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- Sexton, C. E., et al.
(author)
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Alzheimer's disease research progress in Australia: The Alzheimer's Association International Conference Satellite Symposium in Sydney
- 2022
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In: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 18:1, s. 178-190
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Journal article (peer-reviewed)abstract
- The Alzheimer's Association International Conference held its sixth Satellite Symposium in Sydney, Australia in 2019, highlighting the leadership of Australian researchers in advancing the understanding of and treatment developments for Alzheimer's disease (AD) and other dementias. This leadership includes the Australian Imaging, Biomarker, and Lifestyle Flagship Study of Ageing (AIBL), which has fueled the identification and development of many biomarkers and novel therapeutics. Two multimodal lifestyle intervention studies have been launched in Australia; and Australian researchers have played leadership roles in other global studies in diverse populations. Australian researchers have also played an instrumental role in efforts to understand mechanisms underlying vascular contributions to cognitive impairment and dementia; and through the Women's Healthy Aging Project have elucidated hormonal and other factors that contribute to the increased risk of AD in women. Alleviating the behavioral and psychological symptoms of dementia has also been a strong research and clinical focus in Australia.
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- Parker, W. A. E., et al.
(author)
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Prevalence of microspirometry-defined chronic obstructive pulmonary disease in two European cohorts of patients with significant smoking history hospitalised for acute myocardial infarction
- 2023
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In: Thorax. - : BMJ Publishing Group Ltd. - 0040-6376 .- 1468-3296. ; 78:Suppl. 4, s. A66-A66
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Journal article (other academic/artistic)abstract
- Introduction: Smoking is a major risk factor for both chronic obstructive pulmonary disease (COPD) and myocardial infarction (MI). Systemic inflammation also contributes to both diseases and has been suggested as a potential target for intervention. Prevalence of COPD in those with a significant smoking history hospitalised for MI has not been well-characterised. We sought to obtain an accurate estimate of COPD burden in this group and characterise the population.Methods: Two consecutive cohorts of patients hospitalised for MI with a smoking history of ≥10 pack-years were recruited in Sweden and the United Kingdom (UK). Baseline characteristics were recorded, including treatment with inhaled corticosteroids (ICS) and eosinophil count in blood. Microspirometry was performed using the Vitalograph COPD-6 device and symptom burden assessed using the COPD Assessment Test (CAT). The primary outcome was the prevalence of a preliminary diagnosis of clinically-significant COPD, here defined as a ratio of forced expiratory volume in 1 and 6 seconds (FEV1/FEV6) <0.7 and with FEV1 <80% of predicted value.Results: In the UK cohort, 216 participants with MI (26% female, median age 60 (IQR 53–67) years, smoking history 32 (23–45) pack-years) were recruited. The proportion with any COPD was 36%. Clinically-significant COPD was found in 30 participants (13.9%, 95% CI 9.5–19.2). Of these, 43% had a prior COPD diagnosis, 20% had an eosinophil count ≥300 cells/mm3, mean CAT score was 14.4 ± 9.3), 80% had high symptom burden (CAT score >10) and 23% were receiving ICS. The Swedish cohort included 302 participants with MI (24% female, median age 68 (IQR 61–76) years, 26 (15–38) pack years), and clinically-significant COPD was found in 52 (17.2%; 12.9–21.5). In these 52 participants, 17% had a prior COPD diagnosis, 20% had an eosinophil count ≥300 cells/mm3, mean CAT score was 12.9 ± 7.2, 63% had CAT score ≥10 and 15% had treatment with ICS.Conclusions: The prevalence of preliminary diagnosis of clinically-significant COPD in patients with a ≥10 pack-year smoking history hospitalised for MI is similar between two European cohorts and under-recognised. Further work is warranted to determine whether identification and treatment of COPD improves clinical outcomes following MI.
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- Pollard, R. B., et al.
(author)
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Safety and efficacy of the peptide-based therapeutic vaccine for HIV-1, Vacc-4x : A phase 2 randomised, double-blind, placebo-controlled trial
- 2014
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In: The Lancet - Infectious diseases. - 1473-3099 .- 1474-4457. ; 14:4, s. 291-300
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Journal article (peer-reviewed)abstract
- Background: Present combination antiretroviral therapy (cART) alone does not cure HIV infection and requires lifelong drug treatment. The potential role of HIV therapeutic vaccines as part of an HIV cure is under consideration. Our aim was to assess the efficacy, safety, and immunogenicity of Vacc-4x, a peptide-based HIV-1 therapeutic vaccine targeting conserved domains on p24Gag, in adults infected with HIV-1. Methods: Between July, 2008, and June, 2010, we did a multinational double-blind, randomised, phase 2 study comparing Vacc-4x with placebo. Participants were adults infected with HIV-1 who were aged 18-55 years and virologically suppressed on cART (viral load <50 copies per mL) with CD4 cell counts of 400 × 106 cells per L or greater. The trial was done at 18 sites in Germany, Italy, Spain, the UK, and the USA. Participants were randomly assigned (2:1) to Vacc-4x or placebo. Group allocation was masked from participants and investigators. Four primary immunisations, weekly for 4 weeks, containing Vacc-4x (or placebo) were given intradermally after administration of adjuvant. Booster immunisations were given at weeks 16 and 18. At week 28, cART was interrupted for up to 24 weeks. The coprimary endpoints were cART resumption and changes in CD4 counts during treatment interruption. Analyses were by modified intention to treat: all participants who received one intervention. Furthermore, safety, viral load, and immunogenicity (as measured by ELISPOT and proliferation assays) were assessed. The 52 week follow-up period was completed in June, 2011. For the coprimary endpoints the proportion of participants who met the criteria for cART resumption was analysed with a logistic regression model with the treatment effect being assessed in a model including country as a covariate. This study is registered with ClinicalTrials.gov, number NCT00659789. Findings: 174 individuals were screened; because of slow recruitment, enrolment stopped with 136 of a planned 345 participants and 93 were randomly assigned to receive Vacc-4x and 43 to receive placebo. There were no differences between the two groups for the primary efficacy endpoints in those participants who stopped cART at week 28. Of the participants who resumed cART, 30 (34%) were in the Vacc-4x group and 11 (29%) in the placebo group, and percentage changes in CD4 counts were not significant (mean treatment difference -5·71, 95% CI -13·01 to 1·59). However, a significant difference in viral load was noted for the Vacc-4x group both at week 48 (median 23 100 copies per mL Vacc-4x vs 71 800 copies per mL placebo; p=0·025) and week 52 (median 19 550 copies per mL vs 51 000 copies per mL; p=0·041). One serious adverse event, exacerbation of multiple sclerosis, was reported as possibly related to study treatment. Vacc-4x was immunogenic, inducing proliferative responses in both CD4 and CD8 T-cell populations. Interpretation: The proportion of participants resuming cART before end of study and change in CD4 counts during the treatment interruption showed no benefit of vaccination. Vacc-4x was safe, well tolerated, immunogenic, seemed to contribute to a viral-load setpoint reduction after cART interruption, and might be worth consideration in future HIV-cure investigative strategies. Funding: Norwegian Research Council GLOBVAC Program and Bionor Pharma ASA.
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- Schrader, J., et al.
(author)
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Cambial meristem dormancy in trees involves extensive remodelling of the transcriptome
- 2004
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In: The Plant Journal. - Malden : Wiley-Blackwell. - 0960-7412 .- 1365-313X. ; 40:2, s. 173-187
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Journal article (peer-reviewed)abstract
- The establishment of the dormant state in meristems involves considerable physiological and metabolic alterations necessary for surviving unfavourable growth conditions. However, a global molecular analysis of dormancy in meristems has been hampered by the difficulty in isolating meristem cells. We used cryosectioning to isolate purified cambial meristem cells from the woody plant Populus tremula during active growth and dormancy. These samples were used to generate meristem-specific cDNA libraries and for cDNA microarray experiments to define the global transcriptional changes underlying cambial dormancy. The results indicate a significant reduction in the complexity of the cambial transcriptome in the dormant state. Although cell division is terminated in the dormant cambium, the cell cycle machinery appears to be maintained in a skeletal state as suggested by the continued presence of transcripts for several cell cycle regulators. The downregulation of PttPIN1 and PttPIN2 transcripts explains the reduced basipetal polar auxin transport during dormancy. The induction of a member of the SINA family of ubiquitin ligases implicated in auxin signalling indicates a potential mechanism for modulation of auxin sensitivity during cambial dormancy. The metabolic alterations during dormancy are mirrored in the induction of genes involved in starch breakdown and the glyoxysomal cycle. Interestingly, the induction of RGA1 like gene suggests modification of gibberellin signalling in cambial dormancy. The induction of genes such as poplar orthologues of FIE and HAP2 indicates a potential role for these global regulators of transcription in orchestrating extensive changes in gene expression during dormancy.
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- Alström, Per, et al.
(author)
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Comprehensive molecular phylogeny of the grassbirds and allies (Locustellidae) reveals extensive non-monophyly of traditional genera, and a proposal for a new classification
- 2018
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In: Molecular Phylogenetics and Evolution. - : Elsevier BV. - 1055-7903 .- 1095-9513. ; 127, s. 367-375
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Journal article (peer-reviewed)abstract
- The widespread Old World avian family Locustellidae ('grassbirds and allies') comprises 62 extant species in 11 genera. In the present study, we used one mitochondrial and, for most species, four nuclear loci to infer the phylogeny of this family. We analysed 59 species, including the five previously unsampled genera plus two genera that had not before been analysed in a densely sampled dataset. This study revealed extensive disagreement with current taxonomy; the genera Bradypterus, Locustella, Megalurus, Megalurulus and Schoenicola were all found to be non-monophyletic. Non-monophyly was particularly pronounced for Megalurus, which was widely scattered across the tree. Three of the five monotypic genera (Amphilais, Buettikoferella and Malia) were nested within other genera; one monotypic genus (Chaetornis) formed a Glade with one of the two species of Schoenicola; whereas the position of the fifth monotypic genus (Elaphrornis) was unresolved. Robsonius was confirmed as sister to the other genera. We propose a phylogenetically informed revision of genus-level taxonomy, including one new generic name. Finally, we highlight several non-monophyletic species complexes and deep intra-species divergences that point to conflict in taxonomy and suggest an underestimation of current species diversity in this group.
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7. |
- Oliveros, Carl H., et al.
(author)
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Earth history and the passerine superradiation
- 2019
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 116:16, s. 7916-7925
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Journal article (peer-reviewed)abstract
- Avian diversification has been influenced by global climate change, plate tectonic movements, and mass extinction events. However, the impact of these factors on the diversification of the hyper-diverse perching birds (passerines) is unclear because family level relationships are unresolved and the timing of splitting events among lineages is uncertain. We analyzed DNA data from 4,060 nuclear loci and 137 passerine families using concatenation and coalescent approaches to infer a comprehensive phylogenetic hypothesis that clarifies relationships among all passerine families. Then, we calibrated this phylogeny using 13 fossils to examine the effects of different events in Earth history on the timing and rate of passerine diversification. Our analyses reconcile passerine diversification with the fossil and geological records; suggest that passerines originated on the Australian landmass ∼47 Ma; and show that subsequent dispersal and diversification of passerines was affected by a number of climatological and geological events, such as Oligocene glaciation and inundation of the New Zealand landmass. Although passerine diversification rates fluctuated throughout the Cenozoic, we find no link between the rate of passerine diversification and Cenozoic global temperature, and our analyses show that the increases in passerine diversification rate we observe are disconnected from the colonization of new continents. Taken together, these results suggest more complex mechanisms than temperature change or ecological opportunity have controlled macroscale patterns of passerine speciation.
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8. |
- Uy, J. Albert C., et al.
(author)
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Mutations in different pigmentation genes are associated with parallel melanism in island flycatchers
- 2016
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In: Proceedings of the Royal Society of London. Biological Sciences. - : The Royal Society. - 0962-8452 .- 1471-2954. ; 283:1834
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Journal article (peer-reviewed)abstract
- The independent evolution of similar traits across multiple taxa provides some of the most compelling evidence of natural selection. Little is known, however, about the genetic basis of these convergent or parallel traits: are they mediated by identical or different mutations in the same genes, or unique mutations in different genes? Using a combination of candidate gene and reduced representation genomic sequencing approaches, we explore the genetic basis of and the evolutionary processes that mediate similar plumage colour shared by isolated populations of the Monarcha castaneiventris flycatcher of the Solomon Islands. A genome-wide association study (GWAS) that explicitly controlled for population structure revealed that mutations in known pigmentation genes are the best predictors of parallel plumage colour. That is, entirely black or melanic birds from one small island share an amino acid substitution in the melanocortin-1 receptor (MC1R), whereas similarly melanic birds from another small island over 100 km away share an amino acid substitution in a predicted binding site of agouti signalling protein (ASIP). A third larger island, which separates the two melanic populations, is inhabited by birds with chestnut bellies that lack the melanic MC1R and ASIP allelic variants. Formal F-STs outlier tests corroborated the results of the GWAS and suggested that strong, directional selection drives the near fixation of the MC1R and ASIP variants across islands. Our results, therefore, suggest that selection acting on different mutations with large phenotypic effects can drive the evolution of parallel melanism, despite the relatively small population size on islands.
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