Ancylostoma ceylanicum
- Authors: Colella, Vito , Bradbury, Richard , Traub, Rebecca
- Date: 2021
- Type: Text , Journal article
- Relation: Trends in Parasitology Vol. 37, no. 9 (2021), p. 844-845
- Full Text: false
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Effect of contamination and purity priming on attitudes to vaccination and other health interventions : a randomised controlled experiment
- Authors: Bryden, Gabrielle , Rockloff, Matthew , Browne, Matthew , Unsworth, Carolyn
- Date: 2021
- Type: Text , Journal article
- Relation: Vaccine Vol. 39, no. 45 (2021), p. 6653-6659
- Full Text: false
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- Description: The objective of this experiment is to assess whether priming for contamination and purity causes a change in attitudes to health interventions, including vaccination, and complementary and alternative medicines (CAMs). An online priming experiment was conducted with four between-subject experimental conditions including photos of: 1) biological contamination, 2) chemical contamination, 3) pure environments, such as pristine landscapes, and 4) hazard signs/icons indicating physical threats. Two control conditions included photos of neutral scenes and neutral icons, whereby experimental groups were compared against the related control groups (photograph for conditions 1–3 and neutral icons for condition 4). Subjects were randomly assigned to one of the six conditions, and after exposure to the images they were asked to rate 10 conventional and alternative health interventions for effectiveness and safety, as well being assessed for disgust sensitivity using the reduced-item DPSS-R [10]. A total of 642 adults completed the experiment. Exposure to primes did not cause a differential change in ratings of health interventions. Nevertheless, higher levels of sensitivity to disgust were associated with lower ratings of the effectiveness of MMR vaccination, tetanus injection, antibiotics, and surgery; and higher levels of sensitivity to disgust were associated with higher ratings of effectiveness of vitamins/minerals. In conclusion, this online experiment did not find an experimental effect of priming for contamination and purity on subjects’ ratings of the safety and effectiveness of conventional and alternative health interventions. This indicates that attitudes to these health interventions are not influenced by a temporary increase in the salience of feelings of contamination or purity. However, individual differences in disgust sensitivity are related to their attitudes to vaccination and CAM interventions. © 2021 Elsevier Ltd
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.
GCNA interacts with spartan and topoisomerase II to regulate genome stability
- Authors: Dokshin, Gregoriy , Davis, Gregory , Sawle, Ashley , Eldridge, Matthew , Nicholls, Peter , Gourley, Taylin , Romer, Katherine , Molesworth, Luke , Tatnell, Hannah , Ozturk, Ahmet , de Rooij, Dirk , Hannon, Gregory , Page, David , Mello, Craig , Carmell, Michelle
- Date: 2020
- Type: Text , Journal article
- Relation: Developmental Cell Vol. 52, no. 1 (2020), p. 53-68.e6
- Full Text: false
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- Description: GCNA proteins are expressed across eukarya in pluripotent cells and have conserved functions in fertility. GCNA homologs Spartan (DVC-1) and Wss1 resolve DNA-protein crosslinks (DPCs), including Topoisomerase-DNA adducts, during DNA replication. Here, we show that GCNA mutants in mouse and C. elegans display defects in genome maintenance including DNA damage, aberrant chromosome condensation, and crossover defects in mouse spermatocytes and spontaneous genomic rearrangements in C. elegans. We show that GCNA and topoisomerase II (TOP2) physically interact in both mice and worms and colocalize on condensed chromosomes during mitosis in C. elegans embryos. Moreover, C. elegans gcna-1 mutants are hypersensitive to TOP2 poison. Together, our findings support a model in which GCNA provides genome maintenance functions in the germline and may do so, in part, by promoting the resolution of TOP2 DPCs. DNA topoisomerases help unwind DNA but occasionally get trapped, resulting in DNA-protein crosslinks (DPCs). DPCs damage DNA and threaten genomic integrity. Dokshin et al. find that GCNA protein family complements standard DPC processing machinery in resolving topoisomerase II DPCs to ensure heritable genome stability and germline immortality. © 2019 Elsevier Inc.
- Description: We thank S. Cheloufi, D. Bellott, D. Durning, L. Okumura, L. Teitz, and members of the Page and Mello labs for advice and discussion. We thank E. Spooner for mass spectrometry and K. Igarashi for technical assistance. We thank P. Boag and R. Pocock for access to microscopes and technical advice. Some strains provided by the CGC were supported by NIH ( P40 OD010440 ) and the International C. elegans Gene Knockout Consortium . This work was supported by the Life Sciences Research Foundation to M.A.C.; American Cancer Society 129916-PF16-232-RMC to G.A.D.; and NIH grants (R37 GM058800 and P01 HD078253 ) to C.C.M. G.J.H. is supported by Cancer Research UK and by a Royal Society Wolfson Research Professorship. D.C.P. and C.C.M. are Howard Hughes Medical Institute Investigators.
Semiannual versus annual influenza vaccination in older adults in the tropics : An observer-blind, active-comparator-controlled, randomized superiority trial
- Authors: Young, Barnaby , Sadarangani, Sapna , Haur, Sen , Yung, Chee , Barr, Ian , Connolly, John , Chen, Mark , Wilder-Smith, Annelies
- Date: 2019
- Type: Text , Journal article
- Relation: Clinical Infectious Diseases Vol. 69, no. 1 (2019), p. 121-129
- Full Text: false
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- Description: Background. Antibody titres and vaccine effectiveness decline within 6 months after influenza vaccination in older adults. Biannual vaccination may be necessary to provide year-round protection in the tropics, where influenza circulates throughout the year. Methods. Tropical Influenza Control Strategies (TROPICS1) was a single-center, 1:1 randomized, observer-blinded, active-comparator- controlled, superiority study in 200 community-resident adults aged ≥65 years. Participants received a standard-dose trivalent inactivated influenza vaccination (IIV3) at enrollment, and either tetanus-diphtheria-pertussis vaccination or IIV3 6 months later. The primary outcome was the proportion of participants with haemagglutination-inhibition (HI) geometric mean titre (GMT) ≥1:40 1 month after the second vaccination (month 7). Secondary outcomes included GMTs to month 12, the incidence of influenza- like illness (ILI), and adverse reactions after vaccination. Results. At month 7, the proportion of participants with an HI tire ≥1:40 against A/H1N1 increased by 21.4% (95% confidence interval [CI] 8.6-33.4) in the semiannual vaccination group. This proportion was not significantly higher for A/H3N2 (4.3, 95% CI -1.1-10.8) or B (2.1, 95% CI -2.0-7.3). Semiannual vaccination significantly increased GMTs against A/H1N1 and A/H3N2, but not B, at month 7. Participants receiving a repeat vaccination of IIV3 reported a significantly lower incidence of ILI in the 6 months after the second vaccination (relative vaccine effectiveness 57.1%, 95% CI 0.6-81.5). The frequency of adverse events was similar after the first and second influenza vaccinations. Conclusions. Semiannual influenza vaccination in older residents of tropical countries has the potential to improve serological measures of protection against infection. Alternative vaccination strategies should also be studied.
Cognitive behavior therapy for older adults with insomnia and depression : A randomized controlled trial in community mental health services
- Authors: Sadler, Paul , McLaren, Suzanne , Klein, Britt , Harvey, Jack , Jenkins, Megan
- Date: 2018
- Type: Text , Journal article
- Relation: Sleep Vol. 41, no. 8 (2018), p. 1-12
- Full Text: false
- Reviewed:
- Description: Study Objectives: To investigate whether cognitive behavior therapy was effective for older adults with comorbid insomnia and depression in a community mental health setting, and explore whether an advanced form of cognitive behavior therapy for insomnia produced better outcomes compared to a standard form of cognitive behavior therapy for insomnia. Methods: An 8-week randomized controlled clinical trial was conducted within community mental health services, Victoria, Australia. Seventy-two older adults (56% female, M age 75 ± 7 years) with diagnosed comorbid insomnia and depression participated. Three conditions were tested using a group therapy format: cognitive behavior therapy for insomnia (CBT-I, standard), cognitive behavior therapy for insomnia plus positive mood strategies (CBT-I+, advanced), psychoeducation control group (PCG, control). The primary outcomes were insomnia severity (Insomnia Severity Index) and depression severity (Geriatric Depression Scale). Primary and secondary measures were collected at pre (week 0), post (week 8), and follow-up (week 20). Results: CBT-I and CBT-I+ both generated significantly greater reductions in insomnia and depression severity compared to PCG from pre to post (p < .001), which were maintained at follow-up. Although the differences between outcomes of the two treatment conditions were not statistically significant, the study was not sufficiently powered to detect either superiority of one treatment or equivalence of the two treatment conditions. Conclusion: CBT-I and CBT-I+ were both effective at reducing insomnia and depression severity for older adults. Mental health services that deliver treatment for comorbid insomnia with cognitive behavior therapy may improve recovery outcomes for older adults with depression. Trial Registration: Australian and New Zealand Clinical Trials Registry (ANZCTR); URL: https://www.anzctr.org.au; Trial ID: ACTRN12615000067572; Date Registered: December 12, 2014.
N-acetyl cysteine alleviates oxidative stress and protects mice from dilated cardiomyopathy caused by mutations in nuclear A-type lamins gene
- Authors: Rodriguez, Blanca Morales , Khouzami, Lara , Decostre, Valérie , Varnous, Shaida , Pekovic-Vaughan, Vanja , Hutchison, Christopher , Pecker, Françoise , Bonne, Gisèle , Muchir, Antoine
- Date: 2018
- Type: Text , Journal article
- Relation: Human Molecular Genetics Vol. 27, no. 19 (2018), p. 3353-3360
- Full Text: false
- Reviewed:
- Description: Cardiomyopathy caused by lamin A/C gene (LMNA) mutations (hereafter referred as LMNA cardiomyopathy) is an anatomic and pathologic condition associated with muscular and electrical dysfunction of the heart, often leading to heart failure-related disability. There is currently no specific therapy available for patients that target the molecular pathophysiology of LMNA cardiomyopathy. We showed here an increase in oxidative stress levels in the hearts of mice carrying LMNA mutation, associated with a decrease of the key cellular antioxidant glutathione (GHS). Oral administration of N-acetyl cysteine, a GHS precursor, led to a marked improvement of GHS content, a decrease in oxidative stress markers including protein carbonyls and an improvement of left ventricular structure and function in a model of LMNA cardiomyopathy. Collectively, our novel results provide therapeutic insights into LMNA cardiomyopathy.
CHROMagar COL-APSE : A selective bacterial culture medium for the isolation and differentiation of colistin-resistant gram-negative pathogens
- Authors: Abdul Momin, Muhd , Bean, David , Hendriksen, Rene , Haenni, Marisa , Phee, Lynette , Wareham, David
- Date: 2017
- Type: Text , Journal article
- Relation: Journal of Medical Microbiology Vol. 66, no. 11 (2017), p. 1554-1561
- Full Text: false
- Reviewed:
- Description: Purpose. A selective chromogenic culture medium for the laboratory isolation and differentiation of colistin resistant Acinetobacter, Pseudomonas, Stenotrophomonas and Enterobacteriaceae spp. (CHROMagar COL-APSE) was developed, evaluated and compared to an existing selective bacterial culture medium (SuperPolymyxin). Methodology. The medium was challenged with 84 isolates, including polymyxin B (POL B)-susceptible and-resistant type strains and colistin (COL)-resistant organisms recovered from human and animal samples. Susceptibility to COL and POL B was determined by agar dilution and broth microtitre dilution. The lower limit for the detection of COL-resistant organisms was also calculated for both CHROMagar COL-APSE and SuperPolymyxin media. The ability to isolate and correctly differentiate COL-resistant organisms within mixed cultures was also assessed and compared using both media. Results. Using CHROMagar COL-APSE, Gram-negative pathogens (n=71) with intrinsic (n=8) or acquired COL (n=63) resistance were recovered with 100% specificity down to the lower limit of detection of 101 colony-forming units (c.f.u.). The growth on SuperPolymyxin was similar, but notably weaker for COL-resistant non-fermentative bacteria (Acinetobacter, Pseudomonas and Stenotrophomonas). CHROMagar COL-APSE was also more sensitive in supporting the growth of Enterobacteriaceae with COL resistance associated with the carriage of mcr-1. Conclusion. CHROMagar COL-APSE is a sensitive and specific medium for the growth of COL-resistant bacterial pathogens. Due to the low limit of detection (101 c.f.u.), it may be useful as a primary isolation medium in the surveillance and recovery of COL-resistant bacteria from complex human, veterinary and environmental samples, especially those with plasmidmediated MCR-1 or novel mechanisms of polymyxin resistance. © 2017 The Authors.
Characterization of the localized immune response in the respiratory tract of ferrets following infection with influenza A and B viruses
- Authors: Carolan, Louise , Rockman, Steve , Borg, Kathryn , Guarnaccia, Teagan , Reading, Patrick , Mosse, Jennifer , Kelso, Anne , Barr, Ian , Laurie, Karen
- Date: 2016
- Type: Text , Journal article
- Relation: Journal of Virology Vol. 90, no. 6 (2016), p. 2838-2848
- Full Text: false
- Reviewed:
- Description: The burden of infection with seasonal influenza viruses is significant. Each year is typically characterized by the dominance of one (sub)type or lineage of influenza A or B virus, respectively. The incidence of disease varies annually, and while this may be attributed to a particular virus strain or subtype, the impacts of prior immunity, population differences, and variations in clinical assessment are also important. To improve our understanding of the impacts of seasonal influenza viruses, we directly compared clinical symptoms, virus shedding, and expression of cytokines, chemokines, and immune mediators in the upper respiratory tract (URT) of ferrets infected with contemporary A(H1N1)pdm09, A(H3N2), or influenza B virus. Gene expression in the lower respiratory tract (LRT) was also assessed. Clinical symptoms were minimal. Overall cytokine/chemokine profiles in the URT were consistent in pattern and magnitude between animals infected with influenza A and B viruses, and peak expression levels of interleukin-1α (IL-1α), IL-1β, IL-6, IL-12p40, alpha interferon (IFN-α), IFN-β, and tumor necrosis factor alpha (TNF-α) mRNAs correlated with peak levels of viral shedding. MCP1 and IFN-γ were expressed after the virus peak. Granzymes A and B and IL-10 reached peak expression as the virus was cleared and seroconversion was detected. Cytokine/chemokine gene expression in the LRT following A(H1N1)pdm09 virus infection reflected the observations seen for the URT but was delayed 2 or 3 days, as was virus replication. These data indicate that disease severities and localized immune responses following infection with seasonal influenza A and B viruses are similar, suggesting that other factors are likely to modulate the incidence and impact of seasonal influenza. © 2016, American Society for Microbiology.
Changes in the leukocyte methylome and its effect on cardiovascular-related genes after exercise
- Authors: Denham, Joshua , O'Brien, Brendan , Marques, Francine , Charchar, Fadi
- Date: 2015
- Type: Text , Journal article
- Relation: Journal of Applied Physiology Vol. 118, no. 4 (2015), p. 475-488
- Relation: http://purl.org/au-research/grants/nhmrc/1009490
- Full Text: false
- Reviewed:
- Description: Physical exercise has proven cardiovascular benefits, yet there is no clear understanding of the related molecular mechanisms leading to this. Here we determined the beneficial epigenetic effects of exercise after sprint interval training, a form of exercise known to improve cardiometabolic health. We quantified genome-wide leukocyte DNA methylation of 12 healthy young (18-24 yr) men before and after 4 wk (thrice weekly) of sprint interval training using the 450K BeadChip (Illumina) and validated gene expression changes in an extra seven subjects. Exercise increased subjects' cardiorespiratory fitness and maximal running performance, and decreased low-density lipoprotein cholesterol concentration in conjunction with genome-wide DNA methylation changes. Notably, many CpG island and gene promoter regions were demethylated after exercise, indicating increased genome-wide transcriptional changes. Among genes with DNA methylation changes, epidermal growth factor (EGF), a ligand of the epidermal growth factor receptor known to be involved in cardiovascular disease, was demethylated and showed decreased mRNA expression. Additionally, we found that in microRNAs miR-21 and miR-210, gene DNA methylation was altered by exercise causing a cascade effect on the expression of the mature microRNA involved in cardiovascular function. Our findings demonstrate that exercise alters DNA methylation in circulating blood cells in microRNA and protein-coding genes associated with cardiovascular physiology. Copyright © 2015 the American Physiological Society
Distinctive phenotype identification for breast cancer genotypes among hereditary breast cancer mutated genes
- Authors: Hassan, Md Rafiul , ul Haq, Imran , Ramadan, Emad , Kamruzzaman, Joarder , Ahmed, Adel
- Date: 2015
- Type: Text , Journal article
- Relation: Current Bioinformatics Vol. 10, no. 1 (2015), p. 5-15
- Full Text: false
- Reviewed:
- Description: It is well known that the mutations in BRCA1 or BRCA2 gene can cause the hereditary breast cancer. However, it is a tedious and expensive task to identify the mutant genes that impact breast cancer due to the large number of genes and very small number of samples. Furthermore, the expressive energy of the subset of genes in comparison to that of one individual gene at a time is considered to have a profound influence in case of breast cancer. In this paper 7 tumors with BRCA1 mutation and 8 tumors with BRCA2 mutation have been used to identify the subset of discriminative genes. A combination of a non-parametric supervised and an unsupervised statistical method is introduced to analyze the gene expressions and the distinctive genes among the highly expressed genes are identified. The most important genes are filtered using the area under the curve (AUC) measure. These filtered genes are then used to build a hidden Markov model (HMM) to analyse their inter-relationship and identify the best subset among them. In addition, Protein-Protein interaction network is generated to analyse the pathways of the identified genes and their link with BRCA1 or BRCA2. Transcription Factors are identified and Gene Set Enrichment Analysis (GSEA) is calculated for the identified genes subset and the results are compared with the results mentioned in other cancer literature. Experimental results suggest that only 8 genes have been identified out of 3226 genes by the proposed hybrid method. Out of the 8 identified genes, 5 have been linked with breast cancer by other studies. Moreover, 7 genes have been associated with numerous diseases that may result in breast cancer. Furthermore, 8 transcription factors were identified that cover the identified genes and BRCA1 and BRCA2. Lastly, GSEA enrichment score of 0.52 is calculated for the identified genes and it is comparatively better considering the small subset of identified genes.
Impact of intermittent preventive treatment in pregnancy with azithromycin-containing regimens on maternal nasopharyngeal carriage and antibiotic sensitivity of Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus : A cross-sectional survey at delivery
- Authors: Unger, Holger , Aho, Celestine , Ome-Kaius, Maria , Wangnapi, Regina , Umbers, Alexandra , Jack, Wanda , Lafana, Alice , Michael, Audrey , Hanieh, Sarah , Siba, Peter , Mueller, Ivo , Greenhill, Andrew , Rogerson, Stephen
- Date: 2015
- Type: Text , Journal article
- Relation: Journal of Clinical Microbiology Vol. 53, no. 4 (2015), p. 1317-1323
- Full Text: false
- Reviewed:
- Description: Sulfadoxine-pyrimethamine (SP) plus azithromycin (AZ) (SPAZ) has the potential for intermittent preventive treatment of malaria in pregnancy (IPTp), but its use could increase circulation of antibiotic-resistant bacteria associated with severe pediatric infections. We evaluated the effect of monthly SPAZ-IPTp compared to a single course of SP plus chloroquine (SPCQ) on maternal nasopharyngeal carriage and antibiotic susceptibility of Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus at delivery among 854 women participating in a randomized controlled trial in Papua New Guinea. Serotyping was performed, and antibiotic susceptibility was evaluated by disk diffusion and Etest. Potential risk factors for carriage were examined. Nasopharyngeal carriage at delivery of S. pneumoniae (SPAZ, 7.2% [30/418], versus SPCQ, 19.3% [84/436]; P < 0.001) and H. influenzae (2.9% [12/418] versus 6.0% [26/436], P = 0.028), but not S. aureus, was significantly reduced among women who had received SPAZ-IPTp. The number of macrolide-resistant pneumococcal isolates was small but increased in the SPAZ group (13.3% [4/30], versus SPCQ, 2.2% [2/91]; P = 0.033). The proportions of isolates with serotypes covered by the 13-valent pneumococcal conjugate vaccine were similar (SPAZ, 10.3% [3/29], versus SPCQ, 17.6% [16/91]; P = 0.352). Although macrolide-resistant isolates were rare, they were more commonly detected in women who had received SPAZ-IPTp, despite the significant reduction of maternal carriage of S. pneumoniae and H. influenzae observed in this group. Future studies on SPAZ-IPTp should evaluate carriage and persistence of macrolide-resistant S. pneumoniae and other pathogenic bacteria in both mothers and infants and assess the clinical significance of their circulation.
Impact of low-volume, high-intensity interval training on maximal aerobic capacity, health-related quality of life and motivation to exercise in ageing men
- Authors: Knowles, Ann-Marie , Herbert, Peter , Easton, Chris , Sculthorpe, Nicholas , Grace, Fergal
- Date: 2015
- Type: Text , Journal article
- Relation: Age Vol. 37, no. 2 (2015), p. 25
- Full Text: false
- Reviewed:
- Description: There is a demand for effective training methods that encourage exercise adherence during advancing age, particularly in sedentary populations. This study examined the effects of high-intensity interval training (HIIT) exercise on health-related quality of life (HRQL), aerobic fitness and motivation to exercise in ageing men. Participants consisted of males who were either lifelong sedentary (SED; N = 25; age 63 +/- 5 years) or lifelong exercisers (LEX; N = 19; aged 61 +/- 5 years). [Formula: see text] and HRQL were measured at three phases: baseline (Phase A), week seven (Phase B) and week 13 (Phase C). Motivation to exercise was measured at baseline and week 13. [Formula: see text] was significantly higher in LEX (39.2 +/- 5.6 ml kg min(-1)) compared to SED (27.2 +/- 5.2 ml kg min(-1)) and increased in both groups from Phase A to C (SED 4.6 +/- 3.2 ml kg min(-1), 95 % CI 3.1 - 6.0; LEX 4.9 +/- 3.4 ml kg min(-1), 95 % CI 3.1-6.6) Physical functioning (97 +/- 4 LEX; 93 +/- 7 SED) and general health (70 +/- 11 LEX; 78 +/- 11 SED) were significantly higher in LEX but increased only in the SED group from Phase A to C (physical functioning 17 +/- 18, 95 % CI 9-26, general health 14 +/- 14, 95 % CI 8-21). Exercise motives related to social recognition (2.4 +/- 1.2 LEX; 1.5 +/- 1.0 SED), affiliation (2.7 +/- 1.0 LEX; 1.6 +/- 1.2 SED) and competition (3.3 +/- 1.3 LEX; 2.2 +/- 1.1) were significantly higher in LEX yet weight management motives were significantly higher in SED (2.9 +/- 1.1 LEX; 4.3 +/- 0.5 SED). The study provides preliminary evidence that low-volume HIIT increases perceptions of HRQL, exercise motives and aerobic capacity in older adults, to varying degrees, in both SED and LEX groups.
Runs of Homozygosity : Association with Coronary Artery Disease and Gene Expression in Monocytes and Macrophages
- Authors: Christofidou, Paraskevi , Nelson, Christopher , Nikpay, Majid , Qu, Liming , Li, Mingyao , Loley, Christina , Debiec, Radoslaw , Braund, Peter , Denniff, Matthew , Charchar, Fadi , Arjo, Ares Rocanin , Trégouët, David-Alexandre , Goodall, Alison , Cambien, Francois , Ouwehand, Willem , Roberts, Robert , Schunkert, Heribert , Hengstenberg, Christian , Reilly, Muredach , Erdmann, Jeanette , McPherson, Ruth , König, Inke , Thompson, John , Samani, Nilesh , Tomaszewski, Maciej
- Date: 2015
- Type: Text , Journal article
- Relation: American Journal of Human Genetics Vol. 97, no. 2 (2015), p. 228-237
- Full Text: false
- Reviewed:
- Description: Runs of homozygosity (ROHs) are recognized signature of recessive inheritance. Contributions of ROHs to the genetic architecture of coronary artery disease and regulation of gene expression in cells relevant to atherosclerosis are not known. Our combined analysis of 24,320 individuals from 11 populations of white European ethnicity showed an association between coronary artery disease and both the count and the size of ROHs. Individuals with coronary artery disease had approximately 0.63 (95% CI: 0.4-0.8) excess of ROHs when compared to coronary-artery-disease-free control subjects (p = 1.49 x 10
Effects of hypoxia and hypercapnia on human HRV and respiratory sinus arrhythmia
- Authors: Brown, Stephen , Barnes, Matthew , Mündel, Toby
- Date: 2014
- Type: Text , Journal article
- Relation: Acta Physiologica Hungarica Vol. 101, no. 3 (2014), p. 263-272
- Full Text: false
- Reviewed:
- Description: Hypercapnia increase minute ventilation (V'E) with little effect on heart rate (HR), whereas hypoxia may increase HR without affecting V'E. However, the effects of hypercania and hypoxia on both heart rate variability (HRV) and the clustering of the heart beats during spontaneous breathing (respiratory sinus arrhythmia -RSA) are not clear. "From abstract"
Interspecific variations in the faecal microbiota of Procellariiform seabirds
- Authors: Dewar, Meagan , Arnould, John , Krause, Lutz , Dann, Peter , Smith, Stuart
- Date: 2014
- Type: Text , Journal article
- Relation: FEMS Microbiology Ecology Vol. 89, no. 1 (2014), p. 47-55
- Full Text: false
- Reviewed:
- Description: Despite the enormous amount of data available on the importance of gut microbiota in vertebrates (especially mammals), there is no information available on the microbiota of seabirds. Procellariiformes are long-lived seabirds that consume a diet high in lipids and are characterised by their ability to produce and store large amount of stomach oils through the partial digestion of prey (with the exception of the Pelecanoididae). Examining the faecal microbiota of three Procellariiform species (short-tailed shearwater, common diving petrel and fairy prion) provided a unique opportunity to not only characterise the gastrointestinal (GI) microbial composition of seabirds but to also examine the influence of stomach oils on the microbial community. The results indicated that Procellariiform seabirds host a highly diverse community of faecal microorganisms, dominated by three phyla (Firmicutes, Proteobacteria and Bacteroidetes) and that each species has its own species-specific GI microbiota. In addition, significant differences were observed in the microbial communities of oil-producing and non-oil-producing seabirds. This study is the first whole-community examination and classification of the faecal microbiota of Procellariiform seabirds.
Age-related differences revealed in australian fur seal arctocephalus pusillus doriferus gut microbiota
- Authors: Smith, Stuart , Chalker, Andrea , Dewar, Meagan , Arnould, John
- Date: 2013
- Type: Text , Journal article
- Relation: FEMS Microbiology Ecology Vol. 86, no. 2 (2013), p. 246-255
- Full Text: false
- Reviewed:
- Description: The gut microbiota of Australian fur seals (Arctocephalus pusillus doriferus) was examined at different age classes using fluorescent in situ hybridisation (FISH) and 16S rRNA gene pyrosequencing. The FISH results indicated that in the fur seal groups, the predominant phyla are Firmicutes (22.14-67.33%) followed by Bacteroidetes (3.11-15.45%) and then Actinobacteria (1.4-5.9%) consistent with other mammals. Phylum Proteobacteria had an initial abundance of 1.8% in the 2-month-old pups, but < 1% of bacterial numbers for the other fur seal age groups. Significant differences did occur in the abundance of Clostridia, Lactobacilli and Bifidobacteria between 2 months pups and 9 months pups and adult fur seals. Results from the 16S rRNA gene pyrosequencing supported the FISH data and identified significant differences in the composition of Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, Verrucomicrobia and Fusobacteria at all ages. Class Clostridia in phylum Firmicutes dominates the microbiota of the 2 months and 9 months seal pups, whilst class Bacilli dominates the 6 months pups. In addition, a high level of dissimilarity was observed between all age classes. This study provides novel insight into the gut microbiota of Australian fur seals at different age classes. © 2013 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.
Fetal sex affects expression of renin-angiotensin system components in term human decidua
- Authors: Wang, Yu , Pringle, Kirsty , Sykes, Shane , Marques, Francine , Morris, Brian , Zakar, Tamas , Lumbers, Eugenie
- Date: 2012
- Type: Text , Journal article
- Relation: Endocrinology Vol. 153, no. 1 (January 2012), p. 462-468
- Full Text: false
- Reviewed:
- Description: The maternal decidua expresses the genes of the renin-angiotensin system (RAS). Human decidua was collected at term either before labor (i.e. cesarean delivery) or after spontaneous labor. The mRNA for prorenin (REN), prorenin receptor (ATP6AP2), angiotensinogen (AGT), angiotensinconverting enzymes 1 and 2 (ACE1 and ACE2), angiotensin II type 1 receptor (AGTR1), and angiotensin 1-7 receptor (MAS1) were measured by quantitative real-time RT-PCR. Decidual explants were cultured in duplicate for 24 and 48 h, and all RAS mRNA, and the secretion of prorenin, angiotensin II, and angiotensin 1-7 was measured using quantitative real-time RT-PCR, ELISA, and radioimmunoassay, respectively. In the decidua collected before labor, REN mRNA levels were higher if the fetus was female. In addition, REN, ATP6AP2, AGT, and MAS1 mRNA abundance was greater in decidual explants collected from women carrying a female fetus, as was prorenin protein. After 24 h, ACE1 mRNA was higher in the decidual explants from women with a male fetus, whereas after 48 h, both ACE1 and ACE2 mRNA was higher in decidual explants from women with a female fetus. Angiotensin II was present in all explants, but angiotensin 1-7 levels often registered below the lower limits of sensitivity for the assay. After labor, decidua, when compared with nonlaboring decidua, demonstrated lower REN expression when the fetus was female. Therefore, the maternal decidual RAS is regulated in a sex-specific manner, suggesting that it may function differently when the fetus is male than when it is female.
- Description: C1
Field vaccination of sheep with a larval-specific antigen of the gastrointestinal nematode, Haemonchus contortus, confers significant protection against an experimental challenge infection
- Authors: Piedrafita, David , De Veer, Michael , Lydall, Jayne , Kraska, Troy , Elhay, Martin , Meeusen, Els
- Date: 2012
- Type: Text , Journal article
- Relation: Vaccine Vol. 30, no. 50 (2012), p. 7199-7204
- Full Text: false
- Reviewed:
- Description: The availability of effective vaccines would add a valuable tool to the management of gastrointestinal nematode infections in livestock. While some experimental vaccines have shown protection in laboratory trials, few have been tested in the field. In the present study, eight month old sheep kept on pasture were treated with anthelmintic 8 weeks before vaccination with a larval surface antigen of the nematode parasite, Haemonchus contortus, under a commercially acceptable protocol, i.e. 2 immunizations using a commercial adjuvant; they were then given a controlled challenge infection 4 weeks later in indoor pens. Vaccination of sheep with 4 increasing doses of antigen resulted in significant reductions of 61% and 27% in cumulative faecal egg counts in the two highest dose groups, and a 69% reduction in worm burden in the highest dose group. Blood loss, as determined by packed cell volume, was also significantly reduced in the highest dose group of sheep. One outlier sheep showed an unusual increase in egg count without a concomitant increase in worm burden compared to the control sheep, indicating a vaccine-induced stress response. Antigen-specific serum antibody levels steadily increased in sheep while on pasture and decreased when transported to indoor pens. No difference in antibody levels could be detected between vaccinated and unvaccinated sheep, but all showed increased antibody levels compared to uninfected control sheep kept in indoors pens for 2–3 months, suggesting sheep were sensitized to the larval antigen either from low dose pasture contamination or cross reaction with pasture-related antigens. The results of these studies confirm the protective properties of the larval surface antigen and its protective effect when vaccinations are performed in the field.
Is there a role for rare variants in DRD4 gene in the susceptibility for ADHD Searching for an effect of allelic heterogeneity
- Authors: Tovo-Rodrigues, Luciana , Rohde, Luis , Roman, Tatiana , Schmitz, Marcelo , Polanczyk, Guilherme , Zeni, Cristian , Marques, Francine , Contini, Veronica , Grevet, Eugenio , Belmonte-De-Abreu, Paulo , Bau, Claiton , Hutz, Mara
- Date: 2012
- Type: Text , Journal article
- Relation: Molecular Psychiatry Vol. 17, no. 5 (May 2012), p. 520-526
- Full Text: false
- Reviewed:
- Description: Although several studies have demonstrated an association between the 7-repeat (7R) allele in the 48-bp variable number of tandem repeats (VNTRs) in the exon 3 at dopamine receptor D4 (DRD4) gene and attention-deficit/ hyperactivity disorder (ADHD), others failed to replicate this finding. In this study, a total of 786 individuals with ADHD were genotyped for DRD4 exon 3 VNTR. All 7R homozygous subjects were selected for VNTR re-sequencing. Subjects homozygous for the 4R allele were selected paired by age, ancestry and disorder subtypes in order to have a sample as homogeneous as possible with 7R/7R individuals. Using these criteria, 103 individuals (66 with ADHD and 37 control individuals) were further investigated. An excess of rare variants were observed in the 7R alleles of ADHD patient when compared with controls (P = 0.031). This difference was not observed in 4R allele. Furthermore, nucleotide changes that predict synonymous and non-synonymous substitutions were more common in the 7R sample (P = 0.008 for total substitutions and P = 0.043 for non-synonymous substitutions). In silico prediction of structural/functional alterations caused by these variants have also been observed. Our findings suggest that not only repeat length but also DNA sequence should be assessed to better understand the role of DRD4 exon 3 VNTR in ADHD genetic susceptibility.
- Description: C1