| 51. |
- Slater, Ben, 1987-, et al.
(author)
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A cryptic record of Burgess Shale-type diversity from the early Cambrian of Baltica
- 2017
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In: Palaeontology. - : Wiley-Blackwell Publishing Inc.. - 0031-0239 .- 1475-4983. ; 60:1, s. 117-140
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Journal article (peer-reviewed)abstract
- Exceptionally preserved ‘Burgess Shale-type’ fossil assemblages from the Cambrian of Laurentia, South China and Australia record a diverse array of non-biomineralizing organisms. During this time, the palaeocontinent Baltica was geographically isolated from these regions, and is conspicuously lacking in terms of comparable accessible early Cambrian Lagerstätten. Here we report a diverse assemblage of small carbonaceous fossils (SCFs) from the early Cambrian (Stage 4) File Haidar Formation of southeast Sweden and surrounding areas of the Baltoscandian Basin, including exceptionally preserved remains of Burgess Shale-type metazoans and other organisms. Recovered SCFs include taxonomically resolvable ecdysozoan elements (priapulid and palaeoscolecid worms), lophotrochozoan elements (annelid chaetae and wiwaxiid sclerites), as well as ‘protoconodonts’, denticulate feeding structures, and a background of filamentous and spheroidal microbes. The annelids, wiwaxiids and priapulids are the first recorded from the Cambrian of Baltica. The File Haidar SCF assemblage is broadly comparable to those recovered from Cambrian basins in Laurentia and South China, though differences at lower taxonomic levels point to possible environmental or palaeogeographical controls on taxon ranges. These data reveal a fundamentally expanded picture of early Cambrian diversity on Baltica, and provide key insights into high-latitude Cambrian faunas and patterns of SCF preservation. We establish three new taxa based on large populations of distinctive SCFs: Baltiscalida njorda gen. et sp. nov. (a priapulid), Baltichaeta jormunganda gen. et sp. nov. (an annelid) and Baltinema rana gen. et sp. nov. (a filamentous problematicum).
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| 52. |
- Slater, Ben, 1987-, et al.
(author)
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Cochleatina: an enigmatic Ediacaran-Cambrian survivor among small carbonaceous fossils (SCFs)
- 2020
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In: Palaeontology. - : Wiley-Blackwell. - 0031-0239 .- 1475-4983. ; 63:5, s. 733-752
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Journal article (peer-reviewed)abstract
- Conspicuously few body‐fossil taxa are known to span the Ediacaran–Cambrian boundary, a pattern usually taken to signal either a terminal Proterozoic mass extinction, or taphonomic failure. We draw attention to the emerging record of small carbonaceous fossils (SCFs), which exhibit continuous preservation spanning this critical interval. Here we focus on the enigmatic SCF Cochleatina, a morphologically complex coil‐shaped problematicum that ranges across the Ediacaran–Cambrian divide, and is potentially among the oldest fossil occurrences of metazoans. We report new material of Cochleatina canilovica from the Ediacaran of Estonia and Ukraine, which offers new characters for assessing its palaeobiology. Significantly, new specimens include sets of three‐alike triplets of Cochleatina adhering to organic sheets, suggesting a clustering habit, or grouping of elements within an individual during life; an important step in constraining the morphology and ecology of this Ediacaran–Cambrian problematicum. We present revised systematic descriptions for Cochleatina and C. canilovica, and critically evaluate previous biological interpretations, drawing comparisons with metazoan, algal and protistan analogues. We reject hypotheses supporting Cochleatina as a metazoan mouthpart, and suggest new grounds for viewing Cochleatina as a potential multicomponent predator that trapped protists among microbial mats. Most occurrences are from Baltica, but we synthesize sporadic reports of Cochleatina from other palaeocontinents, pointing to its global distribution during the latest ˜10 myr of the Ediacaran and majority of the earliest Cambrian Fortunian Stage. As a rare example of an ‘Ediacaran survivor’, Cochleatina highlights the broader significance of SCFs as a novel means of tracking evolutionary patterns through the Proterozoic–Phanerozoic transition.
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| 53. |
- Slater, Ben J., 1987-, et al.
(author)
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Crossing the boundary : small carbonaceous fossils (SCFs) as a means of tracking Ediacaran–Cambrian 'survivors'
- 2020
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Conference paper (peer-reviewed)abstract
- Only a handful of body‐fossil taxa are known to span the Ediacaran–Cambrian boundary. This pattern has frequently been interpreted as signifying a terminal Proterozoic mass extinction; however, identification of such major evolutionary perturbations is heavily reliant on taphonomic continuity. Unfortunately, the traceability of taxa over this boundary is seriously compromised; the coincident opening and closure of several key taphonomic windows around the Ediacaran–Cambrian transition hampers any detailed tracking of taxonomic ranges from this interval, a problem that may amplify the apparent disconnect between Ediacaran and Cambrian biotas. Before a precise outline of the magnitude, timing and nature of this transition can reasonably be achieved, it is crucial to establish an improved record of non‐biomineralizing taxa in order to distinguish genuine macroevolutionary patterns from any obscuring taphonomic signals. The emerging record of small carbonaceous fossils (SCFs) exhibits a more-or-less continuous pattern of preservation spanning this critical interval. We focus on a number of distinctive SCF taxa (including possible metazoans) that range across the Ediacaran–Cambrian divide. These rare additions to the select club of ‘Ediacaran survivors’ highlight the wider significance of SCFs as a novel source of tracking evolutionary patterns over the Proterozoic–Phanerozoic transition.
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| 54. |
- Slater, Ben, 1987-, et al.
(author)
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Small carbonaceous fossils (SCFs) from the Terreneuvian (lower Cambrian) of Baltica
- 2018
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In: Palaeontology. - : Wiley. - 0031-0239 .- 1475-4983. ; 61:3, s. 417-439
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Journal article (peer-reviewed)abstract
- We describe a new assemblage of small carbonaceous fossils (SCFs) from diagenetically minimally altered clays and siltstones of Terreneuvian age from the Lontova and Voosi formations of Estonia, Lithuania and Russia. This is the first detailed account of an SCF assemblage from the Terreneuvian and includes a number of previously undocumented Cambrian organisms. Recognizably bilaterian-derived SCFs include abundant protoconodonts (total-group Chaetognatha), and distinctive cuticular spines of scalidophoran worms. Alongside these metazoan remains are a range of protistan-grade fossils, including Retiranus balticus gen. et sp. nov., a distinctive funnel-shaped or sheet-like problematicum characterized by terminal or marginal vesicles, and Lontohystrichosphaera grandis gen. et sp. nov., a large (100–550 μm) ornamented vesicular microfossil. Together these data offer a fundamentally enriched view of Terreneuvian life in the epicratonic seas of Baltica, from an episode where records of non-biomineralized life are currently sparse. Even so, the recovered assemblages contain a lower diversity of metazoans than SCF biotas from younger (Stage 4) Baltic successions that represent broadly equivalent environments, echoing the diversification signal recorded in the coeval shelly and trace-fossil records. Close comparison to the biostratigraphical signal from Fortunian small shelly fossils supports a late Fortunian age for most of the Lontova/Voosi succession, rather than a younger (wholly Stage 2) range.
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| 55. |
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| 56. |
- Thrift, Aaron P, et al.
(author)
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Obesity and risk of esophageal adenocarcinoma and Barrett's esophagus : a Mendelian randomization study.
- 2014
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In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 106:11
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Journal article (peer-reviewed)abstract
- BACKGROUND: Data from observational studies suggest that body mass index (BMI) is causally related to esophageal adenocarcinoma (EAC) and its precursor, Barrett's esophagus (BE). However, the relationships may be affected by bias and confounding.METHODS: We used data from the Barrett's and Esophageal Adenocarcinoma Genetic Susceptibility Study: 999 patients with EAC, 2061 patients with BE, and 2169 population controls. We applied the two-stage control function instrumental variable method of the Mendelian randomization approach to estimate the unbiased, unconfounded effect of BMI on risk of EAC and BE. This was performed using a genetic risk score, derived from 29 genetic variants shown to be associated with BMI, as an instrument for lifetime BMI. A higher score indicates propensity to obesity. All tests were two-sided.RESULTS: The genetic risk score was not associated with potential confounders, including gastroesophageal reflux symptoms and smoking. In the instrumental variable analyses (IV), EAC risk increased by 16% (IV-odds ratio [OR] = 1.16, 95% confidence interval [CI] = 1.01 to 1.33) and BE risk increased by 12% (IV-OR = 1.12, 95% CI = 1.00 to 1.25) per 1kg/m(2) increase in BMI. BMI was statistically significantly associated with EAC and BE in conventional epidemiologic analyses.CONCLUSIONS: People with a high genetic propensity to obesity have higher risks of esophageal metaplasia and neoplasia than people with low genetic propensity. These analyses provide the strongest evidence to date that obesity is independently associated with BE and EAC, and is not due to confounding or bias inherent in conventional epidemiologic analyses.
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| 57. |
- Tobias, Jonathan H., et al.
(author)
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Femoral neck width genetic risk score is a novel independent risk factor for hip fractures
- 2024
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In: JOURNAL OF BONE AND MINERAL RESEARCH. - 0884-0431 .- 1523-4681. ; 39:3, s. 241-251
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Journal article (peer-reviewed)abstract
- Femoral neck width (FNW) derived from DXA scans may provide a useful adjunct to hip fracture prediction. Therefore, we investigated whether FNW is related to hip fracture risk independently of femoral neck bone mineral density (FN-BMD), using a genetic approach. FNW was derived from points automatically placed on the proximal femur using hip DXA scans from 38 150 individuals (mean age 63.8 yr, 48.0% males) in UK Biobank (UKB). Genome-wide association study (GWAS) identified 71 independent genome-wide significant FNW SNPs, comprising genes involved in cartilage differentiation, hedgehog, skeletal development, in contrast to SNPs identified by FN-BMD GWAS which primarily comprised runx1/Wnt signaling genes (MAGMA gene set analyses). FNW and FN-BMD SNPs were used to generate genetic instruments for multivariable Mendelian randomization. Greater genetically determined FNW increased risk of all hip fractures (odds ratio [OR] 1.53; 95% CI, 1.29-1.82 per SD increase) and femoral neck fractures (OR 1.58;1.30-1.92), but not trochanteric or forearm fractures. In contrast, greater genetically determined FN-BMD decreased fracture risk at all 4 sites. FNW and FN-BMD SNPs were also used to generate genetic risk scores (GRSs), which were examined in relation to incident hip fracture in UKB (excluding the FNW GWAS population; n = 338 742, 3222 cases) using a Cox proportional hazards model. FNW GRS was associated with increased risk of all incident hip fractures (HR 1.08;1.05-1.12) and femoral neck fractures (hazard ratio [HR] 1.10;1.06-1.15), but not trochanteric fractures, whereas FN-BMD GRS was associated with reduced risk of all hip fracture types. We conclude that the underlying biology regulating FNW and FN-BMD differs, and that DXA-derived FNW is causally related to hip fractures independently of FN-BMD, adding information beyond FN-BMD for hip fracture prediction. Hence, FNW derived from DXA analyses or a FNW GRS may contribute clinically useful information beyond FN-BMD for hip fracture prediction. Femoral neck width (FNW) derived from DXA scans may provide useful information about hip fracture prediction, over and above that provided by BMD measurements. Therefore, we investigated whether FNW is related to hip fracture risk independently of BMD, using a genetic approach. FNW was derived from points automatically placed on the hip in DXA scans obtained from 38 150 individuals (mean age 63.8 yr, 48.0% males) in UK Biobank. Seventy-one distinct genetic factors were found to be associated with FNW. Individuals who were predicted by their genes to have greater FNW had a higher risk of hip but not forearm fractures. In contrast, those with greater genetically determined BMD of the femoral neck had a lower risk of both hip and forearm fractures. We conclude that the underlying biology regulating FNW and BMD of the femoral neck differs, and that FNW derived from DXA analyses may contribute clinically useful information beyond BMD for hip fracture prediction.
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| 58. |
- Voisin, Sarah, et al.
(author)
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An epigenetic clock for human skeletal muscle
- 2020
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In: Journal of Cachexia, Sarcopenia and Muscle. - : Wiley. - 2190-5991 .- 2190-6009. ; 11:4, s. 887-898
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Journal article (peer-reviewed)abstract
- Background: Ageing is associated with DNA methylation changes in all human tissues, and epigenetic markers can estimate chronological age based on DNA methylation patterns across tissues. However, the construction of the original pan‐tissue epigenetic clock did not include skeletal muscle samples and hence exhibited a strong deviation between DNA methylation and chronological age in this tissue.Methods: To address this, we developed a more accurate, muscle‐specific epigenetic clock based on the genome‐wide DNA methylation data of 682 skeletal muscle samples from 12 independent datasets (18–89 years old, 22% women, 99% Caucasian), all generated with Illumina HumanMethylation (HM) arrays (HM27, HM450, or HMEPIC). We also took advantage of the large number of samples to conduct an epigenome‐wide association study of age‐associated DNA methylation patterns in skeletal muscle.Results: The newly developed clock uses 200 cytosine‐phosphate–guanine dinucleotides to estimate chronological age in skeletal muscle, 16 of which are in common with the 353 cytosine‐phosphate–guanine dinucleotides of the pan‐tissue clock. The muscle clock outperformed the pan‐tissue clock, with a median error of only 4.6 years across datasets (vs. 13.1 years for the pan‐tissue clock, P < 0.0001) and an average correlation of ρ = 0.62 between actual and predicted age across datasets (vs. ρ = 0.51 for the pan‐tissue clock). Lastly, we identified 180 differentially methylated regions with age in skeletal muscle at a false discovery rate < 0.005. However, gene set enrichment analysis did not reveal any enrichment for gene ontologies.Conclusions: We have developed a muscle‐specific epigenetic clock that predicts age with better accuracy than the pan‐tissue clock. We implemented the muscle clock in an r package called Muscle Epigenetic Age Test available on Bioconductor to estimate epigenetic age in skeletal muscle samples. This clock may prove valuable in assessing the impact of environmental factors, such as exercise and diet, on muscle‐specific biological ageing processes.
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| 59. |
- Voisin, Sarah, et al.
(author)
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Exercise is associated with younger methylome and transcriptome profiles in human skeletal muscle
- 2024
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In: Aging Cell. - 1474-9726. ; , s. 1-15
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Journal article (peer-reviewed)abstract
- Exercise training prevents age-related decline in muscle function. Targeting epigenetic aging is a promising actionable mechanism and late-life exercise mitigates epigenetic aging in rodent muscle. Whether exercise training can decelerate, or reverse epigenetic aging in humans is unknown. Here, we performed a powerful meta-analysis of the methylome and transcriptome of an unprecedented number of human skeletal muscle samples (n = 3176). We show that: (1) individuals with higher baseline aerobic fitness have younger epigenetic and transcriptomic profiles, (2) exercise training leads to significant shifts of epigenetic and transcriptomic patterns toward a younger profile, and (3) muscle disuse "ages" the transcriptome. Higher fitness levels were associated with attenuated differential methylation and transcription during aging. Furthermore, both epigenetic and transcriptomic profiles shifted toward a younger state after exercise training interventions, while the transcriptome shifted toward an older state after forced muscle disuse. We demonstrate that exercise training targets many of the age-related transcripts and DNA methylation loci to maintain younger methylome and transcriptome profiles, specifically in genes related to muscle structure, metabolism, and mitochondrial function. Our comprehensive analysis will inform future studies aiming to identify the best combination of therapeutics and exercise regimes to optimize longevity.
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| 60. |
- Westbury, Leo D., et al.
(author)
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Predictive value of sarcopenia components for all-cause mortality: findings from population-based cohorts
- 2024
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In: AGING CLINICAL AND EXPERIMENTAL RESEARCH. - : Springer. - 1594-0667 .- 1720-8319. ; 36:1
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Journal article (peer-reviewed)abstract
- Background Low grip strength and gait speed are associated with mortality. However, investigation of the additional mortality risk explained by these measures, over and above other factors, is limited.Aim We examined whether grip strength and gait speed improve discriminative capacity for mortality over and above more readily obtainable clinical risk factors.Methods Participants from the Health, Aging and Body Composition Study, Osteoporotic Fractures in Men Study, and the Hertfordshire Cohort Study were analysed. Appendicular lean mass (ALM) was ascertained using DXA; muscle strength by grip dynamometry; and usual gait speed over 2.4-6 m. Verified deaths were recorded. Associations between sarcopenia components and mortality were examined using Cox regression with cohort as a random effect; discriminative capacity was assessed using Harrell's Concordance Index (C-index).Results Mean (SD) age of participants (n = 8362) was 73.8(5.1) years; 5231(62.6%) died during a median follow-up time of 13.3 years. Grip strength (hazard ratio (95% CI) per SD decrease: 1.14 (1.10,1.19)) and gait speed (1.21 (1.17,1.26)), but not ALM index (1.01 (0.95,1.06)), were associated with mortality in mutually-adjusted models after accounting for age, sex, BMI, smoking status, alcohol consumption, physical activity, ethnicity, education, history of fractures and falls, femoral neck bone mineral density (BMD), self-rated health, cognitive function and number of comorbidities. However, a model containing only age and sex as exposures gave a C-index (95% CI) of 0.65(0.64,0.66), which only increased to 0.67(0.67,0.68) after inclusion of grip strength and gait speed.Conclusions Grip strength and gait speed may generate only modest adjunctive risk information for mortality compared with other more readily obtainable risk factors.
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