| 1. |
- Jones, G., et al.
(författare)
-
Genome-wide meta-analysis of muscle weakness identifies 15 susceptibility loci in older men and women
- 2021
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- Low muscle strength is an important heritable indicator of poor health linked to morbidity and mortality in older people. In a genome-wide association study meta-analysis of 256,523 Europeans aged 60 years and over from 22 cohorts we identify 15 loci associated with muscle weakness (European Working Group on Sarcopenia in Older People definition: n=48,596 cases, 18.9% of total), including 12 loci not implicated in previous analyses of continuous measures of grip strength. Loci include genes reportedly involved in autoimmune disease (HLA-DQA1p=4x10(-17)), arthritis (GDF5p=4x10(-13)), cell cycle control and cancer protection, regulation of transcription, and others involved in the development and maintenance of the musculoskeletal system. Using Mendelian randomization we report possible overlapping causal pathways, including diabetes susceptibility, haematological parameters, and the immune system. We conclude that muscle weakness in older adults has distinct mechanisms from continuous strength, including several pathways considered to be hallmarks of ageing. Muscle weakness has been associated with morbidity and mortality in older people. Here, the authors have investigated this trait further by performing a genome-wide meta-analysis of grip strength and Mendelian randomization to discover causal relationships between muscle weakness and other diseases.
|
|
| 2. |
- Medina-Gomez, C., et al.
(författare)
-
Bone mineral density loci specific to the skull portray potential pleiotropic effects on craniosynostosis
- 2023
-
Ingår i: Communications Biology. - 2399-3642. ; 6:1
-
Tidskriftsartikel (refereegranskat)abstract
- Skull bone mineral density (SK-BMD) provides a suitable trait for the discovery of key genes in bone biology, particularly to intramembranous ossification, not captured at other skeletal sites. We perform a genome-wide association meta-analysis (n similar to 43,800) of SK-BMD, identifying 59 loci, collectively explaining 12.5% of the trait variance. Association signals cluster within gene-sets involved in skeletal development and osteoporosis. Among the four novel loci (ZIC1, PRKAR1A, AZIN1/ATP6V1C1, GLRX3), there are factors implicated in intramembranous ossification and as we show, inherent to craniosynostosis processes. Functional follow-up in zebrafish confirms the importance of ZIC1 on cranial suture patterning. Likewise, we observe abnormal cranial bone initiation that culminates in ectopic sutures and reduced BMD in mosaic atp6v1c1 knockouts. Mosaic prkar1a knockouts present asymmetric bone growth and, conversely, elevated BMD. In light of this evidence linking SK-BMD loci to craniofacial abnormalities, our study provides new insight into the pathophysiology, diagnosis and treatment of skeletal diseases.
|
|
| 3. |
- Bicknell, Russell D. C., et al.
(författare)
-
Cambrian carnage : Trilobite predator-prey interactions in the Emu Bay Shale of South Australia
- 2022
-
Ingår i: Palaeogeography, Palaeoclimatology, Palaeoecology. - : Elsevier. - 0031-0182 .- 1872-616X. ; 591
-
Tidskriftsartikel (refereegranskat)abstract
- The Cambrian explosion represents the rapid emergence of complex marine ecosystems on Earth. The propagation of predator-prey interactions within these systems was almost certainly one of the major drivers of this evolutionary event, sparking an arms race that promoted the proliferation of biomineralised exoskeletons and shells, and the evolution of the first durophagous (shell-crushing) predators. The most commonly documented evidence of Cambrian durophagous predation comes from injured trilobites. However, quantitative analysis based on multiple specimens from single localities is lacking. Such studies are required to reveal the dynamics of ancient predator-prey systems at fine ecological scales (e.g. at the population or community level). This study documents injured specimens of two trilobite species, Redlichia takooensis and Redlichia rex, from the Emu Bay Shale Konservat-Lagersta center dot tte (Cambrian Series 2, Stage 4) on Kangaroo Island, South Australia. A total of 38 injured specimens exhibiting various healed cephalic and thoracic injuries are documented, in addition to the mangled remains of two individuals that probably resulted from the activities of a durophagous predator or scavenger. Specimens of both species show that most injuries are located on the posterior portion of the thorax, indicating that predators preferentially attacked from behind and/or prey individuals presented the posterior of the trunk towards the predator when threatened or fleeing. The larger sample of injured R. takooensis shows that while unilateral injuries are more common than bilateral ones, there is no evidence for a left-or right-side bias, contrasting with previous suggestions that Cambrian trilobites exhibit right-sided injury stereotypy. Comparing the position of injured and non-injured R. takooensis and R. rex in bivariate space, we illustrate that injured specimens of both species typically represent some of the largest individuals of these taxa. This suggests that smaller individuals were completely consumed during an attack and/or larger individuals were more likely to survive an attack and thus record a healed injury. We argue that R. rex, rather than radiodonts, was likely the chief producer of exoskeletal injuries and large shelly coprolites in the Emu Bay Shale biota, and represents one of the earliest cannibalistic trilobites.
|
|
| 4. |
|
|
| 5. |
- Bicknell, Russell D. C., et al.
(författare)
-
Habitat and developmental constraints drove 330 million years of horseshoe crab evolution
- 2022
-
Ingår i: Biological Journal of the Linnean Society. - : Oxford University Press (OUP). - 0024-4066 .- 1095-8312. ; 136:1, s. 155-172
-
Tidskriftsartikel (refereegranskat)abstract
- Records of evolutionary stasis over time are central to uncovering large-scale evolutionary modes, whether by long-term gradual change or via enduring stability punctuated by rapid shifts. The key to this discussion is to identify and examine groups with long fossil records that, ideally, extend to the present day. One group often regarded as the quintessential example of stasis is Xiphosurida, the horseshoe crabs. However, when, how and, particularly, why stasis arose in xiphosurids remain fundamental, but complex, questions. Here, we explore the protracted history of fossil and living xiphosurids and demonstrate two levels of evolutionary stability: developmental stasis since at least the Pennsylvanian and shape stasis since the Late Jurassic. Furthermore, shape and diversity are punctuated by two high-disparity episodes during the Carboniferous and Triassic - transitions that coincide with forays into habitation of marginal environments. In an exception to these general patterns, body size increased gradually over this period and, thus, cannot be described under the same, often-touted, static models of evolution. Therefore, we demonstrate that evolutionary stasis can be modular and fixed within the same group at different periods and in different biological traits, while other traits experience altogether different evolutionary modes. This mosaic in the tempo and mode of evolution is not unique to Xiphosurida but likely reflects variable mechanisms acting on biological traits, for example transitions in life modes, niche occupation and major evolutionary radiations.
|
|
| 6. |
- Frauenfelder, Timothy G., et al.
(författare)
-
New Ankylosaurian Cranial Remains From the Lower Cretaceous (Upper Albian) Toolebuc Formation of Queensland, Australia
- 2022
-
Ingår i: Frontiers in Earth Science. - : Frontiers Media S.A.. - 2296-6463. ; 10
-
Tidskriftsartikel (refereegranskat)abstract
- Australian dinosaur research has undergone a renaissance in the last 10 years, with growing knowledge of mid-Cretaceous assemblages revealing an endemic high-paleolatitude Gondwanan fauna. One of its most conspicuous members is ankylosaurs, which are rare but nonetheless occur in most Australian dinosaur-bearing formations spanning the uppermost Barremian to lower Cenomanian. Here we describe a partial ankylosaur skull from the marine Toolebuc Formation exposed near Boulia in western Queensland, Australia. This skull represents the oldest ankylosaurian material from Queensland, predating the holotype of Kunbarrasaurus ieversi, which was found in the overlying Allaru Mudstone. The ankylosaur skull is encased in a limestone concretion with the maxillary tooth rows preserved only as impressions. Synchrotron radiation X-ray tomography was used to non-destructively image and reconstruct the specimen in 3D and facilitate virtual preparation of the separate cranial bones. The reconstruction of the skull revealed the vomer, palatines, sections of the ectopterygoids and maxillae, and multiple teeth. The palate has posteriorly positioned choanae that differs from the more anterior placement seen in most other ankylosaurians, but which is shared with K. ieversi, Akainacephalus johnsoni, Cedarpelta bilbeyhallorum, Gobisaurus domoculus, and Panoplosaurus mirus. Phylogenetic analyses place the new cranial material within the recently named basal ankylosaurian clade Parankylosauria together with K. ieversi. This result, together with the anatomical similarities to the holotype of K. ieversi, permits its referral to cf. Kunbarrasaurus sp. This specimen elucidates the palatal anatomy of Australian ankylosaurs and highlights one of the most ubiquitous components of Australian mid-Cretaceous dinosaur faunas.
|
|
| 7. |
- Munshi, Bijit, et al.
(författare)
-
Surgical Decision Making in Uncomplicated Type B Aortic Dissection : A Survey of Australian/New Zealand and European Surgeons
- 2020
-
Ingår i: European Journal of Vascular and Endovascular Surgery. - : W B SAUNDERS CO LTD. - 1078-5884 .- 1532-2165. ; 60:2, s. 194-200
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: There is controversy about the role of pre-emptive thoracic endovascular aortic repair (TEVAR) in uncomplicated type B aortic dissection (TBAD). The aim was to understand expert opinions and the factors influencing decision making. Methods: In 2018, surgeons from Australia/New Zealand (ANZ) and Europe (EUR) were contacted to participate in an online survey which comprised questions about preferences for pre-emptive TEVAR, followed by five case scenarios, and two ranking questions for anatomical and technical risk factors respectively. Case 1 was designed to favour TEVAR in a hypertensive patient with partial false lumen thrombosis and large diameter (aortic >= 40 mm, false lumen >= 22 mm). Case 2 had no risk factors mandating TEVAR, according to current evidence. Cases 3, 4, and 5 were designed to test one risk factor respectively, large entry tear on the inner aortic curvature (>= 10 mm), partial false lumen thrombosis, and large diameter alone. Results: There were 75 responses, 42 from EUR and 33 from ANZ. Almost half of surgeons (49.3%) endorsed preemptive TEVAR with 82.3% preferring to perform TEVAR in the subacute phase. In Case 1 and 5, 58.3% and 52.8% of surgeons respectively chose TEVAR, the highest rates obtained in the survey. Cases 1 and 5 included large diameters >= 40 mm, which were ranked the highest in importance when surgeons considered anatomical risk factors. Surgeons who recommend pre-emptive TEVAR were more likely to choose TEVAR in both Case 1 (83.3% vs. 33.3%, p < .001, 95% CI 27.6%-65.8%) and Case 5 (69.4% vs. 38.2%, p = .008, 95% CI 8.2%-50.0%). Conclusion: In this survey about uncomplicated TBAD, about half of surgeons recommended pre-emptive TEVAR in selected cases. The surgeon's predisposition towards intervention and large diameters appear to be the most influential factors in decision making. These findings underline the uncertainty in today's practice and emphasise the need for better predictive tools.
|
|
