore millions of hectares of degraded land. These targets have been questioned as overly ambitious, but without a global evaluation of successes and failures it is impossible to gauge feasibility. Here we examine restoration seeding outcomes across 174 sites on six continents, encompassing 594,065 observations of 671 plant species. Our findings suggest reasons for optimism. Seeding had a positive impact on species presence: in almost a third of all treatments, 100% of species seeded were growing at first monitoring. However, dryland restoration is risky: 17% of projects failed, with no establishment of any seeded species, and consistent declines were found in seeded species as projects matured. Across projects, higher seeding rates and larger seed sizes resulted in a greater probability of recruitment, with further influences on species success including site aridity, taxonomic identity and species life form. Our findings suggest that investigations examining these predictive factors will yield more effective and informed restoration decision-making. © 2021, The Author(s), under exclusive licence to Springer Nature Limited. **Please note that there are multiple authors for this article therefore only the name of the first 5 including Federation University Australia affiliate “Megan Wong” is provided in this record**