| 1. |
- Reinke, Beth A, et al.
(författare)
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Diverse aging rates in ectothermic tetrapods provide insights for the evolution of aging and longevity
- 2022
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Ingår i: Science. - : American Association for the Advancement of Science. - 0036-8075 .- 1095-9203. ; 376:6600, s. 1459-1466
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Tidskriftsartikel (refereegranskat)abstract
- Comparative studies of mortality in the wild are necessary to understand the evolution of aging; yet, ectothermic tetrapods are underrepresented in this comparative landscape, despite their suitability for testing evolutionary hypotheses. We present a study of aging rates and longevity across wild tetrapod ectotherms, using data from 107 populations (77 species) of nonavian reptiles and amphibians. We test hypotheses of how thermoregulatory mode, environmental temperature, protective phenotypes, and pace of life history contribute to demographic aging. Controlling for phylogeny and body size, ectotherms display a higher diversity of aging rates compared with endotherms and include phylogenetically widespread evidence of negligible aging. Protective phenotypes and life-history strategies further explain macroevolutionary patterns of aging. Analyzing ectothermic tetrapods in a comparative context enhances our understanding of the evolution of aging.
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| 2. |
- Cartwright, Ashley, et al.
(författare)
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Characterization of large in-frame von Willebrand factor deletions highlights differing pathogenic mechanisms
- 2020
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Ingår i: Blood Advances. - : Elsevier BV. - 2473-9529 .- 2473-9537. ; 4:13, s. 2979-2990
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Tidskriftsartikel (refereegranskat)abstract
- Copy number variation (CNV) is known to cause all von Willebrand disease (VWD) types, although the associated pathogenic mechanisms involved have not been extensively studied. Notably, in-frame CNV provides a unique opportunity to investigate how specific von Willebrand factor (VWF) domains influence the processing and packaging of the protein. Using multiplex ligation-dependent probe amplification, this study determined the extent to which CNV contributed to VWD in the Molecular and Clinical Markers for the Diagnosis and Management of Type 1 von Willebrand Disease cohort, highlighting in-frame deletions of exons 3, 4-5, 32-34, and 33-34. Heterozygous in vitro recombinant VWF expression demonstrated that, although deletion of exons 3, 32-34, and 33-34 all resulted in significant reductions in total VWF (P < .0001, P < .001, and P < .01, respectively), only deletion of exons 3 and 32-34 had a significant impact on VWF secretion (P < .0001). High-resolution microscopy of heterozygous and homozygous deletions confirmed these observations, indicating that deletion of exons 3 and 32-34 severely impaired pseudo-Weibel-Palade body (WPB) formation, whereas deletion of exons 33-34 did not, with this variant still exhibiting pseudo-WPB formation similar to wild-type VWF. In-frame deletions in VWD, therefore, contribute to pathogenesis via moderate or severe defects in VWF biosynthesis and secretion.
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| 3. |
- de Roos, Paul, et al.
(författare)
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A Consensus Set of Outcomes for Parkinson's Disease from the International Consortium for Health Outcomes Measurement
- 2017
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Ingår i: Journal of Parkinson's Disease. - : IOS Press. - 1877-7171 .- 1877-718X. ; 7:3, s. 533-543
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative condition that is expected to double in prevalence due to demographic shifts. Value-based healthcare is a proposed strategy to improve outcomes and decrease costs. To move towards an actual value-based health care system, condition-specific outcomes that are meaningful to patients are essential.OBJECTIVE: Propose a global consensus standard set of outcome measures for PD.METHODS: Established methods for outcome measure development were applied, as outlined and used previously by the International Consortium for Health Outcomes Measurement (ICHOM). An international group, representing both patients and experts from the fields of neurology, psychiatry, nursing, and existing outcome measurement efforts, was convened. The group participated in six teleconferences over a six-month period, reviewed existing data and practices, and ultimately proposed a standard set of measures by which patients should be tracked, and how often data should be collected.RESULTS: The standard set applies to all cases of idiopathic PD, and includes assessments of motor and non-motor symptoms, ability to work, PD-related health status, and hospital admissions. Baseline demographic and clinical variables are included to enable case mix adjustment.CONCLUSIONS: The Standard Set is now ready for use and pilot testing in the clinical setting. Ultimately, we believe that using the set of outcomes proposed here will allow clinicians and scientists across the world to document, report, and compare PD-related outcomes in a standardized fashion. Such international benchmarks will improve our understanding of the disease course and allow for identification of 'best practices', ultimately leading to better informed treatment decisions.
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| 4. |
- Kraus, Robert H. S., et al.
(författare)
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Genome wide SNP discovery, analysis and evaluation in mallard (Anas platyrhynchos)
- 2011
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Ingår i: BMC Genomics. - : BioMed Central Ltd.. - 1471-2164. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Next generation sequencing technologies allow to obtain at low cost the genomic sequence information that currently lacks for most economically and ecologically important organisms. For the mallard duck genomic data is limited. The mallard is, besides a species of large agricultural and societal importance, also the focal species when it comes to long distance dispersal of Avian Influenza. For large scale identification of SNPs we performed Illumina sequencing of wild mallard DNA and compared our data with ongoing genome and EST sequencing of domesticated conspecifics. This is the first study of its kind for waterfowl. Results: More than one billion base pairs of sequence information were generated resulting in a 16x coverage of a reduced representation library of the mallard genome. Sequence reads were aligned to a draft domesticated duck reference genome and allowed for the detection of over 122,000 SNPs within our mallard sequence dataset. In addition, almost 62,000 nucleotide positions on the domesticated duck reference showed a different nucleotide compared to wild mallard. Approximately 20,000 SNPs identified within our data were shared with SNPs identified in the sequenced domestic duck or in EST sequencing projects. The shared SNPs were considered to be highly reliable and were used to benchmark non-shared SNPs for quality. Genotyping of a representative sample of 364 SNPs resulted in a SNP conversion rate of 99.7%. The correlation of the minor allele count and observed minor allele frequency in the SNP discovery pool was 0.72. Conclusion: We identified almost 150,000 SNPs in wild mallards that will likely yield good results in genotyping. Of these, similar to 101,000 SNPs were detected within our wild mallard sequences and similar to 49,000 were detected between wild and domesticated duck data. In the similar to 101,000 SNPs we found a subset of similar to 20,000 SNPs shared between wild mallards and the sequenced domesticated duck suggesting a low genetic divergence. Comparison of quality metrics between the total SNP set (122,000 + 62,000 = 184,000 SNPs) and the validated subset shows similar characteristics for both sets. This indicates that we have detected a large amount (similar to 150,000) of accurately inferred mallard SNPs, which will benefit bird evolutionary studies, ecological studies (e. g. disentangling migratory connectivity) and industrial breeding programs.
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